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, Minei, Tamar Rachmilewitz, Shmueli, Shifra Fain, Avgeropoulos, Nicholas, Beck, Joseph, Benkers, Tara, Bokstein, Felix, Burton, Eric, Butowski, Nicholas, Campian, Jian, Carrillo, Jose, Cloughesy, Timothy, de Groot, John, De Robles, Paula, Drappatz, Jan, Dunbar, Irine, Fink, Karen, Groves, Morris, Han, Xiaosi, Adila, Hormigo, Jensen, Randy, Kowalska, Agnieszka, Kumthekar, Pyriya, Lee, Mijung, Lesser, Glenn, Lossos, Alexander, Lukas, Rimas, Macdonald, David, Mammoser, Aaron, Mechtler, Laszlo, Mohile, Nimish, Nagpal, Seema, Nicholas, Garth, Kreisl, Teri, Pan, Edward, Peak, Scott, Pearlman, Michael, Perry, James, Peterson, Richard, Piccioni, David, Robins, Henry, Ronan, Lara, Salacz, Michael, Schiff, David, Tran, David, Tzuk-Shina, Tzahala, Walbert, Tobias, Wen, Patrick, Youst, Shlomit, and Y, Wen Patrick
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Cancer ,Orphan Drug ,Clinical Trials and Supportive Activities ,Clinical Research ,6.1 Pharmaceuticals ,6.2 Cellular and gene therapies ,Angiogenesis Inhibitors ,Antineoplastic Combined Chemotherapy Protocols ,Bevacizumab ,Brain Neoplasms ,Glioblastoma ,Humans ,Progression-Free Survival ,Treatment Outcome ,anti-angiogenesis ,gene therapy ,glioblastoma VB-111 ,viral immuno-oncology ,GLOBE Study Investigators ,VB-111 ,glioblastoma ,Neurosciences ,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