REO 013 was an open-label, non-randomized, translational study of REOLYSIN® in patients with metastatic colorectal cancer prior to surgical resection of their liver metastases. Patients received REOLYSIN® monotherapy for five consecutive days in advance of their scheduled operations; half at an early time point (21 to 10 days in advance of surgery) and half at a later time point (fewer than 10 days in advance of surgery). Approximately 10 patients were enrolled. The primary objectives of the trial were to assess the presence, replication and anti-cancer effects of REOLYSIN® within liver metastases by examination of the resected tumours. Secondary objected included safety, anti-tumour activity, and humoral and cellular response.
Interim findings announced by the Company in April 2011 indicated that, on initial histological analysis of the 10 patients treated to that date, there was evidence of selective delivery of virus to tumour versus normal liver and viral replication in the majority (seven) of patients. In two patients, only necrotic tumour was found; in one of these cases virus was detected in immune cells in the tumour. In six of 10 patients there was no evidence of virus in the normal liver surrounding the tumour, with virus found only rarely in liver cells in the other four patients.
Findings from the study were published in the journal Science Translational Medicine in June 2012. The researchers demonstrated that, even though all the treated patients had pre-existing immunity to the virus, intravenously administered REOLYSIN® could still specifically target and infect metastatic liver tumours in 90% of the patients. The researchers were able to determine that REOLYSIN® was able to evade these neutralizing effects of the immune system by binding to specific blood cells that would in turn deliver the virus to the tumour. Analysis of surgical specimens demonstrated greater, preferential expression of reovirus protein in malignant cells compared to either tumour stroma or surrounding normal liver tissue. There was evidence of viral factories within tumour and recovery of replicating virus from tumour (but not normal liver) in all four patients from whom fresh tissue was available. This was the first time that researchers were able to demonstrate that, in patients treated with intravenously delivered oncolytic virus, a virus could cloak itself from neutralizing antibodies after systemic administration through blood cell carriage and specifically target tumour tissue.
The study was sponsored by the University of Leeds.