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Joshua K Sabari,1 Fernando C Santini,1,2 Alison M Schram,2 Isabella Bergagnini,1 Ruqin Chen,1 Chebli Mrad,1 W Victoria Lai,1 Kathryn C Arbour,1 Alexander Drilon2,3 1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 2Developmetal Therapeutics, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 3Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA Abstract: Brigatinib (AP26113) is a dimethylphosphine oxide group-containing tyrosine kinase inhibitor (TKI) constructed around a bisanilinopyrimidine scaffold with potent activity against the anaplastic lymphoma kinase (ALK) and several other targets. Despite the activity of first- and second-generation ALK inhibitors in advanced ALK-rearranged lung cancers, the development of acquired resistance represents an ongoing challenge. Later generation ALK inhibitors such as brigatinib are important potential tools in the management of patients with acquired resistance characterized by continued dependency on ALK. Brigatinib is active in vitro against many ALK kinase domain mutations that may mediate acquired resistance to other ALK TKIs, with reported activity (IC50