Abstract B010: Antitumor cellular immune response elicited by Toca 511 and Toca FC therapy in preclinical and clinical studies

Abstract

Abstract Toca 511 (vocimagene amiretrorepvec), in combination with Toca FC (5-FC; flucytosine extended-release tablets), is an investigational combination product currently under development for the treatment of high-grade glioma (HGG) and other solid tumors. Toca 511 is a gamma-retroviral replicating vector (RRV) delivering a cytosine deaminase transgene to infected cells to convert antifungal drug 5-fluorocytosine (5-FC) into antineoplastic drug 5-fluorouracil (5-FU). Toca 511 can be administered by multiple routes; selectively infects, spreads, and persists in cancer cells; and through multiple mechanisms of action can elicit an antitumor immune response. Treatment directly kills infected cancer cells. Diffusible 5-FU also kills neighboring susceptible cells that contribute to the immune-suppressed tumor microenvironment, especially myeloid immune suppressor cells. After multiple cycles of 5-FC, treated animals that clear tumor are resistant to tumor rechallenge. Adoptive transfer recipients of splenocytes from animals that previously cleared their tumor through treatment with Toca 511 and 5-FC experience a significant survival benefit compared to animals receiving spleen cells from naïve donors. Toca 511 and Toca FC have been administered to 126 recurrent high-grade glioma (rHGG) patients in three phase I studies (NCT01156584, NCT01470794, NCT01985256), and a phase 2/3 trial (Toca 5) is ongoing (NCT02414165). Toca 511 plus Toca FC has been well tolerated in these patients. In the clinical study presented, Toca 511 is injected into resection cavity walls at time of tumor resection, and followed with multiple courses of Toca FC. In a subset of phase I patients that mimic the phase 2/3 rHGG enrollment criteria, there were 3 complete responses and 2 partial responses out of 24 patients observed. The median duration of response is 26.7 months. These responders have an overall survival range from 24.0+ to 42.6+ months and ongoing. Data are consistent with induction of antitumor immune responses after Toca FC administration. Changes in peripheral immune populations as well as interrogation of immunogenic biomarkers in responding compared to nonresponding patients will be presented. Citation Format: Tiffany T. Montellano, Derek Ostertag, Daniel J. Hogan, Oscar R. Diago, Dawn Gammon, Ali Haghighi, William Accomando, Leah Mitchell, Asha Das, Harry Gruber, Douglas J. Jolly. Antitumor cellular immune response elicited by Toca 511 and Toca FC therapy in preclinical and clinical studies [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B010.