On October 18, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the first presentation of results from the pivotal Phase 3 KEYNOTE-B96 trial, also known as ENGOT-ov65, evaluating KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with chemotherapy (paclitaxel) with or without bevacizumab for the treatment of patients with platinum-resistant recurrent ovarian cancer. These late-breaking data will be presented today during a Presidential Symposium session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 (Presentation #LBA3).
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At the first interim analysis, with a median study follow-up of 15.6 months, KEYTRUDA plus chemotherapy with or without bevacizumab (n=322) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), the study’s primary endpoint, reducing the risk of disease progression or death by 30% (HR=0.70 [95% CI, 0.58-0.84]; p<0.0001) in the all comers population of patients with platinum-resistant recurrent ovarian cancer compared to placebo plus chemotherapy with or without bevacizumab (n=321). The 12-month PFS rate for these patients receiving the KEYTRUDA regimen was 33.1% (95% CI, 27.7-38.5) versus 21.3% (95% CI, 16.6-26.4) for patients receiving the placebo regimen. In patients whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1), KEYTRUDA plus chemotherapy with or without bevacizumab (n=234) reduced the risk of disease progression or death by 28% (HR=0.72 [95% CI, 0.58-0.89]; p=0.0014) compared to placebo plus chemotherapy with or without bevacizumab (n=232). The 12-month PFS rate was 35.2% (95% CI, 28.8-41.7) for the KEYTRUDA regimen versus 22.6% (95% CI, 17.0-28.7) for the placebo regimen.
"There are very few treatments we can offer patients living with platinum-resistant recurrent ovarian cancer that are able to reduce the risk of disease progression or death," said Dr. Nicoletta Colombo, director of the Gynecologic Oncology Program at the European Institute of Oncology in Milan, Italy. "Results from KEYNOTE-B96 have the potential to mark a significant step forward in the treatment of platinum-resistant recurrent ovarian cancer and demonstrate that adding pembrolizumab to chemotherapy, with or without bevacizumab, could potentially be an additional effective option for these patients."
At the second interim analysis, with a median study follow-up of 26.6 months, the KEYTRUDA regimen also demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), a key secondary endpoint, in patients whose tumors express PD-L1 (CPS ≥1), reducing the risk of death by 24% (HR=0.76 [95% CI, 0.61-0.94]; p=0.0053) compared to placebo plus chemotherapy with or without bevacizumab. The 12-month OS rate for patients receiving the KEYTRUDA regimen was 69.1% versus 59.3% for patients receiving the placebo regimen. Eighteen-month OS rates were 51.5% and 38.9%, respectively.
"These results build upon the success of KEYTRUDA in gynecologic cancers and support the potential use of KEYTRUDA for patients with platinum-resistant ovarian cancer," said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. "As the first immunotherapy with data demonstrating improved survival in certain patients with platinum-resistant recurrent ovarian cancer, this KEYTRUDA-based regimen underscores our commitment to helping to provide patients with more treatment options to meet their unique needs. These data have the potential to change the treatment paradigm for patients like these with platinum-resistant recurrent ovarian cancer."
Treatment-related adverse events (TRAEs) occurred in 97.8% of patients receiving the KEYTRUDA regimen (n=320) and 95.3% of patients receiving the placebo regimen (n=318); Grade 3-5 TRAEs occurred in 67.5% versus 55.3%, respectively. TRAEs led to death in 0.9% of patients receiving the KEYTRUDA regimen and 1.6% of patients receiving the placebo regimen. No new safety concerns were identified.
Immune-mediated adverse events (AEs) and infusion reactions of any grade occurred in 39.1% of patients receiving the KEYTRUDA regimen and 18.9% of patients receiving the placebo regimen. The most common of these events (occurring in ≥10% of patients) was hypothyroidism (17.8%) in patients receiving the KEYTRUDA regimen. Immune-mediated AEs led to death in 0.6% of patients in the KEYTRUDA arm and in no patients in the placebo arm.
