A randomized phase III study (NCT02224781) is going to evaluate which regimen is better in treatment of patients with stage III/IV unresectable or metastatic melanoma harboring BRAFV600E/K mutation, MEK and BRAF inhibition (trametinib plus dabrafenib) followed by PD-1 and CTLA-4 blockade (nivolumab plus ipilimumab) or PD-1 and CTLA-4 blockade (nivolumab plus ipilimumab) followed by MEK and BRAF inhibition (trametinib plus dabrafenib). The gene discussed is CTLA4; the disease is metastatic melanoma.