Abstract
FGFR-TACC gene fusions (F-T) are the most prevalent fusions in adult glioma, present in 3-6% of IDH-wild-type glioma. F-T emerge as truncal alterations during gliomagenesis, are independent predictors of favorable outcome in gliomas, and are retained in recurrent glioblastoma. In vitro and in vivo, F-T exhibit strong oncogenic activity and confer sensitivity to FGFR inhibitors. Erdafitinib is a potent, oral pan-FGFR tyrosine kinase inhibitor, FDA-approved for salvage therapy of metastatic urothelial carcinoma with FGFR alterations. Although responses to erdafitinib in F-T glioma have been reported as part of basket trials, no clinical study has yet been focused only on F-T gliomas. Here, we present the safety run-in cohort results of a multicenter, single-arm phase 2 study to assess erdafitinib in patients with recurrent/progressive F-T glioma. This cohort was designed to evaluate safety, tolerability and determine the recommended phase 2 dose (RP2D). Six adult patients with recurrent F-T glioma with measurable disease were treated with erdafitinib 8 mg daily continuous dose (median age: 63 years [range 52-72]; female 50%, GBM: 100%). With reporting adverse events (AEs) occurred within dose-limiting toxicity (DLT) period of Cycle 1 (4 weeks), all patients had treatment-emergent AE, mainly grade (G) 1/2. One out of 6 patients experienced a DLT with G3 AE - central serous retinopathy - leading to treatment discontinuation. There was one treatment-unrelated G3 AE - cerebral edema. Five patients had hyperphosphatemia (4 G1 and 1 G2). Preliminary efficacy data was available for 5 patients with best ORR of 1 CR, 1 PR, 2 SD, and 1 PD. The 2 patients with SD have both been on treatment for over 6 months with tumor reduction not yet meeting the 50% required for PR. Based on the safety review committee evaluation, erdafitinib 8mg continuous dose was confirmed as the RP2D. The expansion cohort is on-going.