Background: GS-5745 is a monoclonal antibody inhibitor of matrix metalloproteinase 9 (MMP9), an extracellular enzyme involved in matrix remodeling, tumor growth, and metastasis. We present updated data from a phase I study of patients (pts) with advanced gastric/gastroesophageal adenocarcinoma (GC) treated with GS-5745 and mFOLFOX6 (NCT01803282). Methods: Following a monotherapy dose finding stage, pts with Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced or metastatic GC received mFOLFOX6 and GS-5745 (800 mg IV) every 2 weeks. Treatment continued until disease progression, unacceptable toxicity or withdrawal of consent. Response was assessed every 8 weeks per RECIST version 1.1 criteria. Results: As of April 2016, 40 pts were enrolled in the expanded cohort (12 continue to receive GS-5745). The most frequently observed adverse events (AEs) of any grade include nausea (62.5%), fatigue (60%), diarrhea (45%), peripheral neuropathy (45%) and neutropenia (37.5%). Grade ≥ 3 AEs observed in ≥ 10% of pts include neutropenia (20%) and nausea and neutrophil count decreased (10% each). Among 29 treatment naïve pts, median progression free survival (PFS) is 12 (90% confidence interval (CI) 5.5-18) months (mos), median duration of response (DOR) 10.6 mos and objective response rate (ORR) of 55.2%. For all pts (n=40), PFS is 7.8 (90% CI 5-13.9) mos, median DOR 10.1 mos and ORR of 50%. Median baseline circulating MMP9 was 44.7 (range 16.8-1395.3) ng/mL and all 34 patients with post-baseline samples had undetectable MMP9 levels within 8 weeks. Conclusions: The combination of GS-5745 with mFOLFOX6 is well tolerated and demonstrates activity, particularly in treatment naïve pts. Reduction in circulating MMP9 level after treatment with GS-5745 suggests specific target engagement. A phase III registration study of mFOLFOX6 +/- GS-5745 in treatment naïve metastatic GC pts is underway. Clinical trial information: NCT01803282