TEL AVIV, Israel—VBL Therapeutics has announced that the first patient has been dosed in the company's GLOBE™ Study, a pivotal Phase 3 trial of VB-111, an intravenously-administered, gene-therapy biological agent for the specific inhibition of tumor vascular growth, in recurrent glioblastoma (rGBM). The trial is proceeding under a special protocol assessment granted by the U.S. Food and Drug Administration.
"This is an unusual situation in which the FDA encouraged VBL to launch this single needed pivotal Phase 3 trial for registration even prior to the completion of an ongoing Phase 2 trial," said Dror Harats, M.D., CEO of VBL Therapeutics. "This FDA decision in 2014 was derived from the promising data of an early interim analysis from our ongoing Phase 2 study of VB-111 in rGBM. Later analyses demonstrated even longer overall survival benefit along with statistical significance."
The GLOBE trial is designed to evaluate the efficacy, safety and tolerability of VB-111. The primary endpoint of the study is overall survival. The trial will also measure effects of treatment towards a number of additional clinical endpoints, including progression free survival (PFS), tumor response as measured by Response Assessment in Neuro-Oncology (RANO) criteria and quality of life. VBL has received Fast Track Designation for rGBM in the U.S. and orphan drug status in both the U.S. and EU. Interim data from this pivotal Phase 3 trial is expected in the second half of 2016.
"rGBM is devastating disease for which there are limited treatment options and there is a substantial unmet need for safe therapies that will prolong patients' lives, as the median overall survival with bevacizumab (Avastin®), the current standard of care, is only eight to nine months," said Yael Cohen, M.D., vice president, clinical development of VBL Therapeutics. "We are very encouraged by the clinical activity and tolerability seen with VB-111 to date, including in our Phase 2 study, where we saw a statistically significant benefit in overall survival in patients treated with VB-111 in combination with bevacizumab upon disease progression compared to patients treated with bevacizumab monotherapy (16 months v. 8 months, p=0.05). We believe that VB-111 has the potential to change the treatment paradigm for rGBM patients, who are at great need for an effective therapy."
"The initiation of this clinical trial represents a critical step forward for VBL, as we continue to execute on our goal of developing and commercializing first-in-class treatments for cancer," continued Harats. "Beyond rGBM, VB-111 has shown promising efficacy signals in both recurrent, platinum-resistant ovarian cancer and progressive, differentiated thyroid cancer, and we look forward to further evaluating VB-111 for the treatment of these debilitating solid tumor indications as we continue to build out our proprietary pipeline of anti-angiogenic agents."
This pivotal Phase 3 trial is a randomized, controlled, double-arm, open-label study of VB-111 dosed every two months in combination with bevacizumab dosed every two weeks, compared to bevacizumab monotherapy. The trial is expected to enroll 252 patients with rGBM and will recruit patients from 40-60 sites in the United States, Canada and Israel. Key inclusion criteria include first or second progression of glioblastoma following start of care treatment with temozolomide and radiation, a histologically confirmed diagnosis of glioblastoma and measurable disease by RANO criteria at progression.
The primary efficacy endpoint of the study is overall survival. Secondary endpoints of the study include PFS and tumor response as measured by RANO criteria. An analysis of the Phase 2 study suggested that VB-111 may induce an immuno-therapeutic effect in patients, with post-dosing fever correlating with increased overall survival; this potential finding will continue to be evaluated in the Phase 3 study.
VB-111 is a novel, intravenously administered, anti-angiogenic agent that utilizes VBL's proprietary Vascular Targeting System (VTS™) to target endothelial cells in the tumor vasculature for cancer therapy. VB-111 contains a non-replicating adenovirus, a proprietary modified murine pre-proendothelin promoter (PPE-1-3x) and a Fas-Chimera transgene which is specifically activated in angiogenic tumor blood vessels, leading to their apoptosis. VB-111 is the first agent based on transcriptional targeting of tumor endothelium to be assessed in a clinical trial.
VB-111 completed a Phase 2 study in recurrent glioblastoma (rGBM), which demonstrated a statistically significant improvement in overall survival in patients treated with VB-111 followed by VB-111 in combination with bevacizumab upon disease progression, compared to patients treated with VB-111 followed by bevacizumab alone (p=0.05). VB-111 is also being studied in a Phase 2a trial in recurrent platinum-resistant ovarian cancer, which demonstrated promising evidence of clinical benefit in an interim analysis, and in a Phase 2a study in recurrent, iodine-resistant differentiated thyroid cancer, which demonstrated disease stabilization and safety. VB-111 has Fast Track Designation for recurrent glioblastoma in the U.S. and orphan drug status for glioblastoma in both the U.S. and EU.
Vascular Biogenics Ltd., operating as VBL Therapeutics, is a late-stage clinical biopharmaceutical company focused on the discovery, development and commercialization of first-in-class treatments for cancer. The company's lead oncology product candidate, VB-111, is a gene-based biologic that is initially being developed for recurrent glioblastoma, or rGBM, an aggressive form of brain cancer. VB-111 has received orphan drug designation in both the United States and Europe and was granted Fast Track designation by the FDA for prolongation of survival in patients with glioblastoma that has recurred following treatment with standard chemotherapy and radiation. VBL Therapeutics' pivotal Phase 3 GLOBE trial of VB-111 in rGBM is ongoing under a special protocol assessment granted by the FDA.