Randomized phase II study of pembrolizumab after stereotactic body radiotherapy (SBRT) versus pembrolizumab alone in patients with advanced non-small cell lung cancer: The PEMBRO-RT study.

9023 Background: High dose radiation can lead to increased tumor antigen release, improved antigen presentation and T-cell infiltration. It may therefore enhance the effects of checkpoint inhibition. We evaluated if stereotactic body radiation therapy (SBRT) on a single metastasis preceding pembrolizumab treatment in patients with NSCLC is well tolerated and leads to an increased tumor response. Methods: Patients (n = 74) with advanced NSCLC (≥2nd line) regardless of PD-L1 status were randomized (1:1) between pembrolizumab (200mg q3w) alone (control arm) or pembrolizumab preceded by SBRT (3x8Gy within 7 days prior to the first cycle) on a single metastasis (experimental arm). Sequential biopsies were obtained from the same, non-irradiated tumor site at baseline and after two cycles of pembrolizumab. The primary endpoint was improvement in overall response rate (ORR) at 12 weeks from 20% in the control arm to 50% in the experimental arm according to RECIST 1.1. Results: From July 2015 until the time of writing, 72 patients had been randomized and 64 patients who received at least one cycle of pembrolizumab could be evaluated for the primary endpoint. ORR at 12 weeks was 19% in the control arm (n = 32) vs 41% in the experimental arm (n = 32); the number of patients with a CR, PR, SD and PD were 0/6/7/19 and 1/12/6/13, respectively. Median PFS was 1.8 months in the control arm vs 6.4 months in the experimental arm; HR 0.55 (CI 0.31 – 0.98, p = 0.04). Grade ≥3 toxicity was experienced in 22% of patients in the control arm vs 17% in the experimental arm. The most common AEs were fatigue, nausea, fever and hypothyroidism. No increase in treatment related toxicity was observed in the experimental arm. Conclusions: With 86% of patients evaluable, we conclude that pembrolizumab preceded by SBRT resulted in a doubling of the ORR without increase in toxicity. The primary endpoint of 50% DCR was not (yet) met. This is a well-tolerated and promising treatment strategy to augment the anti-tumor immune response with checkpoint blockade. Definitive results as well as correlations with PD-L1 expression will be available and discussed at ASCO. Clinical trial information: NCT02492568.