Phase II study of BGJ398 in patients with FGFR-Altered advanced cholangiocarcinoma

Milind Javle, Maeve Lowery, Rachna T. Shroff, Karl Heinz Weiss, Christoph Springfeld, Mitesh J. Borad, Ramesh K. Ramanathan, Lipika Goyal, Saeed Sadeghi, Teresa Macarulla, Anthony El-Khoueiry, Robin Kate Kelley, Ivan Borbath, Su Pin Choo, Do Youn Oh, Philip A. Philip, Li Tzong Chen, Thanyanan Reungwetwattana, Eric Van Cutsem, Kun Huei YehKristen Ciombor, Richard S. Finn, Anuradha Patel, Suman Sen, Dale Porter, Randi Isaacs, Andrew X. Zhu, Ghassan K. Abou-Alfa, Tanios Bekaii-Saab

Research output: Contribution to journalArticle

137 Scopus citations

Abstract

Purpose No standard treatment exists for patients with cholangiocarcinoma for whom first-line gemcitabine-based therapy fails. Fibroblast growth factor receptor 2 (FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown preliminary clinical activity against tumors with FGFR alterations. Methods A multicenter, open-label, phase II study (ClinicalTrials.gov identifier: NCT02150967) evaluated BGJ398 antitumor activity in patients age $ 18 years with advanced or metastatic cholangiocarcinoma containing FGFR2 fusions or other FGFR alterations whose disease had progressed while receiving prior therapy. Patients received BGJ398 125 mg once daily for 21 days, then 7 days off (28-day cycles). The primary end point was investigator-assessed overall response rate. Results Sixty-one patients (35 women; median age, 57 years) with FGFR2 fusion (n = 48), mutation (n = 8), or amplification (n = 3) participated. At the prespecified data cutoff (June 30, 2016), 50 patients had discontinued treatment. All responsive tumors contained FGFR2 fusions. The overall response rate was 14.8% (18.8% FGFR2 fusions only), disease control rate was 75.4% (83.3% FGFR2 fusions only), and estimated median progression-free survival was 5.8 months (95% CI, 4.3 to 7.6 months). Adverse events included hyperphosphatemia (72.1% all grade), fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Grade 3 or 4 treatment-related adverse events occurred in 25 patients (41%) and included hyperphosphatemia (16.4%), stomatitis (6.6%), and palmar-plantar erythrodysesthesia (4.9%). Conclusion BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population.

Original languageEnglish (US)
Pages (from-to)276-282
Number of pages7
JournalJournal of Clinical Oncology
Volume36
Issue number3
DOIs
StatePublished - Jan 20 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Javle, M., Lowery, M., Shroff, R. T., Weiss, K. H., Springfeld, C., Borad, M. J., Ramanathan, R. K., Goyal, L., Sadeghi, S., Macarulla, T., El-Khoueiry, A., Kelley, R. K., Borbath, I., Choo, S. P., Oh, D. Y., Philip, P. A., Chen, L. T., Reungwetwattana, T., Van Cutsem, E., ... Bekaii-Saab, T. (2018). Phase II study of BGJ398 in patients with FGFR-Altered advanced cholangiocarcinoma. Journal of Clinical Oncology, 36(3), 276-282. https://doi.org/10.1200/JCO.2017.75.5009