CTNI-33. TARGET TRIAL: A PHASE I/II OPEN-LABEL MULTICENTER STUDY TO ASSESS SAFETY, TOLERABILITY, AND CLINICAL EFFICACY OF AZD4547 IN PATIENTS WITH RELAPSED/REFRACTORY FGFR FUSION POSITIVE GLIOMA

• DOI: 10.1093/neuonc/noad179.0315
• Publication Date: 2023-11-11T23:13:21Z
• Authors: Alberto Picca; Anna Luisa Di Ste...; Julien Savatovsky; Francois Ducray; Olivier Chinot; Elisabeth Cohen-J...; Paule Augereau; Yohann Schmitt; Julie Lerond; Nabila Rousseaux; Christine Fardeau; Karima Mokhtari; Franck Bielle; David Meyronet; Antonio Iavarone; Marc Sanson
• Keywords: Tolerability; Progression-free survival; Clinical endpoint; Refractory (planetary science)

Abstract BACKGROUND AZD4547 is a potent oral FGFR1-3 inhibitor. We tested its safety, tolerability, and efficacy in patients presenting relapsed/refractory (r/r) high-grade gliomas (HGGs) with FGFR fusion phase I/II open label multicenter study (NCT02824133). METHODS the was based on two-stage design included adult HGG expressing FGFR-TACC gene (as centrally confirmed by RT-PCR sequencing) relapsing after at least one line of standard chemoradiation. Patients received (AstraZeneca) dose 80mg bd continuous schedule, until disease progression or inacceptable toxicity. The primary endpoint 6-months progression-free survival rate (PFS6). This research conducted support from AstraZeneca. RESULTS 12 r/r isocitrate dehydrogenase wildtype HGGs positive for fusions (all FGFR3-TACC3) were analysis cohort (male/female ratio = 1.4, median age 61.5 years). Most (67%) first tumor relapse. PFS6 25% (95% confidence interval [CI] 5-57%), PFS 1.4 months. All without six months (n 3) recurrence (versus 56% those progression) remained 14-23 best response stable progressive six. Median OS 17.5 Grade 3 toxicities hematological, metabolic, nail changes, stomatitis, other disorder 1 each). No grade 4 seen. CONCLUSION overall, tolerance acceptable. did not meet predetermined objective ≥ 35% stopped. A molecular characterization ongoing to identify potential markers associated prolonged stabilizations.