In this study, the combination of cobolimab and dostarlimab in patients with locally advanced or metastatic melanoma is reported, including for patients not previously treated with anti–PD-1 therapy (i.e., PD-1–naïve; parts 1c/1e) and patients whose disease had progressed on prior anti–PD-(L)1 treatment (part 2A). Here, PDCD1 is linked to metastatic melanoma.