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OS10.6 Infigratinib (BGJ398) in patients with recurrent gliomas with fibroblast growth factor receptor (FGFR) alterations: a multicenter phase II study
Journal article

OS10.6 Infigratinib (BGJ398) in patients with recurrent gliomas with fibroblast growth factor receptor (FGFR) alterations: a multicenter phase II study

  • Lassman, A B Columbia University Irving Medical Center, New York, NY, United States
  • Sepúlveda-Sánchez, J M Hospital Universitario 12 De Octubre, Madrid, Spain
  • Cloughesy, T University of California at Los Angeles, Los Angeles, CA, United States
  • Gil-Gil, J M Hospital Durans I Reynals. ICO, Hospitalet. Barcelona, Spain
  • Puduvalli, V K The Ohio State University, Columbus, OH, United States
  • Raizer, J Northwestern University, Evanston, IL, United States
  • De Vos, F Y University Medical Center Utrecht Cancer Center, Utrecht University, Utrecht, Netherlands
  • Wen, P Y Dana-Farber Cancer Institute, Boston, MA, United States
  • Butowski, N University of California San Francisco, San Francisco, CA, United States
  • Clement, P UZ Leuven Campus Gasthuisberg, Leuven, Belgium
  • Groves, M D Texas Oncology, Austin, TX, United States
  • Belda-Iniesta, C Hospital Universitario HM Sanchinarro, Madrid, Spain
  • Steward, K QED Therapeutics, San Francisco, CA, United States
  • Moran, S QED Therapeutics, San Francisco, CA, United States
  • Ye, Y QED Therapeutics, San Francisco, CA, United States
  • Roth, P University Hospital Zurich, Zurich, Switzerland
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  • 2019-9-6
Published in:
  • Neuro-Oncology. - Oxford University Press (OUP). - 2019, vol. 21, no. Supplement_3, p. iii21-iii22
Cancer Research
Oncology
Clinical Neurology
English Abstract

BACKGROUND
FGFR mutations and translocations occur in approximately 10% of glioblastomas (GBMs). FGFR3-TACC3 fusion has been reported as predictive of response to FGFR tyrosine kinase inhibitor therapy both pre-clinically and clinically. Infigratinib (BGJ398) is a selective small-molecule pan-FGFR kinase inhibitor that has demonstrated anti-tumor activity in several solid tumors with FGFR genetic alterations. Therefore, we conducted a phase II trial to test the efficacy of infigratinib in FGFR-altered recurrent GBM (NCT01975701).


METHODS
This open-label trial accrued adults with recurrent high-grade gliomas following failure of initial therapy that harbored FGFR1-TACC1 or FGFR3-TACC3 fusions; activating mutations in FGFR1, 2 or 3; or FGFR1, 2, 3, or 4 amplification. Oral infigratinib was administered 125 mg on days 1–21 every 28 days. Prophylaxis for hyperphosphatemia, a common toxicity, was recommended. The primary endpoint was the 6-month progression-free survival (6mPFS) rate by RANO (locally assessed, estimated by K-M method), with a goal of >40%.


RESULTS
As of the Sep 2017 data cut-off, 26 patients (16 men, 10 women; median age 55 years, range 20–76 years; 50% with ≥2 prior regimens) were treated, and 24 (92.3%) discontinued for disease progression (n=21) or other reasons (n=3). All patients had FGFR1 or FGFR3 gene alterations, and 4 had >1 gene alteration. The estimated 6mPFS rate was 16% (95% CI 5.0–32.5%); median PFS was 1.7 months (95% CI 1.1–2.8 months); median OS was 6.7 months (95% CI 4.2–11.7 months); ORR was 7.7% (95% CI 1.0–25.1%). The best overall response was: partial response 7.7% (FGFR1 mutation n=1; FGFR3 amplification n=1); stable disease 26.9%; progressive disease 50.0%; missing/unknown 15.3%. The most common (>15%) all-grade treatment-related adverse events (AEs) were hyperphosphatemia, fatigue, diarrhea, hyperlipasemia, and stomatitis. There were no grade 4 treatment-related AEs. Eleven patients (42.3%) had treatment-related AEs requiring dose interruptions or reductions (most commonly hyperphosphatemia).


CONCLUSIONS
Infigratinib induced partial response or stable disease in approximately one-third of patients with recurrent GBM and/or other glioma subtypes harboring FGFR alterations. Most AEs were reversible and manageable. Further potential combinations are being explored in patients with proven FGFR-TACC fusion genes and analysis of biomarker data is ongoing.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/50361
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