FDA Approves Pembrolizumab Combinations for Platinum-Resistant Ovarian Cancer

The U.S. Food and Drug Administration approved pembrolizumab (Keytruda) and pembrolizumab with berahyaluronidase alfa-pmph (Keytruda Qlex) plus paclitaxel, with or without bevacizumab (Avastin), for the treatment of adults with PD-L1+ (Combined Positive Score [CPS] ≥1), as determined by an FDA-authorized test, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal carcinoma, who have received one or two prior systemic treatment regimens. The approvals were announced by Merck (NYSE: MRK) on February 11, 2026.

Keytruda and Keytruda Qlex are the first and only PD-1 inhibitors approved for adults with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal carcinoma with PD-L1+ tumors. This decision marks a significant milestone as the first immunotherapy regimen to demonstrate an overall survival benefit in this difficult-to-treat population.

The approvals are based on data from the Phase 3 KEYNOTE-B96 trial (also known as ENGOT-ov65), which were presented at the 2025 European Society for Medical Oncology (ESMO) Congress. Results from the trial showed that pembrolizumab plus paclitaxel, with or without bevacizumab, demonstrated a statistically significant improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 28% (HR=0.72 [95% CI, 0.58-0.89]; p=0.0014) in patients with platinum-resistant recurrent ovarian cancer whose tumors express PD-L1 (CPS ≥1) when compared to placebo plus paclitaxel with or without bevacizumab.

In this same population, the pembrolizumab regimen also demonstrated a statistically significant improvement in overall survival (OS), reducing the risk of death by 24% (HR=0.76 [95% CI, 0.61-0.94]; p=0.0053) compared to placebo plus paclitaxel with or without bevacizumab. In patients whose tumors express PD-L1 (CPS ≥1), the median PFS was 8.3 months (95% CI, 7.0-9.4) for those receiving pembrolizumab plus paclitaxel, with or without bevacizumab, versus 7.2 months (95% CI, 6.2-8.1) for those receiving placebo plus paclitaxel with or without bevacizumab. The median OS for these patients receiving the pembrolizumab regimen was 18.2 months (95% CI, 15.3-21.0) versus 14.0 months (95% CI, 12.5-16.1) for those receiving the placebo regimen.

The effectiveness of Keytruda Qlex for its approved indications has been established based upon evidence from the adequate and well-controlled studies conducted with Keytruda and additional data from MK-3475A-D77 comparing the pharmacokinetic, efficacy, and safety profiles of Keytruda Qlex and Keytruda.

Of the 643 enrolled patients, 72% of patients had tumors expressing PD-L1 (CPS ≥1), 73% received bevacizumab in the study, and 46% received prior bevacizumab. A total of 47% had a platinum-free interval of less than 3 months. Patients were enrolled regardless of PD-L1 tumor expression status.

The safety of pembrolizumab in combination with paclitaxel with or without bevacizumab was evaluated in 463 patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS ≥1) enrolled in KEYNOTE-B96. The median duration of exposure to pembrolizumab was 7.4 months (range 1 day to 35.9 months).

Serious adverse reactions occurred in 54% of patients receiving pembrolizumab and paclitaxel with or without bevacizumab. Serious adverse reactions in ≥2% of patients were pneumonia (4.3%), urinary tract infection (3.9%), adrenal insufficiency (3%), hyponatremia (3%), COVID-19 (2.6%), decreased neutrophil count (2.6%), pulmonary embolism (2.6%), abdominal pain (2.1%), anemia (2.1%), colitis (2.1%), diarrhea (2.1%), febrile neutropenia (2.1%), pyrexia (2.1%) and vomiting (2.1%).

Fatal adverse reactions occurred in 3.9% of patients receiving pembrolizumab and paclitaxel with or without bevacizumab, including assisted suicide (0.9%), death (0.4%), intestinal perforation (0.4%), sepsis (0.4%), COVID-19 (0.4%), cardio-respiratory arrest (0.4%), colitis (0.4%), and embolic stroke (0.4%).

Pembrolizumab was permanently discontinued for adverse reactions in 16% of patients. The most common adverse reactions resulting in permanent discontinuation of pembrolizumab (≥1%) were colitis (1.3%) and increased alanine aminotransferase (1.3%). Adverse reactions leading to the interruption of pembrolizumab occurred in 44% of patients. The most common adverse events leading to interruption of pembrolizumab in ≥2% were urinary tract infection (3.9%), adrenal insufficiency (2.6%), pyrexia (2.6%), pneumonitis (2.6%), upper respiratory tract infection (2.6%), neutropenia (2.1%), diarrhea (2.1%) and COVID-19 (2.1%).

The most common (≥20%) adverse reactions for patients treated with pembrolizumab in combination with paclitaxel with or without bevacizumab were: diarrhea (45%), fatigue (43%), nausea (41%), alopecia (38%), peripheral neuropathy (38%), epistaxis (31%), urinary tract infection (27%), constipation (25%), abdominal pain (24%), decreased appetite (24%), vomiting (24%), hypothyroidism (21%), cough (20%), hypertension (20%), and rash (20%). The most common (≥20%) laboratory abnormalities worsening from baseline were: anemia (85%), leukopenia (82%), decreased neutrophil count (71%), lymphopenia (60%), hypoalbuminemia (50%), hyponatremia (53%), hypomagnesemia (45%), and increased aspartate aminotransferase (43%).

Keytruda Qlex is contraindicated in patients with known hypersensitivity to berahyaluronidase alfa, hyaluronidase or to any of its excipients. Keytruda and Keytruda Qlex are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions in any or multiple organs, which can occur during or after treatment, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, other transplant (including corneal graft) rejection; severe and life-threatening infusion or injection-related reactions; fatal and other serious complications in patients who receive allogeneic hematopoietic stem cell transplantation before or after beginning treatment; embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when pembrolizumab is added to a thalidomide analogue plus dexamethasone, which is not recommended outside of controlled trials.