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

Abstract

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