To intensify immune response, two studies (CheckMate-651 and Kestrel) are currently testing the efficacy of the combination of anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and anti-PD-L1 agents versus the EXTREME regimen for first-line R/M HNSCC. The gene discussed is CTLA4; the disease is head and neck squamous cell carcinoma.