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