Adding Ofra-Vec to Chemo Does Not Improve PFS, OS in Platinum-Resistant Ovarian Cancer

Adding ofranergene obadenovec (ofra-vec) to chemotherapy does not improve outcomes in patients with platinum-resistant ovarian cancer, according to research published in the Journal of Clinical Oncology.

Patients who received ofra-vec and chemotherapy did not have an improvement in progression-free survival (PFS) or overall survival (OS) when compared to patients who received chemotherapy alone.

Researchers evaluated ofra-vec and chemotherapy in the phase 3 OVAL trial (ClinicalTrials.gov Identifier: NCT03398655). Ofra-vec is a targeted gene therapy with a dual mechanism of action: vascular disruption and induction of immune infiltration in solid tumors.

The OVAL trial included 409 patients with platinum-resistant ovarian cancer. They were randomly assigned to receive ofra-vec every 8 weeks with weekly paclitaxel (n=204) or placebo with weekly paclitaxel (n=205). Baseline characteristics were well balanced between the treatment arms.

The median PFS was 5.29 months in the ofra-vec arm and 5.36 months in the placebo arm (hazard ratio [HR], 1.03; 95% CI, 0.83-1.29; P =.7823). The median OS was 13.37 months and 13.14, respectively (HR, 0.97; 95% CI, 0.75-1.27; P =.8440).

“The OVAL trial failed to meet its dual primary endpoints of PFS and OS (interim), and the study was terminated early according to the independent data safety monitoring committee recommendation after the first planned unblinded analysis,” the researchers wrote.

The objective response rate was 28.9% in the ofra-vec arm and 29.6% in the placebo arm. The median duration of response was 5.32 months and 4.80 months, respectively.

The rate of grade 3 or higher treatment-related adverse events (AEs) was 25.6% in the ofra-vec arm and 14.8% in the control arm. There were no fatal treatment-related AEs in either arm.

The most common AEs of any grade in the ofra-vec arm were pyrexia (61.1%), fatigue (44.8%), anemia (40.9%), nausea (37.4%), diarrhea (36.0%), alopecia (34.5%), and vomiting (31.0%).

Based on these results, the researchers concluded that there is still “a pressing need to develop effective agents that can affect survival in this area of such a desperate clinical need.”

“Identifying agents that can affect the tumor microenvironment and exploit the potential synergy of targeting angiogenesis and vascular integrity in cancer, which is the interface between tumor cells and the immune system, remains a therapeutic holy grail.”

Disclosures: This research was supported by VBL Therapeutics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

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

This article originally appeared on Cancer Therapy Advisor