The FDA has accepted for review a supplemental Biologics License Application (sBLA) for anti-PD-1 therapy pembrolizumab (Keytruda, Merck) for the first-line treatment of unresectable or metastatic melanoma patients. The FDA granted Priority Review with a PDUFA, or target action, date of December 19, 2015. Additionally, the FDA has extended the action date for a separate sBLA for pembrolizumab for the treatment of patients with ipilimumab-refractory advanced melanoma. The new action date is December 24, 2015.
Pembrolizumab is currently indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
The sBLA submission for first-line use in advanced melanoma was based in part on data from KEYNOTE-006, a Phase 3 study that evaluated pembrolizumab in 834 patients with unresectable or metastatic melanoma with progression of disease.
The sBLA for ipilimumab-refractory advanced melanoma included data from KEYNOTE-002. KEYNOTE-002 is the Phase 2 study, which demonstrated pembrolizumab was superior to chemotherapy in helping more patients with ipilimumab-refractory advanced melanoma achieve progression-free survival (PFS). In an effort to provide the FDA with the most robust data for pembrolizumab in this population, Merck submitted an additional analysis from KEYNOTE-002. The submission constitutes a major amendment that will require additional time for review.
