Pivotal study of ofra-vec (VB-111) combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).

Richard T. Penson Harvard Medical School, Massachusetts General Hospital, Boston, MA info_outline Richard T. Penson, Rebecca Christian Arend, Angeles Alvarez Secord, Antonio Casado Herraez, Thomas J. Herzog, Jonathan A. Ledermann, Kathleen N. Moore, Ronnie Shapira-Frommer, Krishnansu Sujata Tewari, Tamar Rachmilewitz Minei, Dror Harats, Shifra Fain Shmueli, Bradley J. Monk

Authors Richard T. Penson Harvard Medical School, Massachusetts General Hospital, Boston, MA info_outline Richard T. Penson, Rebecca Christian Arend, Angeles Alvarez Secord, Antonio Casado Herraez, Thomas J. Herzog, Jonathan A. Ledermann, Kathleen N. Moore, Ronnie Shapira-Frommer, Krishnansu Sujata Tewari, Tamar Rachmilewitz Minei, Dror Harats, Shifra Fain Shmueli, Bradley J. Monk Organizations Harvard Medical School, Massachusetts General Hospital, Boston, MA, University of Alabama at Birmingham, Birmingham, AL, Duke Cancer Institute, Duke University Medical Center, Durham, NC, San Carlos University Teaching Hospital, Madrid, Spain, University of Cincinnati, University of Cincinnati Cancer Institute, Cincinnati, OH, University College London Cancer Institute, London, United Kingdom, Division of Obstetrics and Gynecology, Department of Gynecologic Oncology, University of Oklahoma Health Science Center, Stephenson Cancer Center, Oklahoma City, OK, Ella Lemelbaum Institute for Immuno Oncology and Melanoma, Sheba Medical Center, Ramat-Gan, Israel, Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of California, Irvine, CA, Vascular Biogenics Ltd., Modiin, Israel, Vascular Biogenics Ltd, Modiin, Israel, GOG Foundation, Creighton University, University of Arizona, Phoenix, AZ Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Ofranergene obadenovec (Ofra-vec, VB-111) is an anti-cancer gene based immune activator and targeted vascular disruptor. The dual mechanism of action triggers a broad antiangiogenic effect and induces of a tumor directed immune response. A phase II trial in patients with platinum resistant ovarian cancer (PROC) demonstrated that ofra-vec in combination with weekly paclitaxel was well tolerated and associated with a CA-125 Objective Response Rate (ORR) of 58%, a trend for improved survival and induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a pivotal phase III study was initiated in collaboration with the GOG Foundation, Inc. Methods: Study NCT03398655 is an international, randomized, double-blind, placebo-controlled, phase III study. Eligible patients have recurrent PROC and may have been previously treated with up to 5 prior lines of therapy (but not >2 for PROC). Patient are randomized 1:1 to receive ofra-vec (1x10 13 Viral Particles) with weekly paclitaxel (80mg/m 2 ), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. The dual primary endpoints are OS and PFS. A pre-planned interim analysis of CA-125 response (GCIG) performed by the DSMC met the pre-defined criteria showing that CA-125 ORR in the treatment arm was at least 10% higher than in the control arm. Study is enrolling in the US, EU, Japan and Israel, with 90% enrollment to date. Completion of accrual is anticipated in Q1 2022. Clinical trial information: NCT03398655.