Dovitinib is an investigational orally active small molecule multi-kinase inhibitor that exhibits potent activity against multiple RTKs involved in tumor growth and angiogenesis.
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.
Following the in-licensing of dovitinib, Oncology Venture got access to biopsy and gene expression data from several of Novartis’ dovitinib studies. In total, Oncology Venture obtained access to information from more than 2,500 patients.
Subsequently, this information has been analyzed in order document the ability of the dovitinib DRP® to track, match and treat those patients where dovitinib is a relevant therapy. This data-mining process was successfully concluded in early 2019 for renal cancer and endometrial cancer.
In both cases, the DRP® for dovitinib was able to identify responding patients. These DRP data-mining results point 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 Oncology Venture, 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.
A molecular model of dovitinib
The dovitinib DRP was developed using biopsies taken during Novartis’ clinical trial program, which spanned multiple cancer indications. OV applied its DRP to the samples in a blinded to proof-of-concept study to assess its ability to identify likely responders to dovitinib. The study found a consistent signal that is indicative of the biomarker’s ability to spot responders.
OV will further refine the Dovitinib DRP biomarker to hone its predictive ability by analyzing data from additional biopsies and genomic data sets from other previous, relevant clinical studies with this promising compound.
Other drugs with a comparable method of action:
- Lenvatinib, a drug acting as a multiple kinase inhibitor, marketed as Lenvima by a partnership between Novartis and Eisai (Lenvatinib was the subject of a deal with an estimated value of up to USD 5.8 billon)