Ofranergene obadenovec (VB-111) in platinum-resistant ovarian cancer; favorable response rates in a phase I/II study are associated with an immunotherapeutic effect

Gynecol Oncol. 2020 Jun;157(3):578-584. doi: 10.1016/j.ygyno.2020.02.034. Epub 2020 Apr 5.


Objective: Report final results of a phase I/II study of VB-111, a targeted anti-cancer gene therapy with a dual mechanism: anti angiogenic/vascular disruption and induction of an anti-tumor directed immune response, in combination with paclitaxel in patients with platinum-resistant ovarian cancer.

Methods: Study NCT01711970 was a prospective, open label, dose escalation study assessing combination treatment of VB-111 and weekly paclitaxel. In the Phase I part of the study, patients were treated with escalating doses of intravenous VB-111 and paclitaxel. In Phase 2, patients were treated with therapeutic doses of VB-111 and paclitaxel 80 mg/m2. Assessments included safety, overall survival (OS), progression free survival (PFS), and tumor response (CA-125 and RECIST).

Results: 21 patients with recurrent platinum-resistant ovarian cancer were enrolled. 17/21 received the therapeutic dose. Patients had a median of 3 prior lines of therapy. Half of the subjects were platinum refractory, and half were previously treated with antiangiogenics. No DLTs were observed. VB-111 was well tolerated and associated with mild flu-like symptoms. In the therapeutic dose cohort, a 58% CA-125 GCIG response rate was seen in evaluable patients. The median OS was 16.6 months in patients treated with therapeutic dose compared to 5.8 months in sub-therapeutic dose (p = 0.028). Tumor specimens taken after treatment demonstrated tumor infiltrated with cytotoxic CD8 T-cells in regions of apoptotic cancer cells.

Conclusions: Treatment with VB-111 in combination with paclitaxel was safe and well tolerated. Favorable tumor responses and overall survival outcomes were associated with induction of an immunotherapeutic effect.

Keywords: Anti-angiogenic; Gene therapy; Immunotherapeutic; Platinum-resistant; Platinum-resistant ovarian cancer; VB-111.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / pharmacology
  • Bleomycin / therapeutic use
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Female
  • Humans
  • Immunotherapy / methods*
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Vinblastine / pharmacology
  • Vinblastine / therapeutic use


  • Bleomycin
  • Vinblastine
  • Cisplatin

Supplementary concepts

  • PVB protocol

Associated data

  • ClinicalTrials.gov/NCT01711970