Nivolumab and Radiation Therapy With or Without Ipilimumab in Treating Patients With Brain Metastases From Non-small Cell Lung Cancer

PRIMARY OBJECTIVES: I. To determine the recommended phase 2 dose (RP2D) of nivolumab with intracranial radiation and ipilimumab in combination with nivolumab and intracranial radiation in non-small cell lung cancer (NSCLC) with brain metastasis. (Phase I) II. To determine the RP2D of nivolumab in combination with stereotactic radiosurgery (SRS). (Phase I) III. To determine the RP2D of nivolumab in combination with whole brain radiation therapy (WBRT). (Phase I) IV. To determine the RP2D of ipilimumab in combination with nivolumab and SRS. (Phase I) V. To determine the RP2D of ipilimumab in combination with nivolumab and WBRT. (Phase I) VI. To estimate the 4-month intracranial progression free survival overall and within each treatment group; nivolumab and SRS; nivolumab and WBRT; nivolumab + ipilimumab and SRS; nivolumab + ipilimumab and WBRT. (Phase II) SECONDARY OBJECTIVES: I. To assess the potential neurocognitive changes in all treatment groups using the Hopkins Verbal Learning Revised (HVLT-R) total recall test. (Phase II) II. To estimate the rate of extracranial progression overall and within each treatment group. (Phase II) III. To estimate overall survival overall and within each treatment group. (Phase II) IV. To estimate the objective response rate of extracranial disease among all groups and within each treatment group. (Phase II) V. To estimate the duration of treatment response extracranially in patients who achieve an objective response. (Phase II) VI. To estimate steroid requirements in patients overall and within each treatment group. (Phase II) OUTLINE: This is a phase I, dose-escalation study of nivolumab followed by a phase II study. Patients are assigned to 1 of 4 groups. GROUP A: Patients receive nivolumab intravenously (IV) over 90 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo SRS once the day after nivolumab administration. GROUP B: Patients then receive nivolumab as in Group A. Patients undergo WBRT once daily for 10 days. GROUP C: Patients receive nivolumab as in Group A and ipilimumab IV over 90 minutes every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo SRS once the day after nivolumab administration. GROUP D: Patients receive nivolumab as in Group A and ipilimumab as in Group C. Patients undergo WBRT once daily for 10 days. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for up to 1 year.