Pembrolizumab and Stereotactic Radiosurgery for Melanoma or Non-Small Cell Lung Cancer Brain Metastases

PRIMARY OBJECTIVE: I. To determine the safety of three different stereotactic radiosurgery (SRS) radiation arms in combination with pembrolizumab for melanoma and non-small cell lung cancer (NSCLC) brain metastasis (BM) patients. SECONDARY OBJECTIVES: I. To evaluate intracranial outcomes - control of the treated lesion in the brain with SRS+ pembrolizumab (i.e. local control), development of additional sites of disease in the brain that were not initially treated with SRS (i.e. anywhere intra-cranial failure), intra-cranial progression free survival (local control of the area that received SRS and anywhere intra-cranial failure), extra-cranial disease response (overall progression free survival), rate of leptomeningeal dissemination, and overall survival. II. To determine the overall response rate of combination SRS and pembrolizumab compared to SRS alone (historical control). III. To determine the overall survival of combination SRS and pembrolizumab compared to pembrolizumab alone (historical control). IV. To evaluate the rate of recurrence at un-irradiated and extra-cranial sites with all three arms. V. Rate of symptomatic radiation necrosis defined as evidence of necrosis on MRI images (radiographic evidence or radionecrosis) and a patient having neurological symptoms attributed to the location where the radiosurgery was done. VI. To compare differences in potential immune biomarkers, pretreatment, during treatment, and post treatment. OUTLINE: Patients are assigned to 1 of 3 arms. ARM A (SRS 6 Gy, CLOSED): Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 3 weeks (Q3W) for at least 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo 5 SRS fractions between days 2-15 of course 1. ARM B (SRS 9 Gy): Patients receive pembrolizumab IV as in Arm A. Patients undergo 3 SRS fractions between days 2-15 of course 1. ARM C (SRS 18-21 Gy): Patients receive pembrolizumab IV as in Arm A. Patients undergo 1 SRS fraction between days 2-3 of course 1. After completion of study treatment, patients are followed up at 30 days, then every 12 weeks for up to 1 year.