Date: 2017-05-12
Type of
information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the 20th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT)
Company: VBL Therapeutics (Israel)
Product: VB-111 (ofranergene obadenovec) and immune checkpoint inhibitor
Action
mechanism:
- gene therapy/immune checkpoint inhibitor. Ofranergene obadenovec is a unique biologic agent that uses a dual mechanism to target solid tumors. Based on a non-integrating, non-replicating, Adeno 5 vector, ofranergene obadenovec utilizes VBL's proprietary Vascular Targeting System (VTS™) to target the tumor vasculature for cancer therapy. Unlike anti-VEGF or TKIs, ofranergene obadenovec 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 retains activity regardless of baseline tumor mutations or the identity of the pro-angiogenic factors secreted by the tumor and shows activity even after failure of prior treatment with other anti-angiogenics. Moreover, ofranergene obadenovec induces specific anti-tumor immune response, which is accompanied by recruitment of CD8 T-cells and apoptosis of tumor cells.
Disease: lung cancer, melanoma
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
Latest
news:
- • On May 12, 2017, VBL Therapeutics has presented new preclinical data indicating that treatment with ofranergene obadenovec (VB-111) augments the anti-tumor activity of a PD-L1 blocker in lung cancer and melanoma models in a poster session at the 20th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), taking place in Washington, DC.
- Immunotherapy with checkpoint inhibitors demonstrates remarkable efficacy in several cancers; yet, only a low percentage of patients seem to benefit from this class of treatment when given as a monotherapy. Several studies have shown that response rates are increased when checkpoint blockade is combined with other anti-cancer treatments. VB-111 is a biologic agent that is being currently studied in a Phase 3 clinical trial for recurrent glioblastoma (rGBM). VB-111 specifically targets angiogenic endothelial cells and promotes antitumor immune response. In the study, VB-111 was evaluated in combination with an anti-PD-L1 checkpoint inhibitor in lung and melanoma cancer models, indications for which PD-1 blockers are already marketed.
- VBL's data show that treatment with either VB-111 or anti-PD-L1 reduced tumor burden in mice induced with Lewis lung carcinoma (LLC), by 42% and 51% versus saline control, respectively; however, the combination of both agents resulted in an amplified effect (67% reduction versus control; p?0.001), and similar results were seen in a melanoma model. In addition, treatment with VB-111 and anti-PD-L1 enhanced infiltration of CD8+ cells to lung tumors.
- VB-111 is currently studied in the pivotal Phase 3 GLOBE trial in rGBM, comparing VB-111 in combination with Avastin® (bevacizumab) to Avastin alone, which is being conducted in the US, Canada and Israel. Enrollment in the study, 256 patients in total, was completed earlier this year, five months ahead of schedule. The study is proceeding under a Special Protocol Assessment (SPA) granted by the FDA, with full endorsement by the Canadian Brain Tumor Consortium (CBTC). The Company expects to report interim data from the GLOBE trial in Q3-2017, with top-line results from the full dataset expected to be available in early 2018.
- VBL plans to launch a Phase 3 study for VB-111 in combination with chemotherapy for platinum-resistant ovarian cancer in the second half of 2017. Launch of an exploratory clinical study on VB-111 in combination with a checkpoint inhibitor in lung cancer is also expected by year-end 2017.
Is
general: Yes
