BACKGROUND: Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and 
ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint 
inhibitor) have been shown to have complementary activity in metastatic 
melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or 
nivolumab plus ipilimumab was compared with ipilimumab alone in patients with 
metastatic melanoma.
METHODS: We assigned, in a 1:1:1 ratio, 945 previously untreated patients with 
unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus 
ipilimumab, or ipilimumab alone. Progression-free survival and overall survival 
were coprimary end points. Results regarding progression-free survival are 
presented here.
RESULTS: The median progression-free survival was 11.5 months (95% confidence 
interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 
months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease 
progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 
to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 
99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 
ligand (PD-L1), the median progression-free survival was 14.0 months in the 
nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with 
PD-L1-negative tumors, progression-free survival was longer with the combination 
therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 
5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 
4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in 
the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group.
CONCLUSIONS: Among previously untreated patients with metastatic melanoma, 
nivolumab alone or combined with ipilimumab resulted in significantly longer 
progression-free survival than ipilimumab alone. In patients with PD-L1-negative 
tumors, the combination of PD-1 and CTLA-4 blockade was more effective than 
either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 
ClinicalTrials.gov number, NCT01844505.).