06/21/2024
CATEGORY:
Validation is based on results from CheckMate -67T, the first Phase 3 trial of the subcutaneous formulation of Opdivo to evaluate and demonstrate noninferior pharmacokinetics and efficacy vs. its intravenous formulation
Application seeks approval for subcutaneous nivolumab formulation to treat multiple Opdivo adult solid tumor indications in the European Union
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY)
today announced that the European Medicines Agency (EMA) has validated the extension application to introduce a new route of administration (subcutaneous use) for Opdivo ® (nivolumab) that includes a new pharmaceutical form (solution for injection) and a new strength (600 mg/vial) across multiple previously approved adult solid tumor indications as monotherapy, monotherapy maintenance following completion of nivolumab plus ipilimumab combination therapy, or in combination with chemotherapy or cabozantinib, based on the results from the Phase 3 CheckMate -67T study. Validation of the application confirms the submission is complete and begins the EMA’s centralized review procedure.
“Subcutaneous nivolumab has the potential to change the way patients living with cancer receive Opdivo treatment and to significantly reduce administration time by utilizing a single injection in three-to-five minutes. By providing patients the same quality of care as IV Opdivo in a fraction of the time, patients can focus on what is important to them rather than spending a longer wait time at the infusion center,” said Susan Parker, vice president, global program lead, product design & development, Bristol Myers Squibb. “We are committed to advancing medicines that improve the patient experience and are evaluating innovative formulations across our broad portfolio. We look forward to working with the EMA to advance this application with the goal of introducing the subcutaneous option of Opdivo.”
In the Phase 3 CheckMate -67T trial, subcutaneous nivolumab demonstrated noninferiority of Cavgd28 (time-averaged Opdivo serum concentration over 28 days) and Cminss (trough serum concentration at steady state), the study’s primary endpoints, vs. intravenous (IV) Opdivo in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received no more than two prior lines of systemic therapy. Additionally, subcutaneous nivolumab showed noninferiority of the key secondary endpoint of objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) vs. IV Opdivo. The safety profile of subcutaneous nivolumab was consistent with the IV formulation. The pharmacokinetics, efficacy and safety results from CheckMate -67T were presented at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. Additional safety analyses and patient reported outcomes were recently presented at the 2024 ASCO Annual Meeting.
About CheckMate -67T
CheckMate -67T is a Phase 3 randomized, open-label trial evaluating subcutaneous administration of Opdivo co-formulated with Halozyme’s proprietary recombinant human hyaluronidase, rHuPH20, or subcutaneous nivolumab (nivolumab and hyaluronidase) compared to intravenous Opdivo, in patients with advanced or metastatic ccRCC who have received prior systemic therapy. This trial presents an opportunity to potentially bring a subcutaneous formulation of Opdivo to patients. A total of 495 patients were randomized to either subcutaneous nivolumab or intravenous Opdivo. The co-primary endpoints of the trial are time-averaged serum concentration over 28 days (Cavgd28) and trough serum concentration at steady-state (Cminss) of subcutaneous nivolumab vs. intravenous Opdivo. Objective response rate (ORR) is a key secondary endpoint.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In September 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
INDICATIONS
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.
OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.
OPDIVO® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma.
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
Please see U.S. Full Prescribing Information for OPDIVO and YERVOY.
Clinical Trials and Patient Populations
Checkmate 227–previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238–adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K–adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 648–previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma
About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, X (formerly Twitter), YouTube, Facebook and Instagram.
Jun. 21, 2024 7:25 AM ET
Bristol-Myers Squibb Company (BMY) Stock, HALO Stock
By: Dulan Lokuwithana, SA News Editor1 Comment
Bristol Myers Squibb (NYSE:BMY) announced Friday that the EU drug regulator, the European Medicines Agency (EMA), validated its request to expand the approval for its cancer therapy Opdivo (nivolumab) to include a subcutaneous formulation.
The PD-1 immune checkpoint inhibitor is already approved in the region as an intravenous infusion for several forms of solid tumors as a single agent or in combination with other medications, such as BMY’s CTLA-4-blocking antibody, Yervoy.
On June 17, 2024, the Food and Drug Administration approved pembrolizumab (Keytruda, Merck) with carboplatin and paclitaxel, followed by single-agent pembrolizumab, for adult patients with primary advanced or recurrent endometrial carcinoma.
Full prescribing information for Keytruda will be posted on Drugs@FDA.
Efficacy was evaluated in KEYNOTE-868/NRG-GY018 (NCT03914612), a multicenter, randomized, double-blind, placebo-controlled trial enrolling 810 patients with advanced or recurrent endometrial carcinoma. The trial included two separate cohorts based on mismatch repair (MMR) status: 222 patients in the mismatch repair deficient (dMMR) cohort, and 588 patients in the mismatch repair (pMMR) proficient cohort. Patients were randomized (1:1) to one of the following treatment arms:
Randomization was stratified according to MMR status, ECOG performance status (0 or 1 vs. 2), and prior adjuvant chemotherapy.
The major efficacy outcome measure was progression-free survival (PFS), assessed by the investigator according to RECIST 1.1. In the dMMR cohort, median PFS was not reached (NR) (95% CI: 30.7, NR) in the pembrolizumab and chemotherapy arm and 6.5 months (95% CI: 6.4, 8.7) in the placebo and chemotherapy arm (Hazard ratio [HR] 0.30 [95% CI: 0.19, 0.48]; p-value <0.0001). In the pMMR cohort, median PFS was 11.1 months (95% CI: 8.7, 13.5) in the pembrolizumab and chemotherapy arm and 8.5 months (95% CI: 7.2, 8.8) for those receiving placebo and chemotherapy arm (HR 0.60 [95% CI: 0.46, 0.78; p-value <0.0001).
Adverse reactions associated with pembrolizumab and chemotherapy were generally similar to those previously reported for pembrolizumab or chemotherapy with the exception of a higher incidence of rash. See the prescribing information for complete adverse reactions.
The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada (HC), and Israel’s Ministry of Health (IMoH). The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
Follow the Oncology Center of Excellence on X @FDAOncology
Jun. 17, 2024 1:47 PM ET
By: Jonathan Block, SA News Editor
https://www.nasdaq.com/market-activity/stocks/mrk/dividend-history
PUBLISHED17 June 2024
AstraZeneca’s Imfinzi (durvalumab) in combination with carboplatin and paclitaxel followed by Imfinzi monotherapy has been approved in the US as treatment for adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).1
The approval by the Food and Drug Administration (FDA) was based on the results of a prespecified exploratory subgroup analysis by MMR status in the DUO-E Phase III trial. Results from DUO-E were published in the Journal of Clinical Oncology.
In the trial, Imfinzi plus carboplatin and paclitaxel followed by Imfinzi monotherapy (Imfinzi arm) reduced the risk of disease progression or death by 58% in patients with dMMR endometrial cancer versus chemotherapy alone (hazard ratio 0.42; 95% confidence interval 0.22-0.80).2
In the US, endometrial cancer is the fourth most common cancer in women, with more than 66,000 patients diagnosed and almost 12,000 deaths in 2022.3,4 Patients diagnosed at an early stage of disease have a five-year survival rate of approximately 80-90%, but there is a significant need for new treatment options for people with advanced disease, where the survival rate falls to less than 20%.5,6
Shannon N. Westin, Professor of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center, and principal investigator of the trial, said, “With the incidence and mortality of endometrial cancer expected to continue to increase significantly in the coming decades, it is more important than ever that we bring new treatment options to patients at the earliest possible moment in their care. This approval underlines clear evidence that durvalumab plus chemotherapy followed by durvalumab monotherapy delivers important clinical benefits for patients with mismatch repair deficient endometrial cancer.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “There have been limited advances in the treatment of endometrial cancer in the last few decades, and continued innovation is critical as the burden of this cancer is expected to grow in the future. Immunotherapy in combination with chemotherapy is emerging as a new standard of care in this setting, and the approval of Imfinzi offers an important new option for patients with mismatch repair deficient disease.”
The safety and tolerability profile of the Imfinzi and chemotherapy regimen was generally manageable, well tolerated and broadly consistent with prior clinical trials with no new safety signals.1,2
The Lynparza (olaparib) and Imfinzi arm, which investigated Imfinzi plus chemotherapy followed by Imfinzi plus Lynparza as maintenance therapy, also met the primary endpoint of progression-free survival (PFS). The trial continues to assess OS as a key secondary endpoint for both arms. Regulatory applications for both Imfinzi as well as Imfinzi and Lynparza regimens are currently under review in the EU, Japan and several other countries based on the DUO-E results.
Notes
Endometrial cancer
Endometrial cancer is a highly heterogeneous disease that originates in the tissue lining of the uterus and is most common in women who have already been through menopause, with the average age at diagnosis being over 60 years old.7-10 It is the sixth most common cancer in women worldwide.11,12 Incidence and mortality of endometrial cancer are expected to increase by approximately 61% and 87% respectively (from 420,400 cases and 97,700 deaths in 2022 to 676,300 cases and 183,100 deaths) in 2050.13
The majority of patients with endometrial cancer are diagnosed at an early stage of disease, where the cancer is confined to the uterus.9,10 They are typically treated with surgery and/or radiation, and the five-year survival rate is high (approximately 80-90%).5,6 Patients with advanced disease (Stage III-IV) usually have a much poorer prognosis, with the five-year survival rate falling to less than 20%.5,6 Immunotherapy combined with chemotherapy is emerging as a new standard of care for advanced endometrial cancer, particularly for patients with dMMR disease, who make up approximately 20-30% of all patients with this type of cancer.6,14,15,16 There remains a high unmet need for treatments for the remaining 70-80% of endometrial cancer patients with pMMR disease.15,16
DUO-E
The DUO-E trial (GOG 3041/ENGOT-EN10) is a three-arm, randomised, double-blind, placebo-controlled, multicentre Phase III trial of 1st-line Imfinzi (durvalumab) plus platinum-based chemotherapy (carboplatin and paclitaxel) followed by either Imfinzi monotherapy or Imfinzi plus Lynparza (olaparib) as maintenance therapy versus platinum-based chemotherapy alone as a treatment for patients with newly diagnosed advanced or recurrent endometrial cancer.
The DUO-E trial randomised 699 patients with newly diagnosed advanced or recurrent epithelial endometrial carcinoma to receive either Imfinzi (1120mg) or placebo, given every three weeks in addition to standard-of-care platinum-based chemotherapy. After 4-6 cycles of chemotherapy, patients (whose disease had not progressed) then received either Imfinzi (1500mg) or placebo every four weeks as maintenance, plus 300mg Lynparza (300mg BID [2x150mg tablets, twice a day]) or placebo until disease progression.
The dual primary endpoint was PFS of each treatment arm versus standard of care. Key secondary endpoints included overall survival (OS), safety and tolerability. The trial continues to assess OS for both Imfinzi monotherapy and Imfinzi plus Lynparza as maintenance therapy in the overall trial population. Mismatch repair (MMR) status, recurrence status and geographic location were stratification factors. The trial was sponsored independently by AstraZeneca and conducted in 253 study locations across 22 countries including the US, Europe, South America and Asia.
For more information about the trial, please visit ClinicalTrials.gov.
Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.
In addition to its indications in unresectable, Stage III NSCLC and ES-SCLC, Imfinzi is currently approved in a number of countries in combination with a short course of tremelimumab (Imjudo) and chemotherapy for the treatment of metastatic NSCLC.
Imfinzi is also approved in a number of countries in combination with chemotherapy in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU.
Since the first approval in May 2017, more than 220,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal cancers and other solid tumours.
AstraZeneca in immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours.
AstraZeneca aims to reimagine cancer care and help transform outcomes for patients with Imfinzi as monotherapy and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also exploring next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer.
AstraZeneca is boldly pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.
AstraZeneca PLC
Jun. 17, 2024 12:41 PM ET
By: Val Brickates Kennedy, SA News Editor1 Comment
AstraZeneca (NASDAQ:AZN) said the FDA has approved its drug Imfinzi, also known as durvalumab, for the treatment of a certain type of endometrial cancer.
The FDA approved Imfinzi in combination with carboplatin and paclitaxel followed by Imfinzi as a monotherapy in the treatment of adults with primary advanced or recurrent endometrial cancer that is mismatch repair deficient, or dMMR.
BLINCYTO® Added to Multiphase Consolidation Chemotherapy Reduced Risk of Death by 58% Showing Superior Overall Survival Versus Chemotherapy Alone
First and Only Bispecific T-cell Engager (BiTE®) Therapy for Consolidation Treatment Regardless of Measurable Residual Disease (MRD) Status
THOUSAND OAKS, Calif., June 14, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the U.S. Food and Drug Administration (FDA) has approved BLINCYTO® (blinatumomab) for the treatment of adult and pediatric patients one month or older with CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) in the consolidation phase, regardless of measurable residual disease (MRD) status.
"B-ALL is an aggressive blood cancer with enduring high unmet need. BLINCYTO has helped thousands of patients with B-ALL over the last 10 years. Today's approval in the frontline consolidation phase, regardless of MRD status, allows us to reach more patients than ever with this transformative, first-in-class Bispecific T-cell Engager (BiTE®) therapy," said Jay Bradner, M.D., executive vice president, Research and Development, and chief scientific officer at Amgen.
The approval marks the third indication for BLINCYTO and is based primarily on the Phase 3 E1910 clinical trial led by ECOG-ACRIN Cancer Research Group that studied patients with newly diagnosed Philadelphia chromosome-negative B-ALL receiving postinduction consolidation treatment, which aims to deepen remission to achieve durable responses. Study results demonstrated that BLINCYTO added to multiphase consolidation chemotherapy showed superior overall survival (OS) versus chemotherapy alone. The 3-year OS was 84.8% in the BLINCYTO plus chemotherapy arm (n=112) and 69% in the chemotherapy arm (n=112), with the hazard ratio for OS of 0.42. With a median follow-up of 4.5 years, the 5-year OS was 82.4% in the BLINCYTO plus chemotherapy arm and 62.5% in the chemotherapy arm.
"In the E1910 study, blinatumomab reduced risk of death and showed a remarkable improvement in overall survival," said Selina M. Luger, M.D., professor of hematology-oncology at the University of Pennsylvania's Perelman School of Medicine and Abramson Cancer Center, chair of the ECOG-ACRIN Leukemia Committee and an investigator on the study. "This approval redefines the standard of care for patients with B-ALL and provides them with a more effective treatment option than standard chemotherapy alone."
"The risk of B-ALL recurrence after the initial phase of treatment is relatively high, making this approval for patients noteworthy," said E. Anders Kolb, M.D., president and chief executive officer of The Leukemia & Lymphoma Society. "B-ALL is the most common type of ALL and having another effective option available earlier in a patient's treatment journey is critical for clinicians who are working to give these patients more time with their loved ones."
The E1910 study was designed and conducted independently from industry. ECOG-ACRIN sponsored the trial with public funding from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). Other NCI-funded network groups took part in the study. In addition, Amgen provided BLINCYTO and support through an NCI Cooperative Research and Development Agreement.
About Acute Lymphoblastic Leukemia (ALL)
ALL, also known as acute lymphoblastic leukemia, is a fast-growing type of blood cancer that develops in the bone marrow and can sometimes spread to other parts of the body, including the lymph nodes, liver, spleen, and central nervous system. ALL is a rare disease, with 6,540 new cases diagnosed in the U.S. in 2023 affecting both children and adults.1 B-ALL begins in immature cells that would normally develop into B-cell lymphocytes, which are white blood cells that grow in bone marrow.2,3 B-ALL is the most common type of ALL, constituting approximately 75% of cases in adults.4
About BLINCYTO® (blinatumomab)
BLINCYTO is the first globally approved BiTE® immuno-oncology therapy that targets CD19 surface antigens on B cells. BiTE® molecules fight cancer by helping the body's immune system detect and target malignant cells by engaging T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. By bringing T cells near cancer cells, the T cells can inject toxins and trigger cancer cell death (apoptosis). BiTE® immuno-oncology therapies are currently being investigated for their potential to treat a wide variety of cancers.
BLINCYTO was granted breakthrough therapy and Priority Review designations by the U.S. FDA and is approved in the U.S. for the treatment of:
In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of:
INDICATIONS
BLINCYTO® (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients one month and older with:
BLINCYTO® IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
Contraindications
BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.
Please see BLINCYTO® full Prescribing Information, including BOXED WARNINGS.
About BiTE® Technology
Bispecific T-cell Engager (BiTE®) technology is a targeted immuno-oncology platform that is designed to engage patient's own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE® immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE® platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing multiple BiTE® molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE® technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE® technology, visit https://www.amgenoncology.com/bite-platform.html.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.
In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.
For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, TikTok, YouTube and Threads.
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SOURCE Amgen
Jun. 14, 2024 5:13 PM ET
By: Val Brickates Kennedy, SA News Editor
The FDA has granted expanded approval for Amgen’s (NASDAQ:AMGN) Blincyto for the treatment of certain adult and pediatric patients with acute lymphoblastic leukemia, or ALL.
More specifically, the agency approved the drug for patients aged one month or older with CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia, or B-ALL, in the consolidation phase, regardless of measurable residual disease, or MRD, status.
