Abstract 54P
Background
FGFR2 fusions occur in 10–20% of pts with iCCA and comutations in tumor suppressor genes may be prognostic. FOENIX-CCA2 is a study of futibatinib (a highly selective irreversible FGFR1–4 inhibitor) in pts with iCCA and FGFR2 fusions/other rearrangements.
Methods
Pts enrolled had locally advanced/metastatic iCCA with FGFR2 fusions/other rearrangements, progressive disease (PD) after ≥1 systemic therapy (tx), no prior FGFR inhibitor tx, and ECOG PS 0/1. Pts received oral futibatinib 20 mg 1x/day until PD/intolerance. Objective response rate (ORR; independent review) was the primary endpoint and duration of response (DOR), PFS and safety were secondary endpoints. Subanalyses by pt characteristic, fusion, comutation and prognostic factor were performed.
Results
Interim data for 67 pts (58% female; median age 57 y) with ≥6 mo of follow-up are reported. Pts had FGFR2 fusions (82%) or rearrangements (18%). The most frequent fusion was FGFR2-BICC1 (n=15). ORR was 37.3%, median DOR 8.3 mo, and disease control rate 82%. In pts with confirmed FGFR2 alterations, ORR was 36.2% (21/58 fusions) and 44.4% (4/9 rearrangements). ORR was 33.3% in pts with FGFR2-BICC1. Best overall response in pts with comutations of interest is shown in the table below. All baseline characteristic subgroups (eg, age, gender, prior tx) had responding pts, including pts aged ≥65 y (ORR=57%; 8/14). Higher phosphate levels trended in responders vs nonresponders. Grade ≥3 treatment-related hyperphosphatemia resolved in a median of 6 d. Management of special interest AEs will be presented. Table: 54P
| Comutation | Patients, n | |||||
| CR | PR | SD | PD | FGFR2 fusion | FGFR2 rearrangement | |
| BAP1 (n=3) | 0 | 0 | 3 | 0 | 2 | 1 |
| IDH1 (n=3) | 0 | 2 | 1 | 0 | 2 | 1 |
| TP53 (n=6) | 1 | 0 | 3 | 2 | 3 | 3 |
| PBRM1 (n=3) | 0 | 0 | 1 | 2 | 3 | 0 |
| PI3K genes a (n=4) | 0 | 1 | 3 | 0 | 1 | 3 |
CR, complete response; PD, disease progression; PR, partial response; SD, stable disease. aTwo mutations in PIK3A, 1 in PIK3B, and 1 in PIK3R1.
Conclusions
These interim data demonstrate manageable AEs and efficacy of futibatinib in iCCA with FGFR2 fusions/other rearrangements. Responses were observed across pt subgroups, including those with common FGFR2 fusions, comutations, and poor prognostic factors.
Clinical trial identification
NCT02052778; EudraCT: 2013-004810-16.
Editorial acknowledgement
Professional medical writing and editorial assistance were provided by Ashfield Healthcare Communications (Lyndhurst, NJ, USA) and funded by Taiho Oncology, Inc.
Legal entity responsible for the study
Taiho Oncology, Inc.
Funding
Taiho Oncology, Inc.
