Randomized controlled phase III trial of weekly paclitaxel ± ofranergene obadenovec (VB-111) for platinum-resistant ovarian cancer (OVAL Study/GOG 3018).

person Rebecca Christian Arend University of Alabama at Birmingham, Birmingham, AL info_outline Rebecca Christian Arend, Bradley J. Monk, Ronnie Shapira-Frommer, Angeles Alvarez Secord, Thomas J. Herzog, Krishnansu Sujata Tewari, Jonathan A. Ledermann, Tamar Rachmilewitz Minei, Marc E. Buyse, Ashley Haggerty, Edwin A Alvarez, Amnon Amit, Carolyn Muller, Antonio Casado Herraez, Laura L. Holman, Joshua Cohen, Marilyn Huang, Adelya Yachnin, Dror Harats, Richard T. Penson

Authors person Rebecca Christian Arend University of Alabama at Birmingham, Birmingham, AL info_outline Rebecca Christian Arend, Bradley J. Monk, Ronnie Shapira-Frommer, Angeles Alvarez Secord, Thomas J. Herzog, Krishnansu Sujata Tewari, Jonathan A. Ledermann, Tamar Rachmilewitz Minei, Marc E. Buyse, Ashley Haggerty, Edwin A Alvarez, Amnon Amit, Carolyn Muller, Antonio Casado Herraez, Laura L. Holman, Joshua Cohen, Marilyn Huang, Adelya Yachnin, Dror Harats, Richard T. Penson Organizations University of Alabama at Birmingham, Birmingham, AL, HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ, Chaim Sheba Medical Center, Ramat Gan, Israel, Division of Gynecologic Oncology, Department of OB/GYN, Duke Cancer Institute of Duke University Health System, Durham, NC, University of Cincinnati, University of Cincinnati Cancer Institute, Cincinnati, OH, Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of California, Irvine, CA, UCL Cancer Institute, University College London and UCL Hospitals, London, United Kingdom, VBL Therapeutics, Modi'in, Israel, International Drug Development Institute, Louvain-La-Neuve, Belgium, Hackensack Medical Center, Hackensack, NJ, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, Rambam Health Care, Haifa, Israel, University of New Mexico, Albuquerque, NM, Hospital Clinico San Carlos, Madrid, Spain, OU Health Stephenson Cancer Center, Oklahoma City, OK, University of California, Los Angeles, Los Angeles, CA, University of Miami Health System, Miami, FL, Kaplan Medical Center, Rehovot, Israel, Vascular Biogenics Ltd., Modiin, Israel, Harvard Medical School, Massachusetts General Hospital, Boston, MA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company VBL Therapeutics 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 1x1013 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.