Rebecca Christian Arend, MD at University of Alabama discusses an abstract from ASCO 2020 Clinical trial in progress: Pivotal study of VB-111 combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018)
Ofranergene obadenovec (VB-111) is a focused, dual-mechanism anti-cancer gene therapy: a broad antiangiogenic effect and the activation of a tumor-directed viral immune response. In a phase II trial of platinum-resistant VB-111 ovarian cancer in conjunction with weekly paclitaxel, the response rate (RR) of CA-125 was 58% and the median overall survival (OS) was 498 days, compared to the subtherapeutic dose of 172.5 days (p = 0.028). The drug mixture was well tolerated. Induction of an immunotherapeutic effect of tumor penetration with CD-8 T cells was correlated with favourable outcomes. In collaboration with the GOG Foundation, Inc., a phase III randomized controlled study, VB-111-701 / GOG-3018 (OVAL), was initiated on the basis of these observations.
An international, randomized, double-blind, placebo-controlled, phase III study is the OVAL study, NCT03398655. Patients with recurrent epithelial ovarian cancer resistant to platinum with detectable disease (RECIST 1.1) and previously treated with up to 5 lines are randomized 1:1 to obtain VB-111 (1x1013 VPs) with weekly paclitaxel (80mg / m2), or weekly placebo paclitaxel. Randomization is stratified by number of previous lines of treatment, previous antiangiogenic therapy and status of the platinum refractory condition. Treatment beyond asymptomatic RECIST progression can proceed until follow-up imagery confirms progression. OS, protection, and tolerability are the prime endpoints. Secondary endpoints include progression-free survival, CA-125 (by GCIG criteria) and RECIST 1.1 objective RR. The 400 patient sample size calculation (event driven) provides 92 percent power to detect a difference in survival using the logrank test at the two-sided 5 percent significance stage. In order to determine if the CA-125 RR per GCIG criterion in the treatment arm is substantially larger than in the control arm and is equivalent to the positive results of the phase II trial, a pre-planned interim review will take place in Q1 2020. Enrolment in the study is underway and over 80 patients in the US and Israel have been enrolled. The extension of enrollment to Europe is expected for 2020. Data on clinical trial: NCT03398655