Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer (NSCLC)

Patients with unresectable stage IIIA or IIIB NSCLC (unresectable as defined by treating physician) will be treated outside this study with concurrent chemoradiation with one of three chemotherapy regimens (cisplatin/etoposide, cisplatin/pemetrexed, or weekly carboplatin/paclitaxel) in addition to standard dose radiation (dosing can range from 59.4 Gy to 66.6 Gy). If repeat imaging between 28-56 days following completion of chemoradiation shows no progressive or metastatic disease, the patients will be eligible for enrollment on the study. Randomization and Stratification: At the time of enrollment, patients will be randomized in a 1:1 fashion to receive either nivolumab 480mg IV every 4 weeks or the combination of nivolumab 3mg/kg IV every 2 weeks with ipilimumab 1mg/kg IV every 6 weeks. Consolidation immunotherapy will be continued until progression or unacceptable toxicity for up to a total of 24 weeks. Subjects will be stratified by stage (IIIA vs. IIIB) and histology (squamous vs. non-squamous). Dose Calculations: Arm 1: The dose of nivolumab will be a fixed dose (not based on subject's weight) at 480mg. Arm 2: The dose of nivolumab will be weight-based at 3mg/kg. The dose of ipilimumab will be weight-based at 1mg/kg. Nivolumab Alone (Arm 1): Arm 1: Nivolumab Administration: Nivolumab 480 mg will be administered as a 60 minute IV infusion on Day 1 of each 28 day cycle. Sites should make every effort to target infusion timing to be as close to 60 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10 min). Treatment will continue for up to 6 cycles, in the absence of prohibitive toxicities or disease progression. Nivolumab Plus Ipilimumab (Arm 2): Arm 2: Nivolumb Administration: Nivolumab 3mg/kg will be administered as a 60 minute IV infusion on Day 1, 15, and 29 of each 42 day cycle. Nivolumab should not be given any earlier than 12 days from the previous dose. Sites should make every effort to target infusion timing to be as close to 60 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10 min). Treatment will continue for up to 4 cycles, in the absence of prohibitive toxicities or disease progression. Arm 2: Ipilimumab Administration: Ipilimumab 1mg/kg will be administered as a 90 minute IV infusion on Day 1 of each 42 day cycle. Sites should make every effort to target infusion timing to be as close to 90 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -five minutes and +10 minutes is permitted (i.e., infusion time is 60 minutes: -5 min/+10 min). Treatment will continue for up to 4 cycles, in the absence of prohibitive toxicities or disease progression. On day 1 of cycle 1, nivolumab will be given first, followed by 30 minutes of monitoring, and then ipilimumab given second, followed by 30 minutes of monitoring. If the subject does not have an infusion reaction during the first cycle, the post-ipilimumab monitoring may be discontinued for subsequent cycles at the discretion of the treating physician. Day 1 monitoring between the nivolumab/ipilimumab infusions will continue throughout all 4 cycles. Post nivolumab monitoring on days 15 and 29 is not mandatory and should follow the guidelines of the local infusion center.