Erdafitinib (Balversa) showed a predictable safety profile and early signs of efficacy in patients with recurrent or progressive IDH–wild-type glioma harboring FGFR-TACC (F3T3) gene fusions in the safety run-in cohort of the phase 2 ETCTN 10559 trial (NCT05859334), researchers reported at the 2025 Society for Neuro-Oncology Annual Meeting.
Eight milligrams daily continuous dosing was identified as the recommended phase 2 dose after the safety run-in cohort completed therapy in October 2024. One dose-limiting toxicity occurred: grade 3 central serous retinopathy, which was the only grade 3 treatment-emergent adverse event and the sole toxicity that led to discontinuation. No grade 4 or higher TEAEs were observed.
All patients experienced at least one TEAE or grade 1 TEAE during the cycle 1 DLT period. Grade 2 events included dyspepsia (n = 2), hyperphosphatemia (n = 1), and hyponatremia (n = 1). Grade 1 hyperphosphatemia was common (n = 4). No TEAEs led to dose reductions or treatment interruptions. One patient had grade 3 cerebral edema deemed unrelated to treatment.
Preliminary efficacy data from five patients showed one complete response, two partial responses, one case of stable disease, and one progressive disease. Two illustrative cases included a 60-year-old woman who achieved a partial response at cycle 1 and a complete response at cycle 13 while remaining on therapy beyond 19 cycles, and a 68-year-old man who achieved a partial response at cycle 8.
“The safety profile of erdafitinib within gliomas is within the expected known safety profile of the agent in other tumor types, and we were able to identify durable responses in this population,” said lead author Macarena de la Fuente, MD, of the University of Miami Miller School of Medicine.
ETCTN 10559 is a multicenter, single-arm study enrolling patients with recurrent or progressive F3T3 fusion–positive glioma. The trial included two planned safety lead-in cohorts: cohort 1 evaluated continuous 8 mg daily dosing (n = 6) and cohort 2 would have evaluated 6 mg daily if at least two DLTs were observed at 8 mg. If one or no DLTs occurred, an additional 21 patients would be enrolled in a dose-expansion cohort.
Patients in the safety run-in cohort had a mean age of 63.3 years (median 64, range 52–72); three were male and three were female. Most were White (n = 5) and not Hispanic or Latino (n = 4). All had grade 4 glioblastoma and had previously received radiation and temozolomide.
F3T3 gene fusions occur in about 3% to 6% of adult IDH–wild-type gliomas, are truncal alterations retained at recurrence, and have shown oncogenic activity and sensitivity to FGFR inhibitors in preclinical studies. Erdafitinib, an oral pan-FGFR tyrosine kinase inhibitor, received FDA approval in 2024 for FGFR-altered advanced urothelial carcinoma; prior basket trials have reported responses in glioma but ETCTN 10559 is the first trial focused on F3T3 fusion–positive gliomas.
The dose-expansion cohort opened in February 2025; 90% of the planned 21 patients have been enrolled and 12 clinical sites have been activated.
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