FDA Accepts Merck’s Keytruda Application for Endometrial Carcinoma

Merck recently announced that FDA accepted for review a new supplemental Biologics License Application seeking approval for its antibody, Keytruda, for patients with advanced endometrial carcinoma.

The single-agent PD-1 therapy is a microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) intended for endometrial carcinoma patients who have disease progression after systemic therapy and are not candidates for curative surgery or radiation. 

“The FDA’s acceptance of our application adds to our momentum of advancing new treatment options to address the most challenging cancers facing women,” Scot Ebbinghaus, MD, vice president of clinical research at Merck Research Laboratories, said in the announcement.

“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,” Ebbinghaus continued. 

Keytruda is already treating certain patients with advanced endometrial carcinoma through the tumor-agnostic MSI-H indication, which received accelerated approval four years ago.

Merck based its application for the drug on overall response data from Cohorts D and K of the KEYNOTE-158 trial.

The KEYNOTE trial is an ongoing, global, Phase 2 study evaluating Keytruda in patients with different 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. The primary endpoint of the study was the overall response rate.

Secondary endpoints included progression-free survival, overall survival, duration of response, and safety.

The agency set a Prescription Drug User Fee Act date of March 28, 2022. 

FDA granted accelerated approval to Keytruda in September 2019, and in July 2021, the agency approved Keytruda and Eisai’s Lenvima to treat patients with advanced endometrial carcinoma. 

FDA based its approval on Merck’s Phase 3 KEYNOTE study, which found that Keytruda plus Lenvima significantly improved overall survival in patients, reducing risk of death by 32 percent and risk of disease progression or death by 40 percent versus chemotherapy. 

The combination treatment also elicited an objective response rate of 30 percent versus 15 percent for patients who received the investigator’s choice of doxorubicin or paclitaxel. 

Merck will continue to advance its gynecologic and breast cancers portfolio with a clinical development program for Keytruda and various other investigational and approved medicines across these areas.