FDA Approves Pembrolizumab Combination in Platinum-Resistant Ovarian Cancer

The FDA approved both pembrolizumab (Keytruda) and subcutaneous pembrolizumab with berahyaluronidase alfa-pmph (Keytruda Qlex) in combination with paclitaxel, with or without bevacizumab (Avastin) for the treatment of adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS ≥1), as confirmed by an FDA-approved test following 1 or 2 prior lines of systemic treatment regimens.¹

Along with the drug approval, the FDA approved the PD-L1 IHC 22C3 pharmDx as a companion diagnostic to identify eligible patients.

The approval was supported by results from the multicenter, randomized, double-blind, placebo-controlled phase 3 KEYNOTE-B96 trial (NCT05116189). The study enrolled 643 patients with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. To be eligible, patients were required to have received at least 1 prior line of platinum-based chemotherapy and demonstrated radiographic evidence of disease progression within 6 months of their last platinum dose.

In the population of 466 patients with tumors expressing PD-L1 (CPS ≥1), the combination demonstrated a statistically significant improvement in the primary end point of progression-free survival (PFS) as assessed by investigator review. The median PFS was 8.3 months (95% CI, 7.0-9.4) in the pembrolizumab arm compared with 7.2 months (95% CI, 6.2-8.1) in the placebo arm (HR, 0.72; 95% CI, 0.58-0.89; P = .0014).

The combination also yielded a significant benefit in overall survival (OS), a key secondary end point. The median OS was 18.2 months (95% CI, 15.3-21.0) with pembrolizumab versus 14.0 months (95% CI, 12.5-16.1) with placebo (HR, 0.76; 95% CI, 0.61-0.94; P = .0053).

Safety Findings

The safety profile of the pembrolizumab combination was generally consistent with prior reports of the individual agents. According to results presented at the 2025 ESMO Congress, any-grade treatment-related adverse events (TRAEs) occurred in 97.8% of the pembrolizumab group and 95.3% of the placebo group.² Grade 3 or higher TRAEs were reported in 67.5% and 55.3% of patients, respectively. Serious TRAEs were more frequent with the addition of pembrolizumab (33.1% vs 19.5%).

Common TRAEs in the pembrolizumab arm included anemia (49.7%), peripheral neuropathy (38.8%), alopecia (37.8%), fatigue (35.3%), and nausea (31.3%). Immune-mediated adverse reactions occurred in 39.1% of patients in the pembrolizumab arm compared with 18.9% in the placebo arm. The most frequent immune-mediated events were hypothyroidism (17.8%), infusion reactions (5.9%), and hyperthyroidism (5.0%). Adverse events led to treatment discontinuation in 35.9% of patients receiving the pembrolizumab combination.

Participants were randomized 1:1 to receive either the pembrolizumab-based regimen or a placebo in combination with paclitaxel (80 mg/m² on days 1, 8, and 15 of a 3-week cycle), with or without bevacizumab (10 mg/kg every 2 weeks), according to information presented at the 2025 ESMO Congress. Stratification factors included PD-L1 status, prior bevacizumab use, and geographic region.

In this analysis it was also reported that the objective response rate (ORR) was 53.0% in the experimental arm, including a 9.9% complete response rate, compared with 46.6% in the placebo arm. Investigators noted that this marks the first time an immune checkpoint inhibitor-based regimen has demonstrated an OS benefit in this difficult-to-treat form of ovarian cancer.

Dosing and Administration

The recommended intravenous dose of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks.¹ The subcutaneous formulation (Keytruda Qlex) is dosed at 395 mg/4800 units every 3 weeks or 790 mg/9600 units every 6 weeks.

Treatment should continue until disease progression, unacceptable toxicity, or for a maximum of 24 months. When scheduled for the same day, pembrolizumab or its subcutaneous formulation must be administered prior to paclitaxel and bevacizumab.

References

1. FDA approves pembrolizumab with paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. FDA. February 10, 2026. Accessed February 10, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-paclitaxel-platinum-resistant-epithelial-ovarian-fallopian-tube-or
2. Colombo N, Zsiros E, Sebastianelli A, et al. 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. Presented at: 2025 European Society for Medical Oncology Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA3.