PUBLISHED12 June 2024
AstraZeneca’s Farxiga (dapagliflozin) has been approved by the US Food and Drug Administration (FDA) to improve glycaemic control in paediatric patients with type-2 diabetes (T2D) aged 10 years and older.1 The FDA approval was based on positive results from the paediatric T2NOW Phase III trial.2 Farxiga was previously approved in the US in adults with T2D as an adjunct to diet and exercise to improve glycaemic control.1
Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit, AstraZeneca, said: “The prevalence of type-2 diabetes continues to rise in children and adolescents, yet oral treatment options have remained limited for this population. Today’s approval represents an important milestone for paediatric patients living with type-2 diabetes in the US, extending this medicine’s potential benefits to even more patients facing high unmet needs and reinforcing AstraZeneca’s commitment to delivering innovative treatments across cardiovascular, renal and metabolic diseases.”
T2D is a chronic disease affecting people of all ages.3,4 The incidence and prevalence of T2D in children and adolescents are increasing globally.5 In the US, there are nearly 30,000 patients under 20 living with T2D with 5,300 new cases diagnosed each year, according to the US Centers for Disease Control and Prevention and recent research.6,7 Younger patients often experience earlier onset of complications and faster advancement of disease compared to adults with the same condition.8-15
Data from the T2NOW Phase III trial, published in The New England Journal of Medicine Evidence, demonstrated a significant reduction in A1C, a marker of average blood sugar, for patients treated with Farxiga compared to patients receiving placebo.2,16 Adjusted mean change in A1C was -0.62% for Farxiga versus +0.41% for placebo, a difference of -1.03% (95% CI: -1.57-0.49; p<0.001).2 Statistical significance was achieved in the primary endpoint and in all secondary endpoints versus placebo at week 26, demonstrating Farxiga can provide clinically meaningful improvements in glycaemia for children and adolescents with T2D.2 The safety results in this patient population were consistent with those in adults with T2D, in line with the well-characterised safety profile for Farxiga.2
Farxiga, a first-in-class, oral, once-daily sodium-glucose cotransporter 2 (SGLT2) inhibitor, was approved in 126 countries, including the EU (marketed under the brand name Forxiga), as an adjunct to diet and exercise to improve glycaemic control in adults with T2D.
Forxiga is also approved for paediatric patients aged 10 years and above with T2D in 56 countries, including the EU and other regions, based on results from the T2GO Phase III clinical trial.17,18
Additional regulatory submissions and rollout plans are under consideration pending further market evaluations.
Notes
T2D
T2D is a chronic disease characterised by pathophysiologic defects leading to elevated glucose levels, or hyperglycaemia.3 Over time, this sustained hyperglycaemia contributes to further progression of the disease.3 The prevalence of diabetes is projected to reach 783 million by 2045.3 T2D is the most common type of diabetes, accounting for over 90% of all diabetes worldwide.19 Significant unmet medical need still exists, as many patients have poor blood sugar control and low medication adherence.3,20
T2NOW
T2NOW was a randomised, double-blind, placebo-controlled Phase III trial designed to evaluate the efficacy and safety of dapagliflozin as add-on treatment in children and adolescents with T2D receiving metformin, insulin or both.2 Patients were randomised to dapagliflozin, saxagliptin or placebo.2 Those receiving an active drug were further randomised to continue their current dose, or up-titrate to a higher dose of the same active treatment.2 The primary endpoint was change in A1C after 26 weeks vs placebo for dapagliflozin (5 or 10 mg) or saxagliptin (2.5 or 5 mg).2 Secondary endpoints included change in fasting plasma glucose and proportion of patients (A1C ≥7% at baseline) achieving A1C <7.0% (53 mmol/mol) after 26 weeks.2
Farxiga
Farxiga (dapagliflozin) in the US and marketed as Forxiga in the rest of world, is a first-in-class, oral, once-daily sodium-glucose cotransporter 2 (SGLT2) inhibitor. As of June 2024, Forxiga was approved in 126 countries as an adjunct to diet and exercise to improve glycaemic control in adults with T2D. Forxiga is approved for paediatric patients aged 10 years and above with T2D in the EU and other countries based on the T2GO trial.17,18
In addition, Forxiga is approved for the treatment of heart failure across the full ventricular ejection fraction range (HFrEF and HFpEF) and CKD in adult patients in more than 100 countries around the world. Forxiga was the first heart failure medication to demonstrate mortality benefit across the full ejection fraction range.21
Research has shown Forxiga’s efficacy in preventing and delaying cardiorenal disease, while also protecting the organs – important findings given the underlying links between the heart, kidneys and pancreas.22-24 Damage to one of these organs can cause the other organs to fail, contributing to leading causes of death worldwide, including T2D, heart failure (HF) and chronic kidney disease (CKD).25-28
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys, liver and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection by slowing or stopping disease progression, and ultimately paving the way towards regenerative therapies. The Company’s ambition is to improve and save the lives of millions of people, by better understanding the interconnections between CVRM diseases and targeting the mechanisms that drive them, so we can detect, diagnose and treat people earlier and more effectively.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca
Jun. 12, 2024 3:30 PM ET
By: Jonathan Block, SA News Editor
June 03, 2024
-- At Median Follow-Up of 24.2 Months, No Additional Risks of Adverse Events Related to Yescarta Were Observed --
-- Findings Also Suggest Efficacy Trend with Median Progression-Free Survival and Durability of Response of More Than a Year --
-- Data Presented Orally at the 2024 American Society of Clinical Oncology Annual Meeting --
SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), announced data from a pilot study in collaboration with Dana-Farber Cancer Institute that demonstrate Yescarta® (axicabtagene ciloleucel) is well-tolerated in patients living with relapsed or refractory (R/R) primary or secondary central nervous system lymphoma (PCNSL and SCNSL). The findings, which also suggest a trend in efficacy, were presented today in an oral session (Abstract #2006) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
Central nervous system lymphoma (CNSL) is an aggressive and rare form of non-Hodgkin lymphoma that has either originated in (primary) or spread to (secondary) the brain, eye, spinal cord or cerebrospinal fluid. The prognosis of PCNSL has historically been poor with a five-year survival rate of only 30%. More than half of the patients experience a relapse after front-line treatment, with a median survival of approximately two months. R/R CNSL is considered an area of unmet clinical need with no standard of care treatment options.
“Patients with central nervous system involvement of large B-cell lymphoma were excluded from the studies that led to the FDA approval of axi-cel in relapsed/refractory large B-cell lymphoma,” said Lakshmi Nayak, MD, Associate Professor of Neurology, Harvard Medical School and Director of the Center for CNS Lymphoma, Dana-Farber Cancer Institute. “We conducted this pilot study to evaluate the safety of axi-cel in CNSL patients and to see if there would be a preliminary signal of efficacy. Not only did we see a high response rate with axi-cel in this heavily pre-treated population, but importantly they were durable. While we need more data to evaluate axi-cel in a larger study, these results are promising and represent a potential breakthrough in the treatment of this particularly rare and aggressive brain cancer for which there are limited options when it recurs.”
In this pilot study of 18 patients with CNSL, at a median follow-up of 24.2 months, no treatment-limiting toxicities and no apparent additional risk of adverse events were reported. Immune effector cell-associated neurologic syndrome (ICANS) was observed among 44% of patients (27.8% Grade >3).
The objective response rate was 94.4% and the complete response rate was 66.7%. The median time to best response was three months. The median duration of response was 13.4 months and 9 patients had progressed. At a median follow-up of 24 months, the median progression-free survival was 14.3 months (95% CI: 6.3-NR) and median overall survival was 26.4 months (95% CI: 11.2-NR).
Ninety percent of patients developed grade 1 or 2 cytokine release syndrome; two patients developed Ommaya-related meningitis requiring explant with subsequent recovery. One patient developed grade 3 electrographic focal status epilepticus that resolved with anti-epileptic agents. Seven patients have died, all from disease progression.
“We are very encouraged by the data presented today that indicate the potential to extend the benefits of Yescarta to people with relapsed/refractory primary and secondary central nervous system lymphoma, whose prognoses are typically very poor,” said Ibrahim Elhoussieny, MD, Vice President, Medical Affairs, Kite. “These early data support that CAR T-cell therapy may potentially offer a treatment option to these patients.”
The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of CRS and neurologic toxicities, and Yescarta is approved with a Risk Evaluation and Mitigation Strategy (REMS) due to these risks; see below for Important Safety Information.
About Central Nervous System Lymphoma
Central nervous system lymphoma (CNSL) is an aggressive and rare form of non-Hodgkin lymphoma that has either originated in (primary) or spread (secondary) to the brain, eye, spinal cord or cerebral spinal fluid. The prognosis of PCNSL has historically been poor with a five-year survival rate of only 30%. More than half of the patients experience a relapse, after which the average survival is approximately two months. R/R CNSL is considered an area of unmet clinical need with no standard of care treatment options.
There is an estimated annual incidence of 1,500 cases of primary CNSL in the United States. Primary CNS comprises 3% of all primary brain tumors and 1% of all cases of non-Hodgkin lymphoma. CNSL is most likely to be seen in the elderly and people with a compromised immune system.
About the Study
The pilot study enrolled 18 patients (13 PCNSL, 4 SCNSL, 1 concurrent systemic and ocular lymphoma), of whom the first six patients were observed for treatment-limiting toxicities (TLTs). The primary endpoint was safety, measured by rate of TLTs and grade 3+ adverse events (AEs). Secondary endpoints included objective response rate, complete response rate, duration of response, progression-free survival and overall survival (OS).
About Yescarta
Please see full US Prescribing Information, including BOXED WARNING and Medication Guide.
YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:
Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.
About Kite
Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, focused on cell therapy to treat and potentially cure cancer. As the global cell therapy leader, Kite has treated more patients with CAR T-cell therapy than any other company. Kite has the largest in-house cell therapy manufacturing network in the world, spanning process development, vector manufacturing, clinical trial production, and commercial product manufacturing.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Gilead acquired Kite in 2017.
Kite, the Kite logo, Yescarta, and GILEAD are trademarks of Gilead Sciences, Inc. or its related companies.
For more information on Kite, please visit the company’s website at www.kitepharma.com . Follow Kite on social media on X ( @KitePharma ) and LinkedIn .
Source: Gilead Sciences, Inc.
PUBLISHED2 June 2024
Detailed positive results from the DESTINY-Breast06 Phase III trial showed that Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to standard-of-care chemotherapy in patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) metastatic breast cancer and the overall trial population (patients with HR-positive, HER2-low and HER2-ultralow [defined as IHC 0 with membrane staining] expression) following one or more lines of endocrine therapy.
These results will be presented today as a late-breaking oral presentation during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract #LBA1000).
Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
In the primary analysis of DESTINY-Breast06, results showed Enhertu reduced the risk of disease progression or death by 38% by blinded independent central review (BICR) versus chemotherapy in patients with HER2-low expression (hazard ratio [HR] 0.62; 95% confidence interval [CI]: 0.51-0.74; p<0.0001). Median PFS was 13.2 months in the Enhertu arm compared to 8.1 months for chemotherapy.
PFS results by BICR in the overall trial population were similar and showed Enhertu achieved a 37% reduction in the risk of disease progression or death compared to chemotherapy, with a median PFS of 13.2 months with Enhertu versus 8.1 months for chemotherapy (HR 0.63; 95% CI: 0.53-0.75; p<0.0001).
A prespecified exploratory analysis showed the clinically meaningful improvement in PFS was consistent between patients with HER2-low and HER2-ultralow expression. In patients with HER2-ultralow expression, Enhertu reduced the risk of disease progression or death by 22% compared to chemotherapy with a median PFS of 13.2 months versus 8.3 months, respectively (HR 0.78; 95% CI: 0.50-1.21).
Giuseppe Curigliano, MD, PhD, Professor of Medical Oncology at the University of Milan and Head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, Italy and principal investigator for the trial, said: “Endocrine therapies are widely used early in the treatment of HR-positive metastatic breast cancer, but following one or more lines of treatment, patients often derive limited efficacy from further endocrine-based therapy. With a median progression-free survival of more than a year, the results from DESTINY-Breast06 show that Enhertu could become a new standard of care for patients with HER2-low- and HER2-ultralow-expressing tumours following endocrine therapy in the metastatic setting.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “DESTINY-Breast06 represents another potential paradigm shift in how we treat patients across the spectrum of HR-positive metastatic breast cancer. The results reinforce the potential for Enhertu to improve outcomes earlier in the treatment landscape and in a broader population of patients with HER2-expressing breast cancer who have never before been eligible for a HER2-directed therapy.”
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “Enhertu continues to deliver pioneering results for a HER2-directed medicine across many different types of cancer. These latest results from DESTINY-Breast06 demonstrate clinically meaningful results with Enhertu even in tumours with very low levels of HER2 expression, suggesting that it may have an important role in treating a wide range of HER2-expressing metastatic breast cancer.”
In patients with HER2-low expression, confirmed objective response rate (ORR) was 56.5% for Enhertu versus 32.2% with chemotherapy. In the overall trial population, confirmed ORR was 57.3% for Enhertu versus 31.2% with chemotherapy and in patients with HER2-ultralow expression the confirmed ORR was 61.8% versus 26.3%, respectively. Complete responses were seen in 13 patients from the Enhertu arm, including nine patients with HER2-low expression. In the HER2-ultralow subgroup, four patients in the Enhertu arm had complete responses. No complete responses were seen in the chemotherapy arm.
Additional Enhertu data at ASCO
DESTINY-Breast03 updated results
Updated overall survival (OS) results from the DESTINY-Breast03 Phase III trial showed Enhertu continued to demonstrate a clinically meaningful survival improvement over trastuzumab emtansine (T-DM1) after more than three years of follow up in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab.
Results showed median OS was 52.6 months in the Enhertu arm compared to 42.7 months for T-DM1 (HR 0.73; 95% CI: 0.56-0.94).
The safety profile of Enhertu continues to be generally manageable and no cumulative toxicities were observed with longer follow-up. Results will be presented during the 2024 ASCO Annual Meeting (abstract #1025).
DESTINY-Breast07 results
Interim results from the DESTINY-Breast07 Phase Ib/II trial of Enhertu alone or in combination with other anticancer therapies as a 1st-line treatment for HER2-positive metastatic breast cancer demonstrated promising clinical activity for Enhertu as a monotherapy (n=75) and in combination with pertuzumab (n=50). Results were presented as an oral presentation at the 2024 ASCO Annual Meeting (abstract #1009).
Results showed a confirmed ORR of 76.0% with Enhertu and 84.0% with Enhertu in combination with pertuzumab. The 12-month PFS rate was 80.8% with Enhertu monotherapy and 89.4% with Enhertu and pertuzumab.
The safety of Enhertu as a monotherapy and in combination with pertuzumab was consistent with the known safety profiles of each therapy. ILD/pneumonitis was reported in seven patients (9.3%) in the Enhertu monotherapy arm and seven patients (14.0%) in the combination arm. All ILD events were Grade 3 or lower.
These are the first data presented for Enhertu as a 1st-line treatment in HER2-positive metastatic breast cancer. Analyses from the ongoing DESTINY-Breast09 Phase III trial will provide further insights regarding the efficacy and safety of Enhertu in this HER2-positive patient population.
Notes
Breast cancer and HER2 expression
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally.1 While survival rates are high for those diagnosed with early breast cancer, only approximately 30% of patients who are diagnosed with or who progress to metastatic disease are expected to live five years after their diagnosis.2
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast cancer.3 Patients with high levels of HER2 expression (IHC 3+ or 2+/ISH+) are classified as HER2-positive and treated with HER2-directed therapies, representing approximately 15-20% of all breast cancers.4 Historically, tumours that were not classified as HER2-positive were classified as HER2-negative.5
HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers.2 Despite being classified as HER2-negative, many of these tumours still carry some level of HER2 expression.5 It is estimated that approximately 60-65% of HR-positive, HER2-negative breast cancers are HER2-low and potentially an additional 25% may be HER2-ultralow.6,7
Endocrine therapies are widely used in the early lines of treatment for HR-positive metastatic breast cancer; however, after two lines of treatment, further efficacy from endocrine therapy is often limited.8 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.8-11
Prior to the approval of Enhertu in HER2-low metastatic breast cancer post chemotherapy based on the DESTINY-Breast04 trial, there were no targeted therapies approved specifically for patients with HER2-low expression. There are no targeted therapies specifically approved for patients with HER2-low expression prior to chemotherapy or for patients with HER2-ultralow expression.12
DESTINY-Breast06
DESTINY-Breast06 is a global, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (defined as IHC 0 with membrane staining) advanced or metastatic breast cancer. Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients were also eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting 1st-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months.
The primary endpoint is PFS in the HR-positive, HER2-low patient population as measured by BICR. Key secondary endpoints include PFS by BICR in the overall trial population (HER2-low and HER2-ultralow), OS in the HER2-low patient population and OS in the overall trial population. Other secondary endpoints include ORR, DOR, time to first subsequent treatment or death, time to second subsequent treatment or death and safety.
DESTINY-Breast06 enrolled 866 patients (n=713 for HER2-low and n=153 for HER2-ultralow) randomised at multiple sites in Asia, Europe, Australia, North America and South America. For more information about the trial, visit ClinicalTrials.gov.
DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomised, open-label, pivotal Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The primary efficacy endpoint of DESTINY-Breast03 is PFS based on BICR. OS is the key secondary efficacy outcome measure. Other secondary endpoints include ORR, DOR, PFS based on investigator assessment and safety.
DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Australia and South America. Primary results from DESTINY-Breast03 were published in The New England Journal of Medicine, with updated OS results published in The Lancet. For more information about the trial, visit ClinicalTrials.gov.
DESTINY-Breast07
DESTINY-Breast07 is a global, randomised, open-label Phase Ib/II dose-finding and dose-expansion trial to explore the safety, tolerability and anti-tumour activity of Enhertu alone or in combination with other anticancer agents in patients with HER2-positive metastatic breast cancer.
The study consists of two phases: a dose escalation phase and a dose expansion phase. The dose escalation phase enrolled patients with locally assessed HER2-positive or advanced metastatic breast cancer in 2nd-line or later treatment. The dose expansion phase enrolled patients with previously untreated for HER2-positive advanced or metastatic breast cancer.
The primary endpoints of DESTINY-Breast07 are safety and tolerability. Secondary endpoints include ORR and PFS based on investigator assessment.
DESTINY-Breast07 enrolled 244 patients at multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Enhertu (5.4 mg/kg) is approved in more than 60 countries for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or in-situ hybridisation [ISH]+) breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.
Enhertu (5.4 mg/kg) is approved in more than 60 countries for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
Enhertu (5.4 mg/kg) is approved in more than 35 countries for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Enhertu (6.4 mg/kg) is approved in more than 40 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 and/or DESTINY-Gastric02 trials.
Enhertu (5.4 mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and who have no satisfactory alternative treatment options based on results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials.
Enhertu development programme
A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers. Trials in combination with other anti-cancer treatments, such as immunotherapy, also are underway.
Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.
AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.
With Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate (ADC), AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap, and next-generation SERD and potential new medicine camizestrant. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease.
To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), Truqap in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.
Jun. 02, 2024 8:00 AM ET
TOKYO & BASKING RIDGE, N.J.--(BUSINESS WIRE)--
PUBLISHED2 June 2024
Positive results from the ADRIATIC Phase III trial showed AstraZeneca’s Imfinzi (durvalumab) demonstrated statistically significant and clinically meaningful improvements in the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) compared to placebo for patients with limited-stage small cell lung cancer (LS-SCLC) who had not progressed following standard-of-care concurrent chemoradiotherapy (cCRT).
These results will be presented today during the Plenary Session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract #LBA5).
Results from the planned interim analysis showed Imfinzi reduced the risk of death by 27% versus placebo (based on an OS hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.57-0.93; p=0.0104). Estimated median OS was 55.9 months for Imfinzi versus 33.4 months for placebo. An estimated 57% of patients treated with Imfinzi were alive at three years compared to 48% on placebo. Imfinzi also reduced the risk of disease progression or death by 24% (based on a PFS HR of 0.76; 95% CI 0.61-0.95; p=0.0161) versus placebo. Median PFS was 16.6 months for Imfinzi versus 9.2 months for placebo. An estimated 46% of patients treated with Imfinzi had not experienced disease progression at two years compared to 34% on placebo.
The OS and PFS benefits observed were generally consistent across key prespecified patient subgroups including age, sex, race, disease stage1 at diagnosis, prior radiation and whether patients received prophylactic cranial irradiation.
David R. Spigel, MD, Chief Scientific Officer at Sarah Cannon Research Institute and investigator in the trial, said: “The ADRIATIC results represent a breakthrough in limited-stage small cell lung cancer, a highly aggressive disease where recurrence rates are high and only 15 to 30 per cent of patients survive five years. Durvalumab is the first systemic treatment to show improved survival for these patients in decades and should become a new standard of care in this setting.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The strong improvement in overall survival seen with Imfinzi after concurrent chemoradiotherapy is transformative in the treatment of limited-stage small cell lung cancer. These tremendous results underscore our ambition to drive up survival rates in this earlier-stage lung cancer setting, and we look forward to working with regulatory authorities to bring Imfinzi to these patients as quickly as possible.”
Notes
Small cell lung cancer
Lung cancer is the leading cause of cancer death among men and women and accounts for about one-fifth of all cancer deaths.2 Lung cancer is broadly split into non-small cell lung cancer and SCLC, with about 15% of cases classified as SCLC, a highly aggressive form of the disease.3-4
LS-SCLC (Stage I-III), which accounts for approximately 30% of SCLC diagnoses, is classified as SCLC that is generally only in one lung or one side of the chest.5-6 LS-SCLC typically recurs and progresses rapidly despite initial response to standard-of-care chemotherapy and radiotherapy.4,7 The prognosis for LS-SCLC is particularly poor, as only 15-30% of patients will be alive five years after diagnosis.8
ADRIATIC
The ADRIATIC trial is a randomised, double-blind, placebo-controlled, multi-centre global Phase III trial evaluating Imfinzi monotherapy and Imfinzi plus Imjudo (tremelimumab) versus placebo in the treatment of 730 patients with LS-SCLC who had not progressed following cCRT. In the experimental arms, patients were randomised to receive a 1500mg fixed dose of Imfinzi with or without Imjudo 75mg every four weeks for up to four doses/cycles each, followed by Imfinzi every four weeks for up to 24 months.
The dual primary endpoints were PFS and OS for Imfinzi monotherapy versus placebo. Key secondary endpoints included OS and PFS for Imfinzi plus Imjudo versus placebo, safety and quality of life measures. The trial included 164 centres in 19 countries across North and South America, Europe and Asia.
Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.
Imfinzi is currently approved in a number of countries across multiple types of lung cancer. Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiation therapy. Imfinzi is also approved for the treatment of extensive-stage SCLC and in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC.
In addition to its indications in lung cancers, Imfinzi is approved in a number of countries in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU and in previously treated patients with advanced bladder cancer in a small number of countries.
Since the first approval in May 2017, more than 220,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal cancers and other solid tumours.
AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most.
The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi and Imjudo; Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.
AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.
AstraZeneca in immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours.
AstraZeneca strives to redefine cancer care and help transform outcomes for patients with Imfinzi as a monotherapy and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T cell engagers.
AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.
Jun. 02, 2024 8:05 AM ET
57% of patients treated with IMFINZI were alive at three years in ADRIATIC Phase III trial
WILMINGTON, Del.--(BUSINESS WIRE)
May 31, 2024
Basel, May 31, 2024 – Novartis is announcing results from a subgroup analysis of patients with high-risk, node-negative (N0) hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) from the Phase III NATALEE trial. The latest analysis demonstrated that Kisqali® (ribociclib) plus endocrine therapy (ET), compared to ET alone, showed an improvement in rates of invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and distant disease-free survival (DDFS) in high-risk EBC patients with N0 disease1,2. These data are being presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting today and are consistent with the significant benefits observed in the broad population of patients with stage II and III HR+/HER2- EBC in the pivotal NATALEE trial, initially presented at ASCO 20231,2.
Kisqali iDFS, DRFS and DDFS rates in key pre-specified subgroup1:
Subgroup3-year iDFS rate, %3-year DRFS rate, %3-year DDFS rate, %High-risk node-negative (N0)Kisqali + ET: 93.2
ET alone: 90.6
(HR=0.72; 95% CI: 0.41, 1.27)Kisqali + ET: 96.3
ET alone: 92.5
(HR=0.58; 95% CI: 0.29, 1.17)Kisqali + ET: 94.3
ET alone: 91.5
(HR=0.70; 95% CI: 0.38, 1.29)
“More than 1 in 3 patients diagnosed with early-stage breast cancer, regardless of nodal involvement, are at risk of experiencing recurrent disease despite treatment with standard chemotherapy and/or endocrine therapy,” said Denise A. Yardley, MD, Associate Director, Breast Cancer Research; Executive Member, Breast Cancer Research Executive Committee, Sarah Cannon Research Institute; and Principal Investigator of the NATALEE clinical trial. “Notably, the NATALEE trial has shed light on the node-negative patient population, an important at-risk subgroup that could benefit from more options to reduce their risk of their cancer returning. The findings from this trial underscore the efficacy of ribociclib in early-stage node-negative breast cancer, highlighting its role as a viable and well-tolerated treatment intervention that could significantly diminish the recurrence risk for this particular group.”
The safety profile of Kisqali at the 400 mg dose in the high-risk, N0 subgroup remains consistent with the well-tolerated profile previously demonstrated in the intent-to-treat population with generally low-grade adverse events (AEs), other than laboratory findings. In the N0 subgroup, the rate of discontinuation due to all grade AEs was 24% vs 8% with Kisqali plus ET vs ET alone1,2. No new safety signals were identified1,2.
“Currently available targeted therapies are approved only for a small proportion of patients, leaving a large number of people diagnosed with HR+/HER2- early breast cancer at risk of cancer returning, particularly those with high-risk N0 tumors,” said Jeff Legos, Executive Vice President, Global Head of Oncology Development, Novartis. “Our robust body of data continues to support the potential for Kisqali to benefit many more patients as they seek to reduce the likelihood of their cancer coming back with the addition of a CDK4/6 inhibitor to their endocrine treatment.”
Novartis submitted NATALEE data to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2023, and further submissions to global authorities are ongoing.
About NATALEE
NATALEE is a global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of Kisqali® (ribociclib) with ET as an investigational adjuvant treatment versus ET alone in patients with stage II and III HR+/HER2- EBC, being conducted in collaboration with TRIO5. The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable5. The primary endpoint of NATALEE is iDFS as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria5. A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial5.
Results previously announced at the San Antonio Breast Cancer Symposium (SABCS) in December 2023 showed Kisqali plus ET, compared to ET alone, lowered the risk of cancer recurrence by 25.1% (HR=0.749; 95% CI: 0.628, 0.892; p=0.0006), along with consistent clinically meaningful iDFS benefit across key pre-specified subgroups5.
NATALEE explored a lower starting dose (400 mg) of Kisqali than the dose approved for treatment in metastatic breast cancer (MBC) (600 mg) with the goal to minimize disruptions to patient quality of life without compromising efficacy. Compared to the 600 mg dose, the safety profile of Kisqali at 400 mg was observed to have lower rates of symptomatic AEs and less need for dose modifications when administered up to three years5. AEs of special interest (grade 3 or higher) are neutropenia (44.3%), liver-related AEs (e.g., elevated transaminases) (8.6%), and QT interval prolongation (1.0%)1,5.
About Early Breast Cancer
More than 90% of patients diagnosed with breast cancer have EBC7. Despite adjuvant ET or being declared on remission, patients with EBC remain at risk for cancer recurrence, peaking within the first three years after initial diagnosis2. Patients with negative-node disease face a risk of recurrence up to 11% within the first three years after diagnosis, and 29% expect to recur within 20 years2.
About Kisqali® (ribociclib)
Kisqali® (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.
In MBC, Kisqali has consistently demonstrated statistically significant OS benefit across three Phase III trials8-19. Updates to the NCCN Guidelines® for breast cancer, released in January 2023, recommend ribociclib (Kisqali) as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of patients with HR+/HER2- when combined with an aromatase inhibitor (AI), making Kisqali the preferred first-line treatment of choice for US prescribers in HR+/HER2- in MBC20. Additionally, Kisqali has the highest rating of any CDK4/6 inhibitor on the ESMO Magnitude of Clinical Benefit Scale, achieving a score of five out of five for first-line pre-menopausal patients with HR+/HER2- advanced breast cancer21. Further, Kisqali in combination with either letrozole or fulvestrant has uniquely, among other CDK4/6 inhibitors, received a score of four out of five for post-menopausal patients with HR+/HER2- advanced breast cancer treated in the first line22.
Kisqali has been approved in 99 countries worldwide, including by the United States Food and Drug Administration (FDA) and the European Commission. In the U.S., Kisqali is approved for the treatment of adult patients with HR+/HER2- advanced or MBC in combination with an AI as initial ET or fulvestrant as initial ET or following disease progression on ET in post-menopausal women or in men. In the EU, Kisqali is approved for the treatment of women with HR+/HER2- advanced or MBC in combination with either an AI or fulvestrant as initial ET or following disease progression. In pre- or peri-menopausal women, the ET should be combined with a luteinizing hormone-releasing hormone agonist23.
Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.
Please see full Prescribing Information for Kisqali, available at www.Kisqali.com
About Novartis
Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide.
Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram.
May 29, 2024 7:15 am ET
Acceptance based on results from the pivotal Phase 3 CCTG IND.227/KEYNOTE-483 trial, which demonstrated a statistically significant improvement in overall survival versus chemotherapy alone in these patients
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the U.S. Food and Drug Administration (FDA) has accepted for priority review a new supplemental Biologics License Application (sBLA) seeking approval for KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy, for the first-line treatment of patients with unresectable advanced or metastatic malignant pleural mesothelioma. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of September 25, 2024.
The sBLA is based on data from the pivotal Phase 2/3 IND.227/KEYNOTE-483 trial. Results from the final analysis of the study, presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, showed KEYTRUDA in combination with chemotherapy demonstrated a statistically significant improvement in overall survival (OS), reducing the risk of death by 21% (HR=0.79 [95% CI, 0.64-0.98]; two-sided p value=0.0324), with a median OS of 17.3 months (95% CI, 14.4-21.3) versus 16.1 months (95% CI, 13.1-18.2) for chemotherapy alone. KEYTRUDA plus chemotherapy also demonstrated a significant improvement in progression-free survival (PFS) (HR=0.80 [95%CI, 0.65-0.99], two-sided p value = 0.0372; median PFS 7.13 months versus 7.16 months respectively) and objective response rate (ORR) compared to chemotherapy alone. At 12 months, the estimated PFS rate was 26% for KEYTRUDA plus chemotherapy versus 17% for chemotherapy alone. The ORR was significantly higher for KEYTRUDA plus chemotherapy versus chemotherapy alone (62% versus 38%, p<0.0001). The safety profile of KEYTRUDA plus chemotherapy in this study was consistent with previously reported studies.
“Malignant pleural mesothelioma is typically diagnosed in advanced stages when curative surgery is not an option, and progresses quickly,” said Dr. Gregory Lubiniecki, vice president, oncology clinical research, Merck Research Laboratories. “We continue to evaluate KEYTRUDA in new and difficult-to-treat tumors and look forward to working with the FDA to help bring KEYTRUDA as a potential treatment option to certain patients with advanced malignant pleural mesothelioma.”
About IND.227/KEYNOTE-483
IND.227/KEYNOTE-483 is a randomized, open-label Phase 2/3 trial (ClinicalTrials.gov, NCT02784171) sponsored and conducted by Canadian Cancer Trials Group (CCTG) in collaboration with National Cancer Institute of Naples (NCIN) and Intergroupe Francophone de Cancérologie Thoracique (IFCT). Merck provided KEYTRUDA and support for the trial. The trial evaluated KEYTRUDA plus chemotherapy versus chemotherapy alone for the treatment of patients with unresected advanced pleural mesothelioma. The study’s primary endpoint is OS and secondary endpoints include PFS and ORR as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) modified for mesothelioma, safety and quality of life. The Phase 3 part of the trial enrolled 440 patients who were randomized to receive:
About malignant mesothelioma
Malignant mesothelioma is a type of cancer that starts in the linings of certain parts of the body, including the chest, abdomen, heart and testicles. Worldwide, it is estimated there were more than 30,000 new cases of mesothelioma diagnosed and more than 25,000 deaths from the disease in 2022. Although the incidence of malignant mesothelioma has gradually declined in the U.S., continued use of and exposure to asbestos around the world has resulted in increasing global rates of this aggressive disease. Pleural mesothelioma, which develops in the lining of the lungs, is the most common form of malignant mesothelioma, accounting for about 75% of all cases. Malignant pleural mesothelioma often progresses rapidly, and the five-year survival rate is only 12%.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Additional Selected KEYTRUDA Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Cancer
KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:
KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
Cervical Cancer
KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1–containing regimen.
Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Merck’s focus on cancer
Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology/.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .
Source: Merck & Co., Inc.
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On May 29, 2024, the Food and Drug Administration granted accelerated approval to selpercatinib (Retevmo, Eli Lilly and Company) for pediatric patients two years of age and older with the following:
This is the first FDA approval of a targeted therapy for pediatric patients < 12 years of age with RET alterations. Selpercatinib was previously granted accelerated approval for the thyroid cancer indications in adults and pediatric patients 12 years of age and older. It also was previously granted accelerated approval for the solid tumor indication in adults.
Full prescribing information for Retevmo will be posted here.
Efficacy in pediatric and young adult patients was evaluated in LIBRETTO-121 (NCT03899792), an international, single-arm, multi-cohort trial. Patients received selpercatinib, 92 mg/m2 orally twice daily, until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. The primary efficacy population included 25 patients ages 2 to 20 with locally advanced or metastatic RET-activated solid tumors non-responsive to available therapies or with no standard systemic curative therapy available.
The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR). The confirmed ORR (RECIST 1.1), as determined by blinded independent review committee was 48% (95% CI: 28, 69). The median DOR was not reached (95% CI: not evaluable [NE], NE), with 92% of responders remaining in response at 12 months. Durable responses were observed in pediatric and young adult patients with RET-mutant MTC (n=14; ORR 43% [95% CI: 18%, 71%]) and RET fusion-positive thyroid cancer (n=10; ORR 60% [95% CI: 26%, 88%]).
