FDA Approval summary: accelerated approval of pembrolizumab for second-line treatment of metastatic melanoma

Abstract

On September 4, 2014, the FDA approved pembrolizumab responses were ongoing. The most common (20%) adverse (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended reactions were fatigue, cough, nausea, pruritus, rash, decreased dose of 2 mg/kg every 3 weeks by intravenous infusion for the appetite, constipation, arthralgia, and diarrhea. Immune-mediated treatment of patients with unresectable or metastatic melanoma adverse reactions included pneumonitis, colitis, hepatitis, hypo-who have progressed following treatment with ipilimumab and, if physitis, and thyroid disorders. The benefits of the observed ORR BRAF V600 mutation positive, a BRAF inhibitor. Approval was with prolonged duration of responses outweighed the risks of based on demonstration of objective tumor responses with pro-immune-mediated adverse reactions in this life-threatening dis-longed response durations in 89 patients enrolled in a random-ease and represented an improvement over available therapy. ized, multicenter, open-label, dose-finding, and activity-estimat-Important regulatory issues in this application were role of dura-ing phase 1 trial. The overall response rate (ORR) by blinded bility of response in the evaluation of ORR for accelerated approv-independent central review per RECIST v1.1 was 24% (95% al, reliance on data from a first-in-human trial, and strategies for confidence interval, 15–34); with 6 months of follow-up, 86% of dose selection.