The DART Study: A phase 2 randomized double-blind study of dalantercept plus axitinib versus placebo plus axitinib in advanced clear cell renal cell carcinoma (RCC)

TPS4583 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 is an ALK1 receptor-fusion protein that acts as a ligand trap by binding to ligands, bone morphogenetic proteins (BMP) 9 and 10. Part 1 of this study evaluated the safety, tolerability, and preliminary activity of escalating dose levels of dalantercept (0.6, 0.9, and 1.2 mg/kg) plus standard doses of axitinib (5 mg PO BID) every 3 weeks in patients with advanced RCC who received at least one prior VEGFR TKI and no more than 3 prior tx. 29 pts were enrolled in Part 1 and the combination was associated with an acceptable safety profile and preliminary activity (25% RR, preliminary median PFS of 8.3 months for all dose levels combined). The mPFS for the 0.9mg/kg dose ...