Ofranergene obadenovec (VB-111) in platinum-resistant ovarian cancer; favorable response rates in a phase I/II study are associated with an immunotherapeutic effect.
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.
['Arend|Rebecca C|RC|', 'Beer|Hannah M|HM|', 'Cohen|Yael C|YC|', 'Berlin|Suzanne|S|', 'Birrer|Michael J|MJ|', 'Campos|Susana M|SM|', 'Rachmilewitz Minei|Tamar|T|', 'Harats|Dror|D|', 'Wall|Jaclyn A|JA|', 'Foxall|McKenzie E|ME|', 'Penson|Richard T|RT|']
D000368:Aged D000971:Antineoplastic Combined Chemotherapy Protocols D001761:Bleomycin D002945:Cisplatin D005260:Female D006801:Humans D007167:Immunotherapy D008875:Middle Aged D010051:Ovarian Neoplasms D014747:Vinblastine
VB-111 Platinum-resistant Platinum-resistant ovarian cancer Immunotherapeutic Gene therapy Anti-angiogenic