The FDA has cleared a batch of VB-111 manufactured in Modiin, Israel, following a technical review.
Recruitment has resumed enrollment in their phase 3 OVAL study (NCT03398655) of ofranergene obadenovec (VB-111; VBL Therapeutics) for the treatment of ovarian cancer.1
VBL Therapeutics previously announced the pause in recruitment, due to the Chemistry, Manufacturing, and Controls (CMC) group’s technical review evaluating the variability of VB-111 manufactured between different source cites. The shortage of VB-111 supply while batches were waiting to be cleared necessitated the pause in recruitment.
“Our team is working to provide the requested information to the FDA as quickly as possible,” Dror Harats, MD, chief executive officer, VBL Therapeutics, previously said in a statement at that time.2 “Since receipt of the notification, we have submitted some of the requested information, and are preparing the remaining documentation, which we believe can be completed and submitted to the agency in the next two to three months. We do not expect a material change to our data readout timelines. We are in regular contact with the FDA and taking the steps necessary to minimize disruption to the trial in the US.”
The investigational gene therapy agent VB-111 is being explored to possibly treat a wide range of solid tumors with a dual mechanism that blocks tumor vasculature along with provoking an anti-tumor immune response. An IV infusion of the therapy is administered once every 6 to 8 weeks.
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In a phase 1 trial and 3 tumor-specific phase 2 trials, the therapy has been shown to be well-tolerated in over 300 patients with promising activity signals. The FDA has previously granted it orphan drug designation for ovarian cancer and fast track designation for recurrent glioblastoma. In a phase 2 trial in radioiodine-refractory thyroid cancer and recurrent platinum-resistant ovarian cancer, VB-111 has demonstrated proof-of-concept and survival benefit (NCT01711970).
The international, randomized, pivotal registration enabling OVAL clinical trial is evaluating a combination of VB-111 and paclitaxel in comparison to placebo plus paclitaxel, in patients with platinum resistant ovarian cancer. The study, which is being conducted in collaboration with the non-profit GOG Foundation, is planning to enroll around 400 patients. As of April 2021, the trial had enrolled over 260 participants.2
VBL previously added progression free survival (PFS) as a second primary end point in the OVAL study following discussion with the FDA in June 2021. Successful completion of either the PFS or the original overall survival (OS) primary endpoint is expected to be enough to support the future submission of their biologics license application. Data readout of the PFS end point is expected in 2022 and readout of the OS end point is expected in 2023.
“The addition of PFS as a second independent primary endpoint has several very important implications on the OVAL study,” said Bradley Monk, MD, FACS, FACOG, Arizona Oncology, and chair, OVAL Study Steering Committee, in a statement at that time.3 “First, it de-risks the study, as it provides 2 options for study success. Second, it should accelerate the time to clinical readout and to potential approval, as PFS data are expected during 2022. Third, keeping OS as a primary endpoint preserves the opportunity of differentiating VB-111 from current ovarian cancer treatments, which were approved based on PFS data and have not as yet shown an OS benefit.”