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

Gynecol Oncol. 2021 May;161(2):496-501. doi: 10.1016/j.ygyno.2021.02.014. Epub 2021 Feb 23.


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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenoviridae / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inducing Agents / administration & dosage
  • Combined Modality Therapy
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Genetic Therapy / methods*
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / therapy*
  • Paclitaxel / administration & dosage*
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Transgenes
  • fas Receptor / genetics


  • Angiogenesis Inducing Agents
  • FAS protein, human
  • Receptors, Tumor Necrosis Factor, Type I
  • fas Receptor
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT03398655