Abstract CT238: TAS-120 in patients with advanced solid tumors bearing FGF/FGFR aberrations: A Phase I study
Authors: Meric-Bernstam Funda , Goyal Lipika , Tran Ben , Matos Ignacio , Arkenau Hendrik-Tobias , He Helen , Huang Jerry , Bahleda Rastislav 
Published: August 2019

Abstract
Background TAS-120, an oral, highly selective, irreversible FGFR1-4 tyrosine kinase inhibitor, inhibits both mutant and wild-type FGFR1-4 isoforms and has demonstrated activity against cell lines and human xenografts of tumors bearing FGFR aberrations. Safety and antitumor activity of TAS-120 was evaluated in this phase 1 study (NCT02052778) in patients with advanced solid tumors. TAS-120 doses of 8-24 mg once daily continuously (QD) or 8-200 mg Monday-Wednesday-Friday were evaluated for safety in the dose-escalation phase. Continuous TAS-120 20 mg QD was determined to be the maximum tolerated dose (MTD). Results in patients with cholangiocarcinoma (CCA) bearing FGFR2 rearrangements have been presented; here we report data in patients with tumors other than CCA.
Methods Patients aged ≥18 years with advanced solid tumors with or without FGF amplifications or FGFR aberrations (including rearrangements/gene fusions, mutations, or amplifications) were treated with escalating doses of TAS-120 during the dose-escalation phase. An expansion phase using doses of 20 mg QD was initiated. FGF/FGFR status was assessed locally or at a designated laboratory. The primary endpoints in the dose-escalation phase were to investigate the safety and to determine the MTD. Objective response rate (ORR) assessed per RECIST 1.1 was the primary endpoint in the expansion phase, and the secondary endpoints were safety, duration of response, progression-free survival, and overall survival.
Results A total of 134 patients with advanced solid tumors were treated in the dose escalation or expansion phases. Tumor types included primary CNS tumors (n=24), urothelial carcinoma (UC; n=21), breast cancer (BC; n=17), colorectal cancer (n=15), gastroesophageal cancer (GC; n=9), and other tumor types. Aberrations in FGFR1, FGFR2, FGFR3, and FGFR4 genes were observed, including amplifications, mutations, and rearrangements, as well as amplifications of FGF ligand genes. Hyperphosphatemia, an on-target, mechanism-based adverse effect of TAS-120, was the most common adverse event. Partial responses were observed in patients with BC (both HER2+ and triple-negative), UC, primary CNS tumors, and GC. Safety and efficacy details will be presented at the time of the congress.
Conclusions Continuous oral TAS-120 doses up to 20 mg QD were safe and showed preliminary evidence of clinical activity in selected patients with several tumor types bearing various FGF/FGFR aberrations. Results will determine which tumor types move into further clinical development.
Citation Format: Funda Meric-Bernstam, Lipika Goyal, Ben Tran, Ignacio Matos, Hendrik-Tobias Arkenau, Helen He, Jerry Huang, Rastislav Bahleda. TAS-120 in patients with advanced solid tumors bearing FGF/FGFR aberrations: A Phase I study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT238.