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.
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.
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): 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 every 8 weeks for 1 year, and then every 12 weeks for up to 3 year.