Abstract 4295: INT230-6, a novel intratumoral anticancer agent, is able to eradicate large established tumors and stimulate potent anti tumor immunity

Abstract

Abstract Historically, intratumoral (IT) administered chemotherapy has not been shown to provide better efficacy than the same drugs delivered intravenously. This is postulated to be due to poor drug diffusion and dispersion throughout the tumor. Intensity has developed a novel formulation of cytotoxic chemotherapy plus a penetration enhancer which improves drug diffusion and uptake into the cancer cell. INT230-6 is a combination of low dose cisplatin, vinblastine and a cell penetration excipient. This technology enables more rapid and improved penetration throughout the tumor including hypoxic and un-vascularized areas. Cohorts of 10 BALB/c mice were inoculated with 1×106 CT26 cells subcutaneously (SC). Tumors were grown to a mean of 325mm3 and then treatment with INT230-6 was administered IT daily for a single cycle of 5 days. Control arms using comparable size tumors pre-dose included no treatment, IV cisplatin and vinblastine, and IT injection of these drugs without the enhancer. INT230-6 treatment resulted in regression from baseline in all animals with a complete regression of the large tumors in 20%. Many tumors continued to shrink in size well beyond multiple half-lives of the chemotherapy and excipient implying an anti-tumor effect not due to direct cytotoxicity from the drugs. INT230-6 administration resulted in a significant extension of overall survival compared to all controls. Notably complete responders with this treatment were resistant to 3 separate attempts at re-inoculation with 1×106 CT26 cells by SC or IV administration without retreatment of drug, while control animals rapidly developed metastatic tumors and died. This apparent tumor immunity persisted for > 440 days suggesting permanent immunity. In a follow-on study, tumors of some animals receiving INT230-6 were shown to be 75% necrotic on day 3 of treatment with an observed increase in the density of CD4 positive cells and CD11c positive cells in the treated tumors on day 10 versus controls. These changes might be involved in the induction of immunity. These results suggest that intratumoral administration of INT230-6 creates the proper tumor cell apoptosis kinetics and antigen presentation to enable a personalized adaptive immune response to develop. Further work is being done to look at repeat dosing and combinations with other immunomodulating agents. Citation Format: Ian B. Walters, Lewis H. Bender, Masaki Terabe, Jay A. Berzofsky. INT230-6, a novel intratumoral anticancer agent, is able to eradicate large established tumors and stimulate potent anti tumor immunity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4295. doi:10.1158/1538-7445.AM2015-4295