Postsurgical Pembrolizumab and Chemo, With or Without Radiotherapy, Falls Short in Phase 3 Trial for Newly Diagnosed, High-Risk Endometrial Cancer

Merck’s blockbuster PD-1 inhibitor pembrolizumab (Keytruda) may be effective against endometrial cancer in some settings, but a statement today from the company shows that’s not so for all settings, as results for a phase 3 trial came up short.

Pembrolizumab and chemotherapy, with or without radiotherapy, failed to meet the primary end point for disease-free survival (DFS) in patients with newly diagnosed, high-risk endometrial cancer who were treated with curative intent, Merck officials said in a statement regarding the KEYNOTE-B21 trial.

According to the statement, a prespecified interim analysis by an independent data monitoring committee found the combination of adjuvant pembrolizumab plus chemotherapy, with or without radiotherapy, failed to meet the trial’s statistical criteria for DFS compared with placebo plus adjuvant chemotherapy, with or without radiotherapy.

Because the trial failed to meet the primary end point for DFS, the other primary end point of overall survival was not formally tested. Safety results for pembrolizumab were consistent with those seen in prior studies, and no new signals were reported. Full results will be shared “with the scientific community,” the statement said.

“While these results were not what we had hoped, we are focused on continuing to build on the established role of [pembrolizumab] in advanced endometrial carcinoma through our approved indications,” Gursel Aktan, PhD, vice president, global clinical development, Merck Research Laboratories, said in the statement. The company will continue to evaluate combinations involving both pembrolizumab as well as including antibody-drug conjugates in endometrial and other types of gynecologic cancers, Aktan said.

Endometrial carcinoma emerges in the inner lining of the uterus and is the most common form of uterine cancer; approximately 67,880 patients will be diagnosed with uterine cancer this year, and there will be roughly 13,250 patient deaths from the disease. Globally, endometrial cancer is the sixth most common cancer in women and has a high rate of recurrence.

Previously, pembrolizumab was approved to treat endometrial carcinoma in the following settings: (1) as a monotherapy when the cancer is positive for microsatellite instability-high or mismatch repair deficient (dMMR), or (2) when used with lenvatinib (Lenvima; Eisai) in previously treated endometrial cancer that is not dMMR. Both conditions require diagnosis with an FDA-approved test.

In its statement, Merck highlighted that FDA has granted priority review for its supplemental biologics license application for pembrolizumab with chemotherapy, followed by pembrolizumab alone, to treat patients with primary advanced or recurrent endometrial carcinoma. The target action date for this indication is June 21, 2024.

Reference

Merck provides update on phase 3 KEYNOTE-B21 trial evaluating Keytruda (pembrolizumab) plus chemotherapy, with or without radiotherapy, for patients with newly diagnosed, high-risk endometrial cancer after surgery with curative intent. News release. Merck. May 9, 2024. Accessed May 9, 2024. https://www.businesswire.com/news/home/20240509681021/en/Merck-Provides-Update-on-Phase-3-KEYNOTE-B21-Trial-Evaluating-KEYTRUDA%C2%AE-pembrolizumab-Plus-Chemotherapy-With-or-Without-Radiotherapy-for-Patients-With-Newly-Diagnosed-High-Risk-Endometrial-Cancer-After-Surgery-With-Curative-Intent