DDEL-07INTRAVENOUS TOCA 511 DELIVERY LEADS TO VIRAL DNA IN RESECTED HGG

Recurrent high grade glioma (HGG) remains resistant to standard therapies with survival ranging from 7.2-8.1 months. A Phase 1 clinical study using an investigational retroviral replicating vector (RRV), Toca 511, in combination with investigational oral Toca FC (extended-release 5-FC), is ongoing to evaluate intravenous (IV) delivery of Toca 511 prior to tumor resection in patients with recurrent HGG. Main objectives of this study (NCT01985256) are to identify the highest tolerated dose of Toca 511 administered intravenously followed by intracranial-parenchymal injection during resection, as well as to analyze resected tumor for presence of virus and transgene. Toca 511 doses have been escalated to 4.6 x 109 TU IV/day for 3 days (1.2 x 109 TU injected into tumor bed), followed by Toca FC at 220 mg/kg/day. The highest planned dose is 9.5 x 109 TU IV/day for 5 days. As of April 8 2015, 10 subjects have been dosed without complications. Treatment is well tolerated with no related grade ≥3 AEs, no DLTs and no subjects having discontinued Toca FC for toxicity. Pharmacokinetic analysis shows consistent dose response with virus in blood 24 hours after initial IV injection enabling multi-day dosing. Tumor samples demonstrated presence of viral DNA signal in a dose dependent manner, with 7/10 tumors having detectable, and 4/10 quantifiable signal. In the top dose group, 3/5 had quantifiable signal in the tumor. Expression of yCD transgene was detectable by IHC. Approximately 4-6 weeks after resection, virus could not be detected above the lower quantification limit in blood. Urine and saliva samples were negative with a single exception (saliva). All subjects remain alive with a maximum follow-up of 14 months (median 4 months). This study confirms the successful targeting of HGG by IV delivery of Toca 511 and tolerability at tested doses. Preliminary efficacy results will be presented.