Published:
12/24/2014

A first-of-its-kind drug is showing early promise in attacking certain lung cancers that are hard to treat because they build up resistance to conventional chemotherapy.

The drug, CO-1686, performed well in a preclinical study involving xenograft and transgenic mice, as reported in the journal Cancer Discovery. It is now being evaluated for safety and efficacy in Phase I and II clinical trials.

The findings stem from a Cooperative Research and Development Agreement that began in 2011 between Clovis Oncology and the Center for Advanced Preclinical Research (CAPR), Center for Cancer Research, NCI. Clovis Oncology developed the drug. CAPR developed transgenic mouse models in which to evaluate the drug and identify causes of drug resistance. CAPR is headed by Terry Van Dyke, Ph.D., NCI, and staffed by researchers of the Frederick National Laboratory for Cancer Research.

The drug, taken as a pill, is designed for use in lung cancer patients with mutations in epidermal growth factor receptors (EGFRs). These mutations account for non-small cell lung cancers in 15 percent of patients of European descent and in one-third of patients of East Asian descent.

Patients treated with conventional chemotherapies, such as erlotinib or gefitinib, may respond well at first, but develop resistance to the drugs in as little as nine months. At that point, few treatment options exist.

The drug resistance is typically caused by the occurrence of a secondary mutation. CO-1686 attacks this secondary mutation, both in primary tumors and in metastatic growths in multiple locations, including the brain and liver. Preliminary findings indicate that the drug works without causing significant side effects. It targets mutant EGFR genes and does not affect normal cells.

Lung cancer is the second most common cancer and the main cause of cancer death in the United States. Although death rates have been declining since 2001, the disease continues to take a significant toll. In 2014, it was projected that 224,210 new cases would be diagnosed, while 159,260 lives would be lost to the disease. Non-small cell lung cancers account for 85 percent of cases and are usually diagnosed at late stage.