Merck’s KEYTRUDA-Based Regimen Achieves Major Milestone in Phase 3 KEYNOTE-B96 Trial for Platinum-Resistant Ovarian Cancer
Merck & Co., Inc. (NYSE: MRK), operating as MSD outside the United States and Canada, announced a significant advancement in the treatment of platinum-resistant recurrent ovarian cancer through its investigational use of KEYTRUDA® (pembrolizumab), a PD-1 immune checkpoint inhibitor. The company revealed that its Phase 3 KEYNOTE-B96 clinical trial, also known under the European designation ENGOT-ov65, met its primary endpoint of progression-free survival (PFS) in patients whose tumors expressed PD-L1 as well as in the overall trial population, regardless of PD-L1 expression.
The trial evaluated the combination of KEYTRUDA and chemotherapy (paclitaxel), with or without the addition of bevacizumab, in women with a highly challenging and previously hard-to-treat subset of ovarian cancer: those with platinum-resistant disease, who typically face a limited prognosis and constrained treatment options.
Key Findings From the KEYNOTE-B96 Study
At a pre-specified interim analysis conducted by an independent Data Monitoring Committee (DMC), Merck’s combination therapy demonstrated statistically significant and clinically meaningful improvements in progression-free survival when compared with a control regimen of placebo plus chemotherapy (with or without bevacizumab). Notably, these results held true both in the PD-L1 positive population and across the full intent-to-treat group, known as “all comers.”
Additionally, the trial met one of its secondary endpoints: overall survival (OS) in patients with PD-L1–expressing tumors, as determined by a Combined Positive Score (CPS) of ≥1. This survival benefit is particularly noteworthy, as it marks the first time an immune checkpoint inhibitor-based regimen has demonstrated a statistically significant OS benefit in ovarian cancer, a malignancy historically resistant to immunotherapy approaches.
The KEYNOTE-B96 trial remains ongoing, with overall survival for the full study population expected to be assessed in a future planned analysis. Merck has confirmed that detailed efficacy and safety results from the trial will be presented at an upcoming medical congress and submitted to regulatory authorities across the globe for potential label expansion of KEYTRUDA.
A Historic First in Ovarian Cancer Immunotherapy
“This marks the first time a KEYTRUDA-based regimen has shown the ability to help certain patients with platinum-resistant ovarian cancer live longer,” said Dr. Gursel Aktan, vice president of global clinical development at Merck Research Laboratories. “It is also the first time an immune checkpoint inhibitor-based therapy has demonstrated an overall survival benefit in any form of ovarian cancer. These results are both exciting and encouraging for patients and clinicians alike.”
Dr. Aktan emphasized that platinum-resistant ovarian cancer represents one of the most difficult gynecologic malignancies to manage, largely because these tumors tend to recur quickly after initial platinum-based chemotherapy and often exhibit resistance to subsequent treatment lines. With few effective systemic therapies currently available, the need for novel therapeutic approaches is urgent.
Study Design and Treatment Regimen
The KEYNOTE-B96/ENGOT-ov65 study was a randomized, multicenter, double-blind, Phase 3 trial that investigated the efficacy and safety of KEYTRUDA plus paclitaxel, with or without bevacizumab, compared to placebo plus paclitaxel (again, with or without bevacizumab), in women with platinum-resistant, recurrent ovarian cancer.
Participants in the study were stratified based on PD-L1 expression, among other baseline characteristics. The primary endpoint of the study was progression-free survival, defined as the length of time during and after treatment that a patient lives without disease progression. Secondary endpoints included overall survival, objective response rate, and duration of response, among others.
Importantly, the safety profile of the KEYTRUDA-based regimen was consistent with what has been observed in earlier studies involving pembrolizumab. No new safety signals emerged during the trial, and adverse events were manageable using existing protocols.
KEYTRUDA’s Broader Gynecologic Oncology Program
Though KEYTRUDA is not currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of ovarian cancer, this trial marks a key step forward in expanding the immunotherapy’s footprint into the gynecologic oncology space. The results from KEYNOTE-B96 complement other efforts by Merck to investigate KEYTRUDA across a range of gynecologic cancers, including cervical and endometrial cancers.
In previously approved indications, KEYTRUDA has already demonstrated substantial benefit in various tumor types, such as non-small cell lung cancer, melanoma, triple-negative breast cancer, and urothelial carcinoma. The company now hopes to translate this success into ovarian cancer, where checkpoint inhibition has, until now, seen limited success due to the immunosuppressive tumor microenvironment typical of the disease.
Complementary Oncology Assets: LYNPARZA and Raludotatug Deruxtecan
While Merck advances the KEYTRUDA program, it continues to benefit from a robust gynecologic oncology portfolio through its partnership with AstraZeneca. The two companies jointly develop and commercialize LYNPARZA® (olaparib), a first-in-class oral PARP inhibitor that is already FDA-approved for multiple ovarian cancer indications.
In the United States, LYNPARZA is approved for:
- First-line maintenance treatment of BRCA-mutated advanced ovarian cancer in patients who responded to platinum-based chemotherapy.
- First-line maintenance treatment of homologous recombination deficiency (HRD)-positive advanced ovarian cancer, in combination with bevacizumab.
- Maintenance treatment of BRCA-mutated recurrent ovarian cancer following response to platinum-based chemotherapy.
All these indications require biomarker-based patient selection using FDA-approved companion diagnostics.
In addition to olaparib, Merck is pursuing another investigational asset, raludotatug deruxtecan (R-DXd), a potential first-in-class CDH6-directed antibody-drug conjugate (ADC). Developed in collaboration with Daiichi Sankyo, R-DXd is currently being evaluated in the Phase 2/3 REJOICE-Ovarian01 trial for the treatment of platinum-resistant ovarian cancer. This trial underscores Merck’s multi-faceted strategy in targeting ovarian cancer using diverse therapeutic mechanisms, including immunotherapy, targeted therapy, and ADC platforms.
The Unmet Need in Platinum-Resistant Ovarian Cancer
Ovarian cancer is one of the most lethal gynecological malignancies, often diagnosed at an advanced stage due to its asymptomatic nature in early development. Platinum-based chemotherapy remains the cornerstone of initial treatment. However, disease recurrence is common, and approximately 20% to 30% of patients develop platinum-resistant disease within six months after completing treatment.
For these patients, survival rates remain poor and therapeutic options are limited, with no curative therapies currently available. The advent of a regimen that can extend both progression-free and overall survival in this setting—particularly through immunotherapy—could transform the treatment landscape.
The successful outcome of the KEYNOTE-B96 trial marks a major milestone for Merck’s oncology program and may lead to a new treatment paradigm for platinum-resistant recurrent ovarian cancer. As Merck prepares to present detailed data at an upcoming medical congress and engages with regulators worldwide, anticipation is building within the oncology community.
Should these results translate into regulatory approval, KEYTRUDA could become the first immune checkpoint inhibitor to be approved for ovarian cancer, and specifically for use in combination with chemotherapy in a platinum-resistant population—a group that has, until now, had very few viable treatment paths.
This development represents more than just a potential label expansion for Merck’s blockbuster immunotherapy. It signifies a broader effort to redefine how ovarian cancer is managed and treated—particularly in cases where standard therapies have failed.
