Phase I study of ACE-041, a novel inhibitor of ALK1-mediated angiogenesis, in patients with advanced solid tumors.

3070 Background: Activin receptor-like kinase-1 (ALK1) is a type I receptor in the TGFs superfamily expressed on endothelial cells and required for capillary network development and vasculature maturation. ACE-041 is a soluble fusion protein consisting of the ALK1 extracellular domain linked to IgG1-Fc and is designed to bind with high affinity to BMP9 and BMP10, preventing activation of ALK1 receptors. In animal models, ACE-041 inhibited tumor angiogenesis and growth. Methods: A standard 3 + 3 dose escalation phase I study was conducted to determine the safety, tolerability, MTD, PK, PD, and antitumor activity of ACE-041 in pts with advanced solid tumors. An expansion cohort was to be treated at MTD or intermediate dose level. Results: 37 pts were enrolled in 8 cohorts: 25 in dose escalation (0.1-4.8 mg/kg SC q3wk), 12 in dose expansion (0.8-1.6 mg/kg). Median age: 65 yr (34-84), 20M/17F, ECOG: 0 (43%)/1 (57%). Most common tumor types: colorectal (19%), NSCLC (16%), sarcoma (14%). Median # prior Rx: 3 (0...