A Phase 2 Study of Erdafitinib in Patients With Recurrent or Progressive IDH-Wild Type Glioma With an FGFR-TACC Gene Fusion
Summary
This phase II trial tests how well erdafitinib works in controlling IDH-wild type (WT), FGFR-TACC gene fusion positive gliomas that have come back after a period of improvement (recurrent) or that are growing, spreading, or getting worse (progressive). Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein that signals tumor cells to multiply. This may help keep tumor cells from growing and may kill them. Giving erdafitinib may help to slow the growth of, or to shrink, tumor cells in patients with recurrent or progressive IDH-wild type gliomas with FGFR-TACC gene fusion.
Detailed description
PRIMARY OBJECTIVE: I. To assess the preliminary anti-tumor activity of erdafitinib in patients with recurrent or progressive IDH-WT glioma with FGFR-TACC gene fusion as measured by the best response at any time during treatment in terms of objective response rate (ORR). SECONDARY OBJECTIVES: I. To determine the safety and tolerability of erdafitinib in patients with recurrent or progressive IDH-WT glioma with FGFR-TACC gene fusion. II. To assess the overall survival (OS) of erdafitinib in patients with recurrent or progressive IDH-WT glioma with FGFR-TACC gene fusion. III. To assess the progression free survival (PFS) at 6 months of patient with IDH-WT glioma with FGFR-TACC gene fusion treated with erdafitinib. OUTLINE: This is a dose-escalation study of erdafitinib followed by a dose-expansion study. Patients receive erdafitinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI), optical coherence tomography (OCT), and collection of blood samples throughout the trial. Additionally, patients may optionally undergo collection of tissue samples on study. After study completion, patients are followed up every 3 months for 2 years.
Arms & interventions
- ProcedureBiospecimen Collection
Undergo collection of blood and/or tissue samples
- DrugErdafitinib
Given PO
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- ProcedureOptical Coherence Tomography
Undergo OCT
Outcome measures
Primary
Objective response rate
Defined as the proportion of patients with either complete response or partial response as per Response Assessment in Neuro-Oncology (RANO) or RANO-low-grade glioma criteria. The response rate will be estimated along with the corresponding 95% confidence interval using the binomial exact method. Univariable and multivariable logistic regression models will be used to estimate the associations between study covariates and response status. Odds ratios and corresponding 95% confidence intervals and p-values will be reported.
Time frame: Up to 2 years
Secondary
Incidence of dose-limiting toxicities
Time frame: Up to 28 days
Incidence of adverse events (AEs) and serious AEs
Time frame: Up to 2 years
Progression-free survival
Time frame: Time between date of enrollment and date of progression or date of death from any cause, assessed at 6 months
Overall survival
Time frame: Time between the date of enrollment and date of death from any cause, censored at the last date of follow-up, assessed up to 2 years
Eligibility criteria
Study locations (27)
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Memorial Hospital East
Shiloh, Illinois, 62269
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Memorial Sloan Kettering Commack
Commack, New York, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
UT MD Anderson Cancer Center
Houston, Texas, 77030
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
References
- Alshiehk Nasany R, de la Fuente MI. Molecularly driven therapies in the treatment of primary brain tumors. Adv Cancer Res. 2025;166:183-201. doi: 10.1016/bs.acr.2025.05.005. Epub 2025 May 27.(PubMed)