Tumor Responses And Preliminary Survival Data In A Phase Ii Trial Of Ofranergene Obadenovec (Vb-111) Combined With Paclitaxel In Patients With Recurrent Platinum Resistant Ovarian Cancer.

5551 Background: Ofranergene obadenovec (VB-111) is a gene therapeutic consisting of a non-replicating adenovirus vector (Ad-5) with a modified murine pre-proendothelin promoter leading to apoptosis of tumor vasculature by expressing a Fas-chimera transgene in angiogenic endothelial cells. Over 170 patients have been treated with VB-111 across different cancer indications with evidence of anti-tumor activity with no significant safety issues. We report results of the phase II study of VB-111 in combination with paclitaxel in patients with recurrent müllerian cancers. Methods: VB-111 was administered as intravenous infusion at escalating doses from 3x1012 (DL1&2) to 1x1013 viral particles (VPs) (DL3, therapeutic dose) every 2 months. Paclitaxel was given at 40 mg/m2 (DL1), and 80mg/m2 weekly (DL2-3). A phase 2 expansion cohort commenced at DL3 (therapeutic dose). Assessments included safety, tumor response (CA-125 and RECIST), histopathology, progression free survival (PFS) and overall survival (OS). Results: Nineteen patients at 2 US centers received up to 7 repeat doses of VB-111, 15/19 received the therapeutic dose. Median age was 65 (41-79) with a median of 3 prior lines of therapy. No DLTs were observed. VB-111 was associated with flu-like symptoms and mild infusion reactions; the drug was safe and well tolerated. In the therapeutic dose cohort, a 60% response rate (RR) was seen by the GCIG criteria (more than 50% reduction in CA-125), 93% had clinical benefit. The median OS was not reached, mean OS was 19.9 months. A dose-response was seen. Within the therapeutic dose cohort (n = 15), responses seen in 3 of the 5 patients who had received prior bevacizumab (RR 60%) and in 5 of the 9 pts with platinum refractory disease or progressive disease within 3 months of platinum (RR 55%). On study biopsies suggest that further to the anti-angiogenic mechanism of action VB-111 induced antitumor immune reaction. Conclusions: VB-111 in combination with weekly paclitaxel was safe and well tolerated in ovarian cancer patients. Anticipated toxicities were observed. Tumor responses were seen and survival data is encouraging. Clinical trial information: NCT01711970.