116MO - Efficacy, safety, and quality of life (QoL) with futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/rearrangements: FOENIX-CCA2

Background

iCCA has a poor prognosis and its incidence is higher in Asian vs Western countries. Futibatinib is an oral, highly selective, irreversible FGFR1–4 inhibitor that demonstrated safety and preliminary efficacy in pts with iCCA harboring FGFR2 aberrations. This study evaluated safety, efficacy, and QoL with futibatinib treatment in pts with iCCA and FGFR2 fusions/rearrangements.

Methods

FOENIX-CCA2 (NCT02052778), a global phase II study, enrolled pts with unresectable/metastatic iCCA harboring an FGFR2 fusion/rearrangement and disease progression after ≥1 line of systemic therapy (including gemcitabine–cisplatin) but no prior FGFR inhibitors. Pts received futibatinib 20 mg once daily until disease progression/intolerability. The primary endpoint was objective response rate (ORR) per independent central radiology review and RECIST v1.1; secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), safety, and patient-reported outcomes (PROs). ORRs of subgroups by baseline demographic, fusion partner, and other molecular alteration (eg, TP53) were also determined.

Results

Of 103 enrolled pts, planned interim data are reported for 67 pts (54% white, 24% Asian) with ≥6 mo of follow-up; 55% of pts received ≥2 prior therapy lines, and 82% had tumors harboring an FGFR2 fusion (BICC1, n=15). ORR was 37.3%, DCR was 82.1%, and median DOR was 8.3 mo. Objective responses occurred regardless of baseline characteristic (subgroup: ≥65 y, ORR: 57.1%), FGFR2 fusion partner (BICC1, 33.3%), or other genetic mutation (TP53, 16.7%). Median PFS was 7.2 mo. The most common treatment-related adverse events (TRAEs; any grade/grade 3) were hyperphosphatemia (81%/27%), diarrhea (37%/0%), and dry mouth (33%/0%); no grade 4–5 TRAEs occurred. TRAEs were managed with dose interruption/reduction (55%/51%); only 1 pt discontinued due to a TRAE. PROs were stable through 273 days (13 cycles) of treatment.

Conclusions

Futibatinib resulted in durable objective responses in pts with iCCA and FGFR2 fusions/rearrangements, including within pt subgroups. Adverse events were manageable, and QoL was maintained.

Clinical trial identification

NCT02052778; EudraCT: 2013-004810-16.

Editorial acknowledgement

Medical writing and editorial assistance were provided by Kelly M. Fahrbach, PhD, and Jennifer Robertson, PhD, of Ashfield Healthcare Communications and funded by Taiho Oncology.

Legal entity responsible for the study

Taiho Oncology, Inc., and Taiho Pharmaceutical Co., Ltd.

Funding

Taiho Oncology, Inc., and Taiho Pharmaceutical Co., Ltd.

