학술논문
Ofranergene Obadenovec (Ofra-Vec, VB-111) With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer: Randomized Controlled Phase III Trial (OVAL Study/GOG 3018).
Document Type
Academic Journal
Author
Arend RC; University of Alabama at Birmingham School of Medicine, Birmingham, AL.; Monk BJ; HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ.; Shapira-Frommer R; Chaim Sheba Medical Center, Ramat Gan, Israel.; Haggerty AF; Hospital of the University of Pennsylvania, Philadelphia, PA.; Alvarez EA; University of California, San Francisco, CA.; Amit A; Rambam Health Care Campus, Haifa, Israel.; Alvarez Secord A; Duke Cancer Institute, Duke University Health System, Durham, NC.; Muller C; University of New Mexico, Albuquerque, NM.; Casado Herraez A; San Carlos University Teaching Hospital, Madrid, Spain.; Herzog TJ; University of Cincinnati Cancer Center, University of Cincinnati, Cincinnati, OH.; Tewari KS; University of California, Medical Center, Orange, CA.; Cohen JG; Department of Surgery, City of Hope, Irvine, CA.; Huang M; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL.; Yachnin A; Kaplan Medical Center, Rehovot, Israel.; Holeman LL; Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, Oklahoma City, OK.; Ledermann JA; UCL Cancer Institute, University College London, London, United Kingdom.; Rachmilewitz Minei T; VBL Therapeutics, Modiin, Israel.; Buyse M; International Drug Development Institute, Louvain-la-Neuve, Belgium.; Fain Shmueli S; VBL Therapeutics, Modiin, Israel.; Lavi M; VBL Therapeutics, Modiin, Israel.; Harats D; VBL Therapeutics, Modiin, Israel.; Penson RT; Massachusetts General Hospital, Boston, MA.
Source
Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE
Subject
Language
English
Abstract
Purpose: To evaluate the addition of ofranergene obadenovec (ofra-vec, VB-111), a novel gene-based anticancer targeted therapy, to once a week paclitaxel in patients with recurrent platinum-resistant ovarian cancer (PROC).
Methods: This placebo-controlled, double-blind, phase III trial (ClinicalTrials.gov identifier: NCT03398655) randomly assigned patients with PROC 1:1 to receive intravenous ofra-vec every 8 weeks with once a week IV paclitaxel or placebo with paclitaxel until disease progression. The dual primary end points were overall survival (OS) and progression-free survival (PFS) as assessed by Blinded Independent Central Review.
Results: Between December 2017 and March 2022, 409 patients were randomly assigned. The median PFS was 5.29 months in the ofra-vec arm and 5.36 months in the control arm, hazard ratio (HR) 1.03 (CI, 0.83 to 1.29; P = .7823). The median OS with ofra-vec was 13.37 months versus 13.14 months, HR 0.97 (CI, 0.75 to 1.27; P = .8440). Objective response rates (ORRs) per RECIST 1.1 were similar in both arms: 28.9% with ofra-vec versus 29.6% with control. In both treatment arms, response to CA-125 was a substantial prognostic factor for both PFS and OS. In the ofra-vec arm, the HR in CA-125 responders compared with that in nonresponders for PFS was 0.2428 (CI, 0.1642 to 0.3588), and for OS, the HR was 0.3343 (CI, 0.2134 to 0.5238). Safety profile was characterized by common transient flu-like symptoms such as fever and chills.
Conclusion: The addition of ofra-vec to paclitaxel did not improve PFS or OS. The PFS and ORR 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 PFS and OS in patients with PROC treated with paclitaxel.
Methods: This placebo-controlled, double-blind, phase III trial (ClinicalTrials.gov identifier: NCT03398655) randomly assigned patients with PROC 1:1 to receive intravenous ofra-vec every 8 weeks with once a week IV paclitaxel or placebo with paclitaxel until disease progression. The dual primary end points were overall survival (OS) and progression-free survival (PFS) as assessed by Blinded Independent Central Review.
Results: Between December 2017 and March 2022, 409 patients were randomly assigned. The median PFS was 5.29 months in the ofra-vec arm and 5.36 months in the control arm, hazard ratio (HR) 1.03 (CI, 0.83 to 1.29; P = .7823). The median OS with ofra-vec was 13.37 months versus 13.14 months, HR 0.97 (CI, 0.75 to 1.27; P = .8440). Objective response rates (ORRs) per RECIST 1.1 were similar in both arms: 28.9% with ofra-vec versus 29.6% with control. In both treatment arms, response to CA-125 was a substantial prognostic factor for both PFS and OS. In the ofra-vec arm, the HR in CA-125 responders compared with that in nonresponders for PFS was 0.2428 (CI, 0.1642 to 0.3588), and for OS, the HR was 0.3343 (CI, 0.2134 to 0.5238). Safety profile was characterized by common transient flu-like symptoms such as fever and chills.
Conclusion: The addition of ofra-vec to paclitaxel did not improve PFS or OS. The PFS and ORR 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 PFS and OS in patients with PROC treated with paclitaxel.