nivolumab plus ipilimumab (n=72) vs. ipilimumab alone (n=37)
randomized controlled trial
nivolumab and ipilimumab
nivolumab (1 mg per kilogram) and ipilimumab (3 mg per kilogram of body weight) combined once every 3 weeks for four doses followed by nivolumab (3 mg per kilogram) every 2 weeks until the occurrence of disease progression or unacceptable toxic effects
ipilimumab
ipilimumab (3 mg per kilogram of body weight) combined once every 3 weeks, nivolumab was replaced with matched placebo during both the combination and maintenance portions of the trial.
After the fourth dose of both agents, ipilimumab was discontinued, and thereafter (maintenance phase), nivolumab was administered as a single agent at a dose of 3 mg per kilogram over a period of 60 minutes, once every 2 weeks.
mML - L1 - BRAF wild
Other inclusion criteria included a known BRAF V600 mutation status, and the availability for immunohistochemical assessment of PD-1 ligand (PD-L1) expression.
double-blind
United States and France
P2/ two sided test procedure without interim analysis. The primary end point was the rate of investigator-assessed, confirmed objective response among patients with BRAF V600 wild-type tumors. In order to preserve an experiment-wide type I error rate of 5%, a hierarchical testing approach was applied to key secondary end points. A hierarchical testing approach was applied to key secondary end points : ORR WT then ORR ITT then PFS WT then PFS ITTNo statistical analysis planned for BRAF mutant population
The objective-response rate and the progression-free survival among patients with advanced melanoma who had not previously received treatment were significantly greater with nivolumab combined with ipilimumab than with ipilimumab monotherapy. (in BRAFwild and all population)