Abstract 859: Novel oncolytic RNA viruses, IVX037 and IVX055, demonstrate potent antitumor activity

Abstract Background: Oncolytic viruses have emerged as promising therapeutic agents to selectively target, infect and destroy cancer cells while synergizing with novel immunotherapies including Checkpoint inhibitors (CPI) and Chimeric Antigen Receptor (CAR) T- cells to increase anti-tumor efficacy. We developed two novel oncolytic non-enveloped RNA viruses, IVX037 and IVX055, using a proprietary receptor-focused bio-selection platform technology. IVX037 and IVX055 are small, single stranded RNA viruses, utilizing independent cell surface receptors to facilitate tumor targeting, cell entry and subsequent potent lytic replication. Intratumoral (i.t) IVX037 challenge of human microsatellite-stable colorectal cancer (MSS-CRC) xenografts increases expression of PD-L1 and mediates a widespread inflammation phenotype, suggested to allow increased migration of anti-tumor lymphocytes, elevation of cellular targets for immune checkpoint and cell-based anti-cancer therapies. Methods: In vitro monolayer cultures of human cancers were challenged with various input multiplicities of IVX037 or IVX055 with lytic infection assessed by a XTT viability assay. For mouse models, immunocompromised mice (SCID or nu/nu) were seeded with single flank human tumor cell administrations. Following development of palpable tumors, IVX037 was administered via i.v or i.t routes. Calliper measurements were employed to assess tumor burden. Checkerboard titrations of IVX037 and a mesothelin targeted CAR-T were utilized to assess anti-tumor activity in monolayer cultures of human gastric cancer cells. Results: IVX037 demonstrated potent oncolytic in vitro activity in human ovarian, gastric, and hepatocellular cancer (HCC) cell cultures. IVX055 induced rapid cell lysis in non-small cell lung, HCC and human bladder cancer in vitro cell preparations. Intratumoral and intravenous administration of IVX037 in human tumor xenograft models using immunocompromised mice were well tolerated and displayed potent anti-tumor activity against ovarian, gastric and HCC cancers. In reference, to cell-based therapies, preliminary in vitrocombination studies with mesothelin-targeted CAR T-cells and IVX037 suggest enhanced tumor cell killing compared to that of either agent alone in a human gastric cancer cell culture model. Conclusions: The promising preclinical anti-tumor activity of IVX037 and IVX055 against a wide range of human malignancies warrants further clinical evaluation in combination with novel immunotherapy strategies. To this end, IVX037 is currently being investigated in an ongoing Phase 1b combination trial with sintilimab (anti-PD-1) in patients with advanced MSS-CRC, gastroesophageal, and ovarian cancer (NCT05427487). Future plans for IVX055 include evaluation in combination with immune checkpoint therapy in patients with advanced non-small cell lung cancer (NSCLC) bearing metastatic liver disease. Citation Format: Darren Shafren, Christine Lee, Jera Peters, Szun Tay, Chloe Evans, Min Quah. Novel oncolytic RNA viruses, IVX037 and IVX055, demonstrate potent antitumor activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 859.