Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma: results of a phase I/II study
Year: 2019
Type: article
Study design: Clinical Trial
Abstract: 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.
Source: Neuro-Oncology
Authors: 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
Institutions: Mays Cancer Center at UT Health San Antonio, Duke Medical Center, Saint Francis Hospital & Medical Center, Tel Aviv University, Tel Aviv Sourasky Medical Center, Rabin Medical Center, Sheba Medical Center, University of California, Los Angeles, Ronald Reagan UCLA Medical Center, Center for Neuro-Oncology, Dana-Farber Cancer Institute
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,132
OpenAlex ID: W2995556690