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PF-03446962 + regorafenib
- Development stage
- Unknown
- Lead developer
- Pfizer
- Modality
- Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
- Administration
- Intravenous, Oral
01
Overview
PF-03446962 + regorafenib is an investigational combination therapy evaluated for the treatment of refractory metastatic colorectal cancer. PF-03446962 is a fully human monoclonal antibody that targets activin receptor-like kinase 1 (ALK-1), a type I receptor in the TGF-beta superfamily involved in angiogenesis. By inhibiting ALK-1, PF-03446962 disrupts tumor blood vessel formation. Regorafenib is an oral small molecule multikinase inhibitor that blocks several protein kinases involved in tumor angiogenesis (including VEGFR1/2/3), oncogenesis, and the tumor microenvironment. The combination was studied to assess whether dual inhibition of ALK‑1 and VEGF pathways could enhance anti-tumor activity; however, clinical trials found unacceptable toxicity and limited efficacy in patients with metastatic colorectal cancer[1][2][8].
- Brand names
- None
- Other names
- regorafenib + PF-03446962
02
Targets
BRAF (B-Raf proto-oncogene, serine/threonine kinase)KIT (c-KIT proto-oncogene receptor tyrosine kinase)PDGFRB (Platelet-derived growth factor receptor beta)RAF1 (c-Raf-1 (Y340D/Y341D))VEGFR3 (Vascular endothelial growth factor receptor 3)VEGFR2 (Vascular endothelial growth factor receptor 2)RET (Rearranged during transfection receptor tyrosine kinase)ACVRL1 (Activin receptor-like kinase 1)
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