Dovitinib: A Pan-Tyrosine Kinase Inhibitor
Dovitinib is a pan-tyrosine kinase inhibitor targeting fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR) and other receptor tyrosine kinases (RTKs). Allarity exclusively in-licensed it (globally) from Novartis, who had completed a Phase 3 study in renal cell carcinoma (RCC) in addition to several promising Phase 2 studies in breast, liver and endometrial cancer and GIST.
The Dovitinib DRP® is validated in 5 different cancers: RCC, gastrointestinal stromal tumor (GIST), liver (HCC), metastatic breast, and endometrial.
How it Works
Dovitinib binds to and inhibits the phosphorylation of type III-V RTKs, such as vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) that promote tumor cell proliferation and survival in certain cancer cells. In addition, this agent also inhibits other members of the RTK superfamily, including fibroblast growth factor receptor 1 and 3, FMS-like tyrosine kinase 3, stem cell factor receptor (c-KIT), and colony stimulating factor receptor 1. This may further lead to a reduction of cellular proliferation and angiogenesis, and an induction of tumor cell apoptosis.
The DRP® for dovitinib was able to identify responding patients, pointing towards a 2-4-fold higher response rate if compared with dovitinib when used without prior DRP® screen. Thus, the results give dovitinib a significant advantage in comparison to other comparable products.
Before being in-licensed by Allarity, dovitinib – in a Phase 3 trial in metastatic renal cell carcinoma – achieved therapeutic equivalence with the current standard of care, sorafenib. Earlier stage studies explored its potential utility in multiple therapeutic indications including liver cancer, breast cancer and various solid tumors.