POSITIVE RESULTS

Keytruda monotherapy beats chemo on PFS in dMMR endometrial cancer

KEYNOTE-C93 hit its progression-free survival goal for pembrolizumab alone, but overall survival, the trial's other primary endpoint, remains immature.

By AppliedXLJuly 15, 2026Trial NCT05173987

Executive Summary

Pembrolizumab given alone cleared the progression-free survival bar against chemotherapy in a frontline trial for a molecularly defined endometrial cancer population, extending an already-approved franchise rather than opening a new one.
The trial's other co-primary endpoint, overall survival, showed only an early trend and remains too immature to call, leaving the durability question for a future analysis.
Pembrolizumab already holds multiple approved uses in this cancer type, and no other PD-1 inhibitor has posted a monotherapy win over platinum doublet chemotherapy in a registrational trial for this population, though numerous mechanism peers remain in earlier-phase testing across other tumor types.
The trial's enrollment target has held flat since a single 2023 adjustment, and its completion date shifted once, meaning the mature dataset needed to answer the overall survival question is not due for some time.

The readout

Merck & Co. disclosed on July 15, 2026 that KEYNOTE-C93 (NCT05173987), a randomized Phase 3 trial comparing pembrolizumab monotherapy to carboplatin plus paclitaxel, met its progression-free survival endpoint in patients with mismatch repair deficient (dMMR, a DNA-repair defect linked to immunotherapy response) advanced or recurrent endometrial cancer. The trial enrolled patients who had not received prior systemic chemotherapy for their disease, or whose disease recurred more than six months after completing adjuvant therapy. An independent data monitoring committee also observed a trend toward improved overall survival, the trial's other co-primary endpoint, but Merck said those OS data were not mature at the time of the analysis and will be evaluated in a future analysis for the full study population. The analysis also showed a clinically meaningful overall response rate, complete response rate, and duration of response for pembrolizumab, and the safety profile was consistent with prior reporting, with no new safety signals identified. KEYTRUDA+1

Probability of Success

Endpoint Met88%

Completes67%

Clinical Significance50%

Regulatory81%

Why it matters

Dr. Brian Slomovitz, the trial's overall principal investigator and director of Gynecologic Oncology at Mount Sinai Medical Center's Braman Comprehensive Cancer Center, said the trial was "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". The trial registered two co-primary endpoints, progression-free survival by blinded independent central review and overall survival, alongside nine secondary endpoints covering response rate, duration of response, and quality-of-life measures. Meeting PFS while OS remains immature is a partial clearance of that registered bar: it establishes the tumor-control signal without yet resolving the survival question the trial was also designed to answer. KEYTRUDA+1

The competitive frame

Pembrolizumab already carries three approved uses in endometrial cancer in the United States: in combination with carboplatin and paclitaxel followed by pembrolizumab alone for primary advanced or recurrent disease, in combination with lenvatinib for mismatch repair proficient disease that has progressed, and as monotherapy for MSI-H or dMMR disease that has progressed after prior systemic therapy. KEYNOTE-C93 tests whether that monotherapy approach can move earlier, into the frontline setting, replacing chemotherapy rather than following it. Among PD-1 inhibitor trials in endometrial carcinoma, GlaxoSmithKline's dostarlimab is the nearest mechanism peer, though it is running in a different endometrial cancer population, and the broader PD-1 field in this indication includes 14 active trials, with 3 completed Phase 3 studies and none terminated to date. That 0-of-3 termination record in this specific target-indication pairing is a small sample, but it is a favorable one, and it sits alongside a broader PD-1 field that AppliedXL's landscape data show is losing new-trial momentum industry-wide, with recent activity running at roughly 16% of its older-period pace. KEYTRUDA

Operational context

The trial's enrollment target was cut from 350 to 280 participants in July 2023, a change that predates this readout and has held steady since, with the primary completion date moving once, from July 2026 to May 2027, in June 2024. The trial has been Active, not recruiting since November 2023, consistent with a study that finished enrollment and is now following patients toward its endpoints rather than a program in operational distress. Merck said it will share the interim results with regulatory authorities and present full data at an upcoming medical meeting, with overall survival for the complete study population to be assessed in a later analysis. NCT05173987+1

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