OP25INTRAVENOUS DELIVERY OF ONCOLYTIC REOLYSIN® TO PRIMARY AND SECONDARY BRAIN TUMOURS

INTRODUCTION: Oncolytic viruses preferentially replicate in cancer cells and kill them through direct cytotoxicity and/or immune mediated cell destruction. REOLYSIN® is a proprietary isolate of reovirus type 3 Dearing. In previous trials using intra-lesional administration REOLYSIN® was well tolerated, and there were early signs of efficacy. However, intravenous delivery is a less invasive means of administration that would permit more frequent dosing. This trial aims to identify whether REOLYSIN® can infect primary and secondary brain tumours following intravenous administration. METHOD: This is an open-label, non-randomised study of intravenous REOLYSIN® administered to patients prior to planned surgery for recurrent high-grade glioma or metastatic brain tumours. 12 patients will be treated with a single infusion of 1x1010 TCID50 of REOLYSIN®. The primary objective is the presence of REOLYSIN® in the resected tumours as assessed by immunohistochemistry, RNA in-situ hybridization and retrieval of infectious virions. RESULTS: 9 patients have completed the study to date, including 4 glioblastoma multiforme, 2 grade III glioma and 2 brain metastases cases. 3 of 4 resected GBM patient tumours and both Gd III gliomas contained REOLYSIN® RNA and/or protein. There was evidence for REOLYSIN® productive infection in 8 of the 9 treated tumours. Grade 3-4 adverse reactions were neutropaenia (1 patient) and lymphopaenia (3 patients). CONCLUSION: We have shown for the first time that an oncolytic virus, REOLYSIN®, infects and replicates in primary and secondary brain tumours following intravenous administration. This trial will pave the way for phase I/II trials and combination studies using REOLYSIN® in brain tumour patients.