Background: CTGF is overexpressed in PDAC and facilitates local desmoplasia, tumor survival and metastasis. FG-3019 is a CTGF-specific monoclonal antibody that decreases tumor growth and metastases and prolongs survival in the KPC mouse model of pancreatic cancer. This study evaluated safety and efficacy of FG-3019 with G/E in patients (Pts) with PDAC. Methods: FG-3019 was combined with G/E in Pts with previously untreated, measurable, Stage 3 or 4 PDAC. Cohorts 1−6 received FG-3019 Q2W at 3, 10, 15, 25, 35 or 45 mg/kg. Cohort 7 received 35 mg/kg on Day 1, then 17.5 mg/kg QW. Cohort 8 received 45 mg/kg on Day 1, then 22.5 mg/kg QW. Results: 75 Pts were enrolled. Baseline characteristics: Stage 3 / 4 (11/64); ECOG=0/1 (30/45). Median of 9 FG-3019 doses were administered (range: 1-73). FG-3019 was well tolerated with no DLT. MTD is > 45 mg/kg. Median OS was 9.4 months in the per-protocol population. Best RECIST response was 2(3%) CR, 8(11%) PR, 39(52%) SD, 12(16%) PD, (14 no RECIST data). OS generally correlated with FG-3019 exposure in Cycle 1. Day 15 C_min ≥ 150 ug/mL was associated with improved OS (p=0.03) and 1 year survival (p=0.03). CA 19.9 response was 52% (C_min ≥ 150) and 38% (C_min < 150). Pts with ascites had low C_min and poor OS. High FG-3019 doses with C_min >150 ug/mL appeared to improve OS. Baseline plasma CTGF correlated inversely with OS (p=0.006). In bivariate analysis, Day 15 C_min ≥ 150 ug/mL and baseline CTGF < median were associated with better survival (p=0.04 and 0.02 respectively). Greatest survival was in Pts with Day 15 C_min> 150 ug/mL and baseline CTGF < median. Conclusions: FG-3019 did not add to toxicity of G/E. Results suggest OS improves with increasing exposure to FG-3019, and the combination of baseline CTGF and plasma FG-3019 levels could be a predictor of efficacy. Given its advantageous safety profile, FG-3019 could be combined with other chemotherapeutic regimens. Clinical trial information: NCT01181245.