Utilizing an interim futility analysis of the OVAL study (VB-111-701/GOG 3018) for potential reduction of risk: A phase III, double blind, randomized controlled trial of ofranergene obadenovec (VB-111) and weekly paclitaxel in patients with platinum resistant ovarian cancer
Rebecca C Arend, Bradley J Monk, Thomas J Herzog, Kathleen N Moore, Ronnie Shapira-Frommer, Jonathan A Ledermann, Krishnansu S Tewari, Angeles Alvarez Secord, Tamar Rachmilewitz Minei, Laurence S Freedman, Austin Miller, Shifra Fain Shmueli, Michal Lavi, Richard T Penson, Rebecca C Arend, Bradley J Monk, Thomas J Herzog, Kathleen N Moore, Ronnie Shapira-Frommer, Jonathan A Ledermann, Krishnansu S Tewari, Angeles Alvarez Secord, Tamar Rachmilewitz Minei, Laurence S Freedman, Austin Miller, Shifra Fain Shmueli, Michal Lavi, Richard T Penson
Abstract
Objective: Report the results from a preplanned interim analysis of a phase III, double blind, randomized controlled study of ofranergene obadenovec (VB-111), a targeted anti-cancer gene therapy, in combination with paclitaxel in patients with platinum resistant ovarian cancer (PROC).
Methods: The OVAL (NCT03398655) study is an on-going study where patients are randomly assigned in a 1:1 ratio to weekly paclitaxel 80 mg/m2 with VB-111 or placebo. The protocol specifies a pre-planned unblinded futility interim analysis of CA-125 response per GCIG criteria in the first 60 evaluable patients. The futility rule determined for this analysis was that the response rate of VB-111 must be greater than the response rate of placebo by at least 10% in order to continue the study. Coincident with the interim analysis, the blinded CA-125 response rate was estimated as a proportion of the first 60 evaluable patients with CA-125 response per GCIG criteria. Post-treatment fever is provided as a possible surrogate marker of VB-111 therapy activity.
Results: The median age of the evaluable patients was 62 years (range 41-82); 97% had high-grade serous cancer; 58% had been treated with 3 or more previous lines of therapy, 70% received prior anti-angiogenic treatment, 43% received prior PARP inhibitors. CA-125 response in the VB-111 and weekly paclitaxel treated arm met the pre-specified interim criterion of an absolute advantage of 10% or higher compared to the control. Blinded results show a 53% CA-125 response rate (32/60) with 15% complete response (n=9). Assuming balanced randomization and an absolute advantage of 10% or higher to the VB-111 arm, it may be deducted that the response in the VB-111 treatment arm is 58% or higher. Among patients with post-treatment fever, the CA-125 response rate was 69%.
Conclusions: At the time of the interim analysis, response rate findings are comparable to the responses seen in a similar patient population in the phase I/II study. The independent data and safety monitoring committee (iDSMC) recommended continuing the OVAL trial as planned. No new safety signals were identified.
Keywords: Futility analysis; Interim analysis; Ovarian cancer; Phase III trial; Platinum resistant.
Conflict of interest statement
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed