Merck’s Phase 3 KEYNOTE-B96 Trial Achieves Key Milestone in Platinum-Resistant Ovarian Cancer, Demonstrating Survival Benefit in All-Comer Population
Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced that its pivotal Phase 3 KEYNOTE-B96 (ENGOT-ov65) clinical trial has met a major milestone, achieving its secondary endpoint of overall survival (OS) in the all-comers population of patients with platinum-resistant recurrent ovarian cancer. This marks an important advancement in the company’s ongoing efforts to improve outcomes for women with this difficult-to-treat disease.
The KEYNOTE-B96 trial evaluated KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 immunotherapy, in combination with chemotherapy (paclitaxel) with or without bevacizumab, compared to placebo plus chemotherapy with or without bevacizumab. The results revealed that the KEYTRUDA-based regimen delivered a statistically significant and clinically meaningful improvement in overall survival versus the control arm.
This outcome builds on previous announcements from earlier interim analyses, where the trial had already achieved its primary endpoint of progression-free survival (PFS) in both the PD-L1–expressing subgroup and the overall study population. At those stages, the study also met one of its secondary endpoints—OS in PD-L1–positive patients—demonstrating early promise for KEYTRUDA in this setting.
Merck confirmed that detailed findings from the prior interim analyses will be featured in a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2025, while the comprehensive data from the final analysis will be presented at a future medical meeting.
A Landmark Achievement in Ovarian Cancer Immunotherapy
The latest results from the KEYNOTE-B96 trial mark a historic milestone for patients and oncologists alike. According to Dr. Gursel Aktan, Vice President of Global Clinical Development at Merck Research Laboratories, the trial represents the first time an immune checkpoint inhibitor-based regimen has shown the potential to benefit all patients with platinum-resistant recurrent ovarian cancer.
“These women face a very poor prognosis and extremely limited treatment options,” said Dr. Aktan. “This impactful outcome underscores Merck’s unwavering commitment to addressing unmet medical needs in gynecologic oncology and to expanding the potential of immunotherapy for women who urgently need new options.”
Trial Design and Results Overview
KEYNOTE-B96 (ENGOT-ov65) was designed to evaluate whether combining KEYTRUDA, a PD-1 immune checkpoint inhibitor, with standard chemotherapy—with or without the addition of bevacizumab—could extend survival in women whose ovarian cancer had become resistant to platinum-based treatments.
Platinum-resistant ovarian cancer is defined as disease that recurs within six months after completion of platinum-based chemotherapy. These patients generally experience poor survival outcomes and have few effective therapies available. Standard options typically include non-platinum chemotherapies such as paclitaxel or pegylated liposomal doxorubicin, with limited benefit and significant toxicity.
In the final analysis, the KEYTRUDA-based regimen significantly improved overall survival across the full study population, not just in PD-L1–positive tumors. The safety profile of the combination was consistent with previous KEYTRUDA studies, and no new safety signals were identified, supporting the therapy’s continued favorable benefit-risk profile in oncology.
Merck’s Broader Commitment to Gynecologic Oncology
While KEYTRUDA is not currently approved for the treatment of ovarian cancer, Merck continues to investigate its role in gynecologic malignancies through multiple late-stage trials.
In addition, Merck and AstraZeneca continue to collaborate on LYNPARZA® (olaparib), a leading PARP inhibitor that has already received three FDA-approved indications in ovarian cancer in the United States:
- First-line maintenance therapy for BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy.
- First-line maintenance therapy in HRD-positive advanced ovarian cancer, in combination with bevacizumab, following a response to platinum-based chemotherapy.
- Maintenance therapy for BRCA-mutated recurrent ovarian cancer after a response to platinum-based chemotherapy.
For each of these indications, treatment eligibility is determined by an FDA-approved companion diagnostic to identify patients most likely to benefit from LYNPARZA.
This multifaceted strategy reflects Merck’s broader ambition to address ovarian cancer through both immunotherapy and targeted therapy approaches, leveraging its expertise in oncology and clinical development partnerships to push the boundaries of care.
Collaboration Spotlight: Expanding the Therapeutic Horizon
In parallel with the KEYNOTE-B96 results, Merck also highlighted progress from its collaborations with partners such as Daiichi Sankyo. Data from the REJOICE-Ovarian01 trial, evaluating raludotatug deruxtecan (R-DXd)—an investigational antibody-drug conjugate—in patients with platinum-resistant, high-grade ovarian, primary peritoneal, or fallopian tube cancers, will also be presented at ESMO 2025.
R-DXd, discovered by Daiichi Sankyo and co-developed with Merck, recently received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA). This designation was granted for the treatment of adult patients with platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancers expressing CDH6 who have previously received bevacizumab. The designation was supported in part by compelling data from the REJOICE-Ovarian01 study.
The partnership between Merck and Daiichi Sankyo underscores the growing importance of targeted antibody-drug conjugates (ADCs) and immune-oncology combinations in shaping the future of ovarian cancer therapy.
Looking Ahead: A New Era of Treatment Possibilities
The success of the KEYNOTE-B96 trial signals a potential paradigm shift in the management of platinum-resistant ovarian cancer, a disease historically marked by high recurrence rates and poor survival outcomes. While regulatory submissions and review processes will determine the future availability of this KEYTRUDA-based regimen, the trial’s achievement in demonstrating an overall survival benefit in all-comer patients stands as a significant step forward.
As Merck continues to pursue innovation across immunotherapy, targeted therapy, and ADC platforms, its expanding oncology portfolio demonstrates a deep and sustained commitment to improving outcomes for women with gynecologic cancers—particularly those with limited remaining options.
With KEYNOTE-B96, Merck has advanced the frontier of immunotherapy in ovarian cancer, potentially paving the way for a new standard of care for patients facing one of the most challenging forms of the disease.
