To determine the potential cooperative anti-tumor effects that could be induced by combining MC1R-targeted α-TRT and ICIs, [212Pb]VMT01 was administered as a monotherapy or in combination with dual ICIs (i.e., anti-CLTA-4 + anti-PD-1) in immunocompetent C57BL6 mice bearing B16-F10 syngeneic murine melanoma tumors (n = 7 in each cohort). This evidence concerns the gene MC1R and melanoma.