The study evaluated pembrolizumab as a standalone first-line treatment in women whose disease was newly diagnosed in the advanced setting or had returned after a prolonged treatment-free interval. According to Merck, the trial achieved its primary endpoint, showing a meaningful reduction in the risk of disease progression when compared with the conventional carboplatin-paclitaxel regimen.

Importantly, the results position pembrolizumab as the first PD-1 checkpoint inhibitor to demonstrate a statistically significant PFS benefit over platinum-doublet chemotherapy as monotherapy in a Phase 3 frontline trial involving patients with dMMR endometrial tumors.

Early Survival Data Show Encouraging Promise

In addition to meeting its primary objective, the study generated preliminary evidence suggesting a potential overall survival (OS) advantage for pembrolizumab. While the data analysis revealed a favorable trend, the survival results were not yet mature enough for a definitive assessment, and further follow-up is ongoing.

Investigators also reported clinically meaningful antitumor activity across several efficacy measures, including overall response rate (ORR), complete response rate (CRR), and duration of response (DOR). No unexpected safety concerns emerged during the trial, and the treatment’s adverse-event profile remained consistent with previous pembrolizumab studies.

Detailed findings will be presented at a future medical congress and submitted to health authorities as part of potential regulatory discussions.

Potential Shift Away From Chemotherapy

Experts involved in the trial noted that the findings may represent an important advance for patients with dMMR endometrial cancer, a subgroup known to be particularly responsive to immune checkpoint blockade. The results suggest that some patients could potentially receive effective first-line treatment without exposure to traditional cytotoxic chemotherapy.

The announcement also adds to the growing body of evidence supporting immunotherapy in endometrial cancer, a disease whose incidence continues to increase globally and for which new treatment strategies remain a significant clinical priority.

Established Presence in Endometrial Cancer

Pembrolizumab already plays a significant role in the management of endometrial cancer in the United States through multiple approved indications. These include its use alongside carboplatin and paclitaxel followed by maintenance therapy in advanced or recurrent disease, its combination with lenvatinib for selected patients with mismatch repair-proficient tumors, and its use as a single agent in previously treated MSI-H or dMMR endometrial cancers that are not suitable for curative surgery or radiation.

The new KEYNOTE-C93 findings may further broaden the clinical utility of pembrolizumab by supporting its use earlier in the treatment pathway.

KEYNOTE-C93 Trial Design

KEYNOTE-C93 (NCT05173987) is a randomized, open-label, Phase 3 study designed to compare pembrolizumab monotherapy with standard platinum-based chemotherapy in patients with advanced or recurrent dMMR endometrial cancer who had not received prior systemic chemotherapy for advanced disease.

A total of 299 participants were enrolled and randomized to one of two treatment arms:

• Pembrolizumab 400 mg administered intravenously every six weeks for up to 18 cycles.
• Paclitaxel 175 mg/m² plus carboplatin (AUC 5 or 6) administered every three weeks for six cycles.

The trial’s co-primary endpoints are progression-free survival, assessed through blinded independent central review using RECIST v1.1 criteria, and overall survival. Overall response rate serves as a key secondary endpoint.

Ongoing Research Efforts

Merck continues to expand its endometrial cancer development program through investigations of pembrolizumab and sacituzumab tirumotecan (sac-TMT), an investigational TROP2-directed antibody-drug conjugate being developed with Kelun-Biotech.

The company previously reported positive results from the TroFuse-005 study, which met its primary endpoints of both progression-free and overall survival in patients whose disease had progressed after platinum-based chemotherapy and immunotherapy. Another study, TroFuse-033, is currently enrolling patients with pMMR endometrial cancer to evaluate sac-TMT in a first-line maintenance setting. Meanwhile, the KEYNOTE-B21 trial remains under evaluation, including ongoing analyses within the dMMR subgroup.

Taken together, the KEYNOTE-C93 findings reinforce the growing role of biomarker-guided immunotherapy in endometrial cancer and suggest that pembrolizumab could emerge as a new chemotherapy-sparing option for patients with dMMR advanced or recurrent disease.