A pilot study of Pan-FGFR inhibitor ponatinib in patients with FGFR-altered advanced cholangiocarcinoma

Daniel H. Ahn, Pedro Luiz Serrano Uson Junior, Peter Masci, Heidi Kosiorek, Thorvardur R. Halfdanarson, Kabir Mody, Hani Babiker, Thomas DeLeon, Mohamad Bassam Sonbol, Gregory Gores, Rory Smoot, Tanios Bekaii-Saab, Amit Mahipal, Aaron Mansfield, Nguyen H. Tran, Joleen M. Hubbard, Mitesh J. Borad

Research output: Contribution to journalArticlepeer-review


Background Biliary tract cancers (BTC) are rare, chemo resistant and are associated with a poor prognosis. Preclinical and early clinical work had demonstrated interesting anti-tumor activity from targeting fibroblast growth factor receptor (FGFR) pathway. We hypothesized that ponatinib, a multi-targeted tyrosine kinase inhibitor with activity against FGFR, would be active in BTC patients with FGFR alterations. Methods This was a multi-center, single institution pilot study of ponatinib in patients with advanced, refractory BTC with FGFR alterations. The primary end point was overall response rate, with secondary points of overall survival (OS), progression-free survival (PFS) and Health Related Quality of Life (HRQoL) assessment. Results Twelve patients were enrolled prior to early termination of the trial. Partial responses were observed in 1 from 12 patients. Median PFS was 2.4 months and median OS was 15.7 months. All observed toxicities were manageable and reversible. Toxicities were mild, with lymphopenia (75%), rash (63%) and fatigue (50%) being the most frequent. No significant detriment in global QoL was observed. Conclusions Ponatinib as a single agent in FGFR altered BTC is tolerable with limited clinical activity. This is the first report of prospective assessment of FGFR inhibition in BTC using ponatinib, and the first study to report its effect on HRQoL. Further development of ponatinib will involve correlative studies to better refine patient selection, focus on combinations with other molecular targeted agents, conventional cytotoxic chemotherapy, and studies to better understand mechanisms of treatment resistance.

Original languageEnglish (US)
Pages (from-to)134-141
Number of pages8
JournalInvestigational New Drugs
Issue number1
StatePublished - Feb 2022


  • Bile duct cancers
  • Cholangiocarcinoma
  • FGFR
  • Next generation sequencing
  • Ponatinib
  • Targetable mutations

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)


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