TEL AVIV, Israel--(BUSINESS WIRE)--VBL Therapeutics, a clinical-stage biotechnology company committed to the development of novel treatments for immune-inflammatory diseases and cancer, today announced the publication of Ph1 data for VB-111 in the journal of Clinical Cancer Research. The manuscript reports a first in man clinical trial of VB-111, VBL’s lead anti-angiogenic Virotherapy candidate, demonstrating its safety and tolerability in patients with advanced metastatic cancer at a single administration of up to 1x1013 Viral Particles (VPs). Notably, tumor response and superior overall survival were found in the 1x1013 VPs cohort compared to sub-therapeutic doses. The data confirm pre-clinical findings in animal models and validate VB-111's mechanism of action, resulting in a targeted expression of the FAS-chimera transgene selectively in tumor vasculature.
The Phase 1 clinical trial, conducted at The Cleveland Clinic and The University of Texas Health Science Center at San Antonio, evaluated the safety, tumor response, overall survival and biodistribution, of a single, intravenous administration of VB-111. The trial enrolled a total of 33 patients across seven dose cohorts, with advanced solid tumors, and no existing curative therapy, who had adequate organ function and performance status. Patients had frequent clinical and laboratory safety evaluations.
“The mechanism behind this anti-angiogenic virotherapy is truly unique” said Pierre Triozzi, M.D., Solid Tumor Oncology Department, Cleveland Clinic, and the principal investigator in the Phase 1 trial. “We have seen antitumor activity after only one dosing, with an excellent safety profile. VB-111 has a real potential for clinical development to treat a variety of advanced metastatic cancers”.
The trial has found VB-111 to be safe and well tolerated up to the maximum administered single dose of 1x1013 VPs. MTD was not reached. There were no drug related serious adverse events. A self-limited febrile reaction was frequent among patients receiving a dose of 1x1012 VPs and above, as has previously been described with adenovirus vectors. Evidence of antitumor activity was found after a single dose administration as well as evidence of a dose response. Disease stabilization was observed in many patients; one patient (with papillary thyroid carcinoma) developed a partial response at 6 months, which persisted for 18 months post-dosing. There was a statistically significant increase in overall survival in cohort 7 (1x1013 VPs) compared to lower doses (cohorts 1-6) (p=0.0098) as well as a trend towards improved progression free survival in this cohort (p=0.10).
For access to the manuscript please see: http://www.ncbi.nlm.nih.gov/pubmed/23589178
“The results to date further demonstrate VB-111’s promise as a targeted cancer treatment with potential efficacy across a broad range of cancers. We continue to explore VB-111’s unique mechanism of action, which allows it to target tumors with precision and specificity, and to advance our ongoing, multi-dose Phase 2 clinical trials in gliobastoma multiforme, differentiated thyroid cancer and ovarian cancer", said Yael Cohen, M.D., vice president of clinical development at VBL. "We are pleased and encouraged by the tumor response and overall survival results in the clinical studies of VB-111, which will be showcased on Saturday, June 1st, at the coming ASCO conference in Chicago.”
VB-111 is an IV-administered anti angiogenic agent that utilizes VTS™, VBL’s proprietary platform technology for cancer therapy. VB-111 works similar to a “biological knife”, cutting off the blood vessels feeding the tumor.
Preclinical pharmacological and toxicology studies of VB-111 showed specificity for the tumor tissue, no significant damage to normal non-cancerous tissues or to the normal vasculatures in the body, and a more than 90 percent tumor burden reduction in a metastatic lung cancer model with one injection, as well as similar efficacy in other tumor models. VB-111 is currently in multi-dose Phase 2 clinical trials for gliobastoma multiforme, differentiated thyroid cancer and ovarian cancer.