Based on these data from the first and second interim analyses of the KEYNOTE-B96 trial, the U.S. Food and Drug Administration (FDA) has accepted for priority review a new supplemental Biologics License Application (sBLA) seeking approval of KEYTRUDA in combination with chemotherapy with or without bevacizumab for the treatment of patients with platinum-resistant recurrent ovarian cancer. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of Feb. 20, 2026. As previously announced, in the final analysis of the trial, KEYNOTE-B96 also met its secondary endpoint of OS for all comers. These final analysis data will be presented at an upcoming medical meeting.
KEYTRUDA is not approved to treat ovarian cancer (see selected KEYTRUDA indications in the U.S. below). LYNPARZA (olaparib), which is being jointly developed and commercialized by AstraZeneca and Merck, has three approved ovarian cancer indications in the U.S.: in first-line maintenance treatment of BRCA-mutated advanced ovarian cancer, following complete or partial response to first-line platinum-based chemotherapy; in first-line maintenance treatment of HRD-positive advanced ovarian cancer in combination with bevacizumab, following complete or partial response to first-line platinum-based chemotherapy; and in maintenance treatment of BRCA-mutated recurrent ovarian cancer, following complete or partial response to platinum-based chemotherapy. For each of these indications, patients are selected for therapy based on an FDA-approved companion diagnostic for LYNPARZA (see indications for LYNPARZA below).
As announced, data from the REJOICE-Ovarian01 trial in collaboration with Daiichi Sankyo evaluating raludotatug deruxtecan (R-DXd) in patients with platinum-resistant, high-grade ovarian, primary peritoneal or fallopian tube cancer will be presented at the 2025 ESMO (Free ESMO Whitepaper) Congress. R-DXd was recently granted Breakthrough Therapy Designation by the U.S. FDA for the treatment of adult patients with platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancers expressing CDH6 who have received prior treatment with bevacizumab, based in part on data from the REJOICE-Ovarian01 trial. R-DXd was discovered by Daiichi Sankyo and is being jointly developed by Daiichi Sankyo and Merck.
About KEYNOTE-B96/ENGOT-ov65
KEYNOTE-B96, also known as ENGOT-ov65, is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT05116189) sponsored by Merck and conducted in collaboration with the European Network for Gynecologic Oncology Trial (ENGOT) groups investigating KEYTRUDA in combination with chemotherapy (paclitaxel) with or without bevacizumab compared to placebo plus chemotherapy with or without bevacizumab for the treatment of platinum-resistant recurrent ovarian cancer. The primary endpoint is PFS, and OS is a key secondary endpoint. The trial enrolled 643 patients who were randomized to receive either KEYTRUDA (400 mg intravenously every six weeks for approximately two years) plus paclitaxel with or without bevacizumab, or placebo plus paclitaxel with or without bevacizumab.
About platinum-resistant ovarian cancer
Ovarian cancer often begins in the fallopian tubes or on the outer surface of the ovaries. It is the eighth most commonly diagnosed cancer and the eighth leading cause of cancer death among women worldwide. Globally, there were more than 324,000 patients diagnosed with ovarian cancer and almost 207,000 deaths from the disease in 2022. In many regions, its incidence has been increasing, with estimates projecting a 42% increase in new cases worldwide by 2040. In the U.S., it is estimated there will be approximately 20,890 patients diagnosed with ovarian cancer and about 12,730 deaths from the disease in 2025.
The primary aim of first-line treatment is to delay disease progression for as long as possible with the intent to achieve long-term remission. Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens. Approximately 25% of these patients develop resistance within six months of completing first-line platinum-based chemotherapy, and this is defined as primary platinum-resistant ovarian cancer. Prognosis is particularly poor for these patients and treatment options are limited.
(Press release, Merck & Co, OCT 18, 2025, View Source [SID1234656770])