Work

Bmet-26phase 2 Study of Vb-111, an Anti-cancer Gene Therapy, as Monotherapy Followed by Combination of Vb-111 With Bevacizumab, in Patients With Recurrent Glioblastoma

Year: 2015

Type: article

Abstract: BACKGROUND: VB-111 is an anti-angiogenic agent consisting of a non-replicating adenovirus vector (Ad-5) with a modified murine pre-proendothelin promoter leading to apoptosis of tumor-vasculature by expressing a fas-chimera transgene in angiogenic-endothelial cells. Safety and efficacy of VB-111 alone and in combination with bevacizumab (BEV) were evaluated in recurrent-Glioblastoma (rGBM) patients in this Phase 1-2 dose-escalation study. METHODS: VB-111 was administered at 3x1012 or 1x1013 bimonthly until progression, followed by BEV standard-of-care (SOC). The protocol was amended to add-on BEV 10mg/Kg biweekly combined with VB-111 bimonthly, until further progression. Assessments included safety, pharmacokinetics, overall survival (OS) (Kaplan Meyer) and tumor response (RANO). RESULTS: 46 patients at 4 sites (US and Israel) received up to 13 doses of VB-111. Upon further progression, 24 received VB-111 with BEV, 22 were treated with BEV SOC. VB-111 was safe and well-tolerated alone and in combination with BEV. There were 30 grade ≥3 AEs, of which 6 were considered possibly related to VB-111: thrombocytopenia, pyrexia, brain edema, depressed consciousness, general weakness, pulmonary embolism. Median OS was 16 months for patients receiving combination therapy versus 8 months for those receiving SOC (p= 0.05). OS of combination therapy was superior to the historical control BELOB BEV arm, 16 versus 8 months (p = 0.003). Of 46 patients who received VB-111, 25 patients spiked a fever post-VB-111 dosing at least once, while 21 didn't. Feverish patients demonstrated a median OS of 16 months, compared to non-feverish patients, with a median OS of 8.5 months (p = 0.03). CONCLUSIONS: VB-111 was safe and well-tolerated alone and in combination with BEV in rGBM patients. OS of patients who received VB-111 followed by combination therapy almost doubled compared to historical BEV data, and compared to patients who received VB-111 monotherapy. Toxicities were as expected in this population. A phase 3 randomized controlled trial is currently underway.

Source: Neuro-Oncology

DOI: 10.1093/neuonc/nov208.26