The most common adverse reactions (≥25%) were musculoskeletal pain, diarrhea, headache, nausea, vomiting, coronavirus infection, abdominal pain, fatigue, pyrexia, and hemorrhage. The most common Grade 3 or 4 laboratory abnormalities (≥5%) were decreased calcium, decreased hemoglobin, and decreased neutrophils.
The recommended selpercatinib dose for pediatric patients 2 to less than 12 years of age is based on body surface area. It is based on weight for patients 12 years of age and older. See the prescribing information for specific dosing information.
LIBRETTO-121 was conducted as part of a pediatric Written Request (WR) under the Best Pharmaceuticals for Children Act (BPCA).
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
Follow the Oncology Center of Excellence on X (formerly Twitter) @FDAOncologyExternal Link Disclaimer.
May 29, 2024 12:32 PM ET
Eli Lilly and Company (LLY) Stock
By: Jonathan Block, SA News Editor
05/29/2024CATEGORY:
Approval based on results from CheckMate -901, the first Phase 3 trial in this patient population with an immunotherapy-chemotherapy combination to demonstrate survival benefit versus standard-of-care chemotherapy alone
First concurrent immunotherapy-chemotherapy combination approved for this patient population in the European Union
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has approved Opdivo® (nivolumab) in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC). With this approval, Opdivo in combination with cisplatin and gemcitabine becomes the first concurrent immunotherapy-chemotherapy approved for the treatment of adult patients with unresectable or metastatic UC in the first-line setting in the European Union.
“With today’s approval by the EC, we’re pleased to be able to offer Opdivo concurrently with chemotherapy to eligible patients with unresectable or metastatic UC,” said Dana Walker, M.D., M.S.C.E., vice president and global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. “This is a major step forward for this patient population and reinforces our goal of advancing and delivering new options to patients with difficult-to-treat cancers. We extend our sincerest gratitude to the patients, their families, investigators and staff who contributed to this important research.”
The EC’s decision is based on results from the CheckMate -901 trial studying Opdivo in combination with cisplatin and gemcitabine, which were presented at the European Society of Medical Oncology (ESMO) Congress 2023. In CheckMate -901, Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy demonstrated statistically significant and clinically meaningful improvements in the primary efficacy endpoints of overall survival (OS) and progression-free survival (PFS) compared to chemotherapy alone, as assessed by Blinded Independent Central Review (BICR). The safety profile was consistent with the known safety profiles of the individual components of the regimen. No new safety concerns were identified.
“In the CheckMate -901 trial, the combination of Opdivo with cisplatin and gemcitabine improved overall survival, reduced the risk of disease progression or death by 28% versus chemo alone, and demonstrated deep and durable responses versus chemo alone,” said Michiel Van der Heijden, M.D, Ph.D., medical oncologist and research group leader, Netherlands Cancer Institute. “These findings are significant and reinforce that concurrent Opdivo and chemotherapy should be considered as a new standard of care for the first line treatment of eligible patients with this difficult-to-treat cancer.”
This approval by the EC for Opdivo in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with unresectable or metastatic UC is valid in all 27 member states of the EU, as well as Iceland, Liechtenstein and Norway.
This approval of Opdivo in combination with cisplatin and gemcitabine based on results of the CheckMate -901 trial, further supports the EU’s previous approval of Opdivo for the adjuvant treatment of adults with muscle-invasive urothelial carcinoma with tumor cell PD-L1 expression ≥1% who are at a high risk of recurrence after undergoing radical resection. In addition to this approved indication in UC, Opdivo-based options are also approved for treatment of 10 different cancer types in the EU including: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma (EAC), esophageal or gastroesophageal junction (GEJ) cancer, colorectal cancer, mesothelioma, renal cell carcinoma, esophageal squamous cell carcinoma (ESCC) and squamous cell cancer of the head and neck.
CheckMate -901 Efficacy and Safety Results
With a median follow up of approximately 33 months of the CheckMate -901 trial, results showed:
About CheckMate -901
CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with Yervoy ® (ipilimumab) or Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy compared to standard-of-care chemotherapy alone, in patients with untreated, unresectable or metastatic urothelial cancer.
In CheckMate -901, evaluating Opdivo with cisplatin and gemcitabine vs. standard-of-care chemotherapy alone, a total of 608 patients eligible for cisplatin-based chemotherapy were randomized to receive either Opdivo 360 mg in combination with cisplatin and gemcitabine every three weeks for up to six cycles followed by 480 mg/Q4 Opdivo monotherapy every 4 weeks until disease progression or death up to a maximum of two years, or cisplatin-gemcitabine alone every three weeks for up to six cycles. The primary endpoints of this study are overall survival (OS) and progression-free survival (PFS).
The OS and PFS outcomes for patients eligible for cisplatin-based chemotherapy are based on the final efficacy analyses of these endpoints.
The CheckMate -901 primary study, evaluating Opdivo plus Yervoy vs. standard-of-care cisplatin- or carboplatin-based chemotherapy in patients with untreated, unresectable or metastatic urothelial carcinoma remains ongoing.
Select Safety Profile from CheckMate -901
Serious adverse reactions occurred in 48% of patients receiving Opdivo with chemotherapy.1 The most frequent serious adverse reactions reported in ≥2% of patients who received Opdivo with chemotherapy were urinary tract infection (4.9%), acute kidney injury (4.3%), anemia (3%), pulmonary embolism (2.6%), sepsis (2.3%), and platelet count decreased (2.3%).1 The most common adverse reactions (reported in ≥20% of patients) were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy.1 Fatal adverse reactions occurred in 3.6% patients who received Opdivo with chemotherapy; these included sepsis (1%).1 Opdivo and/or chemotherapy were discontinued in 30% of patients and were delayed in 67% of patients for an adverse reaction.
About Urothelial Carcinoma
Bladder cancer is the ninth most common cancer in the world, with more than 600,000 new cases diagnosed annually. Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases. In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis. The majority of urothelial carcinomas are diagnosed at an early stage, but rates of recurrence and disease progression are high. Approximately 50% of patients who undergo radical surgery will experience disease recurrence, especially within the first two to three years after surgical removal of the bladder or kidney. For patients whose disease recurs as metastatic cancer, the prognosis is poor, with a median overall survival of approximately 12 to 14 months when treated with systemic therapy.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
INDICATIONS
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.
OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.
OPDIVO® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma.
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
Please see US Full Prescribing Information for OPDIVO and YERVOY.
Clinical Trials and Patient Populations
Checkmate 227—previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238– adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K– adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066—previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma.
About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Source: Bristol Myers Squibb
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May 29, 2024 10:04 AM ET
Bristol-Myers Squibb Company (BMY) Stock
By: Val Brickates Kennedy, SA News Editor6 Comments
Bristol-Myers Squibb (NYSE:BMY) said it has received EU approval for its drug Opdivo as a first-line treatment for adults with unresectable or metastatic urothelial carcinoma, a type of bladder cancer.
The drug was approved for use in combination with cisplatin and gemcitabine, according to the company.
May 28, 2024 6:45 am ET
KEYTRUDA® (pembrolizumab) is the first and only immunotherapy-based regimen to show a statistically significant improvement in OS as pre-operative (neoadjuvant) treatment with chemotherapy and then as a single agent after surgery (adjuvant) compared to pre-operative chemotherapy in patients with high-risk early-stage TNBC
New OS results build on the pathological complete response and event-free survival data previously reported from the KEYNOTE-522 trial
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the Phase 3 KEYNOTE-522 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, met its overall survival (OS) endpoint, in combination with chemotherapy as pre-operative (neoadjuvant) treatment and then continuing as a single agent after surgery (adjuvant) for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC). At a pre-specified interim analysis conducted by an independent Data Monitoring Committee, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in OS compared to pre-operative chemotherapy. The safety profile of KEYTRUDA was consistent with that observed in previously reported studies; no new safety signals were observed. Results will be presented at an upcoming medical meeting and shared with regulatory authorities.
“This is a significant milestone, as it is the first time an immunotherapy-based regimen has demonstrated a statistically significant overall survival benefit compared to chemotherapy alone in patients with high-risk early-stage triple-negative breast cancer,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “To have achieved overall survival from this landmark study is highly encouraging and builds upon the positive pathological complete response and event-free survival results that led to approvals for this regimen around the world.”
KEYNOTE 522 is the fourth study of a KEYTRUDA-based regimen in an earlier stage of cancer to demonstrate an OS benefit, in addition to KEYNOTE-A18 in cervical cancer, KEYNOTE-671 in non-small cell lung cancer and KEYNOTE-564 in renal cell carcinoma.
In the U.S., KEYTRUDA has two approved indications in TNBC: for the treatment of patients with high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery; and in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Merck has a comprehensive clinical development program in various subtypes of breast cancer. This includes KEYNOTE-242 evaluating KEYTRUDA monotherapy as adjuvant treatment in patients with TNBC who have residual disease; KEYNOTE-756 evaluating KEYTRUDA plus chemotherapy in patients with high-risk, early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer; TroFuse-010 evaluating KEYTRUDA plus sacituzumab tirumotecan (sac-TMT), an investigational trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate that Merck is developing in collaboration with Kelun-Biotech, compared to sac-TMT alone and compared to physician’s choice of treatment in patients with unresectable locally advanced or metastatic ER+/HER2- breast cancer; and TroFuse-012 evaluating KEYTRUDA plus sac-TMT versus physician’s choice of treatment in patients with TNBC who received KEYTRUDA-based neoadjuvant therapy and did not achieve a pathological complete response (pCR) at surgery.
About KEYNOTE-522
KEYNOTE-522 (ClinicalTrials.gov, NCT03036488), is a randomized, double-blind Phase 3 trial. The dual primary endpoints were pCR rate, defined as pathological stage ypT0/Tis ypN0 at the time of definitive surgery, and event-free survival, defined as the time from randomization to the time of first occurrence of either disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer or death from any cause. A key secondary endpoint was OS. The study enrolled 1,174 patients who were randomized 2:1 to receive either:
About triple-negative breast cancer (TNBC)
Triple-negative breast cancer is the most aggressive type of breast cancer, which has the highest risk of recurrence within the first five years after diagnosis and is associated with worse outcomes compared to other forms of breast cancer. Approximately 10-15% of patients with breast cancer are diagnosed with TNBC. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. Triple-negative breast cancer tends to be more common in people who are younger than 40 years of age, who are Black or who have a BRCA1 mutation.
About Merck’s research in breast and gynecologic cancers
Merck is advancing research aimed at improving outcomes for patients affected by breast and gynecologic (ovarian, cervical and endometrial) cancers. Merck has a comprehensive clinical development program across these cancers comprised of more than 20 Merck-sponsored Phase 3 studies evaluating KEYTRUDA as monotherapy and in combination with other medicines. In the U.S., KEYTRUDA currently has two approved indications for TNBC, including one for high-risk early-stage disease, and five approved indications across certain types of cervical and endometrial cancers (see indications below). Among Merck’s research efforts are trials focused on evaluating KEYTRUDA in earlier stages of these cancers, as well as identifying new combinations and coformulations with KEYTRUDA.
About Merck’s early-stage cancer clinical program
Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is evaluating our portfolio of medicines and pipeline candidates in earlier disease states, with more than 30 ongoing registrational studies across multiple types of cancer.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.
Additional Selected KEYTRUDA Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.
KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Cancer
KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:
KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
Cervical Cancer
KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.
Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Merck’s focus on cancer
Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit http://www.merck.com/research/oncology.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .
Source: Merck & Co., Inc.
https://seekingalpha.com/symbol/MRK
05/06/2024
CATEGORY:
Application based on results from CheckMate -67T, the first Phase 3 trial of the subcutaneous formulation of nivolumab to evaluate and demonstrate noninferior pharmacokinetics, efficacy and consistent safety vs. its intravenous formulation
Subcutaneous nivolumab has potential to be the first and only subcutaneously administered PD-1 inhibitor
The FDA assigned a target action date of February 28, 2025
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for the subcutaneous formulation of Opdivo® (nivolumab) co-formulated with Halozyme’s proprietary recombinant human hyaluronidase (rHuPH20) (herein referred to as “ subcutaneous nivolumab”) across all previously approved adult, solid tumor Opdivo indications as monotherapy, monotherapy maintenance following completion of Opdivo plus Yervoy (ipilimumab) combination therapy, or in combination with chemotherapy or cabozantinib. The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of February 28, 2025.
“We believe subcutaneous nivolumab has the potential to make a significant difference in the lives of patients, which is reinforced by the FDA’s acceptance of our application,” said Gina Fusaro, Ph.D., vice president, global program lead, Bristol Myers Squibb. “Opdivo is a foundational PD-1 inhibitor approved for many different types of cancer, and our continued investment in research that puts patients first remains a priority. If approved by the FDA, the subcutaneous administration of nivolumab would provide patients and their physicians with a new option that delivers the same well-known benefits as IV Opdivo but with the improved convenience of an injection administered in three-to-five minutes rather than a 30-to-60-minute infusion.”
The FDA filing acceptance is based on the Phase 3 CheckMate -67T study in which subcutaneous nivolumab demonstrated noninferiority of Cavgd28 (time-averaged Opdivo serum concentration over 28 days) and Cminss (trough serum concentration at steady state), the study’s co-primary endpoints, vs. intravenous (IV) Opdivo in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received prior systemic therapy. Additionally, subcutaneous nivolumab showed noninferiority of the key powered secondary endpoint of objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) vs. IV Opdivo. The safety profile of subcutaneous nivolumab was consistent with the IV formulation. The pharmacokinetics, efficacy and safety results from CheckMate -67T were presented at the American Society of Clinical Oncology (ASCO) 2024 Genitourinary Cancers Symposium.
About CheckMate -67T
CheckMate -67T is a Phase 3 randomized, open-label trial evaluating subcutaneous administration of Opdivo co-formulated with Halozyme’s proprietary recombinant human hyaluronidase, rHuPH20, or subcutaneous nivolumab (nivolumab and hyaluronidase) compared to intravenous Opdivo, in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received prior systemic therapy. This trial presents an opportunity to potentially bring a subcutaneous formulation of Opdivo to patients. A total of 495 patients were randomized to either subcutaneous nivolumab or intravenous Opdivo. The co-primary endpoints of the trial are time-averaged serum concentration over 28 days (Cavgd28) and trough serum concentration at steady-state (Cminss) of subcutaneous nivolumab vs. intravenous Opdivo. Objective response rate (ORR) is a key secondary endpoint.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
INDICATIONS
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.
OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.
OPDIVO® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma.
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
Please see US Full Prescribing Information for OPDIVO and YERVOY.
Clinical Trials and Patient Populations
Checkmate 227—previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238– adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K– adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066—previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma
About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Source: Bristol Myers Squibb
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May 06, 2024 12:11 PM ET
Bristol-Myers Squibb Company (BMY) Stock, HALO Stock
By: Val Brickates Kennedy, SA News Editor
The FDA has accepted Bristol Myers (NYSE:BMY) biologics license application for a subcutaneous formulation of its oncology drug Opdivo, also known as nivolumab, with a target action date of Feb. 28.
The subcutaneous version is formulated with Halozyme’s (NASDAQ:HALO) proprietary recombinant human hyaluronidase. Opdivo is currently administered by IV.
https://seekingalpha.com/news/4100501-fda-accepts-bristol-myers-application-for-injected-opdivo
Bristol-Myers Squibb Company (BMY) Stock, HALO Stock
https://seekingalpha.com/symbol/BMY
European Medicines Agency Validates Bristol Myers Squibb’s Application for Opdivo (nivolumab) Plus Yervoy (ipilimumab) for the First-Line Treatment of Adult Patients with Microsatellite...
05/06/2024
CATEGORY:
Application based on results from the CheckMate -8HW study, in which Opdivo plus Yervoy demonstrated statistically significant and clinically meaningful improvement in progression-free survival compared to investigator’s choice of chemotherapy
PRINCETON, N.J.--(BUSINESS WIRE)--
European Medicines Agency Validates Bristol Myers Squibb’s Application for Opdivo (nivolumab) Plus Yervoy (ipilimumab) for the First-Line Treatment of Adult Patients with Microsatellite Instability–High or Mismatch Repair Deficient Metastatic Colorectal Cancer
Bristol Myers Squibb (NYSE: BMY) today announced that the European Medicines Agency (EMA) has validated its Type II variation application for Opdivo® (nivolumab) plus Yervoy ® (ipilimumab) for the first-line treatment of adult patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC). The EMA’s validation of the application confirms the submission is complete and begins the EMA’s centralized review process.
“Colorectal cancer is the third most commonly diagnosed cancer in the world, and more options are needed specifically for patients with MSI-H/dMMR mCRC, who are less likely to benefit from treatment with chemotherapy,” said Dana Walker, M.D., M.S.C.E., vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. “We look forward to working with the European Medicines Agency to discuss bringing the dual immunotherapy combination of Opdivo and Yervoy to patients with MSI-H/dMMR mCRC across Europe.”
