Treatment through progression with ofranogene obadenovec (VB-111), an anti-cancer viral therapy, significantly attenuates tumor growth in recurrent GBM: Individual phase 2 patient data.

2055 Background: Ofranergene obadenovec (VB-111) is a viral cancer-therapy with a dual mechanism: vascular disruption and induction of a tumor directed immune response. Prolongation of overall survival (OS) has been shown in recurrent glioblastoma (rGBM) patients treated through progression with VB-111 in combination with bevacizumab (BEV) compared to historical controls and to patients with limited exposure (LE) to VB-111. Here we present individual patient tumor growth data. Methods: VB-111 was administered at 1x10viral particles bimonthly until progression, followed by BEV standard of care (LE cohort). The protocol was amended to allow treatment through progression (TThP) with VB-111 bimonthly, with the addition of BEV 10mg/Kg biweekly, until further progression (TThP cohort). Tumor dimensions were assessed q2 months by MRI locally and by an independent central lab. The slope of the log tumor measurement over time was calculated for each patient, average slopes were compared across therapy groups using the Wilcoxon Rank Sum test. Results: 46 patients received up to 13 doses of VB-111. All started with VB-111 monotherapy. 22 were included in the LE cohort; 24 in the TThP cohort. Cohorts were comparable by measures of age, performance status, prior lines of therapy, baseline tumor dimensions and progression-free-survival. Spider diagrams demonstrate similar rapid tumor growth in both LE and TThP cohorts during the VB-111 monotherapy period (local site data; median % increase (MPI) per 30d: 14.8 vs 14.1, p = 0.98). In the TThP cohort, growth was attenuated after the 1progression, compared to the preceding VB-111 monotherapy period (MPI: 0.6 vs 14.1, p = 0.0032); responses were seen, including 2 complete responses (CR), one patient remaining in CR over 3 years. A similar attenuation was seen in central lab tumor measurements. Conclusions: Treatment through progression with VB-111 in combination with BEV induced durable tumor growth attenuation, which was associated with prolonged OS of 15 months in patients with rGBM. The GLOBE phase 3 randomized controlled trial of VB-111 in rGBM is currently underway. Clinical trial information: NCT01260506.

Duke Scholars

Author Katherine Barnett Peters Neurosurgery, Neuro-Oncology