1. A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE).
- Author
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Cloughesy, Timothy F, Brenner, Andrew, de Groot, John F, Butowski, Nicholas A, Zach, Leor, Campian, Jian L, Ellingson, Benjamin M, Freedman, Laurence S, Cohen, Yael C, Lowenton-Spier, Noa, Rachmilewitz Minei, Tamar, Fain Shmueli, Shifra, GLOBE Study Investigators, and Wen, Patrick Y
- Subjects
GLOBE Study Investigators ,Humans ,Glioblastoma ,Brain Neoplasms ,Angiogenesis Inhibitors ,Antineoplastic Combined Chemotherapy Protocols ,Treatment Outcome ,Bevacizumab ,Progression-Free Survival ,VB-111 ,anti-angiogenesis ,gene therapy ,glioblastoma ,viral immuno-oncology ,glioblastoma VB-111 ,Brain Disorders ,Cancer ,Clinical Trials and Supportive Activities ,Rare Diseases ,Brain Cancer ,Clinical Research ,Neurosciences ,6.1 Pharmaceuticals ,6.2 Cellular and gene therapies ,Oncology & Carcinogenesis ,Oncology and Carcinogenesis - Abstract
BackgroundOfranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab.MethodsThis pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS).ResultsEnrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91-1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3-5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction.ConclusionsIn this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results.Clinical trials registrationNCT02511405.
- Published
- 2020