Merck’s Phase 3 KEYNOTE-C93 trial shows Keytruda cuts progression or death risk by 43% in dMMR endometrial cancer, while overall survival remains uncertain.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Merck reported positive Phase 3 KEYNOTE-C93 results showing that KEYTRUDA (pembrolizumab) monotherapy significantly improved progression-free survival (PFS) compared with platinum-doublet chemotherapy in patients with mismatch repair-deficient (dMMR) advanced or recurrent endometrial cancer. Pembrolizumab reduced the risk of disease progression or death by 43%, with a hazard ratio (HR) of 0.57 (95% confidence interval [CI], 0.42–0.79; p=0.0002). The findings were presented at the European Society for Medical Oncology (ESMO) Congress 2026 and published simultaneously in The Lancet.
Progression-Free Survival Shows a Sustained Benefit
After a median follow-up of 36.7 months, median PFS reached 38.2 months with pembrolizumab (95% CI, 17.9–not reached), compared with 8.4 months with chemotherapy (95% CI, 6.8–10.4). At 36 months, estimated PFS rates were 52.8% and 30.0%, respectively.
The findings establish a statistically significant PFS advantage for pembrolizumab monotherapy over the chemotherapy control in this trial population. Merck described KEYNOTE-C93 as the first Phase 3 trial of a PD-1 inhibitor to demonstrate a statistically significant and clinically meaningful PFS improvement with monotherapy over chemotherapy in this setting.
Overall Survival Remains Unconfirmed
Overall survival (OS), the trial’s other primary endpoint, numerically favoured pembrolizumab but did not meet the prespecified threshold for statistical significance at this analysis. The HR was 0.77 (95% CI, 0.52–1.15; p=0.1000). Median OS had not been reached in either group.
Estimated 36-month OS rates were 70.7% with pembrolizumab and 62.0% with chemotherapy. Although these results favour pembrolizumab numerically, the confidence interval includes no treatment effect. Further follow-up is needed to determine whether the PFS improvement translates into a statistically significant survival benefit.
Tumour Responses and Treatment Durability
The confirmed objective response rate (ORR) was 64.1% with pembrolizumab (95% CI, 55.8–71.9) and 62.1% with chemotherapy (95% CI, 53.6–70.0). Complete response rates were 33.8% and 26.2%, respectively. ORR was not tested for statistical significance in this analysis, so the numerical differences should not be interpreted as evidence of a statistically significant response advantage.
Median duration of response was not reached with pembrolizumab, compared with 10.2 months with chemotherapy. At 36 months, an estimated 70.7% of pembrolizumab responders and 40.0% of chemotherapy responders maintained their responses. These findings support the potential for durable disease control, although duration-of-response estimates apply only to patients who achieved a response.
Safety Favours Pembrolizumab on Severe Treatment-Related Events
Grade 3 or higher treatment-related adverse events occurred in 18.1% of patients receiving pembrolizumab and 50.7% receiving chemotherapy. Grade 3 or higher anaemia occurred in 2.0% and 18.1%, respectively.
Grade 3 or higher immune-mediated adverse events and infusion reactions occurred in 7.4% of pembrolizumab-treated patients and 3.5% of chemotherapy-treated patients. Merck reported no new safety signals. Two treatment-related deaths occurred in the pembrolizumab group, from hepatic failure and bacterial meningitis; one treatment-related death from pulmonary embolism occurred in the chemotherapy group.
The lower rate of severe treatment-related adverse events with pembrolizumab is relevant when weighing treatment tolerability. However, immune-mediated toxicities remain an important consideration with PD-1 inhibition.
Trial Design and Clinical Interpretation
KEYNOTE-C93 (NCT05173987) was a randomised, open-label Phase 3 trial involving 299 patients with dMMR advanced or recurrent endometrial cancer. Patients were assigned to intravenous pembrolizumab 400 mg every six weeks for up to 18 cycles or paclitaxel 175 mg/m² plus carboplatin at an area under the curve (AUC) of 5 or 6 every three weeks for six cycles. The primary endpoints were PFS, assessed by blinded independent central review using RECIST version 1.1, and OS.
The safety analysis included 149 pembrolizumab-treated patients and 144 chemotherapy-treated patients. These denominators differ from the total randomised population and should not be interpreted as the number assigned to each treatment arm.
Clinical interpretation
KEYNOTE-C93 supports pembrolizumab monotherapy as a potential chemotherapy-free treatment option for appropriately selected patients with dMMR advanced or recurrent endometrial cancer. The substantial PFS difference, sustained responses and lower frequency of severe treatment-related adverse events strengthen the clinical relevance of the findings. However, OS remains inconclusive, and the trial did not compare pembrolizumab monotherapy directly with chemotherapy plus immunotherapy. The results therefore establish an advantage over the chemotherapy control, not superiority over combination treatment. Merck said the findings would be shared with regulatory authorities worldwide; the announcement does not establish a new regulatory approval.
References
KEYTRUDA (pembrolizumab) as Monotherapy Reduced the Risk of Disease Progression or Death by 43% for Certain Patients with Advanced or Recurrent Endometrial Cancer with Mismatch Repair Deficient (dMMR) Tumors Compared to Chemotherapy. Merck, October 26, 2026.
Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Mismatch Repair Deficient (dMMR) Advanced or Recurrent Endometrial Carcinoma (MK-3475-C93/KEYNOTE-C93/GOG-3064/ENGOT-en15), ClinicalTrials.gov ID NCT05173987
Slomovitz B, Zhu J, Yin R et al., 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, randomized, active-comparator controlled, phase 3 trial, The Lancet, October 26, 2026, https://doi.org/10.1016/S0140-6736(26)02095-7
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.