TY - JOUR
T1 - Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma
T2 - Results of a phase I/II study
AU - Brenner, Andrew J.
AU - Peters, Katherine B.
AU - Vredenburgh, James
AU - Bokstein, Felix
AU - Blumenthal, Deborah T.
AU - Yust-Katz, Shlomit
AU - Peretz, Idit
AU - Oberman, Bernice
AU - Freedman, Laurence S.
AU - Ellingson, Benjamin M.
AU - Cloughesy, Timothy F.
AU - Sher, Naamit
AU - Cohen, Yael C.
AU - Lowenton-Spier, Noa
AU - Rachmilewitz Minei, Tamar
AU - Yakov, Niva
AU - Mendel, Itzhak
AU - Breitbart, Eyal
AU - Wen, Patrick Y.
N1 - Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.
PY - 2020/5/15
Y1 - 2020/5/15
N2 - 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.
AB - 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.
KW - VB-111
KW - anti-angiogenesis
KW - gene therapy
KW - glioblastoma
KW - viral immuno-oncology
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U2 - 10.1093/neuonc/noz231
DO - 10.1093/neuonc/noz231
M3 - Article
C2 - 31844886
AN - SCOPUS:85084784761
SN - 1522-8517
VL - 22
SP - 694
EP - 704
JO - Neuro-oncology
JF - Neuro-oncology
IS - 5
ER -