Disclosure

J. Furuse: Honoraria (self), Research grant/Funding (self), during the conduct of the study: Taiho Pharmaceutical; Research grant/Funding (self): J-Pharma; AstraZeneca; Bayer; NanoCarrier; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical; MSD; Sumitomo Dainippon; Yakult Honsha; Daiichi Sankyo; Eisai; Pfizer; Kyowa Hakko Kirin; Chugai Pharma; Sanofi; Takeda; Mochida Pharmaceutical; Eli Lilly Japan; Research grant/Funding (self): Astellas Pharma; Honoraria (self): Novartis; Honoraria (self): Teijin Pharma; Shionogi; EA Pharma; Nihon Servier; Fujifilm Toyama Chemical; Nobel Pharma; Sawai Pharmaceutical; Merck Serono; Nippon Kayaku; Shire; Bayer Yakuhin. L. Goyal: Advisory/Consultancy: Agios; Alentis Therapeutics; AstraZeneca; Honoraria (self), Advisory/Consultancy: Debiopharm Group; Advisory/Consultancy: H3 Biomedicine; Klus Pharma; QED Therapeutics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Taiho Pharmaceutical. F. Meric-Bernstam: Advisory/Consultancy, Research grant/Funding (self): Genentech; Advisory/Consultancy: Inflection Biosciences; Pleris Pharmaceuticals; Clearlight Diagnostics; DarwinHealth; Samsung Bioepis; Spectrum Pharmaceuticals; Aduro Biotech; Origimed; Xencor; Advisory/Consultancy, Research grant/Funding (self): Debiopharm Group; Advisory/Consultancy: Mersana; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Seattle Genetics; Advisory/Consultancy: Silverback Therapeutics; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: IBM Watson Health; Advisory/Consultancy: Roche; Advisory/Consultancy: PACT Pharma; Advisory/Consultancy, Research grant/Funding (self): eFFECTOR Therapeutics; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical; Honoraria (self): Beth Israel Deaconess Medical Center; Honoraria (self): Sumitomo Group; Honoraria (self): Dialectica; Research grant/Funding (self): Novartis; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Calithera Biosciences; Research grant/Funding (self): Bayer; Research grant/Funding (self): Aileron Therapeutics; Research grant/Funding (self): Puma Biotechnology; Research grant/Funding (self): CytomXTherapeutics; Research grant/Funding (self): Jounce Therapeutics; Research grant/Funding (self): Zymeworks; Research grant/Funding (self): Curis; Research grant/Funding (self): Pfizer; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Boehringer Ingelheim; Research grant/Funding (self): Guardant Health; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): GlaxoSmithKline. A. Hollebecque: Honoraria (self), Research grant/Funding (self), Non-remunerated activity/ies: Incyte; Honoraria (self): Amgen; Honoraria (self): Merck Serono; Honoraria (self): Eisai; Non-remunerated activity/ies: Servier; Non-remunerated activity/ies: Lilly. J.W. Valle: Advisory/Consultancy: Ipsen; Advisory/Consultancy: Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck; Advisory/Consultancy: Delcath Systems; Advisory/Consultancy: Agios; Honoraria (self), Advisory/Consultancy: Pfizer; Advisory/Consultancy: PCI Biotech; Advisory/Consultancy: Incyte; Advisory/Consultancy: Keocyt; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy: Pleris Pharmaceuticals; Advisory/Consultancy: Genoscience Pharma; Advisory/Consultancy: Mundipharma EDO GmbH; Advisory/Consultancy: Wren Laboratories; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Nucana; Advisory/Consultancy: Servier; Advisory/Consultancy: Debiopharma Group; Advisory/Consultancy, Speaker Bureau/Expert testimony: Imaging Equipment Limited; Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Honoraria (self), Speaker Bureau/Expert testimony: Ipsen; Honoraria (institution): Celgene. C. Morizane: Research grant/Funding (self): Ono Pharmaceutical; Research grant/Funding (self): Merck; Research grant/Funding (self): Eisai; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceuticals; Honoraria (self), Research grant/Funding (self): Yakult Honsha; Honoraria (self), Research grant/Funding (self): MSD; Honoraria (self), Research grant/Funding (self): J-Pharma; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self): Teijin Pharma; Honoraria (self): Novartis; Honoraria (self): AbbVie. T.B. Karasic: Research grant/Funding (self): Syndax; Research grant/Funding (self): Taiho Pharmaceutical; Research grant/Funding (self): Celgene; Research grant/Funding (self): H3 Biomedicine; Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): Lilly; Research grant/Funding (self): Sirtex Medical. R.K. Kelley: Research grant/Funding (institution): Taiho Pharmaceutical; Agios; Adaptimmune; AstraZeneca; Bayer; Bristol-Myers Squibb; Eli Lilly; EMD Serono; Exelixis; Merck; Partner Therapeutics; QED Therapeutics; Novartis; Non-remunerated activity/ies: Ipsen; Honoraria (self): Genentech/Roche; Honoraria (self): Gilead. P.A. Cassier: Non-remunerated activity/ies, During the conduct of the study: Taiho Pharmaceutical; Honoraria (self), Non-remunerated activity/ies: AstraZeneca; Non-remunerated activity/ies: AbbVie; Non-remunerated activity/ies: Bayer; Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self), Non-remunerated activity/ies: Blueprint; Honoraria (self), Non-remunerated activity/ies: Merck Serono; Non-remunerated activity/ies: GlaxoSmithKline; Non-remunerated activity/ies: Janssen; Non-remunerated activity/ies: Lilly; Honoraria (self), Research grant/Funding (self), Non-remunerated activity/ies: Novartis; Honoraria (self), Non-remunerated activity/ies: Roche/Genentech. H-J. Klumpen: Research grant/Funding (self): Bayer; Non-remunerated activity/ies: Ipsen. N. Uboha: Non-remunerated activity/ies: Taiho Pharmaceutical; Non-remunerated activity/ies: AstraZeneca; Non-remunerated activity/ies: Eli Lilly; Non-remunerated activity/ies: EMD Serono; Non-remunerated activity/ies: Incyte; Non-remunerated activity/ies: Ipsen. E. Mitchell: Honoraria (self), Research grant/Funding (self): Exelixis; Honoraria (self), Research grant/Funding (self): Genentech; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck; Honoraria (self): Novartis. Y. He, K.A. Benhadji: Full/Part-time employment: Taiho Pharmaceutical. J.A. Bridgewater: Honoraria (self): Taiho Pharmaceutical. All other authors have declared no conflicts of interest.