Toca 511 (vocimagene amiretrorepvec) is an investigational retroviral replicating vector that selectively infects dividing cancer cells, integrates into the genome and replicates due to immune defects in tumors. Toca 511 spreads through tumors and stably delivers the gene encoding an optimized yeast cytosine deaminase that converts the prodrug Toca FC (investigational, extended-release of 5-fluorocytosine) into 5-fluorouracil. In preclinical models, 5-fluorouracil kills infected dividing cancer cells, myeloid derived suppressor cells and tumor associated macrophages, enabling immune activation against the tumor. In this dose ascending Ph1 trial (NCT01470794), Toca 511 was injected into the resection cavity wall of patients with rHGG, followed by courses of oral Toca FC. Additional cohorts included combination with bevacizumab or lomustine. Across the Ph1 program, the safety profile remains favorable. Objective responses (ORs) were assessed by IRR using MRI scans prior to Toca FC treatment as baseline. ORs occurred 6-19 months after Toca 511 administration, suggesting an immunologic mechanism. The ORs were observed in 4 patients with IDH1-wildtype and 2 patients with IDH1-mutant tumors, including 5 complete responses (CRs) with the investigational therapy alone, and 1 CR in combination with bevacizumab. The median duration of response (mDoR) was 35.1+ months. As of AUG2017, all responders were CR and remain alive. In a 23-patient subgroup who received high doses of Toca 511 and met Ph3 trial criteria, mOS was 14.4 months, 3-year survival rate was 26.1%, and mDoR was 35.7+ months with a durable response rate of 21.7%. Data suggest a positive association of durable response with OS.