Disclosure
J. Bridgewater: Advisory/Consultancy: Taiho. F. Meric-Bernstam: Advisory/Consultancy: PACT Pharma, Inflection Biosciences, Pieris Pharmaceuticals, Clearlight Diagnostics, DarwinHealth; Advisory/Consultancy: Samsung Bioepis, Spectrum Biotech, Aduro Biotech, OrigiMed; Advisory/Consultancy: Mersana, Silverback Therapeutics, Immunomedics, IBM Watson Health; Research grant/Funding (self): Guradant Health, Daiichi Sankyo, GlaxoSmithKline; Speaker Bureau/Expert testimony: Chugai Pharma; Travel/Accommodation/Expenses: Beth Israel Deaconess Medical Center; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Seattle Genetics; Honoraria (self): Sumitomo Group, Dialectica; Research grant/Funding (self): Novartis, AstraZeneca, Calithera Biosciences, Bayer, Aileron Therapeutics, PUMA Biotechnology, CytomX Therapeutics; Advisory/Consultancy, Research grant/Funding (self): Genentech, Debiopharm, eFFECTOR Therapeutics; Research grant/Funding (self), Travel/Accommodation/Expenses: Taiho Pharmaceutical; Research grant/Funding (self): Jounce Therapeutics, Zymeworks, Curis, Pfizer, Abbvie, Boehringer Ingelheim. A. Hollebecque: Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Incyte; Honoraria (self): Amgen; Travel/Accommodation/Expenses: Servier; Honoraria (self): Merck Serono; Travel/Accommodation/Expenses: Lilly; Honoraria (self): Eisai. J.W. Valle: Advisory/Consultancy: AstraZeneca, Merck, Delcath Systems, Agios; Advisory/Consultancy: PCI Biotech, Incyte, Keocyt, QED Therapeutics, Pieris Pharmaceuticals, Genoscience Pharma; Advisory/Consultancy: Mundipharma EDO GmbH, Wren Laboratories, Nucana, Servier, Debiopharm Group; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Nucana; Advisory/Consultancy, Speaker Bureau/Expert testimony: Imaging Equipment Limited; Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis. C. Morizane: Advisory/Consultancy: Abbvie; Honoraria (self), Advisory/Consultancy: Novartis, Taiho Pharmaceutical,; Honoraria (self): Teijin Pharma, Merck Sharp & Dohme; Honoraria (self), Research grant/Funding (self): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Yakult Honsha; Research grant/Funding (self): ONO Pharmaceutical, Taiho Pharmaceutical, J-Pharma, AstraZeneca, Merck. T. 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. J. Furuse: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Taiho Pharmaceutical; Research grant/Funding (self): Ono Pharmaceutical, Merck Sharp & Dohme, Sumitomo Dainippon, J-Pharma, Yakult Honsha, AstraZeneca, Daiichi Sankyo, Eisai, Bayer, Pfizer, NanoCarrier, Kyowa Hakko Kirin, Taiho Pharmaceutical, Chugai Pharma, Sanofi, Takeda, Mochida Pharmaceutical, Astellas; Honoraria (self): Eisai, Bayer Yakuhin, Taiho Pharmaceutical, Ono Pharmaceutical, Novartis, Yakult Honsha, Teijin pharma, Shionogi, EA pharma, Eli Lilly Japan, Takeda, Chugai Pharma, Mochida Pharmaceutical, Nihon Servier, Sanofi, Fujifilm Toyama Chemical, Nobel pharma, Pfi. R.K. Kelley: Research grant/Funding (institution): Taiho, Novartis, QED, Partner Therapeutics, Exelixis, EMD Serono, Eli Lilly, Bayer, Adaptimmune; Advisory/Consultancy, Research grant/Funding (institution): Agios, AstraZeneca, BMS, Merck; Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Gilead. P. Cassier: Honoraria (institution): Taiho; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution): Abbvie; Honoraria (institution): Bayer; Honoraria (institution): BMS; Honoraria (self), Honoraria (institution): Blueprint; Honoraria (institution): GlaxoSmithKline; Honoraria (institution): Janssen; Honoraria (institution): Lilly; Honoraria (self), Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Honoraria (institution): Roche/Genentech. H-J. Klümpen: Research grant/Funding (institution): Bayer; Advisory/Consultancy: Ipsen. N. Uboha: Advisory/Consultancy, Research grant/Funding (self): Taiho Inc; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly; Advisory/Consultancy: Incyte; Advisory/Consultancy, Research grant/Funding (self): EMD Serono; Advisory/Consultancy, Research grant/Funding (self): Ipsen. E. Mitchell: Advisory/Consultancy, Research grant/Funding (institution): Exilixis; Research grant/Funding (institution): Genentech; Advisory/Consultancy: BMS; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis. Y. He: Full/Part-time employment: Taiho Oncology. K. Benhadji: Shareholder/Stockholder/Stock options, Full/Part-time employment: Lilly; Full/Part-time employment: Taiho Oncology. L. Goyal: Advisory/Consultancy, Travel/Accommodation/Expenses: Debiopharm Group; Advisory/Consultancy: Alentis Therapeutics; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy: H3 Biomedicine; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Klus Pharma; Advisory/Consultancy: Agios; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Taiho Pharmaceutical. All other authors have declared no conflicts of interest.