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Neuro Oncol. 2019 Dec 17. pii: noz232. doi: 10.1093/neuonc/noz232. [Epub ahead of print]

A randomized controlled phase III study of VB-111 combined with bevacizumab vs. bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE).

Author information

1
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
2
University of Texas Health San Antonio Cancer Center, San Antonio, TX, United States.
3
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
4
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, US.
5
Oncology Institute, Chaim Sheba Medical Center, Tel HaShomer, Israel.
6
Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA.
7
UCLA Brain Tumor Imaging Laboratory, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States.
8
Biostatistics and Biomathematics Unit, Gertner Institute for Epidemiology and Health Policy Research, Chaim Sheba Medical Center, Tel Hashomer, Israel.
9
VBL Therapeutics, Modi'in, Israel.
10
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.

Abstract

BACKGROUND:

Ofranergene obadenovec (VB-111) is an anti-cancer 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.

METHODS:

This 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 q8W in combination with bevacizumab 10mg/Kg q2W (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS) and secondary endpoints were objective response rate (ORR) by RANO and Progression Free Survival (PFS).

RESULTS:

256 patients were enrolled 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 vs control arm (HR 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 grade 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 post treatment febrile reaction.

CONCLUSIONS:

In 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.

KEYWORDS:

Anti-angiogenesis; Gene Therapy; Glioblastoma; VB-111; Viral immune-oncology

PMID:
31844890
DOI:
10.1093/neuonc/noz232

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