Toca 511 & Toca FC: Evaluation of Durable Response Rate in the Post-Resection Setting and Association with Survival in Patients with Recurrent High Grade Glioma (S23.006) (2018)

Objective: To assess safety, tolerability, and efficacy of Toca 511 and Toca FC in patients with recurrent high grade glioma (rHGG). Background: 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 (an investigational, extended-release formulation of 5-fluorocytosine) into 5-fluorouracil. 5-fluorouracil kills infected and nearby cancer cells, myeloid derived suppressor cells and tumor associated macrophages, enabling immune activity against the tumor. Design/Methods: 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 investigational therapy with bevacizumab or lomustine. Results: Objective responses (ORs) were assessed by independent radiology review using MRI images 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 with IDH1 mutant tumors, including 5 complete responses (CRs) with the investigational therapy, and 1 CR with the investigational therapy and bevacizumab. The median duration of response (mDoR) was 35.1+ months. Excluding combination cohorts, mDoR was 35.7+ months. As of 8/15/2017, all responders were in CR and alive. In a 23-patient subgroup who received the recommended Ph3 Toca 511 dose, mOS was 14.4 months, 3-year survival rate was 26.1%, and a durable response rate of 21.7% was observed. Across the Ph1 program, the safety profile remains favorable. Conclusions: CRs were observed in patients with IDH1 wildtype and mutant tumors, suggesting a benefit across the rHGG setting. Data suggests a positive association of durable response with overall survival. Disclosure: Dr. Cloughsey has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with ? Tocagen, ROCHE, VBL, CUNOVION, HUMAN LONGEVITY, BOSTON BIOMEDICAL, ALEXION, WELLCOME TRUST, NOVOGEN, NOVOCURE, BMS, ABBVIE, GW PHARMA, CORTICE, MERCK,. Dr. Cloughsey has received compensation for serving on the Board of Directors of NOTABLE LABS. Dr. Landolfi has nothing to disclose. Dr. Vogelbaum has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Tocagen, Medicenna. Dr. Vogelbaum has received royalty, license fees, or contractual rights payments from Cleveland Clinic. Dr. Vogelbaum holds stock and/or stock options in Johnson and Johnson. Dr. Vogelbaum has received research support from Infuseon Therapeutics. Dr. Ostertag has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Tocagen. Dr. Elder has nothing to disclose. Dr. Carter has nothing to disclose. Dr. Chen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Monteris, Tocagen, MRI Intervention, Varian. Dr. Kalkanis has nothing to disclose. Dr. Kesari has nothing to disclose. Dr. Lai has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck. Dr. Lee has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Medtronic, Monteris. Dr. Liau has received personal compensation in an editorial capacity for Journal of Neuro-Oncology. Dr. Nghiemphu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie. Dr. Nghiemphu has received research support from Novartis. Dr. Piccioni has nothing to disclose. Dr. Accomando has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Tocagen. Dr. Accomando has received research support from Tocagen. Dr. Diago has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Tocagen. Dr. Hogan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Tocagen. Dr. Jolly has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Tocagen. Dr. Jolly has received research support from Tocagen. Dr. Wood has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Tocagen. Dr. Kheoh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with JOHNSON & JOHNSON. Dr. Gruber has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Tocagen. Dr. Gruber has received compensation for serving on the Board of Directors of Tocagen. Dr. Gruber holds stock and/or stock options in Tocagen, which sponsored research in which Dr. Gruber was involved as an investigator. Dr. Gruber holds stock and/or stock options in Tocagen. Dr. Das has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Tocagen. Dr. Walbert has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Tocagen.