Key Takeaways from the Phase III KEYNOTE-B96/ENGOT-ov65 Trial
- Keytruda Shows First OS Benefit in Ovarian Cancer: The KEYNOTE-B96 trial marks the first time an immune checkpoint inhibitor—Keytruda (pembrolizumab)—has demonstrated a statistically significant improvement in overall survival (OS) in patients with platinum-resistant recurrent ovarian cancer whose tumors express PD-L1.
- Significant PFS and OS Improvements with Keytruda-Based Regimen. In the interim analysis, the Keytruda plus chemotherapy regimen significantly improved both progression-free survival (PFS) across all patient groups and OS in PD-L1–positive patients, compared to chemotherapy with or without bevacizumab.
- No New Safety Concerns Observed. The safety profile of Keytruda in this trial remained consistent with previous studies, with no new safety signals identified, supporting its continued investigation in gynecologic cancers.
A prespecified interim analysis from the Phase III KEYNOTE-B96/ENGOT-ov65 trial (NCT05116189) found that a Keytruda (pembrolizumab)-based combination produced statistically significant and clinically meaningful survival improvements over chemotherapy-based regimens alone in patients with PD-L1–positive, platinum-resistant recurrent ovarian cancer.1,2
Advancing Treatment Options in Recurrent Ovarian Cancer
The trial investigators noted that the Keytruda combination is the first immune checkpoint inhibitor-based regimen to achieve a statistically significant improvement in overall survival (OS) in patients with ovarian cancer.
“This marks the first time a Keytruda-based regimen has shown the ability to help certain patients with platinum-resistant ovarian cancer live longer, and the first time an immune checkpoint inhibitor-based regimen has demonstrated an overall survival benefit in ovarian cancer,” Gursel Aktan, MD, PhD, vice president, global clinical development, Merck Research Laboratories, said in a press release. “The positive results from this trial add to the growing body of evidence supporting the potential benefit of Keytruda across gynecological cancers, including this difficult-to-treat form of ovarian cancer for which patients are in need of new options.”1
Keytruda is an anti-PD-1 therapy that improves the immune system's ability to detect and fight tumor cells. The humanized monoclonal antibody blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which leads to the activation of T lymphocytes that could affect the tumor and healthy cells.
To date, more than 1600 trials are evaluating Keytruda across a range of cancer types and treatment settings. Keytruda has approved indications in melanoma; non-small cell lung cancer; head and neck squamous cell cancer; classical Hodgkin lymphoma; primary mediastinal large B-cell lymphoma; urothelial carcinoma; gastric cancer; microsatellite instability-high or mismatch repair deficient cancer; microsatellite instability-high or mismatch repair deficient colorectal cancer; esophageal cancer; cervical cancer; hepatocellular carcinoma; Merkel cell carcinoma; renal cell carcinoma; endometrial carcinoma; tumor mutational burden-high cancer; cutaneous squamous cell carcinoma; and triple-negative breast cancer.
Trial Design Highlights: KEYNOTE-B96/ENGOT-ov65 Explained
The randomized, double-blind KEYNOTE-B96/ENGOT-ov65 trial evaluated the efficacy and safety of Keytruda combined with paclitaxel, with or without bevacizumab, vs. placebo plus chemotherapy, with or without bevacizumab, in the treatment of platinum-resistant recurrent ovarian cancer. The trial’s primary endpoint is progression-free survival (PFS), with a key secondary endpoint of OS.
Investigators randomly assigned 643 patients in a 1:1 ratio to receive either Keytruda at a dose of 400 mg administered intravenously (IV) every six weeks (Q6W) for up to 18 cycles for approximately two years plus paclitaxel at a dose of 80 mg/m2 on days one, eight, and 15 of each Q3W cycle, with or without bevacizumab at a dose of 10 mg/kg Q2W.3 The control cohort was administered placebo IV Q6W for approximately two years plus paclitaxel 80 mg/m² on days one, eight, and 15 of Q3W, with or without bevacizumab 10 mg/kg Q2W, at investigator's discretion.
Results of the interim analysis by an independent Data Monitoring Committee found the Keytruda regimen produced a statistically significant and clinically meaningful improvement in PFS regardless of PD-L1 status vs. placebo plus chemotherapy with or without bevacizumab.
Investigators observed a statistically significant and clinically meaningful improvement in OS among patients with tumors expressing PD-L1 (Combined Positive Score [CPS] ≥1) compared to placebo plus chemotherapy with or without bevacizumab.
In terms of safety, the profile of Keytruda was consistent with prior findings and no new safety signals were reported. Full results from the trial will be presented at an upcoming medical meeting and submitted to regulatory authorities.
References
1. Merck Announces Phase 3 KEYNOTE-B96 Trial Met Primary Endpoint of Progression-Free Survival (PFS) in Patients With Platinum-Resistant Recurrent Ovarian Cancer Whose Tumors Expressed PD-L1 and in All Comers. News release. Merck. May 15, 2025. Accessed May 15, 2025. https://www.merck.com/news/merck-announces-phase-3-keynote-b96-trial-met-primary-endpoint-of-progression-free-survival-pfs-in-patients-with-platinum-resistant-recurrent-ovarian-cancer-whose-tumors-expressed-pd-l1-and-in-all-c/
2. Pembrolizumab/Placebo Plus Paclitaxel With or Without Bevacizumab for Platinum-resistant Recurrent Ovarian Cancer (MK-3475-B96/KEYNOTE-B96/ENGOT-ov65). ClinicalTrials.gov. Updated March 7, 2025. Accessed May 15, 2025. https://www.clinicaltrials.gov/study/NCT05116189
3. Nicoletta Colombo et al. ENGOT-ov65/KEYNOTE-B96: Phase 3, randomized, double-blind study of pembrolizumab versus placebo plus paclitaxel with optional bevacizumab for platinum-resistant recurrent ovarian cancer.. JCO 40, TPS5617-TPS5617(2022). DOI: 10.1200/JCO.2022.40.16_suppl.TPS5617
