The U.S. Food and Drug Administration has approved two formulations of Merck's programmed death receptor-1 inhibitor for a defined group of ovarian cancer patients. The approval, announced Tuesday, covers pembrolizumab (Keytruda) and pembrolizumab combined with berahyaluronidase alfa-pmph (Keytruda Qlex) for adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1, defined as a combined positive score of 1 or greater, and who have received one or two prior systemic treatment regimens.
As part of the regulatory package, the FDA also cleared Agilent Technologies' PD-L1 IHC 22C3 pharmDx test to be used as a companion diagnostic to identify patients whose tumors meet the PD-L1 expression threshold for treatment eligibility.
The approval relied on data from the randomized KEYNOTE-B96 study, which enrolled 643 patients with platinum-resistant ovarian cancers. Among the 466 participants whose tumors expressed PD-L1, those treated with Keytruda in combination with paclitaxel, with or without bevacizumab, demonstrated improved outcomes compared with patients receiving placebo plus the same chemotherapy combinations.
Reported efficacy measures included median progression-free survival of 8.3 months in the Keytruda-treated group versus 7.2 months in the placebo group. Median overall survival was 18.2 months with Keytruda compared with 14.0 months for placebo.
The prescribing information sets Keytruda dosing at 200 mg every three weeks or 400 mg every six weeks. For Keytruda Qlex, the recommended dose is 395 mg/4,800 units every three weeks or 790 mg/9,600 units every six weeks. Treatment is to continue until documented disease progression, unacceptable toxicity, or for a maximum of 24 months.
The FDA review was conducted under Project Orbis, an initiative that enables concurrent submission and review of oncology therapies among international regulatory partners. The program includes participating authorities in countries such as Australia, Canada, and Switzerland, and the application for these indications received priority review status from the FDA.
The approved labeling includes several safety warnings. The prescribing information calls out immune-mediated adverse reactions, infusion-related reactions, complications associated with allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.
Key points
- FDA approved Keytruda and Keytruda Qlex for PD-L1 positive, platinum-resistant epithelial ovarian, fallopian tube, and primary peritoneal carcinoma in adults after one or two prior systemic regimens.
- Agilent's PD-L1 IHC 22C3 pharmDx was authorized as a companion diagnostic to identify eligible patients.
- Results from the KEYNOTE-B96 trial showed median progression-free survival of 8.3 months versus 7.2 months and median overall survival of 18.2 months versus 14.0 months in the Keytruda arm versus placebo.
Risks and uncertainties
- The approval is restricted to patients whose tumors express PD-L1 (CPS≥1), limiting eligibility to a subset identified by the companion diagnostic; this directly affects diagnostics and oncology treatment planning.
- Labeling warns of immune-mediated adverse reactions and infusion-related reactions, which are relevant to clinical safety management and hospital oncology services.
- The prescribing information highlights complications tied to allogeneic hematopoietic stem cell transplantation and embryo-fetal toxicity, posing specific safety considerations for transplant patients and those of reproductive potential.