ATIM-26. A PHASE 1 STUDY OF Ad-RTS-hIL-12 + VELEDIMEX IN ADULT RECURRENT GLIOBLASTOMA

Abstract

Glioblastoma (GBM) is an aggressive brain tumor affecting ~74,000 people worldwide annually. Recurrent GBM patients have a median overall survival (mOS) of 6-7 months. OS in patients who have failed temozolomide, bevacizumab or equivalent salvage chemotherapy, is ~3-5 months. New therapies are urgently needed. Ad-RTS-hIL-12 is a novel gene therapy expressing IL-12 under the control of an oral activator ligand, veledimex, via the RheoSwitch Therapeutic System gene switch. Intratumoral administration of Ad-RTS-hIL-12 results in targeted tumor cytotoxicity and induction of systemic T cell memory. Ad-RTS-hIL-12 + veledimex is a treatment strategy to extend the IL-12 therapeutic window. In a multicenter, Phase I dose escalation trial and expansion cohort of subjects with recurrent or progressive Grade III or IV glioma undergoing resection, Ad-RTS-hIL-12 + veledimex was well tolerated; toxicities were predictable and reversible upon discontinuing veledimex with a correlation between veledimex dose, BBB penetration and drug related AEs to assigned dose level. The most common adverse reactions were related to cytokine exposure in the form of fever, decrease in peripheral lymphocytes and platelets, and elevation of liver transaminases. Emerging biomarker data appear to show that serum CD8+/FOXP3 ratio might represents a putative predictor of response. Subjects treated with 20mg of veledimex had a mOS of 12.5 months and when given