Drug intelligence / Profile preview

dalantercept + axitinib

Development stage
Discontinued
Lead developer
Merck
Modality
Fc-Fusion Proteins → Carrier/Scaffold Proteins → Recombinant Proteins and Enzymes, Small Molecules
Administration
Subcutaneous, Oral
01

Overview

Dalantercept + axitinib is a combination therapy investigated for the treatment of advanced renal cell carcinoma (RCC). Dalantercept is a soluble activin receptor-like kinase 1 (ALK1) receptor fusion protein that acts as a ligand trap by binding bone morphogenetic proteins 9 and 10 (BMP9 and BMP10), thereby inhibiting signaling through the ALK1 pathway, which disrupts tumor angiogenesis. Axitinib is an oral small molecule tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptors (VEGFRs), blocking angiogenesis in tumors. The combination was evaluated in phase 2 clinical trials to determine if dual inhibition of ALK1/BMP and VEGF pathways could improve outcomes in RCC. While well tolerated, the addition of dalantercept to axitinib did not improve progression-free survival compared to axitinib alone[2][3][4][5][6][8].

02

Targets

BMP10 (Bone morphogenetic protein 10)BMP9 (Bone morphogenetic protein 9)PDGFRA (Platelet-derived growth factor receptor alpha)PDGFRB (Platelet-derived growth factor receptor beta)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)VEGFR4 (Vascular endothelial growth factor Receptor-3)KIT (c-KIT proto-oncogene receptor tyrosine kinase)ACVRL1 (Activin receptor-like kinase 1)

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