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

• Published in: Gynecologic oncology 2021-05, Vol.161 (2), p.496-501
• Main Authors: Arend, Rebecca C., Monk, Bradley J., Herzog, Thomas J., Moore, Kathleen N., Shapira-Frommer, Ronnie, Ledermann, Jonathan A., Tewari, Krishnansu S., Secord, Angeles Alvarez, Rachmilewitz Minei, Tamar, Freedman, Laurence S., Miller, Austin, Shmueli, Shifra Fain, Lavi, Michal, Penson, Richard T.
• Format: Article
• Language: English
• Subjects: Futility analysis; Interim analysis; Ovarian cancer; Phase III trial; Platinum resistant
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2021.02.014

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). 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. 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%. 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. •OVAL is a Phase III trial using paclitaxel and VB-111 in recurrent ovarian cancer•VB-111 has a dual mechanism targeting tumor vasculature and anti-tumor immunity•CA-125 response in the VB-111 treated arm met the pre-specified interim criterion•Assuming balanced randomization, the response in the VB-111 arm was at least 58%•The OVAL study has been recommended to continue enrollment as planned