Positive Top Line Data Presented for Reolysin® in Randomized Phase III Study in Head and Neck Cancers

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Initial positive top line data from the first endpoint in a double-blinded randomized Phase III clinical study examining Reolysin® (Reovirus Serotype 3 Dearing; Oncolytics), a proprietary formulation of the human reovirus, in combination with carboplatin and paclitaxel in second-line patients with platinum-refractory, taxane-naïve head and neck cancers (REO 018; NCT01166542) were presented earlier today.

The purpose of this phase III study was to evaluate overall survival and progression free survival following intravenous administration of reolysinin combination with paclitaxel and carboplatin versus chemotherapy treatment alone, in patients with metastatic or recurrent Squamous Cell Carcinoma of the Head and Neck.

The endpoint examines initial percentage tumour changes between the pre-treatment and first post-treatment scans (typically performed at six weeks post-first treatment) of all patients enrolled in the study. The analysis was designed to assess early differences in response between loco-regional tumors and metastatic tumors, as classified and observed by the investigators. This is the first, and to this point only, endpoint to be un-blinded for this study.

Stabilized disease
The first analysis compared the relative percentages of patients in the test and control arms with tumours that had either stabilized or exhibited shrinkage. For the purposes of this endpoint, the definition of tumour stabilization was restricted to zero percent growth only. Of the 105 total patients with evaluable metastatic tumors, 86% (n=50) of those in the test arm of the study exhibited tumour stabilization or shrinkage, compared with 67% of patients (n=55) in the control arm. This was statistically significant, with a p-value of 0.025.

The second analysis examined the magnitude of tumour response on a per patient basis using a comparison of percentage tumour shrinkage at six weeks in each patient with evaluable metastatic tumours. This analysis showed that reolysin in combination with carboplatin and paclitaxel was statistically significantly better than carboplatin and paclitaxel alone at stabilizing or shrinking metastatic tumours, yielding a p-value of 0.03.

The researchers noted that at the six week point, there is a numeric trend in favour of the test group towards differing activity between the test and control groups in patients with loco-regional tumours.

Improvement of magnitude
In an intragroup analysis of the test arm, an improvement in the percentage of patients’ metastatic tumours over loco-regional tumours was noted (p=0.083) and an improvement of magnitude of response in metastatic tumours over loco-regional tumours was also noted (p=0.13). By contrast, in an intragroup analysis of the control arm, no statistical differences were noted between the responses of patients with evaluable metastatic tumours and patients with evaluable loco-regional tumours.

“To the best of our knowledge, this is the first successful double-blinded randomized data from a clinical study using an intravenously-administered oncolytic virus. We are delighted to have obtained statistically significant data for Reolysin in a randomized clinical setting,” said Brad Thompson PhD, President and CEO of Oncolytics. “We continue to await the data for the other endpoints of this study, to which all parties still remain blinded at this point.”

For more information:
Mechanism of action of Reolysin
– Hofland P. Patient Enrollment Completed in Phase I Trial Investigating Reolysin® in Combination with FOLFIRI in Patients with Colorectal Cancer; Onco’Zine – The International Cancer Network, August 16, 2012
– Hofland P. Oncolytics Biotech and NCIC CTG Sign Agreement for Randomized Phase II Study in Colorectal Cancer; Onco’Zine – The International Cancer Network, May 12, 2012
– Hofland P. Randomized Phase II Ovarian Cancer Study With Reolysin® To Be Conducted By The Gynecologic Oncology Group (GOG); Onco’Zine – The International Cancer Network, September 2, 2010
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Clinical trials
NCT01274624 – Study of Reolysin® in Combination With FOLFIRI in Patients With Oxaliplatin Refractory/Intolerant KRAS Mutant Colorectal Cancer
NCT01166542 – Efficacy Study of Reolysin® in Combination With Paclitaxel and Carboplatin in Platinum-Refractory Head and Neck Cancers
NCT00998322 – A Study of Reolysin in Combination With Gemcitabine in Patients With Advanced Pancreatic Adenocarcinoma.

Illustration: The reovirus, or respiratory enteric orphan virus, has been demonstrated to replicate specifically in tumor cells that have a constitutively activated Ras pathway. Activating mutations of Ras and mutations along the Ras pathway occur in approximately two-thirds of all tumors. Tumors bearing an activated Ras pathway are deficient in their ability to activate an anti-viral response mediated by the host cellular protein, PKR. Since PKR is responsible for preventing reovirus replication, tumor cells that lack the activity of PKR are susceptible to reovirus infection and eventual cell death. As normal cells do not possess Ras activation, these cells are able to thwart reovirus infection by the activity of PKR. In a tumor cell with an activated Ras pathway, the reovirus is able to freely replicate and kill the host tumor cell. Progeny virus particles are then able to infect and kill surrounding cancer cells. This cycle of infection, replication and cell death is believed to be repeated until there are no longer any tumor cells carrying an activated Ras pathway available. Courtesy: Oncolytics Biotech, Inc

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