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FDA Grants Lorlatinib Breakthrough Therapy Designation for ALK-Positive Metastatic NSCLC

Posted: Friday, April 28, 2017

On April 27, there was good news for patients with anaplastic lymphoma kinase (ALK)-positive metastatic non–small cell lung cancer (NSCLC) who have been deemed unresponsive to previous treatment with one or more ALK inhibitors. Lorlatinib, a next-generation ALK/ROS1 tyrosine kinase inhibitor, was granted Breakthrough Therapy designation by the U.S. Food and Drug Administration. In clinical trials, lorlatinib has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of both ALK and ROS1.

Although initially effective in patients with ALK-positive metastatic NSCLC, earlier-generation ALK inhibitors eventually become associated with a high percentage of treatment resistance. Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood-brain barrier. Lorlatinib continues to be evaluated in clinical studies. For example, the phase III CROWN study, an ongoing, open-label, randomized, two-arm study comparing lorlatinib to crizotinib in the first-line treatment of patients with metastatic ALK-positive NSCLC, recently began enrolling patients.