Ofranergene Obadenovec Receives Fast Track Designation From FDA for Platinum-Resistant Ovarian Cancer

The FDA granted fast track designation to an application for ofranergene obadenovec (ofra-vec; VB-111) as treatment of patients with platinum-resistant ovarian cancer, according to a press release from developer VBL Therapeutics.¹

The agent is currently being examined in combination with paclitaxel in patients with recurrent platinum-resistant ovarian cancer in the phase 3 OVAL trial (NCT03398655). In March 2020, the reported efficacy data in 60 patients, with investigators reporting a CA-125 overall response rate (ORR) of 53%.² At the time, the response rate was presumed to be 58% or higher if the randomization was balanced.

Among patients who had fever following treatment—a frequently observed adverse effect associated with ofra-vec—the ORR was 69%. Investigators concluded that the ORR observed in the phase 3 interim analysis was comparable with that of the phase 2 trial, which included a similar patient population.

“We are pleased to receive FDA fast track designation for [ofranergene obadenovec] in platinum-resistant ovarian cancer. The fast track designation can facilitate the process towards potential registration and, importantly, may help expedite the time to market for [ofra-vec], if approved,” Dror Harats, MD, chief executive officer at VBL Therapeutics, said in a statement. “The readout of the progression-free survival primary end point in the OVAL trial will be an important milestone for VBL in the second half of this year. We believe that, if positive, this will support a Biologics License Application submission to the FDA.”

Ofra-vec is an investigational gene therapy designed to employ a dual mechanism of tumor vasculature blockade and anti-tumor immune response to treat solid tumors. Currently, the trial has completed enrollment of 409 patients, which is being conducted at centers in the United States, Europe, Israel, and Japan. Following an unblinded review of data from 370 patients, the data safety monitoring committee unanimously recommended that the trial continue according to plan.

Ofra-vec was administered at a dose of 1 × 10¹³ virus particles every 2 months and paclitaxel was given at a dose of 80 mg/m² every week. The control arm received the paclitaxel backbone plus placebo.

The primary end points of the study are progression-free survival and overall survival (OS). If either of the primary end points are met, investigators state that this could be enough to support the biologics license application (BLA). Should the PFS end point be met in a readout that’s expected in the second half of 2022, the application could be accelerated by roughly 1 year. The OS read out is expected for 2023. Secondary end points include CA-125 and RECIST1.1 response and ORR.

To be considered for the trial, patients were required to have histologically confirmed epithelial ovarian cancer and platinum-resistant disease. Disease needed to be measurable by RECIST 1.1 criteria and be treatable with chemotherapy. Patients also needed to have adequate hematologic functions and an ECOG performance status of 0 to 1. Patients with non-epithelial tumors or ovarian tumors with low malignant potential, or who received more than 5 prior anticancer ovarian regimens were excluded from the study.

References

1. 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 April 29, 2022. https://bit.ly/3MK9jA5
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 April 29, 2022. https://bit.ly/3y34FZy