Anticancer gene therapy regimen confers survival benefit in recurrent glioblastoma
Continued VB-111 monotherapy priming after progression with bevacizumab combination treatment improved survival outcomes among patients with recurrent glioblastoma, according to results of a phase 1/phase 2 study published in Neuro-Oncology.
“There is a great unmet need for novel therapies that will prolong patient survival, and accordingly survival was selected as the primary endpoint in this study,” Andrew J. Brenner, MD, PhD, associate professor of medicine at Mays Cancer Center of The University of Texas Health Science Center at San Antonio, and colleagues wrote. “Our results demonstrate a survival benefit in patients with recurrent glioblastoma treated with VB-111 [ofranergene obadenovec, VBL Therapeutics] priming followed up on disease progression with combination of VB-111 and bevacizumab [Avastin, Genentech].”
Previous studies have shown that VB-111, a nonreplicating adenovirus carrying a FAS-chimera transgene, results in targeted apoptosis of tumor vascular endothelium and induces a tumor-specific immune response.
Brenner and colleagues tested the safety and efficacy of VB-111 with or without bevacizumab among 72 adults with recurrent glioblastoma.
Researchers assigned patients to four treatment groups:
Subtherapeutic (VB-111 dose escalation, with initial doses of less than 1 x 10¹³ viral particles (VP); n = 16; median age, 56.1 years; 68.4% men);
Limited exposure (VB-111 monotherapy dosed at 1 x 10¹³ VP every 56 days until progression; n = 22; median age, 55.9 years; 57.9% men);
Primed combination (VB-111 monotherapy dosed at 1 x 10¹³ VP every 56 days and continued upon progression in combination with 10 mg/kg IV bevacizumab; n = 24; median age, 60 years; 50% men); and
Unprimed combination (upfront combination of VB-111 dosed at 1 x 10¹³ VP every 28 days and bevacizumab every 2 weeks; n = 10; median age, 42 years; 60% men).
Median OS served as the primary endpoint. Safety, overall response rate and PFS served as secondary endpoints.
Results showed significantly longer median OS in the primed combination group compared with both the limited exposure group (414 days vs. 223 days; HR = 0.48; 95% CI, 0.23-0.99) and the unprimed combination group (414 days vs. 141.5 days; HR = 0.24; 95% CI, 0.09-0.66).
Patients in the combination phase of the primed combination group had longer PFS than those in the limited exposure group (90 days vs. 60 days; HR = 0.36; 95% CI, 0.14-0.93) and the unprimed combination group (90 days vs. 63 days; HR = 1.24; 95% CI, 0.45-3.4).
Patients tolerated VB-111 well, with transient mild to moderate fever as the most common adverse event.
Radiographic responders to VB-111 exhibited characteristic, expansive areas of necrosis in the areas of initial enhancing disease, researchers wrote.
The study’s small sample size, as well as its lack of limits on prior treatments except for bevacizumab, served as limitations.
“VB-111 monotherapy priming that is continued after progression with the addition of bevacizumab is associated with a significant OS and PFS benefit, with a favorable safety profile and a typical radiologic response,” Brenner and colleagues wrote. “The observed radiologic response and survival benefit of the VB-111 primed combination regimen merit further investigation in a randomized controlled trial.” – by John DeRosier
Disclosures: Brenner reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.