The submission is based on results from the CheckMate -8HW study, in which Opdivo plus Yervoy demonstrated a statistically significant and clinically meaningful improvement in the dual primary endpoint of progression-free survival (PFS) compared to investigator’s choice of chemotherapy as assessed by Blinded Independent Clinical Review (BICR) for the first-line treatment of patients with MSI-H/dMMR mCRC. These data from CheckMate -8HW were presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. The study is ongoing to assess the other dual primary endpoint of PFS in patients receiving Opdivo plus Yervoy compared to Opdivo alone, as well as secondary endpoints. The safety profile for the dual immunotherapy combination remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified.
Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -8HW clinical trial.
About CheckMate -8HW
CheckMate -8HW (NCT04008030) is a Phase 3 randomized, open-label trial evaluating Opdivo plus Yervoy compared to Opdivo alone or investigator’s choice chemotherapy (mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab) in patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC).
Approximately 830 patients were randomized to receive either Opdivo monotherapy (Opdivo 240 mg Q2W for six doses, followed by Opdivo 480 mg Q4W), Opdivo plus Yervoy (Opdivo 240 mg plus Yervoy 1 mg/kg Q3W for four doses, followed by Opdivo 480 mg Q4W), or investigator’s choice of chemotherapy. The dual primary endpoints of the trial are progression-free survival (PFS) per blinded independent central review (BICR) for Opdivo plus Yervoy compared to investigator’s choice of chemotherapy in the first line setting and PFS per BICR for Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy. The trial also includes several secondary safety and efficacy endpoints, including overall survival (OS).
The study is ongoing to assess the second dual primary endpoint of PFS in patients receiving Opdivo plus Yervoy compared to Opdivo alone across all lines of therapy, as well as secondary endpoints.
About dMMR or MSI-H Colorectal Cancer
Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system. CRC is the third most commonly diagnosed cancer in the world. In 2020, it is estimated that there were approximately 1,931,000 new cases of the disease; it is the second leading cause of cancer-related deaths among men and women combined.
Mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, leading to microsatellite instability-high (MSI-H) tumors. Approximately 5-7% of metastatic CRC patients have dMMR or MSI-H tumors; they are less likely to benefit from conventional chemotherapy and typically have a poor prognosis.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research programs uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
About Yervoy
Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types.
INDICATIONS
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.
OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.
OPDIVO® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma.
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
Please see US Full Prescribing Information for OPDIVO and YERVOY.
Clinical Trials and Patient Populations
Checkmate 227—previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238– adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K– adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066—previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma
About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Source: Bristol Myers Squibb
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Merck Announces Phase 3 KEYNOTE-811 Trial Met Dual Primary Endpoint of Overall Survival (OS) as First-Line Treatment in Patients With HER2-Positive Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
May 1, 2024 7:15 am ET
These OS results build on positive data previously reported from KEYNOTE-811 that supported its FDA-approved indication
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the Phase 3 KEYNOTE-811 trial evaluating KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with trastuzumab and fluoropyrimidine- and platinum-containing chemotherapy met its dual primary endpoint of overall survival (OS) for the first-line treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Based on results from KEYNOTE-811, KEYTRUDA is approved in combination with trastuzumab and fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved by the U.S. Food and Drug Administration (FDA) under accelerated approval regulations based on the objective response rate (ORR) and durability of response demonstrated at an earlier analysis. Continued approval of this indication may be contingent upon verification and description of clinical benefit at the final analysis of the KEYNOTE-811 study.
In the final analysis of this trial, KEYTRUDA in combination with trastuzumab and chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS compared to placebo in combination with trastuzumab and chemotherapy in the intention-to-treat (ITT) study population, with the greatest benefit observed in patients whose tumors expressed PD-L1 (CPS ≥1). The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. Results will be presented at an upcoming medical meeting and shared with regulatory authorities worldwide.
“Patients diagnosed with advanced gastric cancer often face a poor prognosis, underscoring the need for treatment options that have the potential to extend patients’ lives,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “These overall survival results from KEYNOTE-811 are encouraging and build on the positive progression-free survival, overall response rate and duration of response data from this study.”
As previously announced, at an earlier interim analysis, KEYNOTE-811 met the other dual primary endpoint of progression-free survival (PFS) and these results were presented at the European Society for Medical Oncology (ESMO) Congress 2023.
In the U.S., KEYTRUDA is also approved for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma, based on results from KEYNOTE-859.
Merck has an extensive clinical development program evaluating KEYTRUDA in gastrointestinal cancers and is continuing to study KEYTRUDA for multiple uses in gastric, hepatobiliary, esophageal and colorectal cancers.
About KEYNOTE-811
KEYNOTE-811 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03615326) evaluating KEYTRUDA in combination with trastuzumab and chemotherapy for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma. The dual primary endpoints are PFS per RECIST v1.1 as assessed by blinded independent central review and OS. Secondary endpoints include ORR, duration of response and safety. The trial enrolled 698 patients who were randomized to receive KEYTRUDA (200 mg every three weeks) in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy (investigator’s choice of 5-fluorouracil plus cisplatin or capecitabine plus oxaliplatin), or placebo in combination with trastuzumab and chemotherapy.
About gastric cancer
Gastric (stomach) cancer tends to develop slowly over many years and rarely causes early symptoms, resulting in most cases going undetected until an advanced stage. More than 70% of patients with gastric cancer develop advanced-stage disease. Most gastric cancers are adenocarcinomas (about 90-95%), which develop from cells in the innermost lining of the stomach (known as the mucosa). Gastric cancer is the fifth most diagnosed cancer and the fifth leading cause of cancer death worldwide, with approximately 969,000 patients diagnosed and 660,000 deaths from the disease globally in 2022. In the U.S., it is estimated there will be approximately 26,890 patients diagnosed with gastric cancer and 10,880 deaths from the disease in 2024. The five-year survival rate for patients diagnosed with gastric cancer at an advanced stage is only 7%.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected Important Safety Information for KEYTRUDA
https://www.keytruda.com/
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Additional Selected KEYTRUDA Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.
KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Carcinoma
KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:
KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
Cervical Cancer
KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.
Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract carcinoma (BTC).
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Merck’s focus on cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .
Source: Merck & Co., Inc.
May 01, 2024 8:47 AM ET
By: Preeti Singh, SA News Editor
Merck (NYSE:MRK) has reported positive overall survival data from a late-stage trial of a combination therapy for advanced gastric or gastroesophageal junction (GEJ) cancer.
The Phase 3 KEYNOTE-811 trial, evaluating Merck’s anti-PD-1 therapy Keytruda (pembrolizumab) in combination with trastuzumab and fluoropyrimidine- and platinum-containing chemotherapy, met one of its dual primary endpoints of overall survival for the first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.
PUBLISHED29 April 2024
Positive high-level results from the DESTINY-Breast06 Phase III trial showed that Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to standard-of-care chemotherapy in the primary trial population of patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) metastatic breast cancer following one or more lines of endocrine therapy.
A statistically significant and clinically meaningful improvement in PFS was also observed in the overall trial population (patients with HER2-low and HER2-ultralow [defined as IHC 0 with membrane staining; IHC >0<1+] metastatic breast cancer). A prespecified subgroup analysis showed the clinically meaningful improvement was consistent between patients with HER2-low and HER2-ultralow expression.
Overall survival (OS) data were not mature at the time of the analysis; however, Enhertu showed an early trend towards an OS improvement versus standard-of-care chemotherapy in patients with HER2-low metastatic breast cancer and in the overall trial population. The trial will continue as planned to further assess OS and other secondary endpoints.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “DESTINY-Breast06 shows that Enhertu could become a new standard of care for patients with HER2-low and HER2-ultralow metastatic breast cancer following one or more lines of endocrine therapy. These data underscore the potential for treatment with Enhertu across the spectrum of HR-positive breast cancer, further redefining the treatment of metastatic breast cancer.”
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “The topline results from DESTINY-Breast06 highlight the importance of continuing to challenge current treatment paradigms and established breast cancer classifications to evolve how we treat patients with HR-positive, HER2-expressing metastatic breast cancer. Building on the practice-changing data seen in DESTINY-Breast04, these results reinforce the potential for use of Enhertu earlier in the treatment landscape and in an even broader patient population.”
Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
It is estimated that approximately 60-65% of HR-positive, HER2-negative breast cancers are HER2-low and potentially an additional 25% may be HER2-ultralow.1,2 Endocrine therapies are widely used in the early lines of treatment for HR-positive metastatic breast cancer; however after two lines of treatment, further efficacy from endocrine therapy is often limited.3 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.3-6
The safety profile of Enhertu was consistent with previous breast cancer clinical trials with no new safety signals identified.
The data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.
Notes
DESTINY-Breast06
DESTINY-Breast06 is a global, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (defined as IHC 0 with membrane staining; IHC >0<1+) advanced or metastatic breast cancer. Patients in the trial had no prior chemotherapy for advanced or metastatic disease and either experienced disease progression within 6 months of starting 1st-line treatment with an endocrine therapy combined with a CDK4/6 inhibitor or received at least two previous lines of endocrine therapies in the metastatic setting.
The primary endpoint is PFS in the HR-positive, HER2-low patient population as measured by blinded independent central review (BICR). Key secondary endpoints include OS in patients with HER2-low expression and PFS by BICR and OS in the overall trial population (HER2-low and HER2-ultralow). Other secondary endpoints include objective response rate, duration of response, time to first subsequent treatment or death, time to second subsequent treatment or death and safety. Analysis of the HER2-ultralow subgroup was not powered to demonstrate statistical significance.
DESTINY-Breast06 enrolled 866 patients (n=713 for HER2-low and n=153 for HER2-ultralow) at multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.
Breast cancer and HER2 expression
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.7 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally.7 While survival rates are high for those diagnosed with early breast cancer, only approximately 30% of patients who are diagnosed with or progress to metastatic disease are expected to live five years after their diagnosis.8
HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers.8 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast cancer.9 Patients with high levels of HER2 expression (IHC 3+ or 2+/ISH+) are classified as HER2-positive and treated with HER2-targeted therapies, representing approximately 15-20% of all breast cancers.10 Historically, tumours that were not classified as HER2-positive were classified as HER2-negative; however, many of these tumours still carry some level of HER2 expression.11 It is estimated that approximately 60-65% of HR-positive, HER2-negative breast cancers are HER2-low and potentially an additional 25% may be HER2-ultralow.1,2
Prior to the approval of Enhertu in HER2-low metastatic breast cancer post chemotherapy based on the DESTINY-Breast04 trial, there were no targeted therapies approved specifically for patients with HER2-low expression.12 There are no targeted therapies specifically approved for patients with HER2-ultralow expression.
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Enhertu (5.4 mg/kg) is approved in more than 60 countries for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or 2+/ISH+) breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.
Enhertu (5.4 mg/kg) is approved in more than 60 countries for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
Enhertu (5.4 mg/kg) is approved in more than 35 countries for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Enhertu (6.4 mg/kg) is approved in more than 40 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 and/or DESTINY-Gastric02 trials.
Enhertu (5.4 mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and who have no satisfactory alternative treatment options based on results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials.
Enhertu development programme
A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers. Trials in combination with other anti-cancer treatments, such as immunotherapy, also are underway.
Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.
AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.
With Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate (ADC), AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap, and next-generation SERD and potential new medicine camizestrant. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease.
To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), Truqap in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.
Apr. 29, 2024 8:29 AM ET
AstraZeneca PLC (AZN) StockPFS
By: Jonathan Block, SA News Editor
04/26/2024
CATEGORY:
Recommendation based on results from CheckMate -901, the first Phase 3 trial with an immunotherapy-chemotherapy combination to demonstrate a survival benefit versus standard-of-care chemotherapy alone in cisplatin-eligible adults with unresectable or metastatic urothelial carcinoma
If approved, the Opdivo-based regimen would be the first immunotherapy-chemotherapy combination approved for this patient population in the EU
A decision on the EU marketing authorization is expected by June 2024
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY)
today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of Opdivo® (nivolumab) in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma. The European Commission (EC), which has the authority to approve medicines for the European Union (EU), will now review the CHMP recommendation. The final EC decision is expected in June 2024.
“For eligible patients with unresectable or metastatic urothelial carcinoma, platinum-based chemotherapy in the first-line setting has been the standard of care for decades but the durability of response to chemotherapy alone is poor and once a patient progresses, treatment options become increasingly limited,” said Dana Walker, vice president and Global Program Lead, Genitourinary Cancers, Bristol Myers Squibb. “New treatment options that may improve responses, delay disease progression, and offer survival benefit in the first-line setting are needed. With today’s CHMP positive opinion, we are one step closer to potentially providing eligible patients with unresectable or metastatic urothelial carcinoma in the European Union with a new first-line treatment option.”
The positive CHMP opinion is based on results from a sub-study of the CheckMate -901 trial which were presented at the European Society of Medical Oncology (ESMO) Congress 2023. In the sub-study, Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy demonstrated statistically significant and clinically meaningful improvements in the primary efficacy endpoints of overall survival (OS) and progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR). With a median follow up of approximately 33 months, treatment with Opdivo in combination with cisplatin and gemcitabine reduced the risk of death by 22%, demonstrating a median OS of 21.7 months versus 18.9 months with cisplatin-gemcitabine alone (Hazard Ratio [HR] 0.78; 95% Confidence Interval [CI]: 0.63, 0.96; p=0.0171). Patients receiving Opdivo in combination with cisplatin and gemcitabine had their risk of disease progression or death reduced by 28%, with a median PFS of 7.9 months compared to 7.6 months with cisplatin-gemcitabine alone (HR 0.72; 95% CI: 0.59, 0.88; p=0.0012). The safety profile was consistent with the known safety profiles of the individual components of the regimen. No new safety concerns were identified. Please see Important Safety Information below.
CheckMate -901 is the first Phase 3 trial with an immunotherapy-chemotherapy combination to demonstrate a survival benefit compared to standard-of-care chemotherapy alone in the first-line treatment of adults with unresectable or metastatic urothelial carcinoma.
On March 7, 2024 the U.S. Food and Drug Administration (FDA) approved the use of Opdivo in combination with cisplatin and gemcitabine as a first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma, following a Priority Review. Opdivo and Opdivo-based combinations have shown significant improvements in OS in Phase 3 clinical trials across multiple tumors, including urothelial carcinoma, renal cell carcinoma, non-small cell lung cancer, malignant pleural mesothelioma, melanoma, hepatocellular carcinoma, gastric cancer, squamous cell carcinoma of the head and neck and esophageal squamous cell carcinoma.
Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -901 clinical trial.
About CheckMate -901
CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with Yervoy (ipilimumab) or Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy compared to standard-of-care chemotherapy alone, in patients with untreated, unresectable or metastatic urothelial cancer.
In the sub-study of CheckMate -901, evaluating Opdivo with cisplatin and gemcitabine vs. standard-of-care chemotherapy alone, a total of 608 patients eligible for cisplatin-based chemotherapy were randomized to receive either Opdivo 360 mg in combination with cisplatin and gemcitabine every three weeks for up to six cycles followed by 480 mg/Q4 Opdivo monotherapy every 4 weeks until disease progression or death up to a maximum of two years, or cisplatin-gemcitabine alone every three weeks for up to six cycles. The primary endpoints of this study are overall survival (OS) and progression-free survival (PFS).
The OS and PFS outcomes for patients eligible for cisplatin-based chemotherapy are based on the final efficacy analyses of these endpoints.
The CheckMate -901 primary study, evaluating Opdivo plus Yervoy vs. standard-of-care cisplatin- or carboplatin-based chemotherapy in patients with untreated, unresectable or metastatic urothelial carcinoma remains ongoing.
About Urothelial Carcinoma
Bladder cancer is the 10th most common cancer in the world, with more than 573,000 new cases diagnosed annually. Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases. In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis. The majority of urothelial carcinomas are diagnosed at an early stage, but approximately 50% of patients who undergo surgery will experience disease progression and recurrence within two-to-three years post-surgery. Approximately 20% to 25% of patients with urothelial carcinoma develop metastatic disease. The poor durability of responses seen with chemotherapy alone in the first-line setting presents a major challenge in the treatment of metastatic disease, and there are limited treatment options in the second-line setting for patients with advanced urothelial carcinoma.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
INDICATIONS
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.
OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
Please see U.S. Full Prescribing Information for OPDIVO and YERVOY.
Clinical Trials and Patient Populations
Checkmate 227—previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238– adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K– adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066—previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025– previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma.
About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Source: Bristol Myers Squibb
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Approval is based on the Phase 3 KEYNOTE-859 Trial
KIRKLAND, QC, April 19, 2024 – Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced that Health Canada has granted approval of KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with fluoropyrimidine- and platinum-containing-chemotherapy, for the first-line treatment of adult patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. This approval is based on the results from the Phase 3 KEYNOTE-859 trial, which demonstrated a statistically significant improvement in overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) compared to placebo in combination with chemotherapy in the intention-to-treat (ITT) study population.
“We are proud of the recent expansion of KEYTRUDA®‘s indications in gastric cancers, which often go undetected until an advanced stage, at which point patients face a poor prognosis,” says André Galarneau, PhD, Executive Director & Vice President, Oncology Business Unit at Merck Canada. “This milestone underscores our commitment to helping improve the lives of patients by offering treatment options that can lead to better health outcomes.”
