RBIO-05. IPAX-2: PHASE 1 SAFETY AND DOSE FINDING STUDY OF [131I]IPA PLUS STANDARD OF CARE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract

Abstract BACKGROUND Glioblastoma (GBM) overexpresses the L-type amino transporter (LAT) 1 & 2, which supports internalization of the therapeutic small-molecule amino acid derivative, 4-L-[131I] iodo-phenylalanine ([131I]IPA) and its companion diagnostic, 18F-FET. Previous studies of [123I]IPA SPECT have shown uptake by >85% of gliomas. Results from a phase 1 trial (IPAX-1) that explored [131I]IPA + radiotherapy in patients with recurrent GBM demonstrated a favorable safety and tolerability profile and promising efficacy. The objective of IPAX-2 (NCT05450744) is to evaluate the safety and tolerability of [131I]IPA in patients newly diagnosed with GBM. METHODS IPAX-2 is a phase 1, multicenter, open-label, single-arm, parallel-group, dose-finding study to evaluate the safety of ascending radioactive dose levels of [131I]IPA + best standard of care in newly diagnosed patients with GBM. Eligible participants (N=12) will be 18-65 years of age with histologically-confirmed intracranial GBM following surgical resection; no prior systemic therapy or radiation for GBM; a Karnofsky Performance Status ≥70; a plan to begin chemoradiation 3-6 weeks after surgical resection with Stupp regimen; adequate organ function; and adequate tissue samples previously archived. Four cohorts will encompass a 3 + 3 dose escalation, with [131I]IPA administered in 2 fractions corresponding to ½ of full dose activity via intravenous infusion (2x3.0 GBq, 2x4 GBq, 2x5 GBq, 2x6 GBq). Dose 1 will be administered prior to external beam radiation therapy (EBRT), and Dose 2 will be administered following completion of EBRT. 18F-FET PET will be used to identify suitable candidates with LAT1/2 overexpression, establish a baseline, and provide quantitative follow-up information. Primary outcome measures are 1) incidence rate treatment-emergent adverse events and 2) safety and tolerability by determining the dose-limiting toxicity, maximum tolerated dose, and recommended phase 2 dose. DISCLOSURES: Telix Pharmaceuticals is the sponsor of this study.