FDA Accepts Application for Merck?s KEYTRUDA? (pembrolizumab) as Single Agent for Certain Patients With MSI-H/dMMR Advanced Endometrial Carcinoma
KENILWORTH, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review a new supplemental Biologics License Application (sBLA) seeking approval for KEYTRUDA, Merck?s anti-PD-1 therapy, as a single agent for the treatment of patients with advanced endometrial carcinoma that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. The application is based on overall response data from Cohorts D and K of the KEYNOTE-158 trial, which will be presented for the first time at the European Society for Medical Oncology (ESMO) Congress 2021 (Abstract #795P). The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of March 28, 2022.
?The FDA?s acceptance of our application adds to our momentum of advancing new treatment options to address the most challenging cancers facing women,? said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. ?KEYTRUDA monotherapy is already playing a role for the treatment of certain patients with advanced endometrial carcinoma through the tumor-agnostic MSI-H indication which received accelerated approval four years ago. We look forward to sharing the latest results from KEYNOTE-158, including updated data for KEYTRUDA in certain types of MSI-H/dMMR advanced endometrial carcinoma, at the ESMO Congress in September.?
KEYTRUDA is approved for the treatment of adult and pediatric patients with unresectable or metastatic MSI-H or dMMR solid tumors 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 may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established. This accelerated approval was based on efficacy data from patients enrolled in one of five open-label, multi-cohort trials, including KEYNOTE-158.
KEYTRUDA was also granted accelerated approval in September 2019, and received full approval in July 2021, in combination with LENVIMA?(lenvatinib) for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Merck is rapidly advancing a broad portfolio in gynecologic and breast cancers with an extensive clinical development program for KEYTRUDA and several other investigational and approved medicines across these areas.
About KEYNOTE-158
KEYNOTE-158 (ClinicalTrials.gov,?NCT02628067) is an ongoing global, open-label, non-randomized, multi-cohort, multi-center, Phase 2 study evaluating KEYTRUDA in patients with multiple types of advanced solid tumors ? including endometrial carcinoma ? that have progressed on standard of care therapy. Cohort K enrolled 79 patients with MSI-H endometrial carcinoma and Cohort D enrolled 11 patients with MSI-H endometrial carcinoma for a total of 90 pooled patients who received KEYTRUDA as monotherapy (200 mg fixed dose every three weeks). The primary endpoint was overall response rate as evaluated by independent central review using RECIST v1.1. Secondary endpoints are progression-free survival, overall survival, duration of response, and safety.
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 2020, it was estimated there were more than 417,000 new cases and more than 97,000 deaths from uterine body cancers worldwide (these estimates include both endometrial carcinomas and uterine sarcomas; more than 90% of uterine body cancers occur in the endometrium, so the actual numbers for endometrial carcinoma cases and deaths are slightly lower than these estimates). In the U.S., it is estimated there will be more than 66,000 new cases of uterine body cancer and nearly 13,000 deaths from the disease in 2021. The number of people diagnosed with endometrial carcinoma is increasing and is expected to continue to rise. It is estimated that approximately 30% of endometrial carcinomas are MSI-H or dMMR. The five-year relative survival rate for metastatic endometrial carcinoma (stage IV) is approximately 17%.
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 1,500 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.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) 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:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS =10) as determined by an FDA-approved test.