A study of neo-adjuvant and adjuvant ofra-vec (VB-111) for treatment of surgically accessible recurrent GBM.

Abstract

TPS2075 Background: Ofranergene obadenovec (ofra-vec, VB-111) is an anti-cancer gene based immune activator and targeted vascular disruptor. The dual mechanism of action triggers a broad antiangiogenic effect and induces of a tumor directed immune response. A previous study demonstrated a survival benefit for patients with recurrent glioblastoma (rGBM) treated with ofra-vec monotherapy, that was continued after progression in combination with bevacizumab. Glioblastoma is an immunologically “cold” microenvironment which fosters immunosuppression and antagonizes anti-tumor immune responses. The role of T-cell infiltration in combating cancer has been increasingly recognized and associated with improved participant outcomes. Based on these observations, this study will assess the hypothesis that neoadjuvant use of ofra-vec will lead to a statistically significant increase in tumor infiltrating T lymphocyte (TIL) density within the tumor and enhanced systemic tumor-specific T cell responses. Methods: Study NCT04406272 is a multicenter, randomized, blinded, placebo-controlled, phase 2 surgical trial to evaluate early immunologic pharmacodynamic parameters for the viral cancer therapy ofra-vec in rGBM. 45 participants with rGBM indicated for resection will randomized to one of three treatment arms: Neoadjuvant Arm: intravenous ofra-vec prior to resection, and ofra-vec every 6 weeks after resection. Adjuvant Arm: placebo prior to resection, and ofra-vec every 6 weeks afterwards. The control arm will receive placebo prior to resection followed by standard of care. Upon evidence of contrast-enhancing progression, bevacizumab may be initiated as needed for supportive care; however, ofra-vec will continue until progression is supported at two consecutive time points. Tumor samples will be obtained and archived at the time of surgery, and blood samples will be obtained as pharmacodynamic markers throughout the study to allow DNA sequencing of T cells. The primary endpoint is to evaluate the influence of neoadjuvant ofra-vec on TIL density. Other endpoints include safety and tolerability, peripheral T cell response, 6mPFS and OS. Study is open for enrolment. Clinical trial information: NCT04406272.