FDA approval summary: Pembrolizumab for the treatment of patients with unresectable or metastatic melanoma

Abstract

On December 18, 2015, the FDA granted regular approval to pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) for treatment of patients with unresectable or metastatic melanoma based on results of two randomized, open-label, active-controlled clinical trials. In trial PN006, 834 patients with ipilimumab-na€ve metastatic melanoma were randomized (1:1:1) to pembrolizumab 10 mg/kg i.v. every 2 or 3 weeks until disease progression or ipilimumab 3 mg/kg every 3 weeks for up to four doses. In trial PN002, 540 patients with ipilimumab-refractory metastatic melanoma were randomized (1:1:1) to pembrolizumab 2 or 10 mg/kg i.v. every 3 weeks or to investigator's choice of chemotherapy. In trial PN006, patients randomized to pembrolizumab demonstrated a statistically significant improvement in overall survival compared with ipilimumab [every-2-week arm: hazard ratio (HR) ¼ 0.63; 95% confidence interval (CI), 0.47–0.83; P < 0.001; every-3-week arm: HR ¼ 0.69; 95% CI, 0.52–0.90; P ¼ 0.004]. In both trials, patients receiving pembrolizumab demonstrated statistically significant improvements in progression-free survival. The most common (2%) immune-mediated adverse reactions in a pooled safety analysis were hypothyroidism, pneumonitis, and hyperthyroidism. Key considerations for approval were determination of pembrolizumab dose and interpretation of t b d d i t i RECIST i l t ed RECIST.