Abstract CT115: Phase 1b open-label, non-randomized, multi-center clinical trial of intratumoral IVX037 in combination with sintilimab (anti-PD1) in patients with advanced microsatellite stable (MSS) colorectal,gastroesophageal or ovarian cancer

Abstract 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. 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, ovarian and hepatocellular (HCC) cancers. Significant anti-tumor activity was displayed by intratumoral (IT) injections of IVX037 in human xenografts of microsatellite stable colorectal (MSS-CRC), gastric, HCC and ovarian cancers in SCID mice. In vivo human MSS-CRC xenograft studies in mice, revealed that IT administration of IVX037 induced elevated levels of γ-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). In the Phase 1a monotherapy clinical study, multiple IT administrations of IVX037 were generally well tolerated with no Gr 3 or higher TRAE’s or DLTs seen. The most common Gr 1 and Gr 2 TRAE’s were injection site pain (44%) and fatigue (22%), respectively. Of the 9 patients (pts) administered IVX037 in Phase 1a, one MSS, KRAS G12D mutant CRC pt achieved a biopsy confirmed complete response at day 262 after six IT doses. Two MSS-CRC pts displaying injected lesion reductions also exhibited decreases in serum CEA levels. Serum biomarker analysis highlighted IVX037-mediated induction of potentially beneficial inflammatory cytokines/chemokines (ie.CXCL10) at day 8 for future enhancement of combination Phase 1b CPI therapy (Wong.,et al. AGITG ASM, 2024). Methods: This is a Phase 1b, first-in-human, open-label, non-randomized, multi-center clinical trial of IT IVX037 in combination with an intravenous (IV) immune checkpoint inhibitor, sintilimab (anti-PD1) in patients with advanced MSS-CRC, gastroesophageal or ovarian cancer. Pts must have at least one injectable tumour. A total of 45 participants (15 from each of the three tumor types) will be enrolled and receive IT doses of IVX037 administered on Days 1,15, 29,43,57,71 and 85 at dose of up to 7.5 x 108 TCID50 (a dosage level deemed safe during the Phase 1a study), sintilimab administration will commence on Study Day 8 and be administered every 3 weeks at 200 mg/dose through to Study Day 344. The primary objective is to determine the feasibility, safety and tolerability of IT IVX037 in combination with sintilimab including the incidence of dose-limiting toxicities (DLT). Tumor response will be assessed using iRECIST, with the first response assessment occurring at Day 43. 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. ctDNA levels will also be monitored. Pt recruitment commenced in October 2024, with currently 4 MSS-CRC pts enrolled and no DLT’s. The Phase 1b trial is continuing as planned. Clinical Trial identifier: NCT05427487 Citation Format: Mark Wong, Niall Tebbutt, Tim Price, Shehara Mendis, Rafid Al-Asady, Eugene Hsu, Darren Shafren, Oksana Zdanska, Jia Liu. Phase 1b open-label, non-randomized, multi-center clinical trial of intratumoral IVX037 in combination with sintilimab (anti-PD1) in patients with advanced microsatellite stable (MSS) colorectal,gastroesophageal or ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT115.