Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma: Results of a phase I/II study

Andrew J. Brenner*, Katherine B. Peters, James Vredenburgh, Felix Bokstein, Deborah T. Blumenthal, Shlomit Yust-Katz, Idit Peretz, Bernice Oberman, Laurence S. Freedman, Benjamin M. Ellingson, Timothy F. Cloughesy, Naamit Sher, Yael C. Cohen, Noa Lowenton-Spier, Tamar Rachmilewitz Minei, Niva Yakov, Itzhak Mendel, Eyal Breitbart, Patrick Y. Wen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Background: VB-111 is a non-replicating adenovirus carrying a Fas-chimera transgene, leading to targeted apoptosis of tumor vascular endothelium and induction of a tumor-specific immune response. This phase I/II study evaluated the safety, tolerability, and efficacy of VB-111 with and without bevacizumab in recurrent glioblastoma (rGBM). Methods: Patients with rGBM (n = 72) received VB-111 in 4 treatment groups: subtherapeutic (VB-111 dose escalation), limited exposure (LE; VB-111 monotherapy until progression), primed combination (VB-111 monotherapy continued upon progression with combination of bevacizumab), and unprimed combination (upfront combination of VB-111 and bevacizumab). The primary endpoint was median overall survival (OS). Secondary endpoints were safety, overall response rate, and progression-free survival (PFS). Results: VB-111 was well tolerated. The most common adverse event was transient mild-moderate fever. Median OS time was significantly longer in the primed combination group compared with both LE (414 vs 223 days; hazard ratio [HR], 0.48; P = 0.043) and unprimed combination (414 vs 141.5 days; HR, 0.24; P = 0.0056). Patients in the combination phase of the primed combination group had a median PFS time of 90 days compared with 60 in the LE group (HR, 0.36; P = 0.032), and 63 in the unprimed combination group (P = 0.72). Radiographic responders to VB-111 exhibited characteristic, expansive areas of necrosis in the areas of initial enhancing disease. Conclusions: Patients with rGBM who were primed with VB-111 monotherapy that continued after progression with the addition of bevacizumab showed significant survival and PFS advantage, as well as specific imaging characteristics related to VB-111 mechanism of action. These results warrant further assessment in a randomized controlled study.

Original languageEnglish
Pages (from-to)694-704
Number of pages11
Issue number5
StatePublished - 15 May 2020


FundersFunder number
National Cancer InstituteP50CA211015
National Cancer Institute


    • VB-111
    • anti-angiogenesis
    • gene therapy
    • glioblastoma
    • viral immuno-oncology


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