Long-term follow-up results of CheckMate-067 demonstrate durable benefit of combination anti-programmed-death-1 (PD-1) and anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) therapy in the first-line setting for advanced melanoma.1 While efficacy of this regimen is impressive, grade 3 and higher treatment-related adverse events developed in 59% of patients, highlighting the need for safer approaches.1,2 Lymphocyte activation gene-3 (LAG-3) is a co-inhibitory receptor expressed on activated CD4+ and CD8+ T cells. The gene discussed is PDCD1; the disease is melanoma.