In a phase III trial (OVAL Study/GOG 3018) reported in the Journal of Clinical Oncology, Arend et al found that the addition of ofranergene obadenovec to paclitaxel did not improve survival outcomes in patients with platinum-resistant ovarian cancer. Ofranergene obadenovec is a gene-based targeted therapy with a dual mechanism of action consisting of vascular disruption and induction of immune infiltration in solid tumors.
In the double-blind trial, 409 patients from sites in the United States, Israel, Spain, Poland, and Japan were randomly assigned between December 2017 and March 2022 to intravenous ofranergene obadenovec (1 × 1013 viral particles every 8 weeks) with paclitaxel at 80 mg/m2 once a week (n = 204) or placebo plus paclitaxel (n = 205), with paclitaxel given until disease progression.
The mean number of previous lines of anticancer therapies was three, with 62% of patients receiving at least three previous lines. The dual primary endpoints were overall survival and progression-free survival on blinded independent central review.
At primary analysis, median progression-free survival was 5.29 months (95% confidence interval [CI] = 4.04–5.49) in the ofranergene obadenovec group vs 5.36 months (95% CI = 4.83–5.55) in the control group (hazard ratio [HR] = 1.03, 95% CI = 0.83–1.29, P = .7823). At interim analysis, median overall survival was 13.37 months (95% CI = 10.84–14.72) in the ofranergene obadenovec group vs 13.14 months (95% CI =11.60–15.84) in the control group (HR = 0.97, 95% CI = 0.75–1.27, P = .8440).
The objective response rate by Response Evaluation Criteria in Solid Tumors, version 1.1, was 28.9% (95% CI = 22.76–35.90) in the ofranergene obadenovec arm, with complete responses in 2.8%, vs 29.6% (95% CI = 23.41–36.67) in the control group, with complete responses in 2.2%.
As noted by the investigators, progression-free survival and objective response in the control group (placebo/paclitaxel) were both numerically better than expected based on findings in the AURELIA trial chemotherapy control group in this setting. In this group, median progression-free survival was 3.4 months and the objective response rate was 11.8%.
CA-125 response was a prognostic factor for progression-free and overall survival in both treatment arms. In the ofranergene obadenovec arm, the hazard ratio for progression-free survival in CA-125 responders compared with that in nonresponders was 0.2428 (95% CI = 0.1642–0.3588). For overall survival, the hazard ratio was 0.3343 (95% CI = 0.2134–0.5238).
The safety profile for ofranergene obadenovec was characterized by common transient flu-like symptoms such as fever and chills.
The investigators concluded: “The addition of [ofranergene obadenovec] to paclitaxel did not improve [progression-free or overall survival]. The [progression-free survival and objective response rate] in the control arm exceeded the results that were anticipated on the basis of the AURELIA chemotherapy control arm. CA-125 response was a substantial prognostic biomarker for [progression-free and overall survival] in patients with [platinum-resistant ovarian cancer] treated with paclitaxel.”
Richard T. Penson, MD, MRCP, of the Division of Medical Gynecologic Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, is the corresponding author for the study.
Disclosure: The study was supported by VBL Therapeutics. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.