TPS4149 Background: Lysyl oxidase-like molecule 2 (LOXL2) is an extracellular matrix enzyme that catalyzes the covalent cross-linking of collagen and is widely expressed across desmoplastic tumors. Simtuzumab (GS-6624) is a humanized antibody that specifically inhibits LOXL2 enzymatic activity. Inhibiting LOXL2 is expected to block formation of desmoplasia, which is thought to play an important role in tumor progression and metastasis. Methods: The primary objective and of the study is to compare the additive efficacy of simtuzumab vs. placebo in combination with gemcitabine as measured by improvement in progression free survival (PFS). The secondary objective is to compare the additive efficacy of simtuzumab vs. placebo as measured by overall survival (OS) and objective response rate. Study Design: The study is a randomized, double-blind, placebo controlled Phase 2 trial in subjects with metastatic pancreatic adenocarcinoma. A total of 234 subjects will be randomized to 200 mg simtuzumab, 700 mg simtuzumab, or placebo at a 1:1:1 ratio (78 subjects per treatment group) in combination with gemcitabine in cycles of 28 days. In each cycle, subjects will receive IV GS-6624 or placebo infused on Days 1 and 15, and IV gemcitabine (1000 mg/m2) on Days 1, 8, and 15. CT or MRI scans will be performed every 8 weeks to evaluate response to treatment. Subjects will continue courses of treatment every 28 days in the absence of disease progression or unacceptable toxicity. As of January 30, 2013, 162 subjects have been randomized. Clinical trial information: NCT01472198.