Pembrolizumab Plus Chemotherapy Improves Outcomes in Platinum-Resistant Ovarian Cancer

10/18/2025 – 10:35 AM

Results from the first and second interim analyses of the Phase 3 KEYNOTE-B96 trial were selected for presentation during a Presidential Symposium session at the European Society for Medical Oncology Congress 2025

With these results, KEYNOTE-B96 is the first trial of an immune checkpoint inhibitor-based treatment regimen in platinum-resistant recurrent ovarian cancer to show statistically significant improvements in progression-free survival for all comers and overall survival for patients whose tumors express PD-L1 versus placebo plus chemotherapy with or without bevacizumab

Based on these data, the U.S. FDA has accepted for priority review a new supplemental Biologics License Application (sBLA) for KEYTRUDA plus chemotherapy with or without bevacizumab for certain patients with platinum-resistant recurrent ovarian cancer

Recent data unveiled at the European Society for Medical Oncology (ESMO) Congress 2025 is signaling a potential shift in the treatment landscape for platinum-resistant recurrent ovarian cancer. Merck’s (MRK) Phase 3 KEYNOTE-B96 trial, evaluating KEYTRUDA (pembrolizumab) in combination with chemotherapy (paclitaxel) with or without bevacizumab, has demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) in certain patient subgroups.

The KEYNOTE-B96 trial, also known as ENGOT-ov65, represents a significant advancement as the first trial of an immune checkpoint inhibitor-based regimen to show statistically significant benefits in PFS for the broad population of patients with platinum-resistant recurrent ovarian cancer. Furthermore, it demonstrates an improvement in OS for patients whose tumors express PD-L1, compared to placebo plus chemotherapy with or without bevacizumab.

At the first interim analysis (median follow-up of 15.6 months), KEYTRUDA plus chemotherapy with or without bevacizumab (n=322) exhibited a notable 30% reduction in the risk of disease progression or death (HR=0.70 [95% CI, 0.58-0.84]; p<0.0002). The 6-month PFS rate was 33.1% vs. 21.3% with the placebo regimen. Among patients whose tumors expressed PD-L1 (Combined Positive Score [CPS] ≥1), KEYTRUDA plus chemotherapy with or without bevacizumab (n=234) reduced the risk of disease progression or death by 28% (HR=0.72 [95% CI, 0.58-0.89]; p=0.0014) compared to the placebo. The 12-month PFS rate was 35.2% for the pembrolizumab regimen versus 22.6% for the placebo regimen.

The second interim analysis (median follow-up of 26.6 months) corroborated these findings, demonstrating a statistically significant and clinically meaningful improvement in overall survival (OS) in patients with PD-L1 expressing tumors (CPS ≥1), reducing the risk of death by 24% (HR=0.76 [95% CI, 0.61-0.94]; p=0.0053). The 12-month OS rate for the KEYTRUDA regimen was 69.1% versus 59.3% for the placebo regimen; 18-month OS rates were 51.5% and 38.9%, respectively.

According to Dr. Nicoletta Colombo, director of the Gynecologic Oncology Program at the European Institute of Oncology in Milan, Italy, these results could mark a significant step forward. The KEYNOTE-B96 data have the potential to demonstrate to add pembrolizumab to chemotherapy with or without bevacizumab, could potentially be an additional effective option for these patients.

“These results build upon the success of KEYTRUDA in gynecologic cancers and support the potential use of KEYTRUDA for patients with platinum-resistant ovarian cancer,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories.

Safety data indicated that treatment-related adverse events (TRAEs) occurred in 97.8% and 95.3% of patients receiving the KEYTRUDA and placebo regimens, respectively. Grade 3-5 TRAEs were more frequent in the KEYTRUDA arm (67.5% vs. 55.3%). TRAEs led to death in 0.9% and 1.6% of patients, respectively. Immune-mediated adverse events (AEs) and infusion reactions were more common with the KEYTRUDA regimen (39.1% vs. 18.9%), with hypothyroidism being the most frequent (17.8%).

The FDA has granted priority review to Merck’s supplemental Biologics License Application (sBLA) for KEYTRUDA plus chemotherapy with or without bevacizumab in platinum-resistant recurrent ovarian cancer, setting a Prescription Drug User Fee Act (PDUFA) date of Feb. 20, 2026. Final analysis data which also met its secondary endpoint of OS for all comers, will be presented at an upcoming medical meeting.

This regulatory milestone and forthcoming data is likely to have significant strategic implications for Merck and potentially reshape treatment algorithms for this challenging cancer. The sBLA acceptance and the PDUFA target action date by the FDA indicate a rapid review process, reflecting the unmet medical need in this patient population.

Investors will be watching closely for several key developments: the presentation of the final analysis data (especially OS data for the all-comers population), further insights into the safety profile of the combination regimen, and the FDA’s decision on the sBLA. The competitive landscape in ovarian cancer treatment continues to evolve, with potential implications for sales and market share. It’s worth noting that Merck also has a collaboration with Daiichi Sankyo evaluating raludotatug deruxtecan (R-DXd) in platinum-resistant ovarian cancer as well.