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Ref Type
PMID
Authors C. Morizane, T. Kojima, Y. Kuboki, H. Bando, N. Matsubara, K. Shitara, K. Yoh, H. Hirai, T. Kato, T. Doi
Title Phase I study of the irreversible FGFR inhibitor (i) futibatinib (FBN; TAS-120) in Japanese patients (pts) with advanced (adv) solid tumours
Journal Vol Issue Date Pages Journal Short Title
Annals of Oncology 31 suppl_4
URL https://www.sciencedirect.com/science/article/pii/S0923753420406544
Abstract Text Background: The FGFRi FBN showed tolerability and preliminary efficacy in a phase I dose-escalation (DE)/expansion (EX) study conducted in primarily Caucasian pts with adv solid tumours (NCT02052778), and 20 mg once-daily (QD) FBN was established as the recommended phase II dose (RP2D). Here, we report results from a Japanese phase I DE/EX study of FBN in adv solid tumours. Methods: In DE, pts received 8–160 mg FBN thrice weekly (TIW; accelerated titration or standard 3+3 design), or 16 and 20 mg QD. The primary objective was safety and maximum tolerated dose (MTD) evaluation; secondary were pharmacokinetics (PK) and preliminary efficacy. The EX phase included pts with FGF/FGFR abnormalities receiving FBN at doses < MTD. Results: Sixty-three pts were enrolled in 8 TIW (DE; 29 pts, EX; 11 pts) and 2 QD cohorts (DE; 10 pts, EX; 13 pts). Pts had colorectal (16%), esophageal (13%), gastric (13%), or biliary tract cancer (11%), and 52% had tumors with FGF/FGFR aberrations. No DLTs were observed in the study; MTD was not reached with TIW dosing. QD enrollment was based on prior phase I data and 20 mg QD was determined as the RP2D. Overall, 5% of pts experienced grade (gr) ≥3 treatment-related adverse events (TRAEs). Most common TRAEs (all gr; gr ≥3) were hyperphosphatemia (89%; 0), decreased appetite (22%; 0), nausea (19%; 0), stomatitis (14%; 2%), retinal detachment (13%; 0), and elevated AST (11%; 3%). TRAEs led to dose reductions, interruptions, and discontinuation in 24%, 48%, and 0% of pts, respectively. The PK profile of 20 mg QD FBN (mean Cmax, 253 ng/mL; AUC0-last, 977ng·h/mL; median Tmax, 2.00 h; apparent T1/2, 2.18 h) was similar to that observed in Caucasian pts. Efficacy assessment is ongoing; at data cutoff (July 4, 2019), partial responses were observed in pts with gastric (n=2; tumor shrinkages of 59% and 70%) and breast cancer (n=1; tumor shrinkage, 37%) harboring FGFR2 amplifications. Conclusions: FBN showed manageable safety and preliminary efficacy in Japanese pts with adv solid tumors; RP2D (20 mg QD) in this study was consistent with prior results. Phase 2/3 studies in cholangiocarcinoma (NCT02052778; NCT04093362), gastric (NCT04189445) and breast tumours (NCT04024436) are ongoing. Clinical trial identification: JapicCTI-142552.

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