Merck (NYSE: MRK), known as MSD outside the United States and Canada, today reported that its Phase 3 KEYNOTE-B96 trial (ENGOT-ov65) has met its primary endpoint, showing a statistically significant improvement in progression-free survival (PFS) for patients with platinum-resistant recurrent ovarian cancer. The trial evaluated Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in combination with chemotherapy (paclitaxel), with or without bevacizumab, in patients regardless of their tumors’ PD-L1 expression.
The study also met a key secondary endpoint, demonstrating a statistically significant and clinically meaningful improvement in overall survival (OS) among patients whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1). The trial remains ongoing, and OS results for the broader study population will be assessed in a future analysis.
The positive findings emerged during pre-specified interim analyses conducted by an independent Data Monitoring Committee. The KEYTRUDA-based regimen showed benefit in both PFS and OS when compared with placebo plus chemotherapy, with or without bevacizumab. Importantly, the safety profile observed for KEYTRUDA in this study was consistent with prior data, and no new safety concerns were identified.
“These results represent a significant milestone—this is the first time a KEYTRUDA-based regimen has shown an overall survival benefit in platinum-resistant ovarian cancer,” said Dr. Gursel Aktan, Vice President of Global Clinical Development at Merck Research Laboratories. “It’s also the first instance of any immune checkpoint inhibitor showing an OS benefit in ovarian cancer. These findings further support the growing potential of KEYTRUDA in gynecologic cancers, including for patients facing this particularly challenging form of ovarian cancer.”
Currently, KEYTRUDA is not approved for the treatment of ovarian cancer in the U.S. However, Merck and AstraZeneca’s LYNPARZA® (olaparib) holds three approved indications in this area:
- First-line maintenance treatment for BRCA-mutated advanced ovarian cancer after a complete or partial response to platinum-based chemotherapy.
- First-line maintenance treatment for HRD-positive advanced ovarian cancer, in combination with bevacizumab, following response to platinum-based chemotherapy.
- Maintenance treatment for BRCA-mutated recurrent ovarian cancer following response to platinum-based chemotherapy.
In all LYNPARZA indications, treatment selection is guided by an FDA-approved companion diagnostic.
Additionally, in 2024, Merck launched the Phase 2/3 REJOICE-Ovarian01 trial, investigating raludotatug deruxtecan (R-DXd)—a potential first-in-class CDH6-directed DXd antibody-drug conjugate. This investigational therapy, discovered by Daiichi Sankyo and co-developed with Merck, is being evaluated in patients with platinum-resistant ovarian cancer.
Merck plans to present detailed results from KEYNOTE-B96 at an upcoming medical meeting and share findings with regulatory authorities around the world.
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 an estimated 643 patients who were randomized to receive:
- 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 ovarian cancer
Ovarian cancer often begins in the fallopian tubes or on the outer surface of the ovaries. It is the third most common gynecologic malignancy and seventh most common cancer in women worldwide. Globally, there were approximately 324,603 patients diagnosed with ovarian cancer and about 206,956 deaths from the disease in 2022. 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.
About Merck’s research in women’s cancers
Merck is advancing research aimed at expanding treatment options for certain breast and gynecologic (ovarian, cervical and endometrial) cancers, with a goal of improving outcomes for more patients affected by these diseases. Breast cancer and gynecological cancers are the first and second most commonly occurring cancer types among women worldwide, respectively, and Merck aims to give patients facing these devastating diseases options. With more than 20 clinical trials in more than 18,000 patients around the world, Merck is driving innovative research to purposefully advance standards of care in women’s cancers. Merck’s research efforts include trials focused on evaluating its medicines in earlier stages, as well as identifying novel mechanisms and new combinations with these treatments. Merck is working to develop a portfolio and pipeline to address the impact of women’s cancers on patients, their families and communities globally.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- Stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Malignant Pleural Mesothelioma
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM).
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Cancer
KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical Cancer
KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.
Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma.
KEYTRUDA, as a single agent, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
