Abstract
BACKGROUND: Glioblastoma (GBM) overexpresses LAT1/2, which are the target of 4-L-[(131)I] iodo-phenylalanine ([(131)I]IPA). Previous studies of [(123)I]IPA as SPECT tracer showed retention in glioma tissue, high metabolic stability, and uptake by >85% gliomas. Results from phase 1 IPAX-1 explored [(131)I]IPA+radiotherapy in patients with recurrent GBM and demonstrated a favorable safety profile and promising efficacy. The objective of IPAX-2 (NCT05450744) is to evaluate the safety and tolerability of [(131)I]IPA in patients newly diagnosed with GBM. METHODS: This phase 1, multicenter, open-label, single-arm, parallel-group, dose-finding study aims to evaluate the safety of ascending radioactive dose levels of [(131)I]IPA plus standard of care in newly diagnosed patients with GBM. Eligible patients (N=12) will be aged 18-65 years with histologically-confirmed intracranial GBM following surgical resection; no prior systemic therapy or radiation for GBM; a Karnofsky Performance Status ≥70; plan to begin chemoradiation 3-6 weeks after surgical resection with Stupp regimen; adequate organ function; and adequate tissue samples archived. Four cohorts (n=3/cohort) will encompass 3 + 3 dose escalation, beginning with [(131)I]IPA intravenously administered as 2 doses of 3 GBq each (dose escalation schedule: 2x3 GBq, 2x4 GBq, 2x5 GBq, 2x6 GBq). Dose 1 will be 7 days prior to chemoradiation, and dose 2 after last chemoradiation session. Chemoradiation will consist of 6 weeks of external beam radiation therapy (60Gy/30 fractions) plus temozolomide 75mg/m(2) daily. Following dose 2, patients will receive a 4-week treatment break before starting 6 maintenance cycles of temozolomide 150-200mg/m(2) on days 1-5 every 28 days. [(18)F]FET PET will identify suitable candidates with LAT1/2 overexpression, establish a baseline, and provide quantitative follow-up information. The co-primary objectives are 1) determine dose-limiting toxicity, maximum tolerated dose, and recommended phase 2 dose, and 2) determine the incidence of treatment-emergent adverse events. DISCLOSURE: Sponsored by Telix Pharmaceuticals.