Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the Phase 3 KEYNOTE-B21 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy as adjuvant treatment, with or without radiotherapy, did not meet its primary endpoint of disease-free survival (DFS) for the treatment of patients with newly diagnosed, high-risk endometrial cancer after surgery with curative intent.
At a pre-specified interim analysis conducted by an independent Data Monitoring Committee, adjuvant treatment with KEYTRUDA plus chemotherapy, with or without radiotherapy, did not meet the study’s pre-specified statistical criteria for DFS compared to placebo plus adjuvant chemotherapy, with or without radiotherapy. The study’s other primary endpoint of overall survival (OS) was not formally tested since superiority was not reached for DFS. The safety profile of KEYTRUDA was consistent with that observed in previously reported studies; no new safety signals were identified. A full evaluation of the data from this study is ongoing. Merck will work with investigators to share the results with the scientific community.
“While these results were not what we had hoped, we are focused on continuing to build on the established role of KEYTRUDA in advanced endometrial carcinoma through our approved indications, while rapidly progressing clinical research evaluating KEYTRUDA-based combinations and other investigational candidates, including antibody-drug conjugates, in endometrial and other types of gynecologic malignancies,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “We would like to thank all the patients, the investigators and our study collaborators for their participation in this trial.”
In the U.S., KEYTRUDA has two approved indications in endometrial cancer. One indication, based on KEYNOTE-775/Study 309, is in combination with LENVIMA® (lenvatinib), in collaboration with Eisai, for the treatment of patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. The second indication, based on KEYNOTE-158, is as a single agent, for the treatment of patients with advanced endometrial carcinoma that is MSI-H or mismatch repair deficient (dMMR), as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Merck has a comprehensive clinical development program in endometrial carcinoma, including the NRG-GY018/KEYNOTE-868 trial evaluating KEYTRUDA in combination with standard of care chemotherapy (carboplatin and paclitaxel), followed by KEYTRUDA as a single agent for the treatment of patients with primary advanced or recurrent endometrial carcinoma. As previously announced, the U.S. Food and Drug Administration (FDA) has granted priority review for Merck’s supplemental Biologics License Application (sBLA) based on this study and has set a Prescription Drug User Fee Act (PDUFA), or target action, date of June 21, 2024.
The program also includes the KEYNOTE-C93 study evaluating KEYTRUDA versus chemotherapy in dMMR advanced or recurrent endometrial carcinoma, as well as the MK-2870-005 study evaluating sacituzumab tirumotecan (sac-TMT), an investigational trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate (ADC) being developed in collaboration with Kelun-Biotech, compared to a treatment of physicians’ choice in patients with endometrial carcinoma who have received prior platinum-based chemotherapy and immunotherapy.
About KEYNOTE-B21/ENGOT-en11/GOG-3053
KEYNOTE-B21, also known as ENGOT-en11/GOG-3053, is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT04634877) sponsored by Merck and conducted in collaboration with the European Network for Gynecologic Oncology Trial (ENGOT) groups and the GOG Foundation, Inc. (GOG) investigating adjuvant treatment with KEYTRUDA plus chemotherapy, with or without radiotherapy, compared to adjuvant placebo plus chemotherapy, with or without radiotherapy, for the treatment of newly diagnosed, high-risk endometrial cancer after surgery with curative intent. The primary endpoints are DFS and OS, and secondary endpoints include safety. The trial enrolled an estimated 1,095 patients who were randomized to receive:
- KEYTRUDA (200 mg every three weeks for six cycles) plus concurrent standard of care chemotherapy (for four or six cycles), followed by KEYTRUDA (400 mg every six weeks for an additional six cycles), with or without radiotherapy, or
- Placebo (every three weeks for six cycles) plus concurrent standard of care chemotherapy (for four or six cycles), followed by placebo (every six weeks for an additional six cycles), with or without radiotherapy.
About endometrial carcinoma
Endometrial carcinoma begins in the inner lining of the uterus, which is known as the endometrium, and is the most common type of cancer in the uterus. In the U.S., it is estimated there will be approximately 67,880 patients diagnosed with uterine body cancer and approximately 13,250 patient deaths from the disease in 2024. Globally, endometrial cancer is the sixth most common cancer in women and the 15th most common cancer overall. Following primary treatment, patients face a risk of their cancer returning, often as distant metastasis, which is associated with poorer outcomes.
About Merck’s research in breast and gynecologic cancers
Merck is advancing research aimed at improving outcomes for patients affected by breast and gynecologic (ovarian, cervical and endometrial) cancers. Merck has a comprehensive clinical development program across these cancers comprised of more than 20 Merck-sponsored Phase 3 studies evaluating KEYTRUDA as monotherapy and in combination with other medicines. In the U.S., KEYTRUDA currently has two approved indications for triple-negative breast cancer, including one for high-risk early-stage disease, and five approved indications across certain types of cervical and endometrial cancers (see indications below). Among Merck’s research efforts are trials focused on evaluating KEYTRUDA in earlier stages of these cancers, as well as identifying new combinations and coformulations with KEYTRUDA.
About Merck’s early-stage cancer clinical program
Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with more than 25 ongoing registrational studies across multiple types of cancer.
