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THE CUTTING EDGE PATIENT TREATED WITH CO-1686 news + research • 3 previous treatment lines • Erlotinib immediately before CO-1686 • 625 mg BID A Double Dose of Promising Lung-cancer Findings UCLA scientists report that two new experimental drugs have shown great promise in the treatment of patients with non-small-cell lung cancer, which accounts for about 85 percent of all lung cancers. The drugs — ramucirumab and CO-1686 — were shown in separate clinical trials to increase survival times with fewer toxic side effects than standard treatments. The findings of both trials were presented at the annual meeting of the American Society of Clinical Oncology. Edward Garon, MD (FEL ’06), assistant professor of hematology- oncology, conducted an extensive multi-year Phase 3 clinical trial testing ramucirumab in a population of 1,253 patients whose cancers had progressed during or after first-line chemotherapy treatment. Ramucirumab is an antibody that targets VEGFR-2, an extracellular protein that is important in the formation of the blood vessels that support cancer cells. Patients were given ramucirumab in combination with docetexal, a clinically approved chemotherapy drug considered the cornerstone of second-line treatment in advanced non-small-cell lung cancer. Tumors shrank significantly in 23 percent of patients receiving ramucirumab. The drug is the first new therapy for previously treated non- small-cell lung cancer patients to improve overall survival, when added to standard therapy with findings showing a disease-progression-free survival rate of 4.5 months and median overall survival of 10.5 months. • 82% target lesion reduction at C2 • CNS lesion response Baseline Scans show how therapy with CO-1686 has diminished tumors in lungs of patient with T790M mutation, as well as reduced tumors in metastases that have spread to the brain. Graphic: Courtesy of Dr. Jonathan Goldman Another class of targeted drugs being investigated is EGFR (epidermal growth factor receptor) tyrosine kinase inhibitors. Recent studies, however, have shown that when a patient develops resistance to EGFR inhibitors, more than half the time it is due to the emergence of a new “gatekeeper” mutation, called T790M. CO-1686 is an investigational drug that has been discovered to selectively target both the initial EGFR mutations and the T790M-resistance mutation. Jonathan Goldman, MD (FEL ’08), assistant professor of hematology-oncology, was among the leaders of a study of 88 patients with advanced non-small-cell lung cancer who had previously been treated with an EGFR inhibitor and had developed resistance. In a Phase 1 trial, CO-1686 was administered continuously to the patients in 21-day cycles. Response to the drug was seen in 58 percent of the patients. Treatment-related side effects were for the most part mild and manageable. “Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomized phase 3 trial,” The Lancet, June 2014 The Healing Heart There has been debate over the question of whether or not heart muscle can regenerate itself. Now, UCLA scientists have provided an answer: yes. A study by Reza Ardehali, MD, PhD, assistant professor of cardiology, and colleagues has demonstrated the first direct measure of heart-muscle cells renewing themselves. The findings have important implications for future research that could lead to the regeneration of heart tissue to repair damage caused by disease or heart attack. Illustration: Brad Yeo C2 It was initially believed that heart-muscle cells, or cardiomyocytes, were unable to replicate themselves and that their total number was set at birth; however, research over the past two decades has indicated that these cardiac cells have limited proliferative activity, though there has been no clear agreement within the scientific community as to why and how much. In part, the indirect methods used to measure this potential cell division have been difficult, and at times inaccurate, preventing a scientific consensus. Some groups of researchers used carbon dating to detect the age of human cardiomyocytes to