The SECOMBIT trial (NCT02631447) is evaluating the optimal sequencing of treatment in advanced BRAF mutant melanoma patients by randomizing patients 1:1:1 to first-line targeted BRAF and MEK inhibitors followed by ipilimumab and nivolumab at progression; upfront ipilimumab and nivolumab followed by targeted treatment at progression; or an initial run-in period of targeted treatment for eight weeks, followed by ipilimumab and nivolumab until progressive disease, then a switch back to targeted treatment [19,20]. This evidence concerns the gene BRAF and melanoma.