On September 30, 2015, the U. S. Food and Drug Administration granted accelerated approval to nivolumab (Opdivo Injection, Bristol-Myers Squibb Company) in combination with ipilimumab for the treatment of patients with BRAF V600 wild-type, unresectable or metastatic melanoma.
Approval was based on demonstration of an increase in the objective response rate (ORR), prolonged response durations, and improvement in progression-free survival (PFS) in an international, multicenter, double-blind, randomized, two-arm, active-controlled trial in patients who were previously untreated for unresectable or metastatic, BRAF V600 wild-type melanoma.
The clinical trial randomized (2:1) 142 patients to receive nivolumab plus ipilimumab (n=95) or ipilimumab plus placebo (n=47). Randomization was stratified by BRAF V600 mutation status based on an FDA-approved test. Patients in the nivolumab plus ipilimumab arm received nivolumab 1 mg/kg and ipilimumab 3 mg/kg intravenously every 3 weeks for four doses, then nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Patients in the ipilimumab arm received ipilimumab 3 mg/kg and nivolumab-matched placebo intravenously every 3 weeks for four doses followed by placebo. At the time of disease progression, patients on the ipilimumab arm were offered nivolumab 3 mg/kg every 2 weeks.
Of the 109 patients with BRAF V600 wild-type melanoma, the median age was 66 years and ECOG performance score was 0 (84%) or 1 (15%). Forty-six percent had M1c disease and 20% had elevated baseline LDH.
The trial demonstrated a significant improvement in ORR. The ORR was 60%