FDA approves Keytruda for patients with MSI-H/dMMR advanced endometrial carcinoma, who have disease progression following prior systemic therapy.

The approval is based on new data from Cohorts D and K of the KEYNOTE-158 trial. The objective response rate (ORR) was 46% (95% CI, 35-56) for patients who received Keytruda, including a complete response rate of 12% and a partial response rate of 33%, at a median follow-up time of 16.0 months (range, 0.5 to 62.1 months). Of the responding patients (n=41), 68% had responses lasting 12 months or longer, and 44% had responses lasting 24 months or longer. Median duration of response (DOR) was not reached (range, 2.9 to 55.7+ months).

This is the second indication for Keytruda in endometrial cancer. Keytruda is also indicated 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.

KEYNOTE-158 (ClinicalTrials.gov, NCT02628067) is a multicenter, non-randomized, open-label, multi-cohort trial that enrolled 90 patients with unresectable or metastatic MSI-H or dMMR endometrial carcinoma in Cohorts D and K who received at least one dose of Keytruda Microsatellite instability-high or MMR tumor status was determined using polymerase chain reaction or immunohistochemistry, respectively. Patients with autoimmune disease or a medical condition that required immunosuppression were ineligible. Patients received Keytruda 200 mg intravenously every three weeks until unacceptable toxicity or documented disease progression. Patients treated with Keytruda without disease progression could be treated for up to 24 months. Assessment of tumor status was performed every nine weeks for the first 12 months, and every 12 weeks thereafter. The major efficacy outcome measures were ORR and DOR as assessed by blinded independent central review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ. Among the 90 patients with MSI-H or dMMR endometrial carcinoma enrolled in KEYNOTE-158 treated with Keytruda as a single agent, the median duration of exposure to Keytruda was 8.3 months (range, 1 day to 26.9 months). Adverse reactions occurring in patients with endometrial carcinoma were similar to those occurring in 2,799 patients with melanoma or non-small cell lung cancer treated with Keytruda as a single agent.