New Phase 2 Patient Data Presented at ASCO Strengthen the Evidence for Anti-Tumor Activity of VB-111 in Recurrent GBM
VBL's Phase 2 multi-center study for VB-111 was designed to determine the safety, tolerability and efficacy of VB-111 in patients with rGBM. A total of 46 patients were enrolled in two sequential cohorts. In the first cohort, patients were treated with VB-111 as monotherapy for a median of only one dose and, upon disease progression, switched to Avastin (bevacizumab) alone as standard of care (Limited Exposure cohort). This cohort behaved like an Avastin historical control with a median Overall Survival (mOS) of 8 months.
In the second cohort, patients continued to receive treatment with VB-111 after progression, in combination with Avastin as the standard of care (Treatment Through Progression cohort). This cohort received in median 4 doses of VB-111, about 8 months of treatment.
VBL previously reported that the study met the primary endpoint of statistically-significant increase in median overall survival, with 59 weeks in patients treated continuously with VB-111, compared to 32 weeks in patients with only one dose (in median) of VB-111 (p=0.048), both groups having received Avastin upon progression after a short course of VB-111. 12-Month overall survival was 57% in the VB-111 continuous exposure cohort, compared with only 24% in historical pooled Avastin trials (p=0.03), consistent with data indicating that Avastin monotherapy does not improve OS in rGBM patients.
To further understand the why treatment with VB-111 was associated with prolonged survival, VBL analyzed the tumor growth kinetics in all rGBM patients who participated in the VB-111 Phase 2 trial. These new data demonstrate that tumor growth kinetics was significantly attenuated upon longer treatment with VB-111.
Whereas brief exposure to VB-111 was associated with tumor progression in most patients, longer exposure to VB-111 (median= 4, mean=4.7 doses) led to attenuation of tumor growth kinetics (median % increase (MPI) per 30 days: 0.6 vs 14.1, p=0.0032). Furthermore, tumor regression was more frequent upon longer exposure to VB-111; only 16% of patients with limited exposure to VB-111 had tumors shrink below baseline dimensions during the first 100 days, compared to 61% of patients who continued to receive VB-111 through progression (p=0.002; McNemar's test). Except for longer treatment with VB-111 leading to favorable OS, there was no evidence for difference between the two cohorts in any of the criteria tested, including patient characteristics, initial tumor growth kinetics, and Avastin treatment of both groups.
Overall, VBL's Phase 2 data point to a favorable anti-tumor effect of VB-111 in rGBM, in terms of both regression rate and overall survival following treatment through progression, compared to both brief exposure to VB-111 with subsequent Avastin monotherapy and to historical data of Avastin monotherapy. Notably, responses were seen even with VB-111 monotherapy, including a patient who remains in complete remission after over 3 years.
"The new analysis supports the benefit of continuous exposure to VB-111 in combination with Avastin, on both inhibition of tumor growth and survival in rGBM patients,” said Dr.
VBL's pivotal Phase 3 GLOBE study in rGBM, comparing VB-111 in combination with Avastin to Avastin alone, is currently being conducted in the US,
The new Phase 2 data will be presented in a poster session at
About Ofranergene Obadenovec (VB-111)
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.
Ofranergene obadenovec completed a Phase 2 study in rGBM, which showed a statistically significant improvement in overall survival in patients treated with ofranergene obadenovec through progression, compared to either patients treated with ofranergene obadenovec followed by bevacizumab alone, or to historical bevacizumab data. In a Phase 2 trial for recurrent platinum-resistant ovarian cancer, ofranergene obadenovec demonstrated a statistically significant increase in overall survival and 60% durable response rate (as measured by reduction in CA-125), approximately twice the historical response with bevacizumab plus chemotherapy in ovarian cancer. In a Phase 2 study in recurrent, iodine-resistant differentiated thyroid cancer, ofranergene obadenovec met the primary endpoint demonstrating disease stabilization with a positive safety profile, along with a dose-response and evidence of an overall survival benefit. Ofranergene obadenovec has received Fast Track Designation for recurrent glioblastoma in the U.S. and orphan drug status for glioblastoma in both the U.S. and EU.
Forward Looking Statements
This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “look forward to”, “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions. These forward-looking statements include, but are not limited to, statements regarding the clinical development of ofranergene obadenovec (VB-111), including our expectations regarding the timing of results from the GLOBE study, and its therapeutic potential and clinical results. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include uncertainties associated generally with research and development, clinical trials and related regulatory reviews and approvals, and the risk that historical clinical trial results may not be predictive of future trial results. In particular, results from our pivotal Phase 3 clinical trial of ofranergene obadenovec (VB-111) in rGBM may not support approval of ofranergene obadenovec for marketing in
Avastin® (bevacizumab) is a registered trademark of
Michael Rice LifeSci Advisors, LLC(646) 597-6979 MEDIA CONTACT: Matt Middleman, M.D. LifeSci Public Relations (646) 627-8384