A Phase Ib Study Of Toca 511, A Retroviral Replicating Vector, Followed By Toca Fc In Patients With Advanced Cancer

Abstract Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic retroviral replicating vector (RRV) that selectively infects cancer cells. Toca 511 spreads through tumors, stably delivering an optimized cytosine deaminase (CD) gene that converts the prodrug, Toca FC (investigational, extended-release 5-FC), into 5-FU. Based on preclinical studies, 5-FU kills infected dividing cancer cells and diffuses and kills surrounding cancer cells, myeloid derived suppressor cells, and tumor associated macrophages, thus reestablishing tumor immunity. In a previous Phase 1 study, intravenous (IV) injection of Toca 511 successfully delivered and expressed CD protein to high grade glioma tumors. In animal models of metastatic colorectal cancer, IV Toca 511 infected metastatic sites, and subsequent 5-FC treatment resulted in decreased tumor size and improved survival. Toca 6 is a Phase 1b, multicenter, open-label study in patients with advanced solid tumors or lymphoma (NCT02576665) designed to investigate changes in immune activity after treatment with Toca 511 & Toca FC. Vector deposition and transgene expression in tumor tissue following IV delivery of Toca 511 also is followed. Toca 511 is injected IV daily for 3 days, with subsequent injection either intratumorally after biopsy or, in the brain tumor setting, into resection cavity walls following resection. Oral Toca FC is started approximately 4 weeks later and repeated every 4-6 weeks. A total of 30 patients are planned to be enrolled. In patients treated to date, viral RNA, DNA, and CD protein expression after IV Toca 511 delivery have been detected in liver metastases from colorectal cancer and mesenteric lymph node metastases from pancreas cancer, demonstrating IV delivery of virus to and transgene expression in tumor. Preliminary data indicate treatment has been generally well tolerated to date, with few related adverse events. Data on changes from baseline in immune activity in tumor (infiltrating T-cell subpopulations, B cells, monocytes) and peripheral blood (effector, memory, Treg, and myeloid lineage cells), viral and CD protein expression in tumor, and safety will be presented. Citation Format: Jaime Merchan, Jordi Rodon, Gerald Falchook, Shree Venkat, Derek Ostertag, Dalissa Tejera, Thian Kheoh, Douglas J. Jolly, Harry E. Gruber, Jolene S. Shorr. A phase Ib study of Toca 511, a retroviral replicating vector, followed by Toca FC in patients with advanced cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT067.