Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study

Clin Cancer Res. 2022 Jun 1;28(11):2270-2277. doi: 10.1158/1078-0432.CCR-21-2664.


Purpose: FGFR genomic alterations (amplification, mutations, and/or fusions) occur in ∼8% of gliomas, particularly FGFR1 and FGFR3. We conducted a multicenter open-label, single-arm, phase II study of a selective FGFR1-3 inhibitor, infigratinib (BGJ398), in patients with FGFR-altered recurrent gliomas.

Patients and methods: Adults with recurrent/progressive gliomas harboring FGFR alterations received oral infigratinib 125 mg on days 1 to 21 of 28-day cycles. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by Response Assessment in Neuro-Oncology criteria. Comprehensive genomic profiling was performed on available pretreatment archival tissue to explore additional molecular correlations with efficacy.

Results: Among 26 patients, the 6-month PFS rate was 16.0% [95% confidence interval (CI), 5.0-32.5], median PFS was 1.7 months (95% CI, 1.1-2.8), and objective response rate was 3.8%. However, 4 patients had durable disease control lasting longer than 1 year. Among these, 3 had tumors harboring activating point mutations at analogous positions of FGFR1 (K656E; n = 2) or FGFR3 (K650E; n = 1) in pretreatment tissue; an FGFR3-TACC3 fusion was detected in the other. Hyperphosphatemia was the most frequently reported treatment-related adverse event (all-grade, 76.9%; grade 3, 3.8%) and is a known on-target toxicity of FGFR inhibitors.

Conclusions: FGFR inhibitor monotherapy with infigratinib had limited efficacy in a population of patients with recurrent gliomas and different FGFR genetic alterations, but durable disease control lasting more than 1 year was observed in patients with tumors harboring FGFR1 or FGFR3 point mutations or FGFR3-TACC3 fusions. A follow-up study with refined biomarker inclusion criteria and centralized FGFR testing is warranted.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Follow-Up Studies
  • Glioma* / drug therapy
  • Glioma* / genetics
  • Humans
  • Microtubule-Associated Proteins
  • Neoplasm Recurrence, Local* / drug therapy
  • Neoplasm Recurrence, Local* / genetics
  • Phenylurea Compounds
  • Protein Kinase Inhibitors / adverse effects
  • Pyrimidines
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics


  • Microtubule-Associated Proteins
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyrimidines
  • TACC3 protein, human
  • infigratinib
  • Receptor, Fibroblast Growth Factor, Type 3