On May 26, 2020, the FDA approved nivolumab with ipilimumab and two cycles of platinum-doublet chemotherapy as first-line treatment for patients with metastatic or recurrent non–small cell lung cancer (NSCLC), with no EGFR or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. The approval was based on results from Study CA2099LA (CheckMate 9LA), an open-label trial in which 719 patients with NSCLC were randomized to receive nivolumab with ipilimumab and two cycles of chemotherapy (n = 361) or four cycles of platinum-doublet chemotherapy (n = 358). Overall survival (OS) was improved for patients who received nivolumab with ipilimumab and chemotherapy, with a median OS of 14.1 months [95% confidence interval (CI), 13.2–16.2] compared with 10.7 months (95% CI, 9.5–12.5) for patients who received chemotherapy (HR, 0.69; 96.71% CI, 0.55–0.87; P = 0.0006). Progression-free survival and overall response rate per blinded independent central review were also statistically significant. This was the first NSCLC application reviewed under FDA's Project Orbis, in collaboration with Singapore's Health Sciences Authority, Australia's Therapeutic Goods Administration, and Health Canada. The benefit–risk analysis supports FDA's approval of nivolumab with ipilimumab and chemotherapy.