VBL Therapeutics announced that an investigational new drug (IND) application has received clearance from the U.S. FDA for approval to commence a phase 2 trial in patients with recurrent glioblastoma multiforme (rGBM). The IND was submitted by Patrick Wen, M.D., Director, Center for Neuro-Oncology, Dana-Farber Cancer Institute, on behalf of a group of top neuro-oncology US medical centers.
Specifically, the IND is for a randomized, controlled, clinical trial of VB-111 patients with recurrent glioblastoma multiforme (rGBM) undergoing a second surgery. In this study, VB-111 will be administrated either before and after the surgery (neoadjuvant and adjuvant therapy) or just after the surgery (adjuvant therapy) and will be compared to a standard of care control cohort. The primary endpoint of this study in patients with surgically accessible rGBM is to investigate whether administration of VB-111 as a neo-adjuvant treatment prior to surgery can result in an increase in tumor-infiltrating T lymphocyte (TIL) within the tumor and enhance systemic tumor-specific T cell responses. Secondary endpoints will include progression-free survival at 6 months (PFS-6) and overall survival (OS).
A prior Phase 2 study demonstrated a survival benefit for patients with rGBM primed with VB-111 monotherapy that was continued upon progression with a combination of VB-111 and bevacizumab.
Additional details about the study will be presented at the 2019 Society for Neuro-Oncology annual meeting, to be held on November 20 – 24, 2019 in Phoenix, Arizona.
VB-111 is a unique biologic agent that uses a dual mechanism to target solid tumors:
Based on a non-integrating, non-replicating, Adeno 5 vector, it utilizes VBL’s proprietary Vascular Targeting System (VTS™) to target the tumor vasculature for cancer therapy. Unlike anti-VEGF or TKIs, VB-111 does not aim to block a specific pro-angiogenic pathway; instead, it uses an angiogenesis-specific sensor (VBL’s PPE-1-3x proprietary promoter) to specifically induce cell death in angiogenic endothelial cells in the tumor milieu. This mechanism may retain activity regardless of baseline tumor mutations or the identity of the pro-angiogenic factors secreted by the tumor and may show activity even after the failure of prior treatment with other anti-angiogenic.
Moreover, VB-111 induces a specific anti-tumor immune response, which is accompanied by the recruitment of CD8 T-cells and apoptosis of tumor cells.
Glioblastoma is an aggressive type of cancer that can occur in the brain or spinal cord. Glioblastoma forms from cells called astrocytes that support nerve cells. Glioblastoma can occur at any age but tends to occur more often in older adults. It can be very difficult to treat, and a cure is often not possible. Treatments may slow the progression of cancer and reduce signs and symptoms.