Among the 5,000 studies being discussed by 30,000 oncologists at the 2008 meeting of the American Society of Clinical Oncology (ASCO), a great deal of buzz was generated over the discovery that a substantial subset of patients with non-small cell lung cancer (NSCLC) may not benefit from the most commonly prescribed therapies. About 20% of the more than 180,000 NSCLC patients diagnosed every year in the U.S. have mutations in the K-RAS gene. These patients generally respond poorly to standard chemotherapy treatments as well as newer, more targeted therapies called EGFR inhibitors.

Enter REOLYSIN®, an experimental treatment derived from a common virus called the reovirus. REOLYSIN directly kills many types of cancer cells, works synergistically with many approved chemotherapies and radiation, and may also stimulate the immune system to attack and kill cancer cells.

Following FDA review, Oncolytics Biotech Inc. is initiating a Phase 2 clinical trial at the Ohio State University Medical Center using REOLYSIN in combination with paclitaxel and carboplatin for NSCLC patients with K-RAS or EGFR-activated tumors. Patients with these types of mutations generally represent about half of the NSCLC patients diagnosed annually in the U.S.

REOLYSIN preferentially replicates in cancer cells with an activated RAS pathway. Approximately two thirds of all cancers have an activated RAS pathway, including most metastatic disease. A large number of mutations along the RAS pathway, including mutations in EGFR, Her2, or K-RAS, lead to RAS pathway activation. Recent clinical studies in NSCLC with EGFR-based therapies have shown that the patients with mutations or overexpression of EGFR, which are commonly found in NSCLC, derive some clinical benefit from these therapies. However, patients with mutant K-RAS do not generally derive benefit from EGFR-based therapies.

"In this era of personalized cancer treatment, we are quite excited about this trial," said Dr. Miguel Villalona-Calero, Professor Division of Hematology/Oncology and Department of Internal Medicine and Pharmacology at the Ohio State University Comprehensive Cancer Center, and the principal investigator for the trial.

"Although we have had for some time treatments that target EGFR, K-RAS has been an elusive target. REOLYSIN has the potential to target K-RAS activated tumors, possibly enhancing the beneficial effects produced by chemotherapy."

But it's not only patients with mutant K-RAS who might benefit from REOLYSIN combination treatment. The U.S. National Cancer Institute (NCI) recently tested reovirus in combination with a wide range of common chemotherapeutic agents against NSCLC, and found that the combination of reovirus with cisplatin, gemcitabine, mitomycin or vinblastine was synergistic against NSCLC cell lines that were sensitive to the compounds. Interestingly, the combination of reovirus and paclitaxel was uniformly synergistic in all six NSCLC cell lines examined, including in those resistant to paclitaxel or reovirus.

"Previous preclinical data indicates that reovirus tends to localize in the lungs, and we have seen clinical responses in metastatic lung lesions with REOLYSIN as a monotherapy or in combination with paclitaxel and carboplatin," said Dr. Brad Thompson, President and CEO of Oncolytics. "Assuming we get the response we're anticipating, REOLYSIN could be a strong candidate for late-stage clinical trials in this indication."

Non-small cell lung cancer is the second most common cancer in men and women and is the leading cause of death among cancer patients. More people die of lung cancer than of colon, breast, and prostate cancers combined. During 2008, there will be approximately 215,020 new cases of lung cancer in the U.S., of which 85% to 90% will be non-small cell lung cancer (NSCLC). Only about 15% of those diagnosed with lung cancer are still alive after five years with the disease.

This trial is designed as a single arm, two-stage, open-label, Phase 2 study of REOLYSIN given intravenously with paclitaxel and carboplatin every three weeks. Patients will receive four to six cycles of paclitaxel and carboplatin in conjunction with REOLYSIN, at which time REOLYSIN may be continued as a monotherapy. It is anticipated that up to 36 patients will be treated in this trial.

Eligible patients include those with metastatic or recurrent NSCLC with K-RAS or EGFR-activated tumors, who have not received chemotherapy treatment for their metastatic or recurrent disease. Patients must have demonstrated mutations in K-RAS or EGFR, or EGFR gene amplification in their tumors (metastatic or primary) in order to qualify for the trial.

The primary objectives of the Phase 2 trial are to determine the objective response rate of REOLYSIN in combination with paclitaxel and carboplatin in patients with metastatic or recurrent NSCLC with K-RAS or EGFR-activated tumors, and to measure survival and progression-free survival at six months. The secondary objectives are to determine the median survival and duration of progression-free survival in patients, and to evaluate the safety and tolerability of REOLYSIN in combination with paclitaxel and carboplatin in this patient population.

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