The current first-line SoC treatment options for unresectable stage III/IV melanoma are PD-1 blockade (nivolumab, pembrolizumab), PD-1 blockade combined with CTLA-4 blockade (nivolumab–ipilimumab), PD-1 blockade combined with lymphocyte activation gene-3 (LAG-3) blockade (nivolumab–relatlimab) and, for BRAF V600-mutated melanoma, BRAFi (vemurafenib, dabrafenib, encorafenib) combined with MEKi (cobimetinib, trametinib, binimetinib). This evidence concerns the gene BRAF and melanoma.