Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma

Vincenzo Mazzaferro, Bassel F. El-Rayes, Michele Droz dit Busset, Christian Cotsoglou, William P. Harris, Nevena Damjanov, Gianluca Masi, Lorenza Rimassa, Nicola Personeni, Fadi Braiteh, Vittorina Zagonel, Kyriakos P. Papadopoulos, Terence Hall, Yunxia Wang, Brian Schwartz, Julia Kazakin, Sherrie Bhoori, Filippo de Braud, Walid L. Shaib

Research output: Contribution to journalArticlepeer-review


Background: Next-generation sequencing has identified actionable genetic aberrations in intrahepatic cholangiocarcinomas (iCCA), including the fibroblast growth factor receptor 2 (FGFR2) fusions. Derazantinib (ARQ 087), an orally bioavailable, multi-kinase inhibitor with potent pan-FGFR activity, has shown preliminary therapeutic activity against FGFR2 fusion-positive iCCA. Methods: This multicentre, phase 1/2, open-label study enrolled adult patients with unresectable iCCA with FGFR2 fusion, who progressed, were intolerant or not eligible to first-line chemotherapy (NCT01752920). Subjects received derazantinib in continuous daily doses. Tumour response was assessed according to RECIST 1.1 every 8 weeks. Results: Twenty-nine patients (18 women/11 men; median age, 58.7 years), 2 treatment-naive and 27 who progressed after at least one prior systemic therapy, were enrolled. Overall response rate was 20.7%, disease control rate was 82.8%. Estimated median progression-free survival was 5.7 months (95% CI: 4.04–9.2 months). Treatment-related adverse events (AE) were observed in 27 patients (93.1%, all grades), including asthenia/fatigue (69.0%), eye toxicity (41.4%), and hyperphosphatemia (75.9%). Grade ≥ 3 AEs occurred in 8 patients (27.6%). Conclusion: Derazantinib demonstrated encouraging anti-tumour activity and a manageable safety profile in patients with advanced, unresectable iCCA with FGFR2 fusion who progressed after chemotherapy. A pivotal trial of derazantinib in iCCA is ongoing (NCT03230318).

Original languageEnglish
JournalBritish Journal of Cancer
Publication statusAccepted/In press - Jan 1 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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