The phase 3 OVAL clinical trial has been discontinued after the combination of ofranergene obadenovec and paclitaxel did not achieve the study’s primary end points of improvement in progression-free and overall survival.
The use of ofra-vec (ofranergene obadenovec; VB-111) with paclitaxel as treatment of patients with platinum-resistant ovarian cancer did not significantly improve progression-free survival (PFS) and overall survival (OS), missing the coprimary end points of the phase 3 OVAL study (VB-111-701/GOG-3018, NCT03398655).1
Topline findings from the randomized, controlled, double-arm, double-blind, multi-center OVAL study showed that ofra-vec and paclitaxel achieved a median PFS of 5.29 months compared with 5.36 months in the control arm (HR, 1.03), according to a press release by VBL Therapeutics. The median OS observed in the study was 13.37 months with ofra-vec and paclitaxel vs 13.14 months with paclitaxel alone (HR, 0.97). This result did not support continuation of the study.
The results shown a downward trajectory of the trial since the 2020 planned interim analysis of OVAL. At the time, it was announced that the combination of ofra-vec and paclitaxel met the pre-specified efficacy criterion of an absolute percentage advantage of 10% or higher CA-125 response rate in patients with platinum-resistant ovarian cancer. In 60 patients, the overall CA-125 response rate was 53%, showing a 58% higher response vs the control combination. Also, the response rate was 69% among patients who had post-dosing fever.2
In terms of safety, the addition of ofra-vec to paclitaxel was well-tolerated. Grade ≥ 3 adverse events (AEs) were observed in 9 patients. The most common AEs observed during the study were fatigue (52%), nausea (52%), fever (48%), anemia (38%), diarrhea (33%), and headache (29%). Some cases of fever and the anticipated toxicities of angiogenic and taxanes occurred.
Patients in the study received 1x10e13 VPs of ofra-vec intravenously every 2 months in combination with paclitaxel 80 mg/m2 every week in the experimental arm. Patients in the control arm received an equivalent dose of paclitaxel with placebo. In addition to survival, the study sought to assess the combined CA-125 and RECIST 1.1 response, CA-125 response, objective response rate by RECIST 1.1, and OS100 for a sensitivity analysis of OS.
The patients enrolled in the study were aged 18 years or older with histologically confirmed epithelial ovarian cancer and documented disease that is platinum resistant. All patients had measurable disease per RECIST 1.1, an ECOG performance status of 0 or 1, and adequate hematological functions. The study excluded patients who received prior radiotherapy to the pelvis or whole abdomen or were treated with more than 5 anticancer regimens. Patients were also excluded based on certain infections and comorbidities that may have interfered with study treatment.3
“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 progression-free survival or overall survival,” said Dror Harats, MD, chief executive officer of VBL Therapeutics, in a press release.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.”
Previously, the FDA granted fast track designation to ofra-ve plus paclitaxel for the treatment of platinum-resistant ovarian cancer. Although the OVAL study will not continue, the development of ofra-vec will continue in other studies.
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://bit.ly/3OkJjeP
2. VBL final phase 1/2 study results presented at asco demonstrate vb-111 dose dependent increase in overall survival and 58% ca-125 response rate in platinum-resistant ovarian cancer [news release]. Tel Aviv, Israel: News Release. VBL Therapeutics. June 3, 2019. Accessed July 20, 2022. https://bit.ly/3ahBZNQ.
3. A study of VB-111 with paclitaxel vs paclitaxel for treatment of recurrent platinum-resistant ovarian cancer (OVAL) ClinicalTrials.gov. Updated March 22, 2022. Accessed July 20, 2022. https://clinicaltrials.gov/ct2/show/NCT03398655?term=NCT03398655&draw=2&rank=1