Phase Ii Randomized Study Of Dalantercept In Combination With Axitinib Compared To Axitinib Alone As Second-Line Treatment In Patients With Metastatic Renal Cell Carcinoma.

TPS4595 Background: The treatment of metastatic renal cell cancer (mRCC) with therapies targeting the vascular endothelial growth factor (VEGF) pathway delays disease progression; however, overcoming tumor resistance to these agents remains a therapeutic challenge. Activin receptor-like kinase 1(ALK1) is a type 1 receptor in the TGF-s superfamily and is selectively expressed on activated endothelial cells. While VEGF drives the proliferative stage of angiogenesis, ALK1 is primarily involved in the maturation phase. Dalantercept is a human ALK1-Fc receptor fusion protein that binds to bone morphogenetic proteins (BMP) 9 and 10 (ligands for ALK1) and acts as a ligand trap. Preclinically, dalantercept showed delayed tumor growth in solid tumor models, including RCC models alone and in combination with sunitinib. In RCC models, the addition of dalantercept to sunitinib enhanced the reduction in tumor blood flow compared to sunitinib alone. Dalantercept showed anti-tumor activity in a completed phase 1 study i...