Ofranergene obadenovec (VB-111) in platinum resistant ovarian cancer: Association of favorable response rates in a phase I/II study with an immunotherapeutic effect.

person Yael Chava Cohen Tel Aviv Sourasky Medical Center and Sakler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel info_outline Yael Chava Cohen, Suzanne T. Berlin, Michael J. Birrer, Susana M. Campos, Tamar Rachmilewitz Minei, Dror Harats, Richard T. Penson

Authors person Yael Chava Cohen Tel Aviv Sourasky Medical Center and Sakler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel info_outline Yael Chava Cohen, Suzanne T. Berlin, Michael J. Birrer, Susana M. Campos, Tamar Rachmilewitz Minei, Dror Harats, Richard T. Penson Organizations Tel Aviv Sourasky Medical Center and Sakler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Dana–Farber Cancer Institute, York, ME, The University of Alabama at Birmingham, Birmingham, AL, Dana-Farber Cancer Institute, Boston, MA, VBL Therapeutics, Modiin, Israel, Harvard Medical School, Boston, MA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: VB-111 is a targeted anti-cancer gene therapy with a dual mechanism: anti angiogenic/vascular disruption and induction of an anti-tumor directed immune response. We report final results of a phase I/II study of VB-111 in combination with paclitaxel in patients with platinum-resistant ovarian cancer. Methods: Study NCT01711970 was a prospective, open label, dose escalating study assessing combination treatment of VB-111 Q8W 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 1x10 13 Viral Particles and paclitaxel 80mg/m 2 . Assessments included safety, overall survival (OS), PFS, tumor response (CA-125 and RECIST) and histopathology. Results: 21 patients with recurrent platinum-resistant ovarian cancer were enrolled and treated in 2 US sites. Patients received a mean of 2.3 ±1.8 repeat doses of VB-111. 17/21 received the therapeutic dose. Median age was 65 (41-79) with a median of 3 (1-4) 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 was associated with generally mild flu-like symptoms. In the therapeutic dose cohort, a 58% CA-125 GCIG response rate was seen in evaluable patients including durable responses, and responses in patients with platinum refractory disease and post anti-angiogenic failure . The median OS was 498 days in patients treated with Therapeutic Dose compared to 173 days in Sub-therapueutic dose (p = 0.028). Tumor Specimens taken after treatment demonstrated tumor infiltrated with cytotoxic CD8 T-cells and regions of apoptotic cancer cells. Conclusions: Treatment with VB-111 in combination with weekly Paclitaxel was safe and well tolerated. Favorable tumor responses and overall survival outcomes were associated with induction of an immunotherapeutic effect manifested as tumor infiltration with CD-8 T cells. Encouraging results are the basis for further exploration in the ongoing, placebo controlled, pivotal OVAL study. Clinical trial information: NCT01711970