Final KEYNOTE-B96 Analysis Confirms Survival Benefits With Pembrolizumab Regimen in Ovarian Cancer

The final analysis of the phase 3 KEYNOTE-B96 trial (NCT05116189) establishes pembrolizumab (Keytruda) in combination with paclitaxel, with or without bevacizumab (Avastin), as a significant therapeutic advancement for patients with platinum-resistant recurrent ovarian cancer.¹

Crucially, this regimen is the first PD-1 inhibitor-based treatment to demonstrate a statistically significant and clinically meaningful improvement in overall survival (OS) in this patient population, regardless of PD-L1 expression status. In the all-comers population, the regimen reduced the risk of death by 18% compared to the standard of care.

The final analysis, conducted after a median follow-up of 32.7 months, confirms that the pembrolizumab-based regimen offers superior survival outcomes over the standard chemotherapy-based control.

The study reached its key secondary end point of OS with statistically significant results in both the all-comers population (HR, 0.82; 95% CI, 0.69-0.97) and the PD-L1 (combined positive score [CPS] ≥1) subgroup (HR, 0.76; 95% CI, 0.62-0.93).

The primary end point of PFS was also met, showing substantial reductions in the risk of disease progression or death.

• All-comers: 27% reduction in risk (HR, 0.73; 95% CI, 0.62-0.87).
• PD-L1 (CPS ≥1): 24% reduction in risk (HR, 0.76; 95% CI, 0.62-0.93).

Safety and Tolerability Profile

The safety profile of the pembrolizumab combination was consistent with previous studies, with no new safety signals identified during the KEYNOTE-B96 trial.

• Grade ≥3 treatment-related adverse events (TRAEs): 67.8% in the pembrolizumab armvs 55.3% in the placebo arm.
• Fatal TRAEs: 1.3% in the pembrolizumab arm vs 1.6% in the placebo arm.
• Discontinuation: 16% of patients in the pembrolizumab arm permanently discontinued treatment due to adverse reactions. The most common reasons for discontinuation (≥1%) were colitis and increased alanine amino transferase.

Immune-mediated AEs and infusion reactions occurred in 39.4% of patients receiving the pembrolizumab regimen vs 18.9% in the placebo group. Hypothyroidism was the most frequent immune-mediated AE, occurring in 18.1% of patients in the pembrolizumab arm. Immune-mediated AEs led to death in 0.6% of the pembrolizumab arm.

In the pembrolizumab arm, the most common AEs were diarrhea (45%), fatigue (43%), nausea (41%), and alopecia (38%).

Trial Overview and Methodology

KEYNOTE-B96 is a multicenter, randomized, double-blind, placebo-controlled phase 3 trial conducted in collaboration with the European Network for Gynecologic Oncology Trial (ENGOT) groups.

The trial enrolled a total of 643 patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Patients were enrolled regardless of PD-L1 status; however, 72% of the cohort had tumors expressing PD-L1 (CPS ≥1).

Patients received 400 mg of pembrolizumab every 6 weeks, 80 mg/m2 of paclitaxel on days 1, 8, and 15 of a 3-week cycle, and an optional 10 mg/kg of bevacizumab every 2 weeks, based on investigator choice prior to randomization.

Regulatory and Clinical Significance

In February 2026, the FDA approved pembrolizumab plus paclitaxel (with or without bevacizumab) for adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS ≥1) and who have received 1 or 2 prior systemic treatment regimens.² Additionally, a positive opinion has been granted recommending approval for the same patient population in the European Union by the Committee for Medicinal Products for Human Use (CHMP).

“Results from the final analysis of KEYNOTE-B96, including [OS] data in the all comers population, demonstrate the continued clinical benefit of [pembrolizumab] plus paclitaxel with or without bevacizumab for certain patients with platinum-resistant recurrent ovarian cancer,” said Gursel Aktan, MD, PhD, vice president, global clinical development, Merck Research Laboratories, in a news release.¹ “Taken together, the recent FDA approval and CHMP positive opinion underscore our commitment to the ovarian cancer community and our ongoing focus on delivering therapies that can help patients with unmet needs across women’s cancers.”

REFERENCES

1. Keytruda (pembrolizumab) plus paclitaxel with or without bevacizumab significantly improved key secondary endpoint of overall survival (OS) versus paclitaxel with or without bevacizumab in patients with platinum-resistant recurrent ovarian cancer. News release. Merck. February 27, 2026. Accessed March 2, 2026. https://tinyurl.com/3c939mbj 

2.FDA approves pembrolizumab with paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. News release. US FDA. February 10, 2026. Accessed February 10, 2026. https://tinyurl.com/yy5vzf7z