On February 10, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) as well as pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) in combination with paclitaxel, with or without bevacizumab, for adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (combined positive score [CPS] ≥ 1) as determined by an FDA-authorized test, and who have received one or two prior systemic treatment regimens.
The FDA also approved the PD-L1 IHC 22C3 pharmDx (Agilent Technologies, Inc) as a companion diagnostic device to identify patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 for treatment with pembrolizumab.
KEYNOTE-B96
Efficacy was evaluated in KEYNOTE-B96 (ClinicalTrials.gov identifier NCT05116189), a multicenter, randomized, double-blind, placebo-controlled trial that enrolled 643 patients with platinum-resistant, epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who received one or two prior lines of systemic therapy for ovarian carcinoma. Patients must have received at least one line of platinum-based chemotherapy for ovarian cancer with radiographic evidence of disease progression within 6 months after the last dose. Patients were randomly assigned 1:1 to receive either pembrolizumab plus paclitaxel with or without bevacizumab or placebo plus paclitaxel with or without bevacizumab.
The major efficacy outcome measure was progression-free survival as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1; an additional efficacy outcome measure was overall survival. Among the 466 patients with tumors expressing PD-L1 with CPS ≥ 1, median progression-free survival was 8.3 months (95% confidence interval [CI] = 7.0–9.4 months) in the pembrolizumab arm and 7.2 months (95% CI = 6.2–8.1 months) in the placebo arm (hazard ratio [HR] = 0.72, 95% CI = 0.58–0.89, P = .0014). Median overall survival was 18.2 months (95% CI = 15.3–21.0 months) in the pembrolizumab arm and 14.0 months (95% CI = 12.5–16.1 months) in the placebo arm (HR = 0.76, 95% CI = 0.61–0.94, P = .0053).
The overall safety profile of pembrolizumab in combination with paclitaxel with or without bevacizumab in KEYNOTE-B96 was similar to that observed in prior trials. The prescribing information includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.
Recommended Dosage and Review
The recommended dose of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months. The recommended dose of pembrolizumab and berahyaluronidase alfa-pmph is 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months. Administer pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph prior to paclitaxel with or without bevacizumab when given on the same day. Refer to the prescribing information for the agents administered in combination with pembrolizumab for recommended dosing information.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with Australia’s Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The applications may still be under review at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment, and this application was granted Priority Review.
