FDA Accepts sBLA for Pembrolizumab Monotherapy for Endometrial Cancer

The FDA has accepted a new supplemental biologics license application (sBLA) for pembrolizumab (Keytruda), an 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 diseased progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation, according to a press release by Merck.¹

The sBLA is based on the results of cohorts D and K of the KEYNOTE-158 trial (NCT02628067), which evaluated pembrolizumab monotherapy in participants with advanced solid tumors. The phase 2 parallel assignment, non-randomized, interventional study had an estimated enrollment of 1595 participants with an estimated completion date of June 2026. The primary end point of the study is objective response rate (ORR). Secondary end points include duration of response (DoR), progression-free survival (PFS), and overall survival (OS).²

During the ongoing study, patients receive either 200 mg or 400 mg of pembrolizumab. Solid tumors included in the study include advanced cancer, anal carcinoma, anal cancer, biliary cancer, cholangiocarcinoma, bile duct cancer, neuroendocrine tumor, carcinoid tumor, endometrial carcinoma, endometrial cancer, cervical carcinoma, cervical cancer, vulvar carcinoma, vulvar cancer small cell lung carcinoma, small cell lung cancer, mesothelioma, thyroid cancer, salivary gland carcinoma, salivary gland cancer, salivary cancer, parotid gland cancer, advanced solid tumors, and colorectal carcinoma.

In order to participate in the study, patients must have progressed or are intolerant to therapies with known clinical benefit, have radiologically measurable disease, have an ECOG status of 0 or 1, a life expectancy of at least 3 months, adequate organ function, and must be willing to provide adequate contraception. Patients with a diagnosed immunodeficiency, autoimmune disease, treatment with an anti-cancer monoclonal antibody within 4 weeks prior to study day 1, active infections, or known active central nervous system metastases are not eligible to participate. 

“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 Scot Ebbinghaus, MD, vice president of clinical research at Merck Research Laboratories, in a press release. “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.”

In July 2021, the FDA granted approval to pembrolizumab in combination with lenvatinib (Lenvima). The combination led to a median OS of 17.4 months in patients with MMR proficient (pMMR) disease versus 12 months with chemotherapy. Among all patients, the median OS was 18.3 months for the combination compared to 11.4 months with chemotherapy.

The median PFS for the combination was 6.6 months in patients with pMMR and 7.2 months in the overall population. For patients who received the chemotherapy, the median PFS was 3.8 months for those with pMMR disease and 3.8 months in the general population. The ORR for the combination in patients with pMMR disease was 30.3% versus 15.1% for those who received the combination. The rate of complete responses was 5.2% in the combination cohort versus 2.6% in the chemotherapy cohort. 

_REFERENCE:

_{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/3AxQxp9.}

_{2. Study of Pembrolizumab (MK-3475) in participants with advanced solid tumors (MK-3475-158/KEYNOTE-158). ClinicalTrials.gov. Accessed August 10, 2021.}