Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced the Phase 3 KEYNOTE‑C93 trial evaluating KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, met its primary endpoint of progression-free survival (PFS) for the treatment of patients with mismatch repair deficient (dMMR) advanced or recurrent endometrial cancer who had not previously received systemic chemotherapy or who experienced recurrence more than six months after completing prior adjuvant therapy. KEYTRUDA is the first and only PD-1 inhibitor to show a statistically significant and clinically meaningful improvement in PFS as monotherapy compared to platinum doublet chemotherapy for these patients in a Phase 3 trial.

At a pre-specified interim analysis conducted by an independent Data Monitoring Committee, a trend toward improvement in overall survival (OS), the trial’s other primary endpoint, was observed for KEYTRUDA; however, these OS data were not mature at the time of this analysis. The trial is ongoing, and OS for the full study population will be evaluated at a future analysis. This analysis also showed a clinically meaningful overall response rate (ORR), as well as complete response rate (CRR) and duration of response (DOR) for KEYTRUDA. The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. Results will be presented at an upcoming medical meeting and shared with regulatory authorities.

"This is the first Phase 3 trial of a PD-1 inhibitor to show improved PFS compared to platinum doublet chemotherapy when given as monotherapy in the frontline setting for these patients, potentially providing a chemo-free option," said Dr. Brian Slomovitz, director of Gynecologic Oncology and deputy director of the Braman Comprehensive Cancer Center at Mount Sinai Medical Center in Miami Beach, Florida, and the study’s overall principal investigator.

"These findings build upon the well-established role of KEYTRUDA in endometrial cancer, one of the few cancers with rising incidence rates," said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. "We are committed to helping women facing this disease by advancing potential treatment options. We thank the patients and investigators for their important contributions to this study and look forward to sharing these results with the medical community."

In the U.S., KEYTRUDA is the only anti-PD-1 therapy with three approved indications for patients with certain types of endometrial cancer. KEYTRUDA is indicated: in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma; 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-authorized 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; and as a single agent, for the treatment of adult patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-authorized 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 evaluating KEYTRUDA (both as monotherapy and in combination with chemotherapy) and sacituzumab tirumotecan (sac-TMT), an investigational TROP2-directed antibody-drug conjugate (ADC) being developed in collaboration with Kelun-Biotech, in endometrial cancer. As previously announced, TroFuse-005 (NCT06132958) met its primary endpoints of PFS and OS, as well as its key secondary endpoint of ORR in patients with endometrial cancer who have previously received platinum-based chemotherapy and immunotherapy. In addition, TroFuse-033 (NCT06952504) is enrolling patients with pMMR endometrial cancer to evaluate sac-TMT in an earlier treatment setting of first-line maintenance. The KEYNOTE-B21 trial (NCT04634877) remains ongoing for analysis in the dMMR subgroup.