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|Ref Type||Journal Article|
|Authors||Lassman AB, Sepúlveda-Sánchez JM, Cloughesy T, Gil-Gil MJ, Puduvalli VK, Raizer J, De Vos FYF, Wen PY, Butowski N, Clement PMJ, Groves MD, Belda-Iniesta C, Giglio P, Soifer HS, Rowsey S, Xu C, Avogadri F, Wei G, Moran S, Roth P|
|Title||Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study.|
|Abstract Text||Fibroblast growth factor receptor (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.Adults with recurrent/progressive gliomas harboring FGFR alterations received oral infigratinib 125 mg on days 1-21/28 days. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by Response Assessment in Neuro-Oncology (RANO) criteria. Comprehensive genomic profiling was performed on available pre-treatment archival tissue to explore additional molecular correlations with efficacy.Among 26 patients, the 6-month PFS rate was 16.0% (95% 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 pre-treatment 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.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.|
|Molecular Profile||Treatment Approach|
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|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
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|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|FGFR1 K656E||high grade glioma||predicted - sensitive||Infigratinib||Case Reports/Case Series||Actionable||In a Phase II trial, Truseltiq (infigratinib) treatment resulted in limited efficacy with a 6-month progression-free survival (PFS) rate of 16.0%, a median PFS of 1.7 months, an objective response rate of 4.8% (1/21), and median overall survival of 6.7 months in patients with recurrent glioma harboring alterations in FGFR1 or FGFR3; however, resulted in a partial response with PFS of 21.9 months and stable disease with PFS of 13.2 months in two patients harboring FGFR1 K656E (PMID: 35344029; NCT01975701).||35344029|
|FGFR3 K650E||high grade glioma||predicted - sensitive||Infigratinib||Case Reports/Case Series||Actionable||In a Phase II trial, Truseltiq (infigratinib) treatment resulted in limited efficacy with a 6-month progression-free survival (PFS) rate of 16.0%, a median PFS of 1.7 months, an objective response rate of 4.8% (1/21), and median overall survival of 6.7 months in patients with recurrent gliomas harboring alterations in FGFR1 or FGFR3, however, resulted in stable disease with PFS of 12.9 months in a patient harboring FGFR3 K650E (PMID: 35344029; NCT01975701).||35344029|