823 IPAX-1: Phase ½ Study of 4-L-[131l] IODO-Phenylalanine (131I-IPA) Combined with External Radiation Therapy (XRT) as Treatment for Patients with Glioblastoma Multiforme

Abstract

INTRODUCTION: Many tumor types, including glioblastoma multiforme (GBM),overexpress the L-type amino transporter 1 (LAT-1). I-iodo-phenylalanine( I-IPA) is a small-molecule amino acid derivative taken up by LAT-1 withdesignated orphan status in the United States and European Union for thetreatment of GBM. Tumor accumulation of I-IPA was shown in a proof-of-principlestudy and confirmed with single dosing of 2–7 GBq I-IPA in combination with XRT in recurrentGBM. The I-IPA + XRT as Treatment for Patients with GBM (IPAX-1) study evaluates the safety,tolerability, dosing schedule, and preliminary efficacy of I-IPA in combinationwith second-line XRT in patients with recurrent GBM. METHODS: IPAX-1 is a multi-center, open-label, phase 1/2, dose-finding study recruiting patients with previously confirmed histological diagnosis of GBM and evidence of first recurrence, history of GBM standard therapy, at least 6 months since end of first-line XRT, pathologically increased amino acid tumor uptake shown by molecular imaging, and current indication for repeat radiation. Participants receive intravenous I-IPA either as a single fraction (1f) followed by XRT, or as three equal fractions (3f) at weekly intervals followed by XRT commencing between the first and second I-IPA administration. RESULTS: Good tolerability and safety profile Promising progression free survival median 4.33 months and overall survival median 15.97 months Patients with unmethylated MGMT have a worse response to therapy than methylated MGM. CONCLUSIONS: Early evidence indicates that the combination of 131I-IPA and XRT may have an anti-neoplastic effect.