Primary End Points Not Met in Phase 3 OVAL Trial of Ofra-Vec Plus Paclitaxel in Advanced Ovarian Cancer

The phase 3 OVAL trial (NCT03398655) assessing ofranergene obadenovec (ofra-vec; VB-111) in patients with platinum-resistant ovarian cancer, did not meet its primary end points of overall survival (OS) and progression-free survival (PFS), according to a press release from VBL Therapeutics.¹

Topline data from the trial indicated that among those treated with ofra-vec plus paclitaxel, the median PFS was 5.29 months compared with 5.36 months in the paclitaxel control arm (HR, 1.03). Moreover, findings from an interim OS analysis indicated that median OS was 13.37 months vs 13.14 months (HR, 0.97) in each group, respectively. These results did not support the study’s continuation.

“Given the urgent unmet need for those fighting platinum-resistant ovarian cancer, we are deeply disappointed that the topline data indicate that ofra-vec did not improve progression-free survival or overall survival,” Dror Harats, MD, chief executive officer of VBL Therapeutics, said in the press release. “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 the 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.”

Ofra-vec is a first-in-class targeted investigational gene therapy that could have application across a variety of solid malignancies. It employs a dual mechanism of tumor vasculature blockade and anti-tumor response to treat solid tumors.

OVAL was a randomized, double-blind, placebo-controlled trial that compared ofra-vec plus paclitaxel vs placebo and paclitaxel. A total of 409 patients with recurrent platinum-resistant disease enrolled on the study. The secondary end points were combined CA-125 and RECIST 1.1 response, CA-125 response, overall response rate (ORR), and OS 100 days after study entry for the sensitivity analysis.

Patients were given ofra-vec at 1 x10¹³ virus particles every 2 months and paclitaxel at 80 mg/² every week. In the placebo arm, patients received matched dosing for paclitaxel plus placebo.

Patients could be included in the study if they were older than 18 years; had histologically confirmed epithelial ovarian cancer and documented disease; platinum-resistant disease; disease measurable via RECIST 1.1 criteria requiring chemotherapy; or an ECOG performance score of 0 to 1. Additionally, adequate hematologic functions were required. Those with a known BRCA mutation could be enrolled only after PARP inhibitor treatment failure or being intolerant to or ineligible for PARP treatment.

Exclusion criteria included having non-epithelial tumors; tumor with low malignant potentials like clear cell carcinoma, or grade 1 serous tumors, or mucinous tumors; having a history of active malignancy within 5 years of enrollment; or having previous ovarian cancer that was treated with more than 5 anticancer regiments. Additionally, patients must not have had and prior radiotherapy to the pelvis or the whole abdomen; inadequate liver function; inadequate renal function; or a history of myocardial infarction or transient ischemic attack.

In April 2022, ofra-vec received fast track designation by the FDA. Interim efficacy data that were reported in March 2020 highlighted a CA-125 overall response rate of 53%.²

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://yhoo.it/3PECNAH
2. VBL Therapeutics announces positive outcome of the interim analysis in the OVAL phase 3 ovarian cancer pivotal study. News release. VBL Therapeutics. March 26, 2020. Accessed July 20, 2022. https://bit.ly/3y34FZy