Merck Updates on Phase 3 KEYNOTE-B21 Trial of KEYTRUDA® Combo for High-Risk Endometrial Cancer

Merck, operating as MSD outside the U.S. and Canada, has shared an update on its Phase 3 KEYNOTE-B21 trial which evaluated the efficacy of KEYTRUDA, an anti-PD-1 therapy, in combination with chemotherapy and optional radiotherapy. This study was designed to test the treatment as an adjuvant therapy for patients with newly diagnosed, high-risk endometrial cancer following surgery intended to cure the disease. Unfortunately, the trial did not achieve its primary objective of improving disease-free survival (DFS).

During a pre-specified interim analysis by an independent Data Monitoring Committee, the combination of KEYTRUDA and chemotherapy, with or without radiotherapy, was found not to meet the statistical criteria required for demonstrating DFS superiority compared to the placebo group receiving chemotherapy with or without radiotherapy. Consequently, the study's other primary endpoint, overall survival (OS), was not tested since the DFS superiority criteria were not satisfied. Safety outcomes for KEYTRUDA were consistent with prior studies, with no new safety concerns observed.

Dr. Gursel Aktan, Vice President of Global Clinical Development at Merck Research Laboratories, expressed disappointment in the results but emphasized the company’s commitment to advancing KEYTRUDA's role in treating advanced endometrial carcinoma. Merck plans to continue its clinical research on KEYTRUDA combinations and other investigational treatments, including antibody-drug conjugates, in endometrial and other gynecologic cancers. The company will work with investigators to disseminate the study results to the scientific community.

In the United States, KEYTRUDA holds two approvals for endometrial cancer treatment. First, based on the KEYNOTE-775/Study 309, it is approved in combination with LENVIMA® (lenvatinib) for patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR), or not microsatellite instability-high (MSI-H), who have progressed following prior systemic therapy and are not suitable for curative surgery or radiation. Secondly, based on KEYNOTE-158, KEYTRUDA is approved as a monotherapy for patients with advanced endometrial carcinoma that is MSI-H or mismatch repair deficient (dMMR), who have progressed following prior systemic therapy and are not candidates for curative surgery or radiation.

Merck’s clinical development program for endometrial carcinoma is extensive. It includes the NRG-GY018/KEYNOTE-868 trial, which evaluates KEYTRUDA with standard chemotherapy (carboplatin and paclitaxel), followed by KEYTRUDA monotherapy for primary advanced or recurrent endometrial carcinoma. The FDA has granted priority review for a supplemental Biologics License Application (sBLA) based on this study, with a target action date of June 21, 2024.

Other elements of the program include the KEYNOTE-C93 study comparing KEYTRUDA to chemotherapy in dMMR advanced or recurrent endometrial carcinoma, and the MK-2870-005 study evaluating sacituzumab tirumotecan (sac-TMT), an investigational TROP2-directed antibody-drug conjugate being developed with Kelun-Biotech, against physician's choice treatment for patients with previously treated endometrial carcinoma.

The KEYNOTE-B21 trial, also known as ENGOT-en11/GOG-3053, is a randomized, double-blind Phase 3 trial investigating adjuvant treatment with KEYTRUDA plus chemotherapy, with or without radiotherapy, compared to placebo plus chemotherapy, with or without radiotherapy, in patients with newly diagnosed, high-risk endometrial cancer post-surgery. The trial involved approximately 1,095 patients, exploring DFS and OS as primary endpoints, and safety as a secondary endpoint.

Endometrial carcinoma starts in the uterus's inner lining and is the most common uterine cancer. In the U.S., it is estimated that around 67,880 individuals will be diagnosed with uterine body cancer, and about 13,250 will die from the disease in 2024. Globally, endometrial cancer ranks as the sixth most common cancer in women and the 15th overall. Post-primary treatment, the risk of cancer recurrence, often as distant metastasis, is significant, leading to poorer outcomes.

Merck continues to advance research to improve outcomes for patients with breast and gynecologic cancers, including endometrial cancer. Their clinical development program spans more than 20 Phase 3 studies evaluating KEYTRUDA as a monotherapy and in combination with other therapies. Merck is particularly focused on exploring KEYTRUDA in early-stage cancers and identifying new therapeutic combinations.