Keytruda Monotherapy Cuts Risk of Progression or Death by 43% vs Chemotherapy in dMMR Endometrial Cancer – Merck
Merck, known as MSD outside of the United States and Canada, announced the first presentation of results from the Phase 3 KEYNOTE‑C93 trial, evaluating KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, as monotherapy 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 after receiving prior adjuvant therapy.
Results showed KEYTRUDA as monotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS) for these patients, reducing the risk of disease progression or death by 43% (HR=0.57; [95% CI, 0.42-0.79]; p=0.0002) compared to platinum doublet chemotherapy. These results were presented at the European Society for Medical Oncology (ESMO) Congress 2026 [Presentation #LBA12], and were published simultaneously in The Lancet.
After a median follow-up of 36.7 months (range, 28.4-50.0), median PFS was 38.2 months (95% CI, 17.9-NR) for KEYTRUDA versus 8.4 months (95% CI, 6.8-10.4) for chemotherapy, with 36-month PFS rates of 52.8% (95% CI, 44.2-60.7) versus 30.0% (95% CI, 22.4-37.9), respectively. In addition to an improvement in PFS, a favorable trend in overall survival (OS), the trial’s other primary endpoint, was observed for KEYTRUDA monotherapy versus platinum doublet chemotherapy (HR=0.77 [95% CI, 0.52-1.15]; p=0.1000). Median OS was not reached (NR) (95% CI, NR-NR) for KEYTRUDA versus NR (95% CI, 38.9-NR) for chemotherapy, with 36-month OS rates of 70.7% (95% CI, 62.4-77.5) versus 62.0% (95% CI, 53.1-69.8), respectively. The trial is continuing, and follow-up of OS is ongoing. Results will be shared with regulatory authorities worldwide.
“These results highlight the potential of a chemotherapy-free approach for certain patients with dMMR advanced or recurrent endometrial cancer, with pembrolizumab monotherapy demonstrating a clinically meaningful benefit in progression-free survival compared to chemotherapy,” 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. “After years of platinum-based chemotherapy serving as the frontline standard, these findings could help provide an additional treatment option beyond carboplatin plus paclitaxel in combination with KEYTRUDA for these patients.”
“KEYTRUDA is already part of an established treatment regimen with platinum doublet chemotherapy for patients with primary advanced or recurrent endometrial cancer regardless of mismatch repair status, and we’re excited by these results showing its further potential as a monotherapy option for appropriate patients whose tumors are dMMR,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “As incidence rates of endometrial cancer continue to rise, we remain committed to advancing new potential treatment options for women facing this disease.”
Confirmed objective response rate (ORR), a key secondary endpoint, was 64.1% (95% CI, 55.8-71.9) with KEYTRUDA versus 62.1% (95% CI, 53.6-70.0) with chemotherapy; complete response rates were 33.8% and 26.2%, respectively. ORR was not tested for statistical significance at this analysis. Among responders, median duration of response (DOR) was not reached for patients receiving KEYTRUDA versus 10.2 months for patients receiving chemotherapy; the 24-month DOR rate was 77.0% versus 41.3%, and the 36-month DOR rate was 70.7% versus 40.0%, respectively.
The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies, and no new safety signals were identified in either treatment arm. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 18.1% of patients receiving KEYTRUDA (n=149) versus 50.7% of patients receiving chemotherapy (n=144); the most common Grade ≥3 TRAE was anemia, occurring in 2.0% of patients receiving KEYTRUDA compared with 18.1% of patients receiving chemotherapy. Grade ≥3 immune-mediated adverse events and infusion reactions occurred in 7.4% of patients receiving KEYTRUDA and 3.5% of patients receiving chemotherapy.
About KEYNOTE-C93
KEYNOTE-C93 is a randomized, open-label Phase 3 trial (NCT05173987) evaluating Keytruda monotherapy versus carboplatin plus paclitaxel in patients with dMMR advanced or recurrent endometrial cancer who have not previously been treated with prior systemic chemotherapy. The trial enrolled 299 patients who were randomized to receive either: i) Keytruda (400 mg) intravenously every six weeks for up to 18 cycles, or; ii) Combination of paclitaxel (175 mg/m 2) and carboplatin (AUC 5 or 6) every three weeks for six cycles. The trial’s dual primary endpoints are PFS, as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), and OS. A key secondary endpoint of the study is ORR.
Citation: First-line pembrolizumab versus carboplatin plus paclitaxel in participants with mismatch repair-deficient advanced or recurrent endometrial cancer (KEYNOTE-C93/GOG-3064/ENGOT-en15): interim analysis of a multicentre, open-label, randomised, active-comparator controlled, phase 3 trial. Authors: Brian M Slomovitz, MD ∙ Jianqing Zhu, MD ∙ Rutie Yin, MD et al. Published October 26, 2026. The Lancet. DOI: 10.1016/S0140-6736(26)02095-7
