Phase I/II clinical trial results reported at the American Society for Clinical Oncology (ASCO) Annual Meeting 2015 show promising results for investigational drug brigatinib against ALK+ non-small cell lung cancer (NSCLC), with 58 of 78 ALK+ patients responding to treatment, including 50 of 70 patients who had progressed after previous treatment with crizotinib, the first licensed ALK inhibitor. Progression-free survival (PFS) in patients previously treated with crizotinib was 13.4 months.
"Although still only in an early phase trial, brigatinib is showing an objective response rate in approximately 70 percent of ALK-positive patients post-crizotinib and it's showing about a year of progression-free survival. These results are among the best in the field, offering a lot of hope to people with ALK-positive lung cancer," says D. Ross Camidge, MD, PhD, director of thoracic oncology at the University of Colorado Cancer Center and the trial's principal investigator.
In addition, robust data is emerging on drug activity in patients with brain involvement of the disease. Many lung cancer trials have traditionally excluded patients with brain metastases at baseline, expecting that the presence of metastases would create negative results that could in turn create the appearance of drug failure. Following early recognition of the importance of the brain as a potential differentiator between the activity of new drugs, the brigatinib trial includes patients with untreated brain metastases, showing a greater than 30 percent decrease in size of brain tumors in 8 of 15 patients with brain tumors greater than 10 mm and disappearance of brain metastases in 11 of 33 patients with smaller lesions only. Brain metastases remained controlled for a median 15.6 months.
Based on these promising early results, brigatinib, developed by Ariad Pharmaceuticals, Inc., recently received Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with ALK+ metastatic NSCLC whose tumors are resistant to crizotinib (below structure)