About KEYNOTE-859
KEYNOTE-859 was a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial (ClinicalTrials.gov NCT03675737) evaluating pembrolizumab in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma. The primary endpoint was overall survival (OS) with progression-free survival (PFS) and objective response rate (ORR) included as secondary endpoints as assessed by blinded independent central review (BICR) using RECIST v1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
The trial enrolled 1579 patients who had not previously received systemic therapy for metastatic disease and were randomized 1:1 to receive pembrolizumab (200 mg every three weeks) in combination with fluoropyrimidine- and platinum-containing chemotherapy (n=790), or placebo in combination with chemotherapy (n=789). All patients received investigator’s choice of chemotherapy (5-fluorouracil plus cisplatin [FP] or capecitabine plus oxaliplatin [CAPOX]). All study medications, except oral capecitabine, were administered as an intravenous infusion for every 3-week cycle. Platinum agents could be administered for 6 or more cycles following local guidelines. Treatment continued until RECIST v1.1-defined progression of disease as determined by BICR, unacceptable toxicity, or a maximum of 24 months.
A statistically significant improvement in OS, PFS and ORR was demonstrated in patients randomized to pembrolizumab in combination with chemotherapy compared with placebo in combination with chemotherapy at the pre-specified interim analysis of OS. In the study, there was a 22% reduction in the risk of death with pembrolizumab plus chemotherapy (HR=0.78 [95% CI, 0.70-0.87]; p<0.0001) versus chemotherapy alone. The median OS for patients receiving pembrolizumab plus chemotherapy was 12.9 months (95% CI, 11.9-14.0) versus 11.5 months (95% CI, 10.6-12.1) for those receiving chemotherapy alone.
A positive association was observed between PD-L1 CPS score and the magnitude of the treatment benefit. The median duration of exposure to pembrolizumab was 6.2 months (range, 1 day to 33.7 months).
The most common treatment-related adverse events (≥20% incidence) for patients receiving pembrolizumab plus fluoropyrimidine- and platinum-containing chemotherapy were nausea, diarrhea, anemia, vomiting, platelet count decreased, neutrophil count decreased, palmar-plantar erythrodysesthesia syndrome, decreased appetite and fatigue.
For complete information, refer to the product monograph.
About Gastric Cancer
Gastric (stomach) cancer tends to develop slowly over many years and rarely causes symptoms in its early stages, resulting in nearly half of cases being diagnosed at an advanced stage. About 95% of gastric cancers are adenocarcinomas, which develop from cells in the innermost lining of the stomach, known as the mucosa. It was estimated that gastric cancer accounted for approximately 4,100 cases and 2,000 deaths in Canada in 2023, with the highest mortality rates in Newfoundland and Labrador. Based on statistics from the United States, the relative five-year survival for patients diagnosed with gastric cancer at an advanced stage (cancer that had spread to other parts of the body) is only 5%.
About KEYTRUDA®
KEYTRUDA® is an anti-PD-1 therapy that works by helping increase the ability of the body’s immune system to help detect and fight tumour cells. KEYTRUDA® is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumour cells and healthy cells.
KEYTRUDA® was first approved in Canada in 2015 and currently has indications in several disease areas, including advanced renal cell carcinoma, bladder cancer, non-small cell lung carcinoma, primary mediastinal B-cell lymphoma, classical Hodgkin lymphoma, colorectal cancer, endometrial carcinoma, cervical cancer, esophageal cancer, triple-negative breast cancer, melanoma, and head and neck squamous cell carcinoma.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable, and healthy future for all people and communities. For more information about our operations in Canada, visit www.merck.ca and connect with us on LinkedIn and X @MerckCanada.
® Merck Sharp & Dohme LLC. Used under license.
© 2024 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved.
Apr. 19, 2024 12:03 PM ET
Merck & Co., Inc. (MRK) StockITT, PFS
By: Jonathan Block, SA News Editor
PUBLISHED16 April 2024
Updated exploratory results from the TOPAZ-1 Phase III trial showed AstraZeneca’s Imfinzi (durvalumab) in combination with standard-of-care chemotherapy demonstrated a clinically meaningful long-term overall survival (OS) benefit at three years for patients with advanced biliary tract cancer (BTC).
These results from TOPAZ-1, which are the longest survival follow-up ever reported for a global, randomised Phase III trial in this setting, will be presented on 18 April at the 2024 Cholangiocarcinoma Foundation Conference in Salt Lake City, Utah.
At more than three years (median follow-up of 41.3 months), results showed Imfinzi plus chemotherapy reduced the risk of death by 26% versus chemotherapy alone (based on a hazard ratio [HR] of 0.74; 95% confidence interval [CI], 0.63-0.87). The median OS was 12.9 months for Imfinzi plus chemotherapy versus 11.3 months for chemotherapy alone. More than twice as many patients on the Imfinzi-based regimen were alive at three years versus chemotherapy alone (14.6% versus 6.9%).
The TOPAZ-1 trial met the primary endpoint of OS in October 2021 at a planned interim analysis, showing that the combination reduced the risk of death by 20% versus chemotherapy alone (based on a HR of 0.80; 95% CI, 0.66-0.97; 2-sided p=0.021 at a statistical significance threshold of 0.03).
Do-Youn Oh, MD, PhD, Professor, Division of Medical Oncology, Department of Internal Medicine at Seoul National University Hospital and Seoul National University College of Medicine, and principal investigator in the trial, said: “The latest data from TOPAZ-1 show that twice as many patients with advanced biliary tract cancer were still alive at three years with durvalumab and chemotherapy, an especially meaningful advance in a setting where historically the prognosis has been poor. These results reinforce the long-term benefit of this immunotherapy-based combination as a standard of care for patients with this devastating disease.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “TOPAZ-1 raised the bar for the treatment of advanced biliary tract cancer, showing a remarkable survival benefit for Imfinzi added to chemotherapy with a well-tolerated regimen. These data represent the longest survival follow-up reported for immunotherapy in this setting, and the three-year landmark survival improvement underscores our commitment to improving long-term outcomes in gastrointestinal cancers.”
Stacie Lindsey, CEO, Cholangiocarcinoma Foundation said: “AstraZeneca’s longer survival data in advanced biliary tract cancer represents a meaningful milestone in that we are seeing three-year survival data for the first time for these patients. The data spurs hope that research will continue to improve outcomes for patients living with these challenging and rare cancers.”
Biliary tract cancer
Biliary tract cancer (BTC) is a group of rare and aggressive gastrointestinal (GI) cancers that form in the cells of the bile ducts (cholangiocarcinoma), gallbladder or ampulla of Vater (where the bile duct and pancreatic duct connect to the small intestine).1,2 Approximately 50,000 people in the US, Europe and Japan and about 210,000 people worldwide are diagnosed with BTC each year.3-5 These patients historically have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years. For patients with metastatic disease, the five-year survival rate drops to less than 5%.7
Cholangiocarcinoma is more common in China and Thailand and is on the rise in Western countries.1,6 Gallbladder cancer is more common in certain regions of South America, India and Japan.8
Early-stage BTC affecting the bile ducts and gallbladder often presents without clear symptoms and most new cases of BTC are therefore diagnosed at an advanced stage, when treatment options are limited and the prognosis is poor.6,8,9
TOPAZ-1
TOPAZ-1 is a randomised, double-blind, placebo controlled, multicentre, global Phase III trial of Imfinzi in combination with chemotherapy (gemcitabine plus cisplatin) versus placebo in combination with chemotherapy as a 1st-line treatment in 685 adult patients with unresectable, locally advanced or metastatic BTC including intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer. Patients with ampullary carcinoma were excluded.
The primary endpoint is overall survival and key secondary endpoints included progression-free survival, objective response rate and safety. The trial was conducted in 105 centres across 17 countries including in the US, Europe, South America and several countries in Asia including South Korea, Thailand, Japan and China
Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.
In addition to its indications in unresectable, Stage III NSCLC and ES-SCLC, Imfinzi is currently approved in a number of countries in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC.
Imfinzi is also approved in a number of countries in combination with chemotherapy in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU and in previously treated patients with advanced bladder cancer in a small number of countries.
Since the first approval in May 2017, more than 220,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal cancers and other solid tumours.
AstraZeneca in GI cancers
AstraZeneca has a broad development programme for the treatment of GI cancers across several medicines and a variety of tumour types and stages of disease. In 2020, GI cancers collectively represented approximately 5.1 million new cancer cases leading to approximately 3.6 million deaths.10
Within this programme, the Company is committed to improving outcomes in gastric, liver, biliary tract, oesophageal, pancreatic and colorectal cancers.
In addition to its indications in BTC and HCC, Imfinzi is being assessed in combinations, including with Imjudo, in liver, oesophageal and gastric cancers in an extensive development programme spanning early to late-stage disease across settings.
The Company is also assessing rilvegostomig (AZD2936), a PD-1/TIGIT bispecific antibody, in combination with chemotherapy as an adjuvant therapy in biliary tract cancer.
Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, is approved in the US and several other countries for HER2-positive advanced gastric cancer and is being assessed in colorectal cancer. It also has been assessed in multiple GI settings including biliary tract cancer in the DESTINY-PanTumor02 Phase II trial, and it was recently approved in the US for the treatment of unresectable or metastatic HER2-positive solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options. Enhertu is jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
Lynparza (olaparib), a first-in-class PARP inhibitor, is approved in the US and several other countries for the treatment of BRCA-mutated metastatic pancreatic cancer. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada).
AstraZeneca is advancing multiple modalities that provide complementary mechanisms for targeting Claudin 18.2, a promising therapeutic target in gastric cancer. These include AZD0901, a potential first-in-class antibody drug conjugate licensed from KYM Biosciences Inc., currently in Phase II development, AZD5863, a novel Claudin 18.2/CD3 T-cell engager bispecific antibody licensed from Harbour Biomed in Phase I development, and AZD6422, an armoured autologous chimeric antigen receptor T-cell (CAR-T) therapy, currently being evaluated in an Investigator Initiated Trial (IIT) in collaboration with AbelZeta in China.
In early development, AstraZeneca is developing two Glypican 3 (GPC3) armoured CAR-Ts in HCC. AZD5851, currently in Phase I development, is being developed globally, and C-CAR031 / AZD7003 is being co-developed with AbelZeta in China where it is under evaluation in an IIT.
AstraZeneca in immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours.
AstraZeneca strives to redefine cancer care and help transform outcomes for patients with Imfinzi as a monotherapy and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T cell engagers.
AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.
Apr. 16, 2024 8:32 AM ET
By: Jonathan Block, SA News Editor
PUBLISHED 6 April 2024
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options.
This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
The first tumour-agnostic approval of a HER2-directed therapy and ADC by the Food and Drug Administration (FDA) was based on results from the subgroup of patients with HER2-positive IHC 3+ tumours in each of the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 Phase II trials.
Funda Meric-Bernstam, MD, Chair of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, US, said: “Until the approval of trastuzumab deruxtecan, patients with metastatic HER2-positive solid tumours have had limited treatment options. Based on the clinically meaningful response rates seen across clinical trials, this tumour-agnostic approval means that patients may now be treated with a HER2-directed medicine.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “As the first antibody drug conjugate to be granted a tumour-agnostic indication, Enhertu is truly delivering on its potential across metastatic HER2-targetable tumours. This approval also elevates the importance of testing for biomarkers, including HER2, across a broad range of tumours to ensure these patients with advanced cancer who have few options know whether a targeted medicine might be right for them.”
Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc., said: “This fifth indication in the US is a significant milestone as eligible patients with previously treated metastatic HER2-positive solid tumours may now be treated with Enhertu. The accelerated approval by the FDA for this tumour-agnostic indication is based on the clinically meaningful efficacy seen with Enhertu across numerous types of metastatic cancers.”
In the DESTINY-PanTumor02 Phase II trial, patients with centrally or locally assessed HER2-positive (IHC 3+) solid tumours including either biliary tract, bladder, cervical, endometrial, ovarian, pancreatic or other tumours treated with Enhertu showed a confirmed ORR of 51.4% (95% confidence interval [CI] 41.7-61.0) and a median DoR range of 19.4 months (range 1.3-27.9+ [+ denotes ongoing responses at data cutoff]). In DESTINY-Lung01, patients with centrally confirmed HER2-positive (IHC 3+) non-small cell lung cancer (NSCLC) treated with Enhertu showed a confirmed ORR of 52.9% (95% CI 27.8-77.0) and median DoR range of 6.9 months (range 4.0-11.7+). A confirmed ORR of 46.9% (95% CI 34.3-59.8) and median DoR range of 5.5 months (range 1.3+-9.7+) was seen in patients with centrally confirmed HER2-positive (IHC 3+) colorectal cancer in the DESTINY-CRC02 trial.
The safety of Enhertu was evaluated in 347 patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours in the DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. The safety profile observed across the trials was consistent with previous clinical trials of Enhertu with no new safety concerns identified.
Based on these results, fam-trastuzumab deruxtecan-nxki (Enhertu) has been included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a treatment option for multiple metastatic tumours. See NCCN Guidelines® for detailed recommendations.1
This approval was granted under the FDA’s Real-Time Oncology Review programme after securing Priority Review and Breakthrough Therapy Designation for Enhertu in the US in this setting.
The US regulatory submission was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, Enhertu is also under regulatory review for the same indication by regulatory authorities in Australia, Brazil and Singapore.
Financial considerations
Sales of Enhertu in the US are recognised by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from Enhertu sales in the US as alliance revenue in the Company’s financial statements.
Further details on the financial arrangements were set out in the March 2019 announcement of the collaboration.
Notes
HER2 expression in solid tumours
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of various tissue cells throughout the body and is involved in normal cell growth.2,3 In some cancers, HER2 expression is amplified or the cells have activating mutations.2,4 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis.5
HER2-directed therapies have been used to treat breast, gastric, lung and colorectal cancers for a number of years.3,6,7 Although HER2 is expressed in solid tumour types including biliary tract, bladder, cervical, endometrial, ovarian and pancreatic cancers, testing is not routinely performed in these additional tumour types and as a result, available literature is limited.4 In these solid tumours, HER2-positive expression, classified as immunohistochemistry (IHC) 3+, has been observed at rates from 1% to 28%.8,9 Approximately 1% to 5% of patients with NSCLC have tumours with HER2 overexpression (IHC 3+), however, the levels of protein expression reported vary in the literature.8,10 Approximately 1% to 4% of patients with metastatic colorectal cancer have tumours which are HER2 overexpressing (IHC 3+).8,11,12
DESTINY-PanTumor02
DESTINY-PanTumor02 is a global, multicentre, multi-cohort, open-label Phase II trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) for the treatment of previously treated HER2-expressing tumours, including biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer or other tumours.
The primary efficacy endpoint of DESTINY-PanTumor02 is confirmed ORR as assessed by investigator. Secondary endpoints include DoR, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, tolerability and pharmacokinetics.
DESTINY-PanTumor02 has enrolled 267 patients, including 111 HER2-positive (IHC 3+) adult patients, at multiple sites in Asia, Europe and North America, and is to be expanded to recruit more patients with metastatic HER2-positive IHC 1+, IHC 2+ and IHC 3+ tumours. For more information about the trial, visit ClinicalTrials.gov.
DESTINY-Lung01
DESTINY-Lung01 is a global Phase II, open-label, two-cohort trial evaluating the efficacy and safety of Enhertu (5.4mg/kg or 6.4mg/kg) in patients with HER2-mutant (cohort 2, n=91) or HER2-overexpressing (defined as IHC 3+ or IHC 2+) [cohort 1 and 1a, n=90] unresectable or metastatic non-squamous NSCLC who had progressed after one or more systemic therapies.
The primary endpoint is confirmed ORR by independent central review. Key secondary endpoints include DoR, DCR, PFS, OS and safety.
DESTINY-Lung01 enrolled 181 patients, including 17 HER2-positive (IHC 3+) adult patients, at multiple sites, including Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.
DESTINY-CRC02
DESTINY-CRC02 is a global, randomised, two arm, parallel, multicentre Phase II trial evaluating the efficacy and safety of two doses (5.4mg/kg or 6.4mg/kg) of Enhertu in patients with locally advanced, unresectable or metastatic HER2-positive colorectal cancer of BRAF wild-type, RAS wild-type or RAS mutant tumour types previously treated with standard therapy.
The trial was conducted in two stages. In the first stage, patients (n=80) were randomised 1:1 to receive either 5.4mg/kg or 6.4mg/kg of Enhertu. In the second stage, additional patients (n=42) were enrolled in the 5.4mg/kg arm.
The primary endpoint is confirmed ORR as assessed by blinded independent central review. Secondary endpoints include DoR, DCR, investigator-assessed confirmed ORR, clinical benefit ratio, PFS, OS and safety.
DESTINY-CRC02 enrolled 122 patients, including 64 HER2-positive (IHC 3+) adult patients, at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.
DESTINY-Breast01
DESTINY-Breast01 is a global, single-arm, open-label, two-part multi-centre Phase II trial evaluating the safety and efficacy of Enhertu in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine (T-DM1).
The primary endpoint of the trial is ORR, as determined by independent central review. Secondary objectives include DoR, DCR, clinical benefit rate, PFS and OS.
DESTINY-Breast01 enrolled 253 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads, (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Enhertu (5.4mg/kg) is approved in more than 60 countries for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or in-situ hybridization [ISH]+) breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.
