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 non-small cell lung cancer 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 non-small cell lung cancer patients with K-RAS or EGFR-activated tumors. Patients with these types of mutations generally represent about half of the non-small cell lung cancer 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 non-small cell lung cancer patients with mutations or overexpression of EGFR, which are commonly found in Nnon-small cell lung cancer, derive some clinical benefit from these non-small cell lung cancer therapies. However, lung cancer 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 lung cancer 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 lung cancer 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 lung cancer cell lines that were sensitive to the compounds. Interestingly, the combination of reovirus and paclitaxel was uniformly synergistic in all six lung cancer 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."

This non-small cell lung cancer 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 lung cancer. Lung cancer 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 non-small cell lung cancer 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  of this non-small cell lung cancer trial are to determine the median survival and duration of progression-free survival in lung cancer patients, and to evaluate the safety and tolerability of REOLYSIN in combination with paclitaxel and carboplatin in this lung cancer patient population.

For more information, log on to http://www.oncolyticsbiotech.com/.

About Lung Cancer

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. Lung cancer is the leading cause of cancer deaths in the United States, among both men and women. It claims more lives each year than colon cancer, prostate cancer, lymphoma, and breast 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 Only about 15% of those diagnosed with lung cancer are still alive after five years with lung cancer. 

Although lung cancer claims so many lives each year, lost lung cancer deaths could be prevented. That's because smoking accounts for nearly 90 percent of lung cancer cases. Your risk of lung cancer increases with the length of time and number of cigarettes you smoke. If you quit smoking, even after smoking for many years, you can significantly reduce your chances of developing lung cancer. Protecting yourself from other risk factors for lung cancer, such as exposure to asbestos, radon and secondhand smoke, also decreases your risk of lung cancer.

• Shortness of breath
• Chest pain
• Wheezing
• Hoarseness
• A new cough that doesn't go away
• Changes in a chronic cough or "smoker's cough"
• Coughing up blood, even a small amount