In a Phase III randomized clinical trial (CheckMate 066) administration of nivolumab, a fully human IgG4 anti-PD-1, improved 1- and 2-year OS rate as compared to standard chemotherapy with dacarbazine in previously untreated patients with metastatic melanoma without BRAF mutation (73.0% versus 41.0% at 1 year and 56.7% versus 26.7% at 2 years) [43, 44]. This evidence concerns the gene BRAF and metastatic melanoma.