FDA Approves Keytruda-Based Regimen for PD-L1–Positive Platinum-Resistant Ovarian Cancer

The FDA has approved Keytruda (pembrolizumab) and Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph; Merck) plus paclitaxel, with or without bevacizumab, for the treatment of adults with PD-L1–positive platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who have received one or two prior systemic treatment regimens.¹

The regulatory action, based on findings from the Phase III KEYNOTE-B96/ENGOT-ov65 trial (NCT05116189), introduces the first PD-1–based regimen for this platinum-resistant population.²

Regulatory decision brings PD-1 inhibition to platinum-resistant ovarian cancer

“For many patients with ovarian cancer, the disease can become platinum-resistant, at which point recurrence is not just a setback—it’s when options can become limited, and the reality patients face can change very quickly,” Bradley Monk, MD, gynecologic oncologist and medical director of the Late-Stage Clinical Research Program at Florida Cancer Specialists and Research Institute, said in a press release. “For patients who have been previously treated with standard platinum-based therapies, the FDA approvals of these pembrolizumab-based regimens offer the possibility of more time.”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.

Keytruda mechanism of action as a PD-1 inhibitor

• Keytruda blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
• By inhibiting this pathway, Keytruda enhances T-cell–mediated immune responses against tumor cells.
• Keytruda Qlex combines pembrolizumab with berahyaluronidase alfa to facilitate subcutaneous administration; its efficacy has been established based on studies of intravenous Keytruda and additional comparative data evaluating pharmacokinetics, efficacy, and safety.

KEYNOTE-B96 trial design and patient population

• KEYNOTE-B96 (ENGOT-ov65) is a multicenter, randomized, double-blind, placebo-controlled Phase III trial (NCT05116189).
• The study evaluated Keytruda plus paclitaxel, with or without bevacizumab, compared with placebo plus paclitaxel, with or without bevacizumab, in platinum-resistant recurrent ovarian cancer.
• A total of 643 patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who had received one or two prior systemic regimens, including at least one platinum-based therapy, were enrolled.
  Patients were enrolled regardless of PD-L1 status; 72% had tumors expressing PD-L1 (CPS ≥1).
• The primary endpoint was progression-free survival (PFS) by investigator assessment per RECIST v1.1, and overall survival (OS) was a key secondary endpoint.
• Keytruda 400 mg or placebo was administered on day one of each six-week cycle; paclitaxel 80 mg/m² was administered on days one, eight, and 15 of each three-week cycle. Bevacizumab use was determined by investigator choice prior to randomization.

Progression-free and overall survival outcomes

• In patients with PD-L1–positive tumors (CPS ≥1), Keytruda plus paclitaxel, with or without bevacizumab, reduced the risk of disease progression or death by 28% compared with placebo plus paclitaxel (HR=0.72; 95% CI, 0.58–0.89; p=0.0014).
• Median PFS was 8.3 months with the Keytruda regimen versus 7.2 months with placebo.
• The Keytruda regimen reduced the risk of death by 24% compared with placebo (HR=0.76; 95% CI, 0.61–0.94; p=0.0053).
• Median OS was 18.2 months in the Keytruda arm compared to 14.0 months in the placebo arm.
• Among enrolled patients, 73% received bevacizumab in the study, 46% had received prior bevacizumab, and 47% had a platinum-free interval of less than three months.

Safety profile and adverse events (AEs) for Keytruda plus Keytruda Qlex

• The safety analysis included 463 patients with PD-L1–positive tumors treated with Keytruda in combination with paclitaxel, with or without bevacizumab.
• Serious AEs occurred in 54% of patients.
• Fatal AEs occurred in 3.9% of patients.
  Keytruda was permanently discontinued due to AEs in 16% of patients and interrupted in 44%.
• The most common AEs (≥20%) included diarrhea, fatigue, nausea, alopecia, peripheral neuropathy, epistaxis, urinary tract infection, constipation, abdominal pain, decreased appetite, vomiting, hypothyroidism, cough, hypertension, and rash.
• Common laboratory abnormalities worsening from baseline included anemia, leukopenia, decreased neutrophil count, lymphopenia, hypoalbuminemia, hyponatremia, hypomagnesemia, elevated liver enzymes, hypocalcemia, increased alkaline phosphatase, elevated creatinine, hypokalemia, and neutropenia.

Keytruda and Keytruda Qlex carry warnings for severe and potentially fatal immune-mediated AEs affecting multiple organ systems, infusion or injection-related reactions, transplant-related complications, embryo-fetal toxicity, and increased mortality in certain multiple myeloma combinations outside controlled trials. Keytruda Qlex is contraindicated in patients with known hypersensitivity to berahyaluronidase alfa or hyaluronidase.

“Historically, the prognosis has been poor for patients living with platinum-resistant recurrent ovarian cancer who have limited treatment options that may reduce the risk of disease progression or death,” Gursel Aktan, MD, vice president, global clinical development, Merck Research Laboratories, added in the release. “These approvals mark an important moment for the ovarian cancer community, reflecting years of focused investment in Keytruda.”¹

References

1. KEYTRUDA® (pembrolizumab) and KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph), Plus Paclitaxel ± Bevacizumab, Approved for Certain Adults with PD-L1+ (CPS ≥1) Platinum-Resistant Ovarian Carcinoma as Second or Third Line Treatment. News release. Merck. February 11, 2026. Accessed February 11, 2026. https://www.merck.com/news/keytruda-pembrolizumab-and-keytruda-qlex-pembrolizumab-and-berahyaluronidase-alfa-pmph-plus-paclitaxel-%c2%b1-bevacizumab-approved-for-certain-adults-with-pd-l1-cps-%e2%89%a51/

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 February 11, 2026. https://www.clinicaltrials.gov/study/NCT05116189