A Study to Evaluate the Efficacy of Brigatinib (AP26113) in Participants With Anaplastic Lymphoma Kinase (ALK)-Positive, Non-small Cell Lung Cancer (NSCLC) Previously Treated With Crizotinib

Inclusion Criteria

• Have histologically or cytologically confirmed locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is anaplastic lymphoma kinase (ALK+).
• Must meet one of the following two criteria:
• Have documented ALK rearrangement by a positive result from the Vysis® ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit; or
• Have documented ALK positivity by a different test and tissue available for the Vysis® FISH test. Tissue should be derived preferably from a biopsy taken after progression with crizotinib. If such a sample is not available, testing may be performed with archived tumor tissue.
• Had progressive disease while on crizotinib, as assessed by the investigator or treating physician.
• Have at least 1 measurable lesion per RECIST v1.1. Note: Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy. Brain lesions may not be used as target lesions if they were: 1) previously treated with whole brain radiation therapy (WBRT) within 3 months, or 2) previously treated by stereotactic radiosurgery (SRS) or surgical resection.
• Recovered from toxicities related to prior anticancer therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0) grade ≤2.
• Are a male or female participants ≥18 years old.
• Have a life expectancy ≥3 months.
• Have adequate organ and hematologic function, as determined by:
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN; ≤5 x ULN is acceptable if liver metastases are present)
• Total serum bilirubin ≤1.5 x ULN (<3.0 x ULN for participants with Gilbert syndrome)
• Serum creatinine ≤1.5 x ULN
• Serum lipase/amylase ≤1.5 x ULN
• Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥75000/µL
• Hemoglobin ≥10 g/dL
• Have Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Have normal QT interval on screening electrocardiogram (ECG) evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ≤450 ms in males or ≤470 ms in females.
• For female participants of childbearing potential, a negative pregnancy test must be documented prior to enrollment.
• Female and male participants who are fertile must agree to use a highly effective form of contraception with their sexual partners throughout study participation.
• Must provide a signed and dated informed consent indicating that the participants has been informed of all pertinent aspects of the study, including the potential risks, and is willingly participating.
• Have the willingness and ability to comply with scheduled visits and study procedures.

Exclusion Criteria

• Received any prior ALK-targeted TKI other than crizotinib.
• Received crizotinib within 3 days of the first dose of brigatinib (Day 1, Cycle 1).
• Received cytotoxic chