649 Phase 1a open-label, non-randomized, multi-center clinical trial of intratumoral IVX037 in patients with advanced microsatellite stable (MSS) colorectal, gastroesophageal or ovarian cancer

Background

Oncolytic viruses have emerged as promising therapeutic agents to selectively infect and destroy cancer cells while synergizing with checkpoint inhibitors to increase efficacy of immunotherapy. IVX037 is a novel bio-selected, receptor targeted, non-genetically modified, naturally occurring oncolytic strain of a human enteric RNA picornavirus. It is a non-enveloped, single-positive-stranded RNA virus with a capsid diameter of ~25nm. IVX037 challenge can induce selective in vitro tumor cell lytic infection via specific viral capsid cellular receptor interactions in cell cultures of human colorectal, gastric and ovarian cancers. Significant anti-tumor activity was displayed by a single intratumoral injection of IVX037 in human xenografts of microsatellite stable (MSS) -colorectal, gastric and ovarian cancers in SCID mice. In vivo human MSS colorectal cancer xenograft studies in mice, revealed that intratumoral administration of IVX037 induced elevated levels of gamma-INF response genes (CXCL10, RIG-I) and up-regulated expression of a key immune-checkpoint molecule, PD-L1, indicating an inflammation phenotype within the treated tumor microenvironment (TME). The induction of a virally inflamed TME is suggested to potentially allow increased migration of anti-tumor lymphocytes both within injected and distant lesions and elevated levels of cellular targets for immune checkpoint therapies.

Methods

This is a Phase 1a, first-in-human, open-label, non-randomized, multi-center clinical trial of intratumoral IVX037 in patients with advanced MSS colorectal , gastroesophageal or ovarian cancer. Patients (pts) must have one injectable tumour of liver/nodal/peritoneal disease. Pts will be sequentially enrolled into 3 dose escalation cohorts to receive 1 (n=3 pts), 2 (n=3 pts) or 3 (n=15 pts) doses of up to 3 x 10⁸ TCID₅₀ of IVX037 intratumorally, administered on Days 1, 15 and 29 of Cycle 1, as applicable. The primary objective is to determine the feasibility, safety and tolerability of intratumoral IVX037 including the incidence of dose-limiting toxicities (DLT). The secondary objective is to assess the maximum tolerated dose (MTD) of IVX037, administered as either 1, 2 or 3 injections per lesion. Tumor response will be assessed using RECIST 1.1, with the first response assessment occurring at Day 50. Several biomarker effects of IVX037 administration in peripheral blood and tumor tissue addressing tumor infiltrating lymphocytes and cellular target expression levels for immune checkpoint therapies will be assessed.