Among patients treated with first-line nivolumab plus chemotherapy (n = 269), those with high tumor mutational burden (TMB; ≥10 mutations per megabase) had improved overall survival (<i>v</i> the low TMB subgroup; hazard ratio [HR], 0.48 [95% CI, 0.25 to 0.93]; <i>P</i> = .03), particularly when combined with PD-L1 positivity (<i>v</i> all other biomarker-defined subgroups; HR, 0.33 [95% CI, 0.14 to 0.76]; <i>P</i> = .006). The gene discussed is CD274; the disease is neoplasm.