Ofranergene obadenovec (VB-111) in platinum-resistant ovarian cancer; favorable response rates in a phase I/II study are associated with an immunotherapeutic effect
Rebecca C Arend, Hannah M Beer, Yael C Cohen, Suzanne Berlin, Michael J Birrer, Susana M Campos, Tamar Rachmilewitz Minei, Dror Harats, Jaclyn A Wall, McKenzie E Foxall, Richard T Penson, Rebecca C Arend, Hannah M Beer, Yael C Cohen, Suzanne Berlin, Michael J Birrer, Susana M Campos, Tamar Rachmilewitz Minei, Dror Harats, Jaclyn A Wall, McKenzie E Foxall, Richard T Penson
Abstract
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.
Conflict of interest statement
Declaration of competing interest HB, SB, SC, MF, and JW have no conflicts of interest to disclose. RA has financial activities with CLOVIS, TESARO, AstraZeneca and VBL Therapeutics. MB is on the Data Safety and Monitoring Board for VBL Therapeutics. YC and TRM report personal fees during the conduct of the study and have a patent Methods of Anti-Tumor Therapy pending. RP reported grants and personal fees from VBL during the conduct of the study. DH is CEO of VBL.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed