FDA Accepts for Review Supplemental Biologics License of Pembrolizumab for MSI-H/dMMR Advanced Endometrial Cancer

The phase 2 KEYNOTE-158 trial has demonstrated promising responses in patients with microsatellite instability–high/ mismatch repair deficient advanced endometrial carcinoma, and led to the FDA accepting a review of a new supplemental biologics license application for the drug.

A new supplemental biologics license application (sBLA) for pembrolizumab (Keytruda) has been accepted for review by the FDA for patients with advanced endometrial carcinoma who are microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), according to a press release from Merck.1

This review is based on overall response data from cohorts D and K from the phase 2 KEYNOTE-158 trial (NCT02628067). The full results of this trial will be presented at the European Society for Medical Oncology (ESMO) Congress in September 2021.

A prescription drug user free act or target action date was set by the FDA for 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,” Scot Ebbinghaus, MD, vice president of clinical research at Merck Research Laboratories, said in a press release.

The ongoing global, open-label, non-randomized, multi-cohort, multi-center KEYNOTE-158 trial is currently treating patients with a number of different types of advanced solid tumors who have progressed on standard of care therapies. Cohort K has a total of 79 patients with MSI-H endometrial carcinoma, and cohort D has 11 patients with MSI-H endometrial carcinoma. Both groups received a 200 mg fixed dose of pembrolizumab every 3 weeks.

The primary end point of the trial is overall response rate (ORR), with secondary end points being progression-free survival, overall survival (OS), duration of response, and safety.

Data from the KEYNOTE-158 trial have previously read out, indicating that patients with PD-L1–positive previously treated advanced cervical cancer demonstrated durable anti-tumor activity after being treated with pembrolizumab.2After a median follow-up of 10.2 months, patients had an ORR of 12.2% (n = 12/98; 95% CI, 6.5%-20.4%), with 3 patients achieving complete responses and 9 partial responses. Moreover, patients who had PD-L1–positive tumors achieved an ORR of 14.6%, almost all of whom had underwent 1 or more prior lines of chemotherapy for recurrent or metastatic disease. Patients with PD-L1­–positive tumors had longer median OS at 11 months (95% CI, 9.1-14.1) compared with 9.4 months in the overall patient population (95% CI, 7.7-13.1).

Pembrolizumab has previously been granted full approval by the FDA in July 2021 in combination with lenvatinib (Lenvima) for the treatment of advanced MSI-H/dMMR endometrial carcinoma for patients who have progressed on prior systemic therapies and are not candidates for surgery or radiation.3

“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,” concluded Ebbinghaus.


1. FDA accepts application for Merck’s Keytruda (pembrolizumab) as single agent for certain patients with MSI-H/dMMR advanced endometrial carcinoma. News Release. Merck. August 10, 2021. Accessed August 10, 2021. https://bit.ly/3izvLzu

2. Chung HC, Ros W, Delord JP, et al. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results From the phase II KEYNOTE-158 study. J Clin Oncol. 2019;37(17):1470-1478. doi:10.1200/JCO.18.01265

3. FDA approves Keytruda (pembrolizumab) plus Lenvima (lenvatinib) combination for patients with certain types of advanced endometrial carcinoma. News release. Merck. July 22, 2021. Accessed August 10, 2021. https://bit.ly/2V76N0X