Pembrolizumab Monotherapy Improves PFS in Frontline dMMR Endometrial Cancer

Pembrolizumab (Keytruda) monotherapy significantly improved progression-free survival (PFS) compared with platinum doublet chemotherapy in patients with mismatch repair-deficient (dMMR) advanced or recurrent endometrial cancer who had not previously received systemic chemotherapy or who experienced recurrence more than 6 months after completing prior adjuvant therapy, according to topline results from the phase 3 KEYNOTE-C93/ENGOT-en15/GOG-3064 trial (NCT05173987) announced in a news release from developer Merck.¹ The trial is the first phase 3 study of a PD-1 inhibitor to show a statistically significant and clinically meaningful PFS improvement as monotherapy compared with chemotherapy in the frontline setting for this population.

What were the key findings from KEYNOTE-C93?

At a prespecified interim analysis conducted by an independent data monitoring committee, pembrolizumab also showed a trend toward improved overall survival (OS), the trial's other primary end point, though OS data were not yet mature. The same analysis showed a clinically meaningful overall response rate (ORR), complete response rate, and duration of response favoring pembrolizumab. The safety profile was consistent with previously reported studies of the agent, and no new safety signals were identified. The trial is ongoing, with full-population OS data expected at a future analysis; results will be presented at an upcoming medical meeting and shared with regulatory authorities.

The trial’s principal investigator Brian Slomovitz, MD, director of gynecologic oncology and deputy director of the Braman Comprehensive Cancer Center at Mount Sinai Medical Center in Miami Beach, Florida, said, “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 [chemotherapy]-free option.”¹

What is the KEYNOTE-C93 trial design?

KEYNOTE-C93 is a randomized, open-label trial evaluating pembrolizumab monotherapy vs carboplatin plus paclitaxel in patients with dMMR advanced or recurrent endometrial cancer with no prior systemic chemotherapy. A total of 299 patients were enrolled and randomly assigned to receive either pembrolizumab at 400 mg intravenously every 6 weeks for up to 18 cycles, or paclitaxel at 175 mg/m² plus carboplatin at area under the curve 5 or 6 every 3 weeks for 6 cycles.

The trial's dual primary end points are PFS, assessed by blinded independent central review per RECIST v1.1 criteria, and OS; ORR is a key secondary end point.

How does this fit into the treatment landscape for dMMR endometrial cancer?

Pembrolizumab already holds 3 FDA-approved indications in endometrial cancer, including as a single agent for advanced disease that is dMMR or microsatellite instability-high following progression on prior systemic therapy. CancerNetwork® previously covered long-term survival data from the phase 3 NRG-GY018 trial, presented at the 2026 American Society of Clinical Oncology Annual Meeting, showed a sustained OS benefit with pembrolizumab plus chemotherapy in both dMMR and mismatch repair-proficient endometrial cancer.² The frontline dMMR space also includes dostarlimab-gxly (Jemperli) plus chemotherapy, including long-term data from the RUBY trial, showing a 4-year PFS rate of 57.9% and a modeled cure rate of 54% with the combination.³

“These findings build upon the well-established role of [pembrolizumab] in endometrial cancer, one of the few cancers with rising incidence rates,” stated Gursel Aktan, MD, PhD, vice president of global clinical development at Merck Research Laboratories, added in the release.¹ “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.”

References

1. KEYTRUDA (pembrolizumab) as monotherapy significantly improved progression-free survival (PFS) in certain patients with advanced or recurrent endometrial cancer with mismatch repair deficient (dMMR) tumors compared to chemotherapy. News release. Merck. July 15, 2026. Accessed July 16, 2026. https://tinyurl.com/5f7je8dt
2. Eskander RM, Sill M, Beffa L, et al. Updated overall survival analysis and examination of subsequent therapy in endometrial cancer (EC) participants treated with pembrolizumab plus carboplatin/paclitaxel (CP) as compared to CP plus placebo in the NRG-GY018 trial. J Clin Oncol. 2026;44(suppl 16):5502. doi:10.1200/JCO.2026.44.16_suppl.5502
3. Powell MA, Zub O, Raaschou-Jensen N, et al. Long-term survival rates and cure modeling with dostarlimab plus chemotherapy in dMMR/MSI-H primary advanced or recurrent endometrial cancer in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial. J Clin Oncol. 2026;44(suppl 16):5501. doi:10.1200/JCO.2026.44.16_suppl.5501