Ofranergene Obadenovec (Ofra-Vec, VB-111) With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer: Randomized Controlled Phase III Trial (OVAL Study/GOG 3018)
Authors: Arend Rebecca C. , Monk Bradley J. , Shapira-Frommer Ronnie , Haggerty Ashley F. , Alvarez Edwin A. , Amit Amnon , Alvarez Secord Angeles , Muller Carolyn , Casado Herraez Antonio , Herzog Thomas J. , Tewari Krishnansu S. , Cohen Joshua G. , Huang Marilyn , Yachnin Adelya , Holeman Laura L. , Ledermann Jonathan A. , Rachmilewitz Minei Tamar , Buyse Marc , Fain Shmueli Shifra , Lavi Michal , Harats Dror , Penson Richard T. ,   on behalf of the OVAL/GOG-3018 Investigators, Pothuri Bhavana , Stephan Jean-Marie , Callahan Michael , Bradley William , Estevez Purificacion , Yunokawa Mayu , Chambers Setsuko , Holman Laura , Landrum Lisa , Seidel Jean , Lentz Samuel , Barroilhet Lisa , McCann Georgia , Rosengarten Ora , Tsoref Daliah , Lucci Joseph , Barlin Joyce , Fleming Evelyn , Van Le Linda , John Veena , Churucca Cristina , Blecharz Pawel , Breuer Shani , Reid Thomas , Cunningham Mary , Jewell Andrea , Ueland Frederick , Teneriello Michael , Woliver Thomas , Podzielinski Iwona , Marie Roque Dana , Krivak Thomas , Godoy Heidi , Gil Marta , Garcia Yolanda , Ramlau Rodryg , Takano Masashi , Nishio Shin , Grosse-Perdekamp Maria , Taylor Nicholas , Perez Sara , Sudo Kazuki , Matsumoto Takashi , Tokunaga Hideki , Morris Shelly , Barter James , Markham Merry , Brown Amy , Schink Julian , Bell Maria , Marquez Raul , Caballero Cristina , Kubiatowski Tomasz , Kikuchi Akira , Harano Kenichi , Kagabu Masahiro , Dimitrova Irina , Elder Jeffrey , Mahmood Tariq , Wong Cheung , Tchabo Nana , Chu Christina , Einstein Mark , Farley John , Anderson Charles , Romero Noguera Ignacio , Watari Hidemichi , Suzuki Shiro , Saito Tsuyoshi 
Published: October 2023

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.