Enhertu (5.4mg/kg) is approved in more than 55 countries for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
Enhertu (5.4mg/kg) is approved in more than 35 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Enhertu (6.4mg/kg) is approved in more than 45 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial and/or DESTINY-Gastric02 trial.
Enhertu (5.4 mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on the results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Enhertu development programme
A comprehensive clinical development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca.
Apr. 05, 2024 4:14 PM ET
AstraZeneca PLC (AZN) Stock, DSKYF Stock
By: Jonathan Block, SA News Editor
China's National Medical Products Administration Accepts Astellas and Pfizer's Supplemental Biologics License Application for enfortumab vedotin with KEYTRUDA® (pembrolizumab) for First-Line Treatment of Advanced Bladder Cancer
- Pivotal trial found the enfortumab vedotin plus pembrolizumab combination significantly extended overall and progression-free survival vs platinum-containing chemotherapy-
- If approved, enfortumab vedotin with KEYTRUDA would be the first combination in China to offer an alternative to chemotherapy, the current standard of care in first-line locally advanced or metastatic urothelial cancer-
TOKYO, March 28, 2024 /PRNewswire/ -- Astellas Pharma Inc. (TSE:4503, President and CEO: Naoki Okamura, "Astellas") today announced that on March 27, 2024 the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted the supplemental Biologics License Application (sBLA) for enfortumab vedotin with KEYTRUDA® (pembrolizumab) as a combination therapy for the first-line treatment of adult patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). If approved, enfortumab vedotin with KEYTRUDA has the potential to change the treatment paradigm, becoming the first combination treatment to offer an alternative to platinum-containing chemotherapy, the current standard of care in first-line la/mUC.
Urothelial cancer (UC) encompasses cancers of both the lower urinary tract (bladder and urethra) and upper tract (ureter and renal pelvis), with disease that originates in the lower tract accounting for 90% to 95% of all UC cases.i,ii Globally, approximately 614,000 new cases of bladder cancer and approximately 220,000 deaths are reported annually.iii It is estimated that approximately 93,000 people in China were diagnosed with bladder cancer and approximately 41,000 deaths were reported in 2022.iv
Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas
"Locally advanced or metastatic urothelial cancer is a life-threatening condition in China with nearly half of those diagnosed succumbing to the disease. The CDE's acceptance of our sBLA for enfortumab vedotin and pembrolizumab brings us one step closer to delivering a much-needed, innovative new treatment option for this patient population."
Professor Guo Jun, lead PI in China for the EV-302 trial, director of the Department of Melanoma and Urological Oncology at Beijing Cancer Hospital, executive board member of the Chinese Society Of Clinical Oncology (CSCO)
"In China, the recommended first-line treatment for advanced urothelial cancer is platinum-based chemotherapy, and there are currently no other treatments approved in the first-line setting. Given the efficacy brought by chemotherapy, alternate treatment options are extremely needed to extend survival benefits and potentially improve the prognosis of those patients. The results of the EV-302 study demonstrated that enfortumab vedotin in combination with pembrolizumab, as the first non-platinum first-line treatment, can achieve a clinically meaningful improvement in response rate, nearly double the median progression-free survival, and significantly improve the overall survival benefit of patients with locally advanced or metastatic urothelial cancer compared to chemotherapy."
The sBLA for the first-line use of this combination is based on results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39). The study found that the combination improved overall survival (OS) and progression-free survival (PFS) with statistically significant and clinically meaningful results in patients with previously untreated la/mUC compared to platinum-containing chemotherapy. The safety results were consistent with those previously reported with this combination, and no new safety issues were identified.
The NMPA is also reviewing enfortumab vedotin as a treatment for patients with locally advanced or metastatic urothelial cancer (la/mUC) who received prior treatment with a PD-1/L1 inhibitor and platinum-based chemotherapy.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency is reviewing the enfortumab vedotin in combination with pembrolizumab therapy, as well as Japan's Ministry of Health, Labour and Welfare (MHLW). The U.S. Food and Drug Administration approved the combination therapy in December 2023.
About EV-302
The EV-302 trial is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in patients with previously untreated la/mUC. The study enrolled 886 patients with previously untreated la/mUC who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status. Patients were randomized to receive either enfortumab vedotin in combination with pembrolizumab or platinum-containing chemotherapy. The dual primary endpoints of this trial are OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Select secondary endpoints include ORR per RECIST v1.1 by BICR, DOR per RECIST v1.1 by BICR, and safety.
The EV-302 trial is part of an extensive clinical program evaluating this combination in multiple stages of urothelial cancer and other solid tumors. Findings from EV-302 were presented at the European Society for Medical Oncology (ESMO) Congress 2023 in October 2023.
About Bladder and Urothelial Cancer
Ongoing Investigational Trials
The EV-302 trial (NCT04223856) is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC) who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status.
The EV-103 trial (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter Phase 1b/2 study investigating enfortumab vedotin alone or in combination with pembrolizumab and/or chemotherapy in first- or second-line settings in patients with la/mUC and in patients with muscle-invasive bladder cancer (MIBC).
Enfortumab vedotin in combination with pembrolizumab is being investigated in an extensive program in multiple stages of urothelial cancer, including two Phase 3 clinical trials in MIBC in EV-304 (NCT04700124, also known as KEYNOTE-B15) and EV-303 (NCT03924895, also known as KEYNOTE-905). The use of enfortumab vedotin in combination with pembrolizumab in second-line urothelial cancer and MIBC has not been proven safe or effective.
The EV-202 trial (NCT04225117) is an ongoing, multi-cohort, open-label, multicenter Phase 2 study investigating enfortumab vedotin alone in patients with previously treated advanced solid tumors. This study also has a cohort that is investigating enfortumab vedotin in combination with pembrolizumab in patients with previously untreated recurrent/ metastatic head and neck squamous cell carcinoma.
The EV-203 trial (NCT04995419) is a Phase 2, multicenter, single-arm bridging study in China designed to evaluate the efficacy, safety, and pharmacokinetic performance of enfortumab vedotin as treatment for patients in China. A total of 40 patients were enrolled in the study.
About Enfortumab Vedotin
Enfortumab vedotin is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.viii Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4-expressing cells, followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).ix
Indication
PADCEV®, in combination with pembrolizumab, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC).
PADCEV, as a single agent, is indicated for the treatment of adult patients with locally advanced or mUC who:
About Astellas
Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients. For more information, please visit our website at https://www.astellas.com/en.
About the Astellas, Pfizer and Merck Collaboration
Astellas and Pfizer have a clinical collaboration agreement with Merck to evaluate the combination of Astellas' and Pfizer's PADCEV™ (enfortumab vedotin) and Merck's KEYTRUDA® (pembrolizumab) in patients with previously untreated metastatic urothelial cancer. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the United States and Canada).
SOURCE ASTELLAS PHARMA INC.
Mar. 28, 2024 11:54 AM ET
Pfizer Inc. (PFE) Stock, ALPMF Stock, ALPMY StockMRK
By: Dulan Lokuwithana, SA News Editor
Astellas (OTCPK:ALPMF) announced Thursday that Chinese regulators agreed to review a request to expand the label of Padcev, an antibody-drug conjugate it co-develops with Pfizer (NYSE:PFE), as a first-line option for certain patients with bladder cancer.
On Wednesday, China’s Center for Drug Evaluation accepted a supplemental biologics license application ((sBLA)) for Padcev in combination with Merck’s (MRK) PD-1 inhibitor Keytruda for treatment naïve adults with locally advanced or metastatic urothelial cancer, the company said.
03/20/2024 CATEGORY:
Opdivo plus Yervoy demonstrates statistically significant and clinically meaningful improvement in overall survival compared to investigator’s choice of sorafenib or lenvatinib
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced the Phase 3 CheckMate -9DW trial evaluating Opdivo (nivolumab) plus Yervoy (ipilimumab) as a first-line treatment for patients with advanced hepatocellular carcinoma (HCC) who have not received prior systemic therapy met its primary endpoint of improved overall survival (OS) compared to investigator’s choice of sorafenib or lenvatinib at a pre-specified interim analysis.
The dual immunotherapy combination of Opdivo plus Yervoy demonstrated a statistically significant and clinically meaningful improvement in OS compared to investigator’s choice of sorafenib or lenvatinib. The safety profile for the combination of Opdivo plus Yervoy remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified.
“Advanced stage liver cancer patients remain in need of additional treatment options that may help improve survival,” said Dana Walker, M.D., M.S.C.E., vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. “The overall survival benefit demonstrated by the combination of Opdivo plus Yervoy in the CheckMate -9DW trial demonstrates its potential to improve outcomes compared to well-established TKI treatment options.”
The company will complete a full evaluation of the data and work with investigators to share the results with the scientific community at an upcoming medical conference, as well as discuss with health authorities.
Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -9DW clinical trial.
About CheckMate -9DW
CheckMate -9DW is a Phase 3 randomized, open-label trial evaluating the combination of Opdivo plus Yervoy compared to investigator’s choice of sorafenib or lenvatinib monotherapy in patients with advanced hepatocellular carcinoma who have not received prior systemic therapy.
Approximately 668 patients were randomized to receive Opdivo plus Yervoy (Opdivo 1mg/kg plus Yervoy 3 mg/kg Q3W for up to four doses, followed by Opdivo monotherapy 480 mg Q4W) infusion, or single agent sorafenib or lenvatinib as oral capsules in the control arm. The primary endpoint of the trial is overall survival and key secondary endpoints include objective response rate and time to symptom deterioration.
About Hepatocellular Carcinoma
Liver cancer is the third most frequent cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and accounts for 90% of all liver cancers. HCC is often diagnosed in an advanced stage, where effective treatment options are limited and are usually associated with poor outcomes.
Up to 70% of patients experience recurrence within five years, particularly those still considered to be at high risk after surgery or ablation. While most cases of HCC are caused by hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, metabolic syndrome and nonalcoholic steatohepatitis (NASH) are rising in prevalence and expected to contribute to increased rates of HCC.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research programs uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
About Yervoy
Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types.
https://www.opdivo.com/about-opdivo/how-the-combination-works
INDICATIONS
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.
OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.
OPDIVO® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma.
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram
Source: Bristol Myers Squibb
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Mar. 20, 2024 7:28 AM ET
Bristol-Myers Squibb Company (BMY) Stock
By: Dulan Lokuwithana, SA News Editor1 Comment
Bristol-Myers Squibb (NYSE:BMY) announced Wednesday that its immunotherapy combo, Opdivo plus Yervoy, reached its main goals in a late-stage trial as a first-line option for hepatocellular carcinoma, the most common form of liver cancer.
Citing interim data from its CheckMate-9DW trial, Bristol-Myers (BMY) said Opdivo plus Yervoy led to a statistically significant and clinically meaningful improvement in overall survival, thus meeting the trial's primary endpoint against a comparator.
Bristol-Myers Squibb Company (BMY) Stock
https://www.opdivo.com/about-opdivo/how-the-combination-works
March 15, 2024 6:45 am ET
KEYTRUDA plus CRT is the first immunotherapy-based regimen to demonstrate a statistically significant improvement in OS in these patients
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the Phase 3 KEYNOTE-A18 trial, also known as ENGOT-cx11/GOG-3047, investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemoradiotherapy (CRT) met its primary endpoint of overall survival (OS) for the treatment of newly diagnosed patients with high-risk locally advanced cervical cancer.
At a pre-specified interim analysis conducted by an independent Data Monitoring Committee, KEYTRUDA in combination with concurrent CRT showed a statistically significant and clinically meaningful improvement in OS versus concurrent CRT alone. The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. Results will be presented at an upcoming medical meeting and shared with regulatory authorities worldwide.
As previously reported, KEYNOTE-A18 met its other primary endpoint of progression-free survival (PFS) in 2023. These PFS data were presented at the European Society for Medical Oncology (ESMO) Congress 2023 and supported the U.S. Food and Drug Administration's approval of KEYTRUDA in combination with CRT for the treatment of patients with FIGO (International Federation of Gynecology and Obstetrics) 2014 Stage III-IVA cervical cancer in January 2024.
“This is the first Phase 3 trial in which an immunotherapy-based regimen has shown a statistically significant and clinically meaningful improvement in overall survival compared to chemoradiotherapy alone,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “Building on the positive progression-free survival findings from this study, these results underscore our commitment to exploring the role of KEYTRUDA across different types of cancers in earlier stages of disease, where there is a greater potential for better outcomes.”
“These findings are important for patients and the medical community alike and reinforce previous data from the KEYNOTE-A18 trial, now showing this regimen has the potential to extend the lives of patients with locally advanced cervical cancer,” said Prof. Domenica Lorusso, the study’s overall principal investigator, lead investigator for ENGOT, and professor of Obstetrics and Gynecology at Humanitas University.
In the U.S., KEYTRUDA has two additional approved indications in cervical cancer: in combination with chemotherapy, with or without bevacizumab, for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test; and as a single agent, for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
About KEYNOTE-A18/ENGOT-cx11/GOG-3047
KEYNOTE-A18, also known as ENGOT-cx11/GOG-3047, is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT04221945) sponsored by Merck and conducted in collaboration with the European Network for Gynecological Oncology Trial (ENGOT) groups and the GOG Foundation, Inc. (GOG) investigating KEYTRUDA in combination with CRT (cisplatin and external beam radiotherapy [EBRT] followed by brachytherapy [BT]) compared to placebo plus concurrent CRT for the treatment of newly diagnosed high-risk (stage IB2-IIB with lymph node-positive disease, and stage III-IVA with and without lymph node-positive disease) locally advanced cervical cancer where patients are treated with definitive intent. The primary endpoints are PFS and OS, and secondary endpoints include complete response rate, objective response rate and safety. The trial enrolled 1,060 patients with cervical cancer who had not previously received any definitive surgery, radiation, or systemic therapy for cervical cancer. Patients were randomized (1:1) to receive either:
About cervical cancer
Cervical cancer forms in the cells lining the cervix, which is the lower part of the uterus. All women are at risk for cervical cancer, and it is most frequently diagnosed between the ages of 35 and 44. While screenings and prevention have resulted in declining cervical cancer rates, the disease continues to affect many people in the U.S. and around the world. Cervical cancer is the fourth most common cancer in women globally. In the U.S., it is estimated there will be approximately 13,820 new patients diagnosed with invasive cervical cancer and about 4,360 deaths from the disease in 2024.
About Merck’s research in breast and gynecologic cancers
Merck is advancing research aimed at improving outcomes for patients affected by breast and gynecologic (ovarian, cervical and endometrial) cancers. Merck has a comprehensive clinical development program across these cancers comprised of more than 20 Merck-sponsored Phase 3 studies evaluating KEYTRUDA as monotherapy and in combination with other medicines. In the U.S., KEYTRUDA currently has two approved indications for triple-negative breast cancer, including one for high-risk early-stage disease, and five approved indications across certain types of cervical and endometrial cancers (see indications below). Among Merck’s research efforts are trials focused on evaluating KEYTRUDA in earlier stages of these cancers, as well as identifying new combinations and coformulations with KEYTRUDA.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Cervical Cancer
KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.
Additional Selected KEYTRUDA Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.
KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Carcinoma
KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:
KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.
Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract carcinoma (BTC).
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Merck’s focus on cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .
Source: Merck & Co., Inc.
Mar. 15, 2024 7:35 AM ET
By: Dulan Lokuwithana, SA News Editor
Merck (NYSE:MRK) announced Friday that its anti-PD1 immunotherapy Keytruda, in combination with chemoradiotherapy (CRT), reached the primary endpoint of overall survival (OS) as a first-line option for cancer in the cervix, a part of the uterus.
Tuesday, March 12, 2024 - 06:45am View pdf Open in tab
NEW YORK--(BUSINESS WIRE)--
Pfizer Inc. (NYSE: PFE) today announced that a Phase 3 study of the antibody-drug conjugate ADCETRIS® (brentuximab vedotin) in combination with lenalidomide and rituximab for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) showed a statistically significant and clinically meaningful improvement in overall survival (OS) compared to lenalidomide and rituximab plus placebo. Positive outcomes were also observed in key secondary endpoints, including progression free survival (PFS) and overall response rate (ORR).
The safety and tolerability of ADCETRIS in the ECHELON-3 trial were consistent with what has been previously presented for patients with relapsed/refractory DLBCL treated with ADCETRIS in clinical trials. Full data will be submitted for presentation at an upcoming medical meeting.
“This is the third Phase 3 study in a type of lymphoma to demonstrate an overall survival benefit for an ADCETRIS combination. Based on the strong results from ECHELON-3, we’re excited that ADCETRIS could address an area of high unmet need in patients with relapsed or refractory DLBCL irrespective of CD30 expression,” said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. “The results are particularly encouraging because the study evaluated heavily pre-treated patients, including some who received prior CAR-T therapy.”
DLBCL is the most common type of lymphoma and is a fast-growing, aggressive blood cancer. Approximately 40% of patients with DLBCL do not respond to initial treatment or develop relapsed disease after first-line treatment.
ADCETRIS is a standard of care for patients with certain lymphomas and is approved for seven indications in the U.S with more than 55,000 patients treated since its first U.S. approval in 2011. More than 140,000 patients have been treated with ADCETRIS globally. Pfizer plans to share the ECHELON-3 data with the U.S. Food and Drug Administration (FDA) to potentially support regulatory filing in the U.S.
