The phase II and III trials of PD-1 inhibitors in melanoma that followed, including KEYNOTE-006, KEYNOTE-002, CheckMate 037, CheckMate 069, and CheckMate 067, provided the basis to expand FDA approval of these PD-1 inhibitors as first-line therapy for untreated advanced melanoma regardless of BRAF mutation status, for ipilimumab-refractory melanoma, and in combination with ipilimumab as first-line therapy for unresectable or metastatic melanoma (nivolumab) (71, 192, 193). This evidence concerns the gene PDCD1 and melanoma.