On April 27, 2017 Pfizer Inc. reported that its investigational next-generation ALK/ROS1 tyrosine kinase inhibitor, lorlatinib, was granted Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC), previously treated with one or more ALK inhibitors (Press release, Pfizer, APR 27, 2017, View Source [SID1234518709]). Schedule your 30 min Free 1stOncology Demo! Enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA), Breakthrough Therapy designation is intended to expedite the development and review of a potential new medicine if it is intended to treat a serious or life-threatening disease and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies.1 The Breakthrough Therapy designation is distinct from the FDA’s other mechanisms to expedite drug development and review.2 ALK gene rearrangement is a genetic alteration that drives the development of lung cancer in some patients. 3,4 Due to additional mutations that the tumor may acquire during treatment, disease progression remains a challenge in patients with ALK-positive metastatic NSCLC.5
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"This regulatory designation recognizes the potential for lorlatinib to provide an important treatment option for patients with ALK-positive NSCLC whose cancers have progressed despite treatment. Pfizer’s rapid development of lorlatinib reflects a commitment to developing biomarker-driven therapies to meet the evolving needs of patients," said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development. "We look forward to working with the FDA to accelerate the development of this therapy."
The Breakthrough Therapy designation is supported by the efficacy and safety data of an ongoing Phase 1/2 clinical trial of lorlatinib, which includes patients with ALK-positive NSCLC who were previously treated with one or more ALK inhibitors.
Additionally, the Phase 3 CROWN study (NCT03052608) recently began enrolling patients. CROWN is an ongoing, open label, randomized, two-arm study comparing lorlatinib to crizotinib in the first-line treatment of patients with metastatic ALK-positive NSCLC. Please visit clinicaltrials.gov for more information on this study.
About Non-Small Cell Lung Cancer
Worldwide, lung cancer is the leading cause of cancer death in both men and women.6 NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.7 Approximately 57 percent of NSCLC patients are diagnosed late with metastatic, or advanced, disease where the five-year survival rate is only 5 percent. 8 NSCLC can be further categorized into distinct subsets that are classified by a number of factors, including histology and the molecular makeup of the tumor. Epidemiology studies suggest that approximately 3 to 5 percent of NSCLC tumors are ALK-positive.9
About Lorlatinib
Lorlatinib is an investigational next-generation ALK/ROS1 tyrosine kinase inhibitor that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of both ALK and ROS1. Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier. Lorlatinib is an investigational agent and has not received regulatory approval for any indication anywhere in the world.