Gene Therapy Shows Promise for Ovarian Cancer Treatment in New Study

A novel anticancer gene therapy has shown potential for treating platinum-resistant ovarian cancer. A recent study found ofranergene obadenovec (VB-111, VBL Therapeutics), a first-in-class targeted therapy, to be well tolerated in more than 300 patients with cancer.¹

Results of the analysis were presented during the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.^1,2

VB-111 is administered by intravenous infusion once every 6-8 weeks. The drug has a dual mechanism of action: apoptosis of angiogenic endothelium and vascular disruption that leads to tumor starvation and induction of an antitumor-directed immune response.¹

The recent analysis of VB-111 was a phase 3 potential registration study conducted with 400 patients and 95 sites around the world. The primary endpoint was overall survival (OS), with secondary endpoints of progression-free survival, CA-125 and RECIST response.¹

This study compared the CA-125 objective response rate (ORR) according to Gynecologic Cancer InterGroup criteria in the treatment and control arms among the first 60 evaluable patients. According to VBL Therapeutics, the CA-125 ORR in those patients was 53% and, assuming a balanced randomization, the response rate in the treatment arm (VB-111 in addition to weekly paclitaxel) was 58% or higher. In patients who had post-dosing fever—a marker for VB-111 treatment—the response rate was 69%.^1,2

“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,” said Tami Rachmilewitz, MD, vice president of Clinical Development of VBL Therapeutics, in a prepared statement.²

The CA-125 response rate observed in the phase 3 interim analysis is at least as good as the response rate seen in the prior phase 2 study that enrolled a similar patient population and showed OS benefit, according to researchers. In the previously reported phase 2 study of VB-111 in platinum-resistant ovarian cancer, 58% of the patients treated with VB-111 and paclitaxel demonstrated a CA-125 response. Those patients with a CA-125 response demonstrated a median OS of 808 days, compared with survival of 351 days for those patients without a CA-125 response.²

The most recent study was conducted in collaboration with the GOG Foundation, an independent not-for-profit organization that aims to promote excellence in the quality and integrity of clinical and basic scientific research.²

Further interim analysis is expected to be conducted in the third quarter of 2020.¹

“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 said in a prepared statement.²

REFERENCES

• 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. Presented at: 2020 ASCO Annual Meeting, Virtual Science Program. May 29-31, 2020.
• VBL Presents Positive Interim Data from the OVAL Phase 3 Pivotal Study in Ovarian Cancer at the ASCO20 Annual Meeting, Showing 58% or Higher Objective Response Rate [news release]. Tel Aviv, Israel; June 1, 2020: VBL Therapeutics website. http://ir.vblrx.com/news-releases/news-release-details/vbl-presents-positive-interim-data-oval-phase-3-pivotal-study Accessed June 4, 2020.