VBL Therapeutic’s investigational therapy VB-111 (ofranergene obadenovec) continues to show promising response rates in women with platinum-resistant ovarian cancer, with more than half of patients enrolled in a Phase 3 trial responding to a combination treatment.
Since the OVAL trial (NCT03398655) has met pre-specified criteria, as an interim analysis found, an independent data safety monitoring committee (DSMC) is recommending that the study continue as planned. The results of the analysis showed that at least 10% more patients responded to VB-111 plus standard of care treatment than to standard therapy alone.
The trial has recruited more than 100 of its targeted 400 participants. Enrollment is ongoing at 62 clinical sites across the United States and Israel, and is expected to expand to Europe and Japan later this year. For more information about study locations, go here.
The findings from this pre-planned interim analysis were recently presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, held virtually due to the COVID-19 pandemic. The poster was titled “Pivotal Study of VB-111 Combined with Paclitaxel vs. Paclitaxel for Treatment of Platinum-Resistant Ovarian Cancer (OVAL, VB-111-701/GOG-3018): Results of Pre-planned CA-125 Response Interim Analysis.”
VB-111 is an anti-cancer viral gene therapy that targets tumors through a dual mechanism. In addition to delivering a gene therapy that eliminates blood vessels required for tumor growth, the viral vector where the gene is inserted induces specific immune responses that kill tumor cells.
A combination of VB-111 plus standard of care chemotherapy Taxol (paclitaxel) was investigated in a prior Phase 1/2 trial (NCT01711970) in women with platinum-resistant recurrent ovarian cancer. In that trial, 58% of patients attained a response to treatment – deemed as 50% or greater reduction in levels of the ovarian cancer biomarker CA-125.
In addition, women receiving a therapeutic dose of VB-111 lived significantly longer — 498 days, or about one year, four months — than those receiving a sub-therapeutic VB-111 dose (173 days). A sub-therapeutic dose is one that is not expected to bring benefits, based on prior analyses. Those with CA-125 responses also lived significantly longer compared with those without responses — 808 days vs. 351 days.
The therapeutic benefits were associated with greater entry into a tumor of a group of immune cells called CD8+ T-cells, which are potent killers of tumor cells.
Those findings prompted the launch of OVAL, a randomized, placebo-controlled trial comparing a combination of VB-111 plus Taxol versus Taxol alone in people who failed to respond to prior platinum-based chemotherapy and received up to five prior lines of therapy (except radiation therapy).
OVAL’s primary goal is to determine whether the addition of VB-111 to Taxol extends overall survival. Secondary endpoints include the proportion of patients who respond to treatment, and the time to disease progression or death. Patient-reported outcome measures also will be assessed.
The recent interim analysis investigated CA-125 responses in the first 60 participants included in the trial. To date, 53% of patients overall have responded to treatment, including nine complete responses — having CA-125 levels within normal range, which is suggestive of cancer elimination — and 23 partial responses.
While the data is blinded, the researchers estimate at least a 58% response rate in the VB-111 arm. In addition, among those experiencing post-treatment fever, which is a common side effect of VB-111 treatment and a potential marker for this therapy, 69% attained CA-125 responses.
The findings show that OVAL met its pre-established criteria of at least 10% higher response rates with VB-111 than with Taxol alone, and that responses in this trial are as good as those recorded in the prior Phase 1/2 trial.
Following these encouraging results, the DSMC recommended that OVAL continue as planned, without modification.
“The OVAL interim data are very encouraging as they demonstrate the potential benefit of VB-111 over standard-of-care in a randomized-controlled setting,” Tami Rachmilewitz, MD, vice president of clinical development at VBL Therapeutics, said in a press release.
“With over 25% of the patients already enrolled in the study, we look forward to further advancing the OVAL study by expansion to Europe and Japan later this year,” Rachmilewitz added.
The OVAL trial is being conducted in collaboration with the nonprofit Gynecologic Oncology Group (GOG) Foundation, which promotes excellence in clinical research into different types of cancers.
VB-111 has been named an orphan drug in Europe for the treatment of ovarian cancer.
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