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pazopanib + trametinib
- Development stage
- Phase 1
- Lead developer
- Novartis
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Combination of the multikinase VEGF pathway inhibitor pazopanib and the MEK1/2 inhibitor trametinib, investigated as an oral targeted therapy regimen to achieve vertical inhibition of the VEGF–RAS–RAF–MEK–ERK pathway in solid tumors. Pazopanib inhibits VEGFR1-3, PDGFR, KIT and related kinases to suppress angiogenesis, while trametinib inhibits MEK1/2 to block MAPK signaling downstream of receptor tyrosine kinases. Clinical studies reported tolerability at or near single-agent doses but generally modest activity in soft tissue sarcoma and cholangiocarcinoma, with some clinical activity observed in differentiated thyroid cancer expansion cohorts; additive or cumulative toxicity has been described. Typical dosing explored: pazopanib 800 mg once daily with trametinib 2 mg once daily, continuous 28‑day cycles.
- Brand names
- Votrient + Mekinist
- Other names
- pazopanib plus trametinibtrametinib plus pazopanib
02
Targets
BRAF (B-Raf proto-oncogene, serine/threonine kinase)CSF1R (Macrophage colony-stimulating factor receptor)FGFR1 (Fibroblast growth factor receptor 1)FGFR3 (Fibroblast growth factor receptor 3)ITK (Interleukin 2-inducible T-cell kinase)Kinase suppressor of Ras 1/2-mitogen-activated protein kinase kinase complex interface (KSR1/2-MEK complex interface)LCK (Proto-oncogene tyrosine-protein kinase Lck)MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)MEK2 (Dual specificity mitogen-activated protein kinase kinase 2)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)
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