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 and overall survival of combination SRS and pembrolizumab compared to SRS alone (historical control).~III. To determine the overall response rate and overall survival of combination SRS and pembrolizumab compared to pembrolizumab alone (historical control).~IV. To evaluate treatment response at un-irradiated and extra-cranial sites (i.e. the abscopal effect) with all three arms.~V. 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.
This pilot trial studies the side effects of giving pembrolizumab together with stereotactic radiosurgery to treat patients with melanoma or non-small cell lung cancer that has spread to the brain. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Giving pembrolizumab together with stereotactic radiosurgery may be a better treatment for patients with melanoma or non-small cell lung cancer that has spread to the brain.