Background: The combination of durvalumab (D; anti–PD-L1) and tremelimumab (T; anti–CTLA-4) has the potential to amplify T-cell responses against tumors through immune checkpoint blockade, resulting in antitumor activity. Methods: This is an ongoing Phase Ib/II study in patients (pts) with metastatic or recurrent gastric or gastroesophageal junction carcinoma. An initial safety run-in was conducted in 6 pts who received D 20 mg/kg and T 1 mg/kg IV Q4W for 4 cycles followed by D 10 mg/kg Q2W for ≤12 mo. For Phase II expansion, all pts were immunotherapy naive and had progressed after systemic platinum- or fluoropyrimidine-based chemotherapy. Second-line (2L) pts were randomized 2:2:1 to D+T, D 10 mg/kg Q2W up to 12 mo, or T 10 mg/kg Q4W for 7 doses then Q12W for 2 doses. Third-line (3L) pts received D+T. Tumor cell PD-L1 expression was assessed by IHC (Ventana SP263). Results: As of Sept 13, 2017, 58 pts received D+T (35% PD-L1 > 1%), 24 pts received D (38% PD-L1 > 1%), and 12 pts received T (50% PD-L1 > 1%); median duration of follow-up was 9.2, 3.5, and 9.2 mo, respectively. Drug-related grade 3/4 adverse events (AEs) occurred in 17 pts (29%) who received D+T; most frequent was colitis (5%). Six (50%) and 4 (17%) pts had grade 3/4 AEs related to T or D alone, respectively. Ten pts (17%) who received D+T discontinued due to drug-related AEs; most frequent was colitis (5%). One pt (4%) with D and 4 pts (33%) with T discontinued due to drug-related AEs. There were no drug-related deaths. In the T cohort, 1 pt (8%) had a confirmed PR; progression-free survival (PFS) and overall survival (OS) rates are not presented due to small sample size. Clinical activity in the other cohorts is shown below. Conclusions: D+T has a manageable safety profile in 2L and 3L advanced gastric cancer, with encouraging OS versus D monotherapy. Clinical trial information: NCT02340975