CALGARY, Canada—Calgary-based Oncolytics Biotech Inc. reported new colorectal-cancer drug findings at the American Society of Clinical Oncology’s 2013 Gastrointestinal Cancers Symposium (ASCO GI), held this week in San Francisco.
Oncolytics presented a poster reporting results from a phase 1 study in patients with colorectal cancer. In the study, REOLYSIN, a biologic agent developed by Oncolytics, was administered (along with a standard chemotherapy regimen called FOLFIRI, composed of folinic acid, fluorouracil and irinotecan) to 18 patients with colorectal cancer.
The primary objectives were dose-limiting toxicity to determine maximum tolerated dose and pharmacokinetics; secondary endpoints were antitumor activity, response rate, progression-free and overall survival. The combination of REOLYSIN and FOLFIRI was found to be safe, well-tolerated and resulted in disease control in the majority of the patients. The researchers were encouraged by this activity and safety trial, and are planning advanced-phase studies.
The results will come as encouraging news to those who have been diagnosed with colorectal cancer, who face some stark statistics: According to the U.S. National Cancer Institute (a division of NIH), more than 140,000 Americans were diagnosed with this cancer in 2012, while nearly 52,000 died of it the same year. Globally, more than one million people get colorectal cancer annually, resulting in the deaths of about half a million.
Triggered by uncontrolled cell growth in the colon or rectum, colorectal cancer is often curable when confined to these areas, but the prognosis is much bleaker when it has spread, with management focusing on surgery, chemotherapy and radiation, with all of the attendant risks of these procedures. For example, while chemotherapy can shrink tumors, they often grow back and become resistant, or refractory to the treatment.
Oncolytics’ approach to treatment comes from an area called oncolytic virotherapeutics. Here, viruses are harnessed to infect, multiply within and subsequently lyse cancer cells; the virus targets tumors without affecting normal tissue. Oncolytics developed REOLYSIN from naturally occurring reovirus. The virus has demonstrated impressive results in clinical trials on its own, but particularly in combination with certain chemotherapeutics. In preclinical studies in a wide variety of cancer cell lines, investigators found that when used together, reovirus and chemotherapy resulted in more efficient and synergistic anti-cancer activity than when each agent was used on its own.
Many consider reovirus, from which REOLYSIN is derived, to be the most promising form of oncolytic virus. This virus preferentially replicates in cancer cells that feature a common mutation known as an “activated Ras pathway," while sparing normal cells. This makes it intrinsically tumor selective without the need for any genetic manipulation.
Reovirus is a virus with no known associated disease. It replicates in the cytoplasm and therefore does not integrate into the cell’s DNA. Reovirus is found everywhere in nature and has been isolated from untreated sewage, river and stagnant waters. Exposure to reovirus is common in humans, with half of all children by the age of 12 having been exposed and up to 100 percent testing positive by adulthood.