About ECHELON-3
ECHELON-3 is an ongoing, randomized, double-blind, multicenter Phase 3 study evaluating ADCETRIS plus lenalidomide and rituximab versus lenalidomide and rituximab plus placebo in adult patients with relapsed/refractory DLBCL, regardless of CD30 expression, who have received two or more prior lines of therapy and are ineligible for stem cell transplant or CAR-T therapy. In this global study, 230 patients were randomized across North America, Europe and Asia-Pacific. The primary endpoint is OS in the intent to treat population, with key secondary endpoints of PFS and ORR as assessed by investigator. Other secondary endpoints include complete response rate, duration of response, safety and tolerability.
AboutDiffuse Large B-cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of lymphoma and is an aggressive, difficult to treat disease.1 More than 25,000 cases of DLBCL are diagnosed each year in the United States, accounting for more than 25 percent of all lymphoma cases.2
DLBCL can develop spontaneously or as a result of diseases such as chronic lymphocytic lymphoma/small lymphocytic lymphoma, follicular lymphoma, or marginal zone lymphoma.3 Up to 40 percent of patients relapse or have refractory disease after frontline treatment.
About ADCETRIS
ADCETRIS is an antibody-drug conjugate (ADC) comprised of a CD30-directed monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seagen's proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.
ADCETRIS is approved in seven indications in the U.S.:
Pfizer and Takeda jointly develop ADCETRIS. Under the terms of the collaboration agreement, Pfizer has U.S. and Canadian commercialization rights, and Takeda has rights to commercialize ADCETRIS in the rest of the world. Pfizer and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.
ADCETRIS® (brentuximab vedotin) for injection U.S. Important Safety Information
Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here.
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes game-changing mechanisms of action to attack cancer from multiple angles, including antibody-drug conjugates (ADCs), small molecules, bispecific antibodies and other immunotherapy biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to extend and improve patients’ lives.
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety, and value in the discovery, development, and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments, and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments, and local communities to support and expand access to reliable, affordable health care around the world. For more than 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on X at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240311435653/en/
Source: Pfizer Inc.
Mar. 12, 2024 7:45 AM ET
Pfizer Inc. (PFE) Stock, TAK Stock
By: Dulan Lokuwithana, SA News Editor
Pfizer (NYSE:PFE) announced Tuesday that a Phase 3 trial for its antibody-drug conjugate Adcetris developed with Takeda (NYSE:TAK) generated positive results in a new lymphoma condition, potentially supporting a future regulatory filing.
According to the company, its ongoing ECHELON-3 trial showed a statistically significant and clinically meaningful improvement for Adcetris as a combination therapy in terms of overall survival, the trial’s primary endpoint.
ECHELON-3 enrolled adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), the commonest form of lymphoma.
There were favorable outcomes for key secondary endpoints, progression-free survival (PFS) and overall response rate (ORR)
The global trial of 230 patients was designed to evaluate Adcetris plus lenalidomide and rituximab against lenalidomide and rituximab plus placebo.
No new safety and tolerability issues were found in the study. Adcetris, added to Pfizer’s (PFE) portfolio with its Seagen acquisition in 2023, is indicated for multiple lymphoma conditions in the U.S.
On March 6, 2024, the Food and Drug Administration approved nivolumab (Opdivo, Bristol-Myers Squibb Company) in combination with cisplatin and gemcitabine for first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma (UC).
Full prescribing information for Opdivo will be posted here.
Efficacy was evaluated in CHECKMATE-901 (NCT03036098), a randomized, open-label trial enrolling 608 patients with previously untreated unresectable or metastatic UC. Patients were randomized (1:1) to receive either nivolumab in combination with cisplatin and gemcitabine (up to 6 cycles) followed by nivolumab alone for up to two years or cisplatin and gemcitabine (up to 6 cycles). On both arms, patients discontinuing cisplatin were permitted to receive carboplatin. Randomization was stratified by tumor PD-L1 expression and presence of liver metastasis.
The major efficacy outcome measures were overall survival (OS) and progression-free survival (PFS), assessed by blinded independent central review using RECIST v1.1.
Statistically significant benefits in both OS and PFS were demonstrated for nivolumab in combination with cisplatin and gemcitabine followed by nivolumab compared to cisplatin and gemcitabine alone. Median OS was 21.7 months (95% CI: 18.6, 26.4) for patients who received nivolumab in combination with cisplatin and gemcitabine and 18.9 months (95% CI: 14.7, 22.4) for those who received cisplatin and gemcitabine alone, (hazard ratio [HR] 0.78 [95% CI: 0.63, 0.96]; two-sided p-value 0.0171). Median PFS was 7.9 months (95% CI: 7.6, 9.5) and 7.6 months (95% CI: 6.0, 7.8), respectively (HR 0.72 [95% CI: 0.59, 0.88]; two-sided p-value 0.0012).
The most common adverse reactions (≥15%) in patients receiving nivolumab with platinum-doublet chemotherapy were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritis.
The recommended nivolumab dose for this indication is:
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.
This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
Follow the Oncology Center of Excellence on X (formerly Twitter) @FDAOncology
Mar. 07, 2024 12:45 PM ET
Bristol-Myers Squibb Company (BMY) Stock
By: Dulan Lokuwithana, SA News Editor
The U.S. Food and Drug Administration (FDA) on Thursday approved Bristol Myers' (NYSE:BMY) immunotherapy Opdivo (nivolumab) in combination with chemotherapy as a first-line option for adults with urothelial carcinoma, a type of bladder cancer.
The decision was based on the company's CHECKMATE-901 trial for patients with untreated, unresectable, or metastatic UC.
The 608-patient trial indicated that those who received the treatment lived 21.7 months with a statistically significant effect compared to 18.9 months in those who received the chemo combo of cisplatin and gemcitabine.
Bristol-Myers Squibb Company (BMY) Stock
February 23, 2024 at 1:00 AM EST
Priority Review granted based on positive results from two Phase 3 trials; if approved, Dupixent would be the only biologic therapy for COPD and the first new treatment approach for this disease in more than a decade
Regulatory submissions are also under review in China and Europe
Dupixent is the leading biologic treatment for all five of its FDA-approved indications in new-to-brand prescriptions in the U.S.
TARRYTOWN, N.Y. and PARIS, Feb. 23, 2024 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for Dupixent® (dupilumab) in a sixth potential indication as an add-on maintenance treatment in certain adult patients with uncontrolled chronic obstructive pulmonary disease (COPD). The target action date for the FDA decision is June 27, 2024. Regulatory submissions are under review in China and Europe.
The sBLA, as well as other submissions around the world, is supported by data from the Phase 3 COPD clinical research program evaluating the efficacy and safety of Dupixent in adults who were current or former smokers with uncontrolled COPD with evidence of type 2 inflammation (i.e., blood eosinophils ≥300 cells per μL). All patients were on background maximal standard-of-care inhaled therapy (nearly all on triple therapy). The primary endpoint was met in both trials (BOREAS, NOTUS), showing Dupixent significantly reduced annualized moderate or severe acute COPD exacerbations by 30% and 34%, respectively, compared to placebo. In both trials, Dupixent rapidly and significantly improved lung function compared to placebo, with improvements sustained at 52 weeks.
Safety results in both trials were generally consistent with the known safety profile of Dupixent in its approved indications. Adverse events more commonly observed with Dupixent (≥5%) compared to placebo in either trial were back pain, COVID-19, diarrhea, headache and nasopharyngitis.
Priority Review is granted to regulatory applications seeking approval for therapies that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions. The potential use of Dupixent in COPD is currently under clinical development, and its safety and efficacy for this indication have not been fully evaluated by any regulatory authority.
About COPD
COPD is a respiratory disease that damages the lungs and causes progressive lung function decline. Symptoms include persistent cough, breathlessness and excessive mucus production that may not only impair the ability to perform routine daily activities, but can also lead to anxiety, depression and sleep disturbances. COPD is also associated with a significant health and economic burden due to recurrent acute exacerbations that require systemic corticosteroid treatment and/or lead to hospitalization. Smoking and exposure to noxious particles are key risk factors for COPD, but even individuals who quit smoking can still develop or continue having the disease. There have been no new treatment approaches approved for more than a decade. In the U.S., approximately 300,000 people live with uncontrolled COPD with evidence of type 2 inflammation.
About Regeneron and Sanofi’s COPD Clinical Research Program
Regeneron and Sanofi are motivated to transform the treatment paradigm of COPD by examining the role different types of inflammation play in the disease progression through the investigation of two potentially first-in-class biologics, Dupixent and itepekimab.
Dupixent inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and the program focuses on a specific population of people with evidence of type 2 inflammation. Itepekimab is a fully human monoclonal antibody that binds to and inhibits interleukin-33 (IL-33), an initiator and amplifier of broad inflammation in COPD.
Itepekimab is currently under clinical investigation, with two Phase 3 trials currently enrolling, and its safety and efficacy have not been evaluated by any regulatory authority.
About Dupixent
Dupixent, which was invented using Regeneron’s proprietary VelocImmune® technology, is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant. The Dupixent development program has shown significant clinical benefit and a decrease in type 2 inflammation in Phase 3 trials, establishing that IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in multiple related and often co-morbid diseases. These diseases include approved indications for Dupixent, such as atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), prurigo nodularis and chronic spontaneous urticaria (CSU).
Dupixent has received regulatory approvals in one or more countries around the world for use in certain patients with atopic dermatitis, asthma, CRSwNP, EoE, prurigo nodularis or CSU in different age populations. Dupixent is currently approved for one or more of these indications in more than 60 countries, including in Europe, the U.S. and Japan. Approximately 800,000 patients are being treated with Dupixent globally.
About Regeneron's VelocImmune® Technology
Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial portion of all original, FDA-approved or authorized fully human monoclonal antibodies. This includes REGEN-COV® (casirivimab and imdevimab), Dupixent, Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb) and Inmazeb® (atoltivimab, maftivimab and odesivimab-ebgn).
Dupilumab Development Program
Dupilumab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement. To date, dupilumab has been studied across more than 60 clinical trials involving more than 10,000 patients with various chronic diseases driven in part by type 2 inflammation.
In addition to the currently approved indications, Regeneron and Sanofi are studying dupilumab in a broad range of diseases driven by type 2 inflammation or other allergic processes in Phase 3 trials, including chronic spontaneous urticaria, chronic pruritus of unknown origin, chronic obstructive pulmonary disease with evidence of type 2 inflammation and bullous pemphigoid. These potential uses of dupilumab are currently under clinical investigation, and the safety and efficacy in these conditions have not been fully evaluated by any regulatory authority.
U.S. INDICATIONS
DUPIXENT is a prescription medicine used:
Please see accompanying full Prescribing Information including Patient Information.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for over 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.
For more information about Regeneron, please visit www.Regeneron.com or follow Regeneron on LinkedIn.
About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people's lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.
Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY.
Feb. 23, 2024 5:40 AM ET
Sanofi (SNY) Stock, REGN Stock
By: Preeti Singh, SA News Editor1 Comment
Sanofi (NASDAQ:SNY) and partner Regeneron Pharmaceuticals (NASDAQ:REGN) announced Friday the receipt of priority review for their supplemental biologics license application (sBLA) for Dupixent (dupilumab), an anti-inflammatory medication.
Dupixent is a monoclonal antibody used for allergic diseases, such as eczema, asthma and nasal polyps. The drug was recently approved in Japan for the treatment of chronic spontaneous urticaria.
February 20, 2024 6:45 am ET
Acceptance based on results from the pivotal Phase 3 NRG-GY018 trial
Results showed KEYTRUDA plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival versus chemotherapy in these patients, regardless of mismatch repair status
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the U.S. Food and Drug Administration (FDA) has accepted for priority review a new supplemental Biologics License Application (sBLA) seeking approval for KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with standard of care chemotherapy (carboplatin and paclitaxel), followed by KEYTRUDA as a single agent for the treatment of patients with primary advanced or recurrent endometrial carcinoma. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of June 21, 2024.
The sBLA is based on data from the Phase 3 NRG-GY018 trial. Results from the study, presented at the 2023 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer and simultaneously published in the New England Journal of Medicine, showed KEYTRUDA plus chemotherapy reduced the risk of disease progression or death by 46% (HR=0.54 [95% CI, 0.41-0.71]; p<0.00001) in patients whose cancer was mismatch repair proficient (pMMR) and by 70% (HR=0.30 [95% CI, 0.19-0.48]; p<0.00001) in patients whose cancer was mismatch repair deficient (dMMR), compared to chemotherapy alone.
“Endometrial cancer is the most common type of gynecological cancer, and frontline treatment options are limited for patients with advanced stage or recurrent disease,” said Dr. Ramez Eskander, principal investigator and gynecologic oncologist, University of California San Diego, Moores Cancer Center. “The use of KEYTRUDA in this setting has the potential to address a significant unmet need for these patients.”
“If approved, KEYTRUDA would be the first immunotherapy indicated for the frontline treatment of advanced endometrial cancer regardless of mismatch repair status,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “We are committed to working closely with the FDA to bring KEYTRUDA to these patients who are in need of additional treatment options, and we thank our collaborators for their partnership on this study.”
This trial was sponsored by the U.S. National Cancer Institute (NCI), part of the National Institutes of Health. NRG Oncology designed and led the trial with funding from the NCI and participation from all the National Clinical Trials Network (NCTN) Groups. Merck provided funding and support through a Cooperative Research and Development Agreement (CRADA) between Merck and NCI.
This review is also being conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among its international partners. Health authorities in Israel, Canada, Australia, Singapore and Brazil will review this application as part of Project Orbis.
In the U.S., KEYTRUDA has two approved indications in endometrial cancer. One indication, based on KEYNOTE-775/Study 309, is in combination with LENVIMA® (lenvatinib), in collaboration with Eisai, for the treatment of patients with advanced endometrial carcinoma that is pMMR, as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. The second indication, based on KEYNOTE-158, is as a single agent, for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Merck has a comprehensive clinical development program in breast and gynecologic (ovarian, cervical, and endometrial) cancers, comprised of more than 20 Merck-sponsored Phase 3 studies evaluating KEYTRUDA as monotherapy and in combination with other medicines. In endometrial cancer, Merck is evaluating KEYTRUDA in the first-line setting for advanced or recurrent disease that is dMMR (KEYNOTE-C93/ENGOT-en15/GOG-3064) and in the adjuvant setting (KEYNOTE-B21/ENGOT-en11/GOG-3053).
About NRG-GY018
NRG-GY018, also known as Merck’s KEYNOTE-868, is a randomized, blinded, placebo-controlled Phase 3 trial (ClinicalTrials.gov, NCT03914612) evaluating KEYTRUDA in combination with standard of care chemotherapy (carboplatin and paclitaxel) versus placebo plus standard of care chemotherapy for the treatment of measurable stage III, IVA, IVB or recurrent endometrial cancer in pMMR and dMMR cohorts. The primary endpoint is progression-free survival (PFS), and secondary endpoints include overall survival, objective response rate, duration of response and safety. The trial enrolled 816 patients who were randomized to receive:
Enrolled patients were required to have MMR IHC testing prior to randomization; 591 patients were determined to have pMMR tumors, and 225 were determined to have dMMR tumors.
About endometrial carcinoma
Endometrial carcinoma begins in the inner lining of the uterus, which is known as the endometrium, and is the most common type of cancer in the uterus. In the U.S., it is estimated there will be approximately 67,880 new cases of uterine body cancer and approximately 13,250 deaths from the disease in 2024. Globally, endometrial cancer is the sixth most common cancer in women and 15th most common cancer overall.
About Merck’s research in breast and gynecologic cancers
Merck is advancing research aimed at improving outcomes for patients affected by breast and gynecologic (ovarian, cervical and endometrial) cancers. Merck has a comprehensive clinical development program across these cancers, comprised of more than 20 Merck-sponsored Phase 3 studies evaluating KEYTRUDA as monotherapy and in combination with other medicines. In the U.S., KEYTRUDA currently has two approved indications for triple-negative breast cancer and five approved indications across gynecologic cancers (see indications below). Among Merck’s research efforts are trials focused on evaluating KEYTRUDA in earlier stages of these cancers, as well as identifying new combinations and coformulations with KEYTRUDA. Merck is also evaluating multiple investigational candidates in breast and gynecologic cancers.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Endometrial Carcinoma
KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) as determined by an FDA-approved test or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or mismatch repair deficient (dMMR), as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.
Additional Selected KEYTRUDA Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.
KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Cancer
KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:
KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic MSI-H or dMMR solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
Cervical Cancer
KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.
Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract carcinoma (BTC).
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA, in combination with lenvatinib, is indicated for the first-line treatment of adult patients with advanced RCC.
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .
Merck’s focus on cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X, Facebook, Instagram, YouTube and LinkedIn.
Source: Merck & Co., Inc.
Feb. 20, 2024 12:51 PM ET
By: Val Brickates Kennedy, SA News Editor
Merck (NYSE:MRK) said the FDA has accepted its supplemental Biologics License Application for priority review of its drug Keytruda as a treatment for primary advanced or recurrent endometrial carcinoma.
The drugmaker is seeking to have the drug approved in combination with standard-of-care chemotherapy, carboplatin and paclitaxel, which is then followed by Keytruda as a single agent. The FDA has set a target action date of June 21 for the application.