Abstract 544P
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.
Editorial acknowledgement
Legal entity responsible for the study
Taiho Pharmaceutical Co., Ltd.
Funding
Taiho Pharmaceutical Co., Ltd.
Disclosure
C. Morizane: Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self): Novartis; Honoraria (self), Research grant/Funding (institution): Yakult Honsha; Honoraria (self): Teijin Pharma; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy: MSD K.K.; Research grant/Funding (institution): ONO Pharmaceutical; Research grant/Funding (institution): J-Pharma; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck biopharma; Advisory/Consultancy: AbbVie. T. Kojima: Advisory/Consultancy, Research grant/Funding (institution): Ono; Advisory/Consultancy, Research grant/Funding (institution): MSD; Research grant/Funding (institution): Shionogi; Research grant/Funding (institution): Astellas Amgen; Advisory/Consultancy: Astellas; Research grant/Funding (institution): Chugai; Advisory/Consultancy: Oncolys; Research grant/Funding (institution): Parexel; Research grant/Funding (institution): Merck Serono; Advisory/Consultancy: Merck Biopharma; Advisory/Consultancy: Bristol-Myers Squibb. Y. Kuboki: Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): ONO; Honoraria (self): Bayer; Honoraria (self): Sanofi; Honoraria (self): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Takeda; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Chugai; Research grant/Funding (institution): GSK. H. Bando: Honoraria (self): Taiho Parmaceutical; Honoraria (self): Eli Lilly Japan. N. Matsubara: Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceutical Co.Ltd.; Honoraria (self), Research grant/Funding (institution): MSD K.K.,; Honoraria (self), Research grant/Funding (institution): Bayer Yakuhin, Ltd.,; Honoraria (self): Sanofi K.K.; Honoraria (self), Research grant/Funding (institution): Janssen Pharmaceutical K.K.; Research grant/Funding (institution): Astellas Pharma Inc.,; Research grant/Funding (institution): AstraZeneca K.K.; Research grant/Funding (institution): TAIHO Phamaceutical Co.,Ltd.; Research grant/Funding (institution): Pfizer Japan Inc.. K. Shitara: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: AbbVie ; Honoraria (self): Yakult; Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution): Taiho Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: GlaxoSmithKline; Research grant/Funding (institution): Chugai Pharm; Research grant/Funding (institution): Medi Science; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dainippon Sumitomo Pharma. K. Yoh: Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Lilly; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Daiichi Sankyo; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Kyowa Kirin; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Takeda. H. Hirai: Full/Part-time employment: Taiho. T. Kato: Honoraria (self), Research grant/Funding institution): Taiho. T. Doi: Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self): Astellas; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Honoraria (self): Ono; Honoraria (self): Oncolys Biopharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Taiho; Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Sumitomo Dainippon; Advisory/Consultancy: Rakuten Medical; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy: Takeda; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Kyowa Hakko Kirin; Research grant/Funding (institution): IQVIA; Research grant/Funding (institution): Pfizer.