IMMU-30. IGV-001: A BIOLOGIC-DEVICE COMBINATION PRODUCT ELICITS POTENT ANTI-GBM RESPONSES AS A MONOTHERAPY AND IN COMBINATION WITH CHECK POINT INHIBITION

Abstract INTRODUCTION Imvax is developing GoldspireTM, a personalized immunotherapy that combines whole tumor-derived cells with an antisense oligonucleotide against insulin-like growth factor 1 receptor (IGF-1R; IMV-001) in biodiffusion chambers (BDCs; 0.1 µm pore). BDCs are irradiated and implanted at abdominal sites for ~48h to deliver an antigenic payload and immunostimulatory factors that together train the immune system to attack tumor cells. The lead product, IGV-001, was evaluated in newly diagnosed glioblastoma (ndGBM) patients in a phase 1b study. Median overall survival (OS) of highest exposure IGV-001-treated Stupp-eligible patients (n=10) was 38.2 mos compared with 16.2 mos in standard-of-care-treated patients (p=0.044; ClinicalTrials.gov NCT02507583). A Phase 2b study in ndGBM is currently underway (ClinicalTrials.gov NCT04485949), where a primary endpoint of progression-free survival and key secondary endpoints of overall survival and safety will be evaluated. METHODS The orthotopically implanted GBM (luciferase-expressing GL261-luc2) model was utilized to evaluate the efficacy of mIGV-001 (the murine version of IGV-001) alone or in combination with anti-PD-1 immunotherapy. The following four groups were compared: mIGV-001 or BDC placebo + isotype or anti-PD-1 antibody (4 doses total every 3-4 days). GL261-luc2 cells were treated with IGF-1R antisense IMV-001. The treated cell suspension was loaded into clinical-grade BDCs (0.1-µm pore size, polyvinylidene difluoride membrane) at a density of 1 × 106 cells per BDC and then irradiated with 5–6 Gy. mIGV-001 or BDCs filled with saline were administered 28 days prior to tumor challenges and tumor progression and survival were monitored for an additional 100 days. RESULTS Preventative treatment with mIGV-001 limited tumor progression and extended OS in mice orthotopically (i.e., intracranially) challenged with GL261-luc2 cells. The therapeutic benefit of mIGV-001 was enhanced with anti-PD-1 treatment and the combination therapy was superior to either monotherapy.