Different classes of checkpoint inhibitors are potentially complementary. Preliminary studies in melanoma and non-small cell lung cancer pts show improved response rates but also increased toxicity with combination PD-1 and CTLA-4 inhibition. CheckMate 067 was a 3-arm trial that randomized Tx-naïve melanoma pts to nivolumab (nivo, PD-1 inhibitor) plus ipilimumab (ipi, CTLA-4 inhibitor) f/b nivo vs. nivo alone vs. ipi alone. 3-yr OS was 58%, 52%, and 34% in combo, nivo alone and ipi alone groups. The overall HR was significantly better in the combo compared to both single agents. But, Tx-related G3-4 AEs occurred in 59% with combo, compared to 21% and 28% with nivo alone and ipi alone. (WolchokJD et al., NEJM 2017)