Background: Preclinical evidence suggests simultaneous blockade of vascular endothelial growth factor receptor 2 (VEGFR-2) and programed cell death 1 protein (PD-1) induces synergistic antitumor effects. We assessed safety and preliminary efficacy of ramucirumab (anti-VEGFR-2) plus pembrolizumab (anti-PD-1) in patients (pts) with treatment naïve advanced G/GEJ adenocarcinoma. Methods: This ongoing, multi-cohort, phase 1a/b trial enrolled ECOG PS 0-1 pts with treatment naïve advanced G/GEJ adenocarcinoma with measurable disease and baseline tumor tissue. PD-L1 status was assessed by DAKO PD-L1 22C3 IHC pharmDx assay using the combined positive score with ≥1% being positive. Ramucirumab was administered at 8 mg/kg on Days 1 & 8 with pembrolizumab 200 mg on Day 1 q3W. Primary objective was safety and tolerability of study treatment; preliminary efficacy was examined. Results: As of 31-July-2017, 28 treatment naïve G/GEJ adenocarcinoma pts were treated. Median age was 63 y, 75% male, 57% had ECOG PS of 0, and 68% were PD-L1 positive. At data cutoff, 8 (28%) pts continued to receive study treatment. Median duration of follow-up was 8.1 mo (IQR 6-10). Median treatment duration was 4.3 mo (IQR 2-7). All grades treatment-related adverse events (TRAEs) occurred in 27 (96%) of patients; TRAEs in ≥15% of pts were fatigue (36%), hypertension (25%) and headache (18%). Seventeen (61%) pts experience grade 3 TRAEs, most commonly hypertension (14%), diarrhea (11%), and elevated alanine (7%) or aspartate (7%) aminotransferase. No grade 4-5 TRAEs occurred. An objective response was achieved by 7 (25%) pts, 6 positive and 1 negative for PD-L1. Disease control rate was 68%. Median time to response was 2.7 mo (95% CI 1.3-2.8) and median duration of response was 10 mo (95% CI 9.7-10.3). Median progression-free survival was 5.3 mo (95% CI 3.2-11). Median overall survival has not been reached. Conclusions: Ramucirumab plus pembrolizumab demonstrated encouraging antitumor activity in treatment naïve advanced G/GEJ adenocarcinoma with no grade 4 TRAE observed. Clinical trial information: NCT02443324