SUMMARY: The FDA on February 10, 2026, approved Pembrolizumab (KEYTRUDA®) as well as Pembrolizumab and Berahyaluronidase alfa-pmph (KEYTRUDA QLEX®) in combination with Paclitaxel, with or without Bevacizumab (AVASTIN®), for adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS≥1) as determined by an FDA-authorized test, and who have received one or two prior systemic treatment regimens. The FDA also approved the PD-L1 IHC 22C3 pharmDx as a companion diagnostic device to identify patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS≥1) for treatment with Pembrolizumab.
It is estimated that in the United States, approximately 21,010 women will be diagnosed with ovarian cancer in 2026 and 12,450 women will die of the disease. Ovarian cancer ranks fifth in cancer deaths among women. It accounts for more deaths than any other cancer of the female reproductive system. Approximately 75% of the ovarian cancer patients are diagnosed with advanced disease. Approximately 85% of all ovarian cancers are epithelial in origin, and approximately 70% of all epithelial ovarian cancers are High-Grade Serous adenocarcinomas. Patients with newly diagnosed advanced ovarian cancer are often treated with platinum-based chemotherapy following primary surgical cytoreduction. Approximately 70% of these patients will relapse within the subsequent 3 years and are incurable, with a 5-year Overall Survival rate of about 20-30%.
Platinum-resistant recurrent ovarian cancer therefore remains a significant therapeutic challenge, with historically limited options and modest improvements in survival. Previous studies, such as the Phase III AURELIA trial, established weekly Paclitaxel with Bevacizumab as an effective chemotherapy regimen. The potential for chemotherapy to enhance antitumor immune responses provided the rationale for combining Pembrolizumab, an anti–PD-1 antibody, with Paclitaxel, with or without Bevacizumab, in this patient population.
Trial Design
The ENGOT-ov65/KEYNOTE-B96 trial (NCT05116189) was a multicenter, randomized, double-blind, placebo-controlled Phase III study that enrolled 643 patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Eligible patients had received one to two prior systemic therapies, including at least one platinum-based regimen, and had evidence of disease progression within six months after platinum therapy. Patients with primary platinum-refractory disease were excluded.
Participants were randomized 1:1 to receive Pembrolizumab 400 mg every six weeks or placebo, in combination with weekly Paclitaxel 80 mg/m² on days 1, 8, and 15 of each 3-week cycle, with or without Bevacizumab 10 mg/kg every 2 weeks. Prior use of PARP inhibitors, Bevacizumab, or PD-1/PD-L1 agents was allowed. Patients had an ECOG performance status of 0–1, with a median age of 61–62 years and predominance of high-grade serous histology (86%). Approximately one-third of patients had PD-L1 CPS ≥10.
Efficacy Results
The Primary endpoint was Progression-Free Survival (PFS) per RECIST v1.1, with Overall Survival (OS) as a key Secondary endpoint.
- First interim analysis (median follow-up 15.6 months):
- Overall population: median PFS 8.3 months with Pembrolizumab vs 6.4 months with placebo (HR 0.70; P<0.0001).
- PD-L1 CPS ≥1 population: median PFS 8.3 months vs 7.2 months (HR 0.72; P=0.0014).
- Second interim analysis (median follow-up 26.6 months):
- PD-L1 CPS ≥1 population: OS improved to 18.2 months with Pembrolizumab vs 14.0 months with placebo (HR 0.76; P=0.0053).
- Benefits were observed across subgroups, including older patients, prior PARP inhibitor exposure, and short platinum-free interval.
- Objective Response Rates were higher with Pembrolizumab (53.0% vs 46.6% in PD-L1 CPS ≥1 patients) with longer Duration of Response.
The PFS and OS improvements were consistent regardless of Bevacizumab use, supporting both doublet and triplet strategies in routine practice.
Safety Profile
Pembrolizumab combined with weekly Paclitaxel, with or without Bevacizumab, demonstrated a manageable safety profile. Adverse events were consistent with known toxicities of checkpoint inhibitors and chemotherapy, including immune-mediated events, infusion reactions, and myelosuppression. No unexpected safety signals were reported, confirming the feasibility of this regimen in a platinum-resistant population.
Clinical Implications
KEYNOTE-B96 demonstrates a clinically meaningful improvement in both Progression-Free and Overall Survival, representing one of the longest reported OS durations in platinum-resistant ovarian cancer. The regimen leverages the immune-modulating effects of weekly Paclitaxel and the potential vascular-normalizing and immunosuppressive effects of Bevacizumab, addressing multiple barriers to effective immune activation.
These results support PD-L1 CPS as a predictive biomarker while emphasizing the importance of integrating immunotherapy with established chemotherapy backbones. The findings provide a foundation for sequencing this strategy alongside emerging therapies, including antibody-drug conjugates and other targeted agents, in this difficult-to-treat population.
Conclusion
KEYNOTE-B96 establishes Pembrolizumab plus weekly Paclitaxel, with or without Bevacizumab, as a viable and effective treatment option for patients with platinum-resistant ovarian cancer, delivering meaningful improvements in survival with a manageable safety profile. This trial highlights the potential of immunotherapy combinations in a disease historically considered immunologically “cold” and provides a new evidence-based option in a setting of high unmet need.
Pembrolizumab vs placebo plus weekly paclitaxel ± bevacizumab in platinum-resistant recurrent ovarian cancer: Results from the randomized double-blind phase 3 ENGOT-ov65/KEYNOTE-B96 study. Colombo N, Zsiros E, Sebastianelli A, et al. Presented at: European Society of Medical Oncology Congress 2025; October 17–20, 2025; Berlin, Germany. Abstract LBA3.
