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trametinib + sorafenib
- Development stage
- Phase 1
- Lead developer
- Moffitt Cancer Center
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Trametinib + sorafenib is a combination therapy investigated by the H. Lee Moffitt Cancer Center and Research Institute for the treatment of advanced hepatocellular carcinoma (HCC). Trametinib is a highly selective, reversible, allosteric inhibitor of MEK1 and MEK2, while sorafenib is a multikinase inhibitor that targets Raf kinases (C-Raf and B-Raf) and receptor tyrosine kinases involved in angiogenesis and tumor progression, such as VEGFR-1, -2, -3, PDGFR-beta, c-Kit, and FLT-3. The combination was evaluated in a Phase 1a/1b clinical trial (NCT02292173) to determine if dual inhibition of the MAPK pathway and other signaling cascades could overcome sorafenib resistance and improve outcomes in HCC. However, the study concluded that the combination showed limited anticancer activity in an unselected patient population, leading to the discontinuation of its development for this specific indication.
- Brand names
- Nexavar
- Other names
- trametinibsorafenib
02
Targets
BRAF (B-Raf proto-oncogene, serine/threonine kinase)RAF1 (c-Raf-1 (Y340D/Y341D))FLT3 (Fms related receptor tyrosine kinase 3)KIT (c-KIT proto-oncogene receptor tyrosine kinase)MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)MEK2 (Dual specificity mitogen-activated protein kinase kinase 2)PDGFRB (Platelet-derived growth factor receptor beta)RET (Rearranged during transfection receptor tyrosine kinase)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)VEGFR4 (Vascular endothelial growth factor Receptor-3)
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