Ofra-Vec Continues to Show No Benefit in Platinum-Resistant Ovarian Cancer
Follow-up data were presented from the discontinued phase 3 OVAL study.
Ofranergene obadenovec (ofra-vec; VB-111; VBL Therapeutics) has continued to show no benefit in patients with platinum-resistant ovarian cancer (PROC) in updated follow-up data from the phase 3 OVAL study (NCT03398655).1
The updated data were presented at the 2023 American Society of Clinical Oncology (ASCO) meeting, held June 2-6, 2023, held both virtually and in Chicago, Illinois, by investigator Rebecca Christian Arend, MD, assistant professor and associate scientist, Comprehensive Cancer Center Experimental Therapeutics Program, University of Alabama, Birmingham.
““The addition of ofranergene obadenovec to paclitaxel did not improve progression-free survival (PFS) or overall survival (OS),” Arend and colleagues wrote in the abstract.1
Ofra-vec is a nonreplicating adeno-associated virus vector gene therapy that includes a murine pro-endothelin 1 (PPE-1-3X) promoter and pro-apoptotic Fas-tumor necrosis factor receptor 1 (TNFR1) chimeric transgene. The therapy is designed to provide both vascular disruption and immune activation in a dual mechanism of action.
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The randomized, double-blind, placebo-controlled multicenter OVAL study assessed ofra-vec with paclitaxel compared with paclitaxel treatment alone in patients with PROC. Patients were randomized 1:1 to receive 1x1013 viral particles of ofra-vec intravenously (IV) every 8 weeks with weekly IV 80 mg/m2 of paclitaxcel or placebo with paclitaxel until disease progression. The study primarily evaluated PFS and OS in 409 patients randomized at 86 clinical sites across the United States, Israel, Poland, Spain, and Japan between December 2017 and March 2022.
Independent review found that patients treated with ofra-vec had a median PFS of 5.29 months compared with 5.36 months in the control arm (hazard ratio [HR], 1.03; 95% CI [0.83-1.29]; P =.7823) and a median OS of 13.37 months compared with 13.14 months in the control arm (HR, 0.97; 95% CI [0.75-1.27]; P = .8440). Objective response rates (ORR) were also similar between arms, with an ORR of 28.9% in the ofra-vec arm and 29.6% in the control arm. ORR to decreasing CA-125 was 41.1% in the ofra-vec arm compared with 49.4% in the control arm.
Investigators also found that CA-125 response was a significant prognostic factor for PFS and OS, with an HR in CA-125 responders compared to non-responders of 0.2428 (95% CI, .1642-.3588) for PFS, and 0.3343 (95% CI, .2134-.5238) for OS in the ofra-vec arm.1 Common adverse events with ofra-vec treatment included transient flu like symptoms such as fever and chills and the overall safety profile was consistent with previous data.
“Given the urgent unmet need for those fighting platinum-resistant ovarian cancer, we are deeply disappointed that the top-line data indicate that ofra-vecdid not improve PFS or OS,” Dror Harats, MD, chief executive officer, VBL Therapeutics, said in a statement when topline data from OVAL were released in July 2022.2 “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.”
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