A pivotal Phase 2 study of derazantinib for previously-treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 aberrations: FIDES-01

BACKGROUND AIMS: To evaluate safety and efficacy of FGFR1-3 kinase inhibitor derazantinib, in advanced intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions or rearrangements (FGFR2F), mutations (FGFR2M), or amplifications (FGFR2A), previously treated with chemotherapy. APPROACH RESULTS: Open-label, non-controlled Phase 2 trial. Patients with advanced iCCA, ≥1 prior chemotherapy, and FGFR2F (Substudy 1) or FGFR2M/FGFRA (Substudy 2), received once-daily oral derazantinib 300 mg until disease progression, unacceptable toxicity, consent withdrawal or investigator decision to stop. Efficacy was assessed by central radiology review using RECIST v1.1. Primary endpoints were objective response rate (ORR; Substudy 1) and 3-month progression-free survival (PFS3; Substudy 2). Other endpoints were PFS, ORR (Substudy 2), disease control rate (DCR), duration of response (DOR), and overall survival (OS). In Substudy 1, ORR and DCR were 22.3% (23/103 partial responses) and 75.7%, respectively; median (95% CI) PFS was 8.1 (5.5,8.3) months, DOR was 6.5 (4.6,9.2) months, and OS was 17.2 (12.5,22.4) months. In Substudy 2, PFS3 was 63% (27/43), ORR was 9.3% (3 partial, 1 complete response), DCR was 69.8%, and OS was 11.9 (8.4,15.9) months. There were no Grade 4 or 5 drug-related events. FGFR inhibitor class-specific toxicities included drug-related hyperphosphataemia (38%, Grade 3: 3%) and dry eye (36%). Nail disorders (10%, any grade or causality), stomatitis (5%), retinal events (5%), and palmar-plantar erythrodysesthesia (1%) were infrequent. CONCLUSIONS: In previously chemotherapy treated, FGFR-inhibitor-naïve patients with iCCA harboring FGFR2 fusions, mutations, or amplifications, derazantinib showed clinically meaningful efficacy with durable objective responses, and a manageable safety profile.

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Journal
Hepatology
Published
2026-10-27
DOI
https://doi.org/10.1097/hep.0000000000001902
Primary Topic
Cholangiocarcinoma and Gallbladder Cancer Studies
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article
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article

A pivotal Phase 2 study of derazantinib for previously-treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 aberrations: FIDES-01

Amit Mahipal, Friedrich Foerster, Nevena Damjanov, Thomas R. Jeffry Evans et al.
Hepatology
Cholangiocarcinoma and Gallbladder Cancer Studies
article

A pivotal Phase 2 study of derazantinib for previously-treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 aberrations: FIDES-01

Amit Mahipal, Friedrich Foerster, Nevena Damjanov, Thomas R. Jeffry Evans, Gaël S. Roth, Mitesh J. Borad, Monica Niger, Marc Frederick Engelhardt, Francesca Bergamo, Mikael Saulay, Michele Droz Dit Busset, Manuel Häckl, Jorge Adeva, Milind M. Javle, Gianluca Masi, Nicola Personeni, Kabir Mody, Vincenzo Mazzaferro, Walid Labib Shaib, Giovanni Brandi, Phil McKernan, Silke Friedmann, Arndt Vogel, Vincent Channing Tam, Ghassan K. Abou‐Alfa, Teresa Mercade Macarulla, John A. Bridgewater, Antoine Hollebecque, Laura Williams Goff, Thorvardur Ragnar Halfdanarson, Mathieu Bernat, William P. Harris, Stephan DiSean Kendall, Hani Babiker, Jennifer Knox, David C. Cunningham
article en

Abstract

BACKGROUND AIMS: To evaluate safety and efficacy of FGFR1-3 kinase inhibitor derazantinib, in advanced intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions or rearrangements (FGFR2F), mutations (FGFR2M), or amplifications (FGFR2A), previously treated with chemotherapy. APPROACH RESULTS: Open-label, non-controlled Phase 2 trial. Patients with advanced iCCA, ≥1 prior chemotherapy, and FGFR2F (Substudy 1) or FGFR2M/FGFRA (Substudy 2), received once-daily oral derazantinib 300 mg until disease progression, unacceptable toxicity, consent withdrawal or investigator decision to stop. Efficacy was assessed by central radiology review using RECIST v1.1. Primary endpoints were objective response rate (ORR; Substudy 1) and 3-month progression-free survival (PFS3; Substudy 2). Other endpoints were PFS, ORR (Substudy 2), disease control rate (DCR), duration of response (DOR), and overall survival (OS). In Substudy 1, ORR and DCR were 22.3% (23/103 partial responses) and 75.7%, respectively; median (95% CI) PFS was 8.1 (5.5,8.3) months, DOR was 6.5 (4.6,9.2) months, and OS was 17.2 (12.5,22.4) months. In Substudy 2, PFS3 was 63% (27/43), ORR was 9.3% (3 partial, 1 complete response), DCR was 69.8%, and OS was 11.9 (8.4,15.9) months. There were no Grade 4 or 5 drug-related events. FGFR inhibitor class-specific toxicities included drug-related hyperphosphataemia (38%, Grade 3: 3%) and dry eye (36%). Nail disorders (10%, any grade or causality), stomatitis (5%), retinal events (5%), and palmar-plantar erythrodysesthesia (1%) were infrequent. CONCLUSIONS: In previously chemotherapy treated, FGFR-inhibitor-naïve patients with iCCA harboring FGFR2 fusions, mutations, or amplifications, derazantinib showed clinically meaningful efficacy with durable objective responses, and a manageable safety profile.

Hepatology
University of Pisa (IT), WellStar Health System (US), Mayo Clinic (US), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), University of Milan (IT), Johannes Gutenberg University Mainz (DE), Vanderbilt University (US), University of Washington (US), Trinity College Dublin (IE), Cornell University (US), Beatson West of Scotland Cancer Centre (GB), Centre Hospitalier Universitaire de Grenoble (FR), Jacksonville College (US), Institut Gustave Roussy (FR), Princess Margaret Cancer Centre (CA), Medizinische Hochschule Hannover (DE), Fred Hutch Cancer Center (US), Utah Cancer Specialists (US), University Medical Center of the Johannes Gutenberg University Mainz (DE), IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT), Hospital Universitario 12 De Octubre (ES), Istituto Oncologico Veneto (IT), Hospital Clínic de Barcelona (ES), University Hospitals Seidman Cancer Center (US), Royal Marsden Hospital (GB), GERCOR (France) (FR), Mayo Clinic in Arizona (US), Basilea Pharmaceutica (Switzerland) (CH), Mayo Clinic in Florida (US), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), IRCCS Humanitas Research Hospital (IT), Weill Cornell Medicine (US), Vall d'Hebron Institute of Oncology (ES), Mayo Clinic Comprehensive Cancer Center (Minnesota) (US), Abramson Cancer Center (US), Vanderbilt-Ingram Cancer Center (US), Fondation Gustave Roussy (FR), Arthur J.E. Child Comprehensive Cancer Centre (CA), University College London (GB), Case Western Reserve University (US), University of Glasgow (GB), University of Pennsylvania (US), Université Grenoble Alpes (FR)
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Cholangiocarcinoma and Gallbladder Cancer Studies
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