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afatinib + nintedanib
- Development stage
- Phase 2
- Lead developer
- Boehringer Ingelheim
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
A combination of two oral small-molecule tyrosine kinase inhibitors used investigationally together in solid tumors. Afatinib is an irreversible ErbB family blocker that covalently inhibits EGFR (ErbB1), HER2 (ErbB2), and HER4, thereby suppressing signaling across ErbB homo- and heterodimers and downstream proliferation pathways. Nintedanib is a triple angiokinase inhibitor that competitively inhibits VEGFR-1/2/3, PDGFR-α/β, and FGFR-1/2/3, exerting anti-angiogenic and anti-fibrotic effects; it also has activity against additional kinases such as FLT3 and Src family kinases. The combo has been explored in early-phase trials across advanced solid tumors (e.g., establishing MTDs for continuous afatinib plus nintedanib), with limited activity in unselected castration-resistant prostate cancer on sequential schedules. Primary rationale is dual blockade of tumor cell ErbB signaling and tumor microenvironment/angiogenesis pathways.
- Brand names
- Vargatef
- Other names
- nintedanibafatinib
02
Targets
EGFR (Epidermal growth factor receptor)FLT3 (Fms related receptor tyrosine kinase 3)ERBB2 (Erb-b2 receptor tyrosine kinase 2)ERBB4 (Erb-b2 receptor tyrosine kinase 4)LCK (Proto-oncogene tyrosine-protein kinase Lck)LYN (LYN proto-oncogene, Src family tyrosine kinase)SRC (Proto-oncogene tyrosine-protein kinase Src)FGFR3 (Fibroblast growth factor receptor 3)FGFR1 (Fibroblast growth factor receptor 1)FGFR2 (Keratinocyte growth factor receptor)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)
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