Abstract
5505 Background: Ofranergene obadenovec (ofra-vec, VB-111) is a nonreplicating adenoviral vector with a murine pro-endothelin 1 (PPE-1-3X) promoter and pro-apoptotic Fas-tumor necrosis factor receptor 1 (TNFR1) chimeric transgene thought to have a dual mechanism of action: vascular disruption and immune activation. Methods: This is a randomized, placebo-controlled, double-blind, multi-center randomized phase III trial (ClinicalTrials.gov identifier: NCT03398655) of ofranergene obadenovec combined with paclitaxel vs paclitaxel with placebo for the treatment of patients with recurrent platinum resistant ovarian cancer (PROC). Patients were randomly assigned 1:1 to receive IV VB-111 1x10 13 viral particles (VPs) every 8 weeks with weekly IV paclitaxel 80 mg/m2 or placebo with paclitaxel until disease progression. The dual primary endpoints were overall survival (OS) and progression free survival (PFS) as assessed by Blinded Independent Central Review (BICR). Results: Between December 2017 and March 2022, 409 patients were randomized at 86 clinical sites in US, Israel, Spain, Poland and Japan. The median PFS was 5.29 months in the VB-111 arm and 5.36 months in the control arm; hazard ratio (HR) 1.03 (CI: 0.83-1.29, p = 0.7823), and median OS with was 13.37 months vs. 13.14 months HR 0.97 (CI: 0.75–1.27 p = 0.8440). Objective response rates (ORR) were similar in both arms: RECIST 1.1 ORR was 28.9% with VB-111 vs. 29.6% with control (CA-125 ORR 41.1% vs 49.4%). In both treatment arms response to CA-125 was a substantial prognostic factor for both PFS and OS. In the VB-111 arm, the HR in CA-125 responders compared to non-responders was for PFS HR 0.2428 (CI: 0.1642-0.3588), and for OS HR 0.3343 (CI: 0.2134-0.5238). Safety profile was consistent with the known safety profile of ofra-vec and was characterized by common transient flu like symptoms such as fever and chills. Conclusions: The addition of ofranergene obadenovec to paclitaxel did not improve PFS or OS. Clinical trial information: NCT03398655 .