ATIM-05. COMPLEMENTARY CLINICAL AND ANCILLARY DATA FROM 123 PATIENTS WITH RECURRENT HIGH GRADE GLIOMA FROM THREE PHASE 1 TRIALS OF TOCA 511 AND TOCA FC: UPDATE AND JUSTIFICATION FOR A PHASE 2/3 TRIAL

Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector. The vector infects human cells with selectivity for cancer cells because genome integration is dependent on cell division and viral replication is inhibited by innate and adaptive immune responses, defective in malignant tissues. Toca 511 spreads through cancer cells and stably delivers the gene for an optimized yeast cytosine deaminase that converts courses of the prodrug Toca FC (an investigational, extended-release version of 5-fluorocytosine) into 5-fluorouracil (5-FU). The 5-FU directly kills cancer cells likely leading to activation of antigen presenting cells in the tumor microenvironment. 5-FU can also diffuse into nearby immunosuppressive myeloid cells and kill them, leading to further activation of the immune system against the tumor by removing an important inflammatory brake. The safety, viral kinetics, immune response, and preliminary efficacy of Toca 511 and Toca FC have been investigated since 2010 in three, open-label, ascending dose, Phase 1 studies of 123 patients with recurrent high grade glioma (rHGG), each evaluating different methods of Toca 511 administration (intratumoral injection, injection into the cavity wall following resection, and intravenous injection followed by resection and injection into resection cavity wall) followed by multiple courses of oral Toca FC. Results to date include good tolerability; no persistent viremia; successful gene transduction within resected tumors; and median overall survival with stereotactic biopsy needle, resection cavity wall, and intravenous/cavity wall vector injection ranging from 12.1–13.6 months. Analysis of pretreatment resected tumor samples for mRNA expression patterns showed a survival-related signature that otherwise does not correlate with survival in publically available databases. Preliminary data from these studies supported initiation of a randomized, Phase 2/3 study in patients with rHGG (NCT02414165) in 2015. Updated and pooled safety data, immune response findings, and updated efficacy data for the Phase 1 studies will be presented.