Vascular Biogenics Ltd (VBLT)

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ASCO abstract 2074: VB-111 for rGBM

Background:
Ofranergene obadenovec (VB-111) is a gene-therapy specifically targeting angiogenic endothelial cells thereby leading to tumor starvation. Safety and efficacy of VB-111 in combination with bevacizumab (BEV) were evaluated in recurrent Glioblastoma (rGBM) patients in this Phase 2 study and were compared to pooled BEV data generated using meta-analysis.

Methods: VB-111 was administered at 1x1013 viral particles bimonthly until progression, followed by BEV standard of care (limited exposure cohort). The protocol was amended to add BEV 10mg/Kg biweekly combined with VB-111 bimonthly, until further progression (continuous exposure cohort). A systematic literature review identified reports of rGBM BEV monotherapy published between 1.1.2009 and 30.11.2015. Data were pooled in a meta-analysis and served as historical controls for comparison of VB-111 extended exposure cohort.

Results: 46 patients at 4 sites received up to 13 doses of VB-111. Upon further progression, 24 received VB-111 with BEV, 22 were treated with BEV as standard of care. VB-111 was safe and well-tolerated alone and combined with BEV. Median OS was 59 weeks for continuous exposure versus 33 weeks for limited exposure cohort (p = 0.048). Eight reports of BEV monotherapy were identified, with a total of 694 rGBM patients. VB-111 continuous exposure had superior OS compared to the pooled meta-analysis of BEV monotherapy, 59 versus 39 weeks (p = 0.0295, log-rank test), with a Hazard Ratio of 0.62 (95% CI: 0.40-0.96). Of 46 patients who received VB-111, 25 patients spiked a fever post- dosing of VB-111 at least once, which was associated with increased median OS of 64 weeks versus 34 weeks among patients without fever (p = 0.03).

Conclusions:
VB-111 was safe and well-tolerated alone and combined with BEV in rGBM patients. VB-111 continuous exposure significantly increased OS compared to a historical BEV meta-analysis controls, and compared to VB-111 limited exposure. Toxicities were as expected in this population. The GLOBE phase 3 randomized controlled trial of VB-111 in rGBM is currently underway. Clinical trial information: NCT01260506

http://abstracts.asco.org/176/AbstView_176_167566.html