Abstract 784: Nonclinical activity of the FGFR, VEGFR and PDGFR inhibitor lucitanib in FGFR3 translocated tumor models

Lucitanib (S 80881, E-3810, CO-3810) is an oral, potent inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors 1 through 3 (FGFR1-3), vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3) and platelet-derived growth factor receptors alpha and beta (PDGFRα-ß). A Phase 1/2 clinical study (Soria et al., 2014, Ann. Oncol. 25(11):2244-51) showed compelling activity of lucitanib in solid tumors and, in particular, a 50% (6 of 12 patients) RECIST partial response rate in breast cancer patients with FGF-aberrant (FGFR1 and/or FGF3/4/19 gene amplified) tumors. On-going clinical studies are further defining the activity of lucitanib in breast (NCT02053636; NCT02202746) and lung cancer (NCT02109016). FGFR gene translocations (fusions; e.g. FGFR3-TACC3) resulting in constitutively active FGFR signaling and tumor proliferation are observed in a wide variety of cancers (Stransky et al., 2014; Nat. Comm. (5):5006), and inhibition of FGFR signaling in FGFR translocated tumors with lucitanib may be a potential new therapeutic strategy. We evaluated the nonclinical activity of lucitanib in FGFR3 translocated models with the hypothesis that the combined blockade of FGFR and VEGFR signaling would be more effective than targeting each receptor tyrosine kinase independently. The in vitro activity of lucitanib was first evaluated in a panel of bladder carcinoma cell lines (n = 8) with and without FGFR3 translocation. Lucitanib preferentially inhibited the gr...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Experimental and Molecular Therapeutics Source Type: research