Background: The safety and efficacy of concurrent radiotherapy (SRS) and single agent (anti-PD-1) checkpoint inhibitor have not been established. We report the first results of an interim analysis from a prospective pilot phase II trial of cocurrent anti-PD-1 (pembrolizumab) and SRS for brain metastases Methods: Food and Drug Administration (FDA) and Institutional Review Board (IRB) approval were obtained to conduct a prospective trial with three different radiation dose arms (Arm A: 6 Gray (Gy) in 5 fractions (fx), 9 Gy in 3 fractions, and 18-21 Gy in single fraction) in combination with Pembrolizumab. Patients with not more than 10 brain metastasis who have not received prior brain radiation were eligible. Routine statistical methods were used to estimate control of brain metastases within the irradiated volume (local control, LC), anywhere intra-cranial control (AICC), progression free survival (PFS), and overall survival (OS). RECSIST 1.1 criteria were used to assess. Safety was monitored using NCI CTCAE v 4.0 criteria for toxicity assessment while intracranial and extracranial treatment response was assessed according to RECIST 1.1 criteria. Patients were enrolled from 2017-2020. Results: We report interim analysis from the first 18 patients of planned 36 patients who have completed treatments on each of the three different radiation dose arms (12 patients per arm). All patients received PD1 on day 0, immediately followed by SRS within 2-3 days. At 6 months, the LC (94.0% [CI: 65-99.1]), AICC (70.6% [CI: 43.1-86.65]), PFS (50% [24.5-71]), and OS (77.4% [50.3-90.9]) were higher than expected with either SRS alone or PD1 alone, and appear to be comparable to dual checkpoint, but with much less toxicity. No grade 4 or grade 5 toxicity was noted. The primary endpoint of safety, based on the absence of grade 3 CNS toxicity at 3 months was met with all three radiation dose arms. Overall rate of grade 1-3 toxicity was also within acceptable range. Conclusions: Preliminary prospective results of concurrent SRS and single agent pembrolizumab for brain metastases in melanoma and NSCLC supports this strategy as a safe and promising option compared with dual agent therapy. Clinical trial information: NCT02858869