Background: Connective tissue growth factor (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 orthotopic and KPC mouse models. This study evaluates safety and efficacy of FG-3019 with gemcitabine/erlotinib in patients with PDAC. Methods: In a nongoing open-label, dose-escalation study, FG-3019 was used in combination with gemcitabine and erlotinib in patients with previously untreated, measurable, locally advanced or metastatic 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 and then 17.5 mg/kg QW. Cohort 8 received 45 mg/kg on Day 1 and then 22.5 mg/kg QW. Results: 75 patients were enrolled at 7 centers. Baseline data: Stage III= 15, Stage IV=60; ECOG=0 (n=32), ECOG=1 (N=43). No SAEs or DLTs related to FG-3019 occurred at any dose. In per protocol population (n=68) median PFS and OS were 4.3 and 9.4 months respectively. Baseline plasma CTGF levels correlated inversely with PFS and OS (p=0.0029) (ITT population). Median FG-3019 Cmax and Cmin increased linearly with dose. Because of considerable overlap between subjects across cohorts, outcomes are correlated with drug exposure. OS, but not PFS, correlated with exposure after the first FG-3019 dose (Day 1 Cmax, p=0.009; Day 15 Cmin, p=0.005; ITT population). 47% of evaluable subjects had >50% decrease in CA19.9.The magnitude of reduction correlated with Day 1 Cmax (p=0.04) and inversely with baseline plasma CTGF (p=0.01). As FG-3019 accumulated over time, minimum FG-3019 exposure (Cmin) of 150 ug/mL on Day 43 appeared to be a threshold. Median OS was 7.7 and >8.6 months for subjects < (n=15) or ≥ (n=43) 150 ug/mL respectively on Day 43 (p=0.0034). Day 43 Cmin < 150, none alive at 12 months: Day 43 Cmin >150, 8 alive at 12 months, 17 alive 6.7-12 months. Conclusions: FG-3019 combined with gemcitabine/erlotonib is well tolerated. Interim results in this open-label study suggest OS improves with increasing exposure to FG-3019. Clinical trial information: NCT01181245.