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Gene Therapy Fails to Improve Survival in Platinum-Resistant Ovarian Cancer

Ofra-vec continues to be evaluated in phase 2 trials for glioblastoma and colorectal cancer.

The phase 3 OVAL trial (NCT03398655) of ofranergene obadenovec (VB-111; VBL Therapeutics) in combination with paclitaxel has failed to meet its primary endpoint in improving progression-free survival (PFS) or overall survival (OS) in patients with platinum-resistant ovarian cancer.1

“Given the urgent unmet need for those fighting platinum-resistant ovarian cancer, we are deeply disappointed that the top-line data indicate that ofra-vec did not improve PFS or OS,” Dror Harats, MD, chief executive officer, VBL Therapeutics, said in a statement.1 “Based on this outcome, we plan to discontinue the OVAL trial and will review the data from our ongoing Phase 2 trials in metastatic colorectal cancer and recurrent glioblastoma multiforme to determine next steps with the ofra-vec program. We extend our deepest gratitude to all the patients, families and healthcare professionals who participated in this trial.”

The international, randomized, double-blind, placebo-controlled OVAL trial enrolled 409 adult patients with recurrent platinum-resistant ovarian cancer. The trial was conducted in collaboration with the GOG Foundation.

Investigators in the OVAL trial found that patients treated with ofra-vec and paclitaxel had a median PFS of 5.29 months compared to 5.36 months in patients treated with paclitaxel alone (hazard rate [HR], 1.03). Similarly, patients treated with the ofra-vec/paclitaxel combination had an OS of 13.37 months compared to 13.14 months in patients treated with paclitaxel alone (HR, 0.97).

READ MORE: Gene-Mediated Immunotherapy for Ovarian Cancer Clears Safety Hurdle, Will Continue Dosing

The FDA previously granted fast track designation to ofra-vec in this indication based on safety inspections by an independent data safety monitoring committee on the first 370 enrolled patients and findings from a prespecified interim analysis.2,3 The interim analysis, published in the journal Gynecologic Oncology in early 2021, included data on the first 60 enrolled patient who had a median of 3 prior therapies.

The interim analysis demonstrated a 10% advantage in patients treated with ofra-vec plus paclitaxel compared to patients treated with paclitaxel alone, passing the futility analysis.3 Investigators found that 53% of patients experienced a CA-125 response, with 15% having a complete remission, and predicted an estimated response rate of 58%.

“New and novel approaches that have the potential to significantly extend progression free survival or survival are eminently required in platinum-resistant ovarian cancer. VB-111, with its very unique mechanism of action, could be one of those novel approaches and I look forward to the progress of the OVAL trial, which is well designed to test this hypothesis,” investigator Bradley J. Monk, MD, FACOG, FACS, Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine, had previously said.4

While VBL has discontinued the OVAL trial in ovarian cancer, it continues to evaluate ofra-vec in phase 2 trials in colorectal cancer and glioblastoma. Ofra-vec has received orphan drug designation for the treatment of glioblastoma. VBL estimates that its current cash runway will support planned operations for at least the next 12 months.

REFERENCES
1. VBL Therapeutics announces top-line data from phase 3 OVAL trial of ofra-vec in patients with platinum-resistant ovarian cancer. News release. VBL Therapeutics. July 19, 2022. Accessed July 20, 2022. https://www.biospace.com/article/releases/vbl-therapeutics-announces-top-line-data-from-phase-3-oval-trial-of-ofra-vec-in-patients-with-platinum-resistant-ovarian-cancer/?keywords=vbl
2. VBL therapeutics receives FDA fast track designation for ofra-vec for the treatment of platinum-resistant ovarian cancer. News release. VBL Therapeutics. April 26, 2022. Accessed July 20, 2022. Accessed April 26, 2022. https://ir.vblrx.com/news-releases/news-release-details/vbl-therapeutics-receives-fda-fast-track-designation-ofra-vec
3. Arend RC, Monk BJ, Herzog TJ, et al. Utilizing an interim futility analysis of the OVAL study (VB-111-701/GOG 3018) for potential reduction of risk: A phase III, double blind, randomized controlled trial of ofranergene obadenovec (VB-111) and weekly paclitaxel in patients with platinum resistant ovarian cancer. Gynecol Oncol. 2021;161(2):496-501. Accessed July 20, 2022. doi:10.1016/j.ygyno.2021.02.014
4. VBL Therapeutics announces peer-reviewed publication of positive results of pre-specified interim analysis of OVAL, a phase 3 registration enabling study of VB-111 in ovarian cancer. News release. VBL Therapeutics. March 4, 2021. Accessed July 20, 2022. https://www.globenewswire.com/news-release/2021/03/04/2186957/0/en/VBL-Therapeutics-Announces-Peer-reviewed-Publication-of-Positive-Results-of-Pre-specified-Interim-Analysis-of-OVAL-a-Phase-3-Registration-Enabling-Study-of-VB-111-in-Ovarian-Cancer.html