RBTT-11. NRG ONCOLOGY NRG-BN006: A PHASE II/III RANDOMIZED, OPEN-LABEL STUDY OF TOCA 511 AND TOCA FC WITH STANDARD OF CARE COMPARED TO STANDARD OF CARE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract

Abstract The standard of care (SOC) in newly diagnosed glioblastoma (nGBM) includes resection and chemoradiotherapy. With a median overall survival (OS) of only 16–18 months for well-selected patients in clinical trials, better therapeutic options are needed. Toca 511 (vocimagene amiretrorepvec) is a retroviral replicating vector encoding a codon optimized, heat stabilized cytosine deaminase that converts Toca FC (extended-release 5- fluorocytosine,5-FC) into 5-fluorouracil. Preclinical evidence demonstrates that Toca 511 & 5-FC kill cancer cells and immunosuppressive myeloid cells in the tumor microenvironment, leading to durable antitumor immune responses. Three phase (P) 1 studies in patients with recurrent high grade glioma have demonstrated tolerable safety profile and encouraging efficacy. NRG-BN006 is a randomized P2/3 trial of Toca 511 & Toca FC with SOC versus SOC for patients with nGBM. Optune use is allowed on the SOC arm, but not on the experimental arm. Patients will be stratified by age and KPS score for 1:1 randomization. The primary endpoint is progression-free survival for P2 and OS for P3. The secondary endpoints include objective response rate in patients with measurable disease and safety. Key inclusion criteria include presumptive diagnosis of glioblastoma with anticipated 80% resection, unifocal tumor, and KPS≥70. Immune monitoring and molecular profiling will be performed. P2 has 90% power to detect a hazard ratio (HR)=0.67 in 250 nGBM patients. P3 has 85% power to detect a HR=0.75 in 720 nGBM patients. Since patients are enrolled prior to surgery and confirmatory diagnosis of GBM, approximately 900 patients will be enrolled, and two interim analyses are planned for OS. In addition, two interim safety analyses will be conducted for the experimental treatment, with the first 15 and 30 eligible and analyzable patients randomized to the experimental arm. NRG-BN006 is anticipated to start enrollment in Q4 2019. Supported by grants U10CA180868, U10CA180822 from NCI and Tocagen.