New Approach Uses a Common Virus to Combat Deadly Lung Cancer

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.