PRIMARY OBJECTIVES:~I. To determine whether local consolidative therapy (LCT; radiotherapy +/- surgical resection, radiofrequency ablation, or cryoablation for up to 3 lesions) followed by up to 2 years of treatment with ipilimumab (1mg/Kg every 6 weeks) and nivolumab (3 mg/Kg, every 2 weeks) prolongs overall survival (OS) compared with up to 2 years treatment with ipilimumab (1mg/Kg every 6 weeks) and nivolumab (3 mg/Kg, every 2 weeks) alone in metastatic or recurrent non-small cell lung cancer (NSCLC) patients with non-progressive disease after 12 weeks of treatment with ipilimumab (1mg/Kg every 6 weeks) and nivolumab (3 mg/Kg, every 2 weeks).~II. Determine whether LCT followed by up to 2 years of treatment with ipilimumab (1mg/Kg every 6 weeks) and nivolumab (3 mg/Kg, every 2 weeks) prolongs overall survival compared with up to 2 years of treatment with ipilimumab (1mg/Kg every 6 weeks) and nivolumab (3 mg/Kg, every 2 weeks) alone in the subgroup of patients with oligometastatic NSCLC (up to 3 metastases) with non-progressive disease after 12 weeks of treatment with ipilimumab (1mg/Kg every 6 weeks) and nivolumab (3 mg/Kg, every 2 weeks).~SECONDARY OBJECTIVES:~I. To determine if there is a progression free survival (PFS) difference in the overall group and the oligometastatic group in patients that receive LCT + ipilimumab/nivolumab vs. ipilimumab/nivolumab alone.~II. To determine whether there is a PFS and (overall survival) OS difference in patients that undergo complete vs. non-complete LCT after 12 weeks of induction treatment with ipilimumab (1mg/Kg every 6 weeks) and nivolumab (3 mg/Kg, every 2 weeks).~III. To determine whether LCT improves time to progression of non-irradiated lesions (TTP-NIL) and time to appearance of new metastases (TANM) in the overall study population and the oligometastatic subgroup.~IV. To determine whether LCT improves the time to progression of target vs. non-target lesions in the overall study population and the oligometastatic subgroup.~V. To assess whether LCT prolongs PFS and OS in squamous histology and non-squamous histologies.~VI. To assess the safety and tolerability of nivolumab and ipilimumab with or without LCT.~VII. To assess quality of life patient reported outcomes in patients treated with nivolumab and ipilimumab with or without LCT.~VIII To explore the association of baseline genomic and gene expression profiles (from tumor, germline deoxyribonucleic acid [DNA], and cell free [cf] DNA) with clinical benefit and toxicities in patients treated with nivolumab and ipilimumab with or without LCT.~IX. To explore the association of baseline immune profiles (from tumor and blood) with clinical benefit and toxicities in patients treated with nivolumab and ipilimumab with or without LCT.~EXPLORATORY OBJECTIVE:~I. To identify novel prognostic and predictive markers present at diagnosis, and to determine modulation of markers by induction immunotherapy in order to inform future translational studies.~OUTLINE:~INDUCTION PHASE: Patients receive nivolumab intravenously (IV) over 90 minutes on days 1, 15, and 29, and ipilimumab IV over 60 minutes on day 1. Treatment repeats every 6 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.~Patients with non-progressive disease after completion of Induction Phase are randomized to 1 of 2 arms.~ARM A: Patients receive nivolumab IV over 60 minutes on days 1, 15, and 29 and ipilimumab IV over 90 minutes on day 1. Courses repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity.~ARM B: Patients receive LCT consisting of surgery and/or radiation 14 days after completion of Induction Phase. Patients then receive nivolumab and ipilimumab as in arm A beginning within 4 weeks after LCT. Courses repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 8 weeks and then every 3 months for up to 1 year.
This phase III trial studies how well nivolumab and ipilimumab works with or without local consolidation therapy in treating patients with stage IV non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Local consolidation therapy, such as surgery or radiation therapy, may improve survival outcomes in patients with non-small cell lung cancer. It is not yet known whether giving nivolumab and ipilimumab with local consolidation therapy works better than nivolumab and ipilimumab alone in treating patients with stage IV non-small cell lung cancer.