Ofranergene Obadenovec Plus Paclitaxel Did Not Improve Survival Outcomes Among Patients With Recurrent, Platinum-Resistant Ovarian Cancer

Results from the phase 3 OVAL/GOG 3018 study found that the addition of ofranergene obadenovec, a novel gene-based anticancer targeted therapy, to paclitaxel did not improve progression-free survival (PFS) or overall survival (OS) among patients with recurrent platinum-resistant ovarian cancer. 

According to Rebecca C. Arend, MD, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, and coauthors, “Platinum-resistant ovarian cancer has a poor prognosis, [therefore we] compared the efficacy and safety of [ofranergene obadenovec] and paclitaxel with those of paclitaxel and placebo in patients with [platinum-resistant ovarian cancer].”

In this double-blind study, 409 patients with recurrent, platinum-resistant ovarian cancer were randomized on a 1-to-1 basis to receive once weekly paclitaxel plus either intravenous ofranergene obadenovec every 8 weeks or placebo until disease progression. Dual primary end points included OS and PFS, as assessed by blinded independent central review. Secondary end points included objective response rate (ORR), hazard ratio (HR) based on CA-125 response, and safety. 

At the data cutoff point, median PFS was 5.29 months in the ofranergene obadenovec arm and 5.36 months in the placebo arm (HR, 1.03; confidence interval [CI] 0.83 to 1.29; P = .7823). Median OS was 13.37 months in the ofranergene obadenovec arm and 13.14 months in the placebo arm (HR 0.97; CI 0.75 to 1.27; P = .8440). ORR was 28.9% in the ofranergene obadenovec arm and 29.6% in the placebo arm. In the ofranergene obadenovec arm, HR in CA-125 responders compared to that of nonresponders was 0.2428 for PFS and 0.3343 for OS. The most common adverse events were flu-like symptoms including fever and chills. 

“The addition of [ofranergene obadenovec] to paclitaxel did not improve progression-free survival or overall survival,” concluded Dr Arend and coauthors. “The negative results were unexpected in view of the phase I/II experience and the interim analysis of CA-125 response.” 

“Physicians are reminded that promising preliminary results are not always confirmed in larger randomized trial settings,” added associate editor of Journal of Clinical Oncology, Gini F. Fleming, MD, University of Chicago Medicine, Chicago, Illinois. “We continue to need improved treatments for patients with platinum-resistant ovarian cancer.”

Source: 

Arend RC, Monk BJ, Shapira-Frommer R, et al. Ofranergene obadenovec (Ofra-Vec, VB-111) with weekly paclitaxel for platinum-resistant ovarian cancer: Randomized controlled phase III trial (OVAL Study/GOG 3018). J Clin Oncol. Published online: October 31, 2023. doi:10.1200/JCO.22.02915.