AB051. P-19. A phase II study of infigratinib (BGJ398) in previously-treated advanced cholangiocarcinoma containing FGFR2 fusions
Poster Abstracts

AB051. P-19. A phase II study of infigratinib (BGJ398) in previously-treated advanced cholangiocarcinoma containing FGFR2 fusions

Milind Javle1, R. Kate Kelley2, Sameek Roychowdhury3, Karl Heinz Weiss4, Ghassan K. Abou-Alfa5, Teresa Macarulla6, Saeed Sadeghi7, Dirk Waldschmidt8, Andrew X. Zhu9, Lipika Goyal9, Mitesh Borad10, Wei Peng Yong11, Ivan Borbath12, Anthony El-Khoueiry13, Philip Philip14, Susan Moran15, Yining Ye16, Mary Ising17, Nancy Lewis17, Tanios Bekaii-Saab10

1Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA;2Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA;3Internal Medicine, Ohio State Comprehensive Cancer Center/James Cancer Hospital, Columbus, OH, USA;4Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany;5Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA;6Medical Oncology, Hospital Vall d’Hebron, Barcelona, Spain;7Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA;8Gastroenterology and Hepatology, Klinikum der Universität zu Köln, Köln, Germany;9Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA;10Internal Medicine, Mayo Clinic, Scottsdale, AZ, USA;11Hematology-Oncology, National University Cancer Institute Singapore, Singapore, Singapore;12HepatoGastroenterology and Digestive Oncology, Cliniques universitaires St Luc Bruxelles, Woluwe-Saint-Lambert, Belgium;13Department of Medicine, USC/Kenneth Norris Comprehensive Cancer Center, Los Angeles, CA, USA;14Division of Oncology, Karmanos Cancer Institute, Detroit, MI, USA;15Clinical Development, 16Biostatistics and Data Management, QED Therapeutics, San Francisco, CA, USA;17Translation Clinical Oncology, Novartis, USA

Correspondence to: Milind Javle. Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA. Email: mjavle@mdanderson.org.

Background: Fibroblast growth factor receptor 2 (FGFR2) fusions occur in 13–17% of intrahepatic cholangiocarcinomas (IHC). A multicenter, open-label, phase II study (NCT02150967) evaluated the antitumor activity of infigratinib, an ATP-competitive FGFR1–3-selective oral tyrosine kinase inhibitor, in patients (pts) with previously-treated advanced IHC containing FGFR2 fusions.

Methods: Pts received infigratinib 125 mg orally daily for 21 days of 28-day cycles until unacceptable toxicity, disease progression, investigator discretion, or withdrawal of consent. Primary endpoint: investigator-assessed confirmed overall response rate (cORR, RECIST 1.1). Secondary endpoints: progression-free survival (PFS), disease control rate (DCR), best overall response, overall survival (OS), safety, pharmacokinetics.

Results: Seventy-one pts (62% women; median age 53 years; median 2 prior lines of therapy) were included. At the prespecified data cutoff (8th, Aug, 2018), median duration of treatment was 5.5 months, median duration of follow-up was 8.4 months, and 62 pts had discontinued treatment. The ORR (confirmed and unconfirmed) was 31.0% (95% CI, 20.5–43.1%) and the cORR (in pts with potential for confirmation) was 26.9% (95% CI, 16.8–39.1%). Other efficacy findings: cORR in pts receiving ≤1 prior lines of treatment was 39.3% (n=28), and ≥2 17.9% (n=39); DCR 83.6% (95% CI, 72.5–91.5%); median duration of response 5.4 (95% CI, 3.7–7.4) months; median PFS 6.8 (95% CI, 5.3–7.6) months; median OS 12.5 (95% CI, 9.9–16.6) months. Most common any-grade treatment-emergent adverse events (TEAEs): hyperphosphatemia (73.2%), fatigue (49.3%), stomatitis (45.1%), alopecia (38.0%), constipation (35.2%). Grade 3/4 TEAEs occurred in 47 pts (66.2%), including hypophosphatemia (14.1%), hyperphosphatemia (12.7%), and hyponatremia (11.3%).

Conclusions: Infigratinib-associated toxicity is manageable, and our efficacy findings suggest clinically meaningful activity after chemotherapy in pts with IHC containing FGFR2 fusions. The efficacy of infigratinib in this study supports FGFR2 as a therapeutic target in FGFR2-fusion IHC.

Keywords: Infigratinib; cholangiocarcinoma; fibroblast growth factor receptor 2 fusions (FGFR2 fusions); intrahepatic

Cite this abstract as: Javle M, Kelley RK, Roychowdhury S, Weiss KH, Abou-Alfa GK, Macarulla T, Sadeghi S, Waldschmidt D, Zhu AX, Goyal L, Borad M, Yong WP, Borbath I, El-Khoueiry A, Philip P, Moran S, Ye Y, Ising M, Lewis N, Bekaii-Saab T. A phase II study of infigratinib (BGJ398) in previously-treated advanced cholangiocarcinoma containing FGFR2 fusions. Hepatobiliary Surg Nutr 2019;8(Suppl 1):AB051. doi: 10.21037/hbsn.2019.AB051

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