DART Study: A phase II randomized trial of dalantercept plus axitinib versus placebo plus axitinib in advanced clear cell renal cell carcinoma (RCC): Results from Part 1.

407 Background: Activin receptor-like kinase 1 (ALK1) is a novel target in angiogenesis involved in blood vessel maturation and stabilization. Concurrent targeting of ALK1 and vascular endothelial growth factor (VEGF) signaling results in dual angiogenic blockade and augmented inhibition of tumor growth in RCC xenograft models. Dalantercept (Dal) is an ALK1 receptor-fusion protein that acts as a ligand trap and has demonstrated monotherapy activity with an acceptable safety profile in a completed phase I study. Methods: Part 1 of this study evaluated the safety, tolerability, and preliminary activity of escalating dose levels of Dal plus fixed dose axitinib in pts with advanced RCC. 3-6 pts each received Dal (0.6, 0.9, or 1.2 mg/kg) SC Q3W and axitinib 5 mg PO BID. Key eligibility: predominantly clear cell RCC, 1 prior VEGFR TKI, ≤3 prior tx. Results: As of September 12, 2014, 29 pts were enrolled in three cohorts (n=6, 9, 14) at dose levels of 0.6, 0.9 and 1.2 mg/kg, respectively. At the 1.2 mg/kg dose l...