e16505 Background: Recent studies demonstrated that TGF-β signaling attenuation in combination with paclitaxel inhibits epithelial-to-mesenchymal transition and cancer stem-like cells features, especially in diffuse type. We are reporting dose finding part in phase 1b study evaluating the combination of vactosertib, a highly selective and potent TGF-β inhibitor, with paclitaxel as a second line treatment in patients with metastatic gastric adenocarcinoma (GA). Methods: Eligible patients (pts) are ≥19 years old, have ECOG status ≤1, and have progressed on the first line treatment of metastatic GA treated with the combination therapy of fluoropyrimidine and platinum, or trastuzumab containing combination therapy in HER2-positive GA. The primary objective is to assess the safety and recommended phase 2 dose (RP2D) of vactosertib given 5 days on/2 days off in combination with weekly paclitaxel 80 mg/m2. Three dose levels of vactosertib (100, 200, and 300 mg BID) were tested. Results: As of Jan. 25, 2020, 12 pts were enrolled to the study (6, 3, and 3 pts in 100, 200, and 300 mg BID, respectively) and finished the safety evaluation. Median age was 50 (range, 39-65), 50% were male, and 75% had gastrectomy (4 pts with subtotal gastrectomy; 5 pts with total gastrectomy). At all cohorts, no dose limiting toxicity was observed. The most frequently reported treatment related adverse events (AEs) were anemia (50.0%), anorexia (41.6%), fatigue (33.3%), and urticaria (33.3%). AEs were mostly grade 1 or 2 and manageable. One case of grade 3 anorexia was reported as a treatment-related severe adverse event. Among 6 evaluable patients in 200/300 mg BID cohorts, the best responses to treatment were partial response in 1 patient; 57% decrease from baseline, 16.7% of overall response rate, and 83.3% of disease control rate at 12 weeks. Median progression free survival of the RP2D cohort has not been reached yet. Updated safety, PK, efficacy and biomarker data will be presented at the meeting. Conclusions: The combination of vactosertib plus paclitaxel has been well tolerated. The anti-tumor activity of this combination in patients with metastatic GA is now under exploration in the phase 2a part of the study. Clinical trial information: NCT03698825 .