Subjects will be randomized 2:1 and patients in both arms will begin treatment with nivolumab 360 mg intravenously every 3 weeks and ipilimumab 1 mg/kg intravenously every 6 weeks. At five weeks of treatment, subjects will have ctDNA response evaluation with Guardant360 Response assay. At the next cycle of treatment (+/- 2 days), patients in the larger arm will receive treatment based on the Guardant360 Response assay results, as described below. Subjects will undergo ctDNA evaluation with Guardant360 Response assay 6- week post-randomization and at the time of progression. Response to therapy will be assessed by interval imaging with CT scan of the chest/abdomen/pelvis (and MRI brain if applicable) with response evaluated by irRECIST criteria every 12 weeks until disease progression.
This clinical trial plans to assess to what extent the on-treatment circulating tumor DNA (ctDNA) can predict the subset of patients with NSCLC who will respond to immunotherapy treatment only and which patients will need both immunotherapy and chemotherapy modalities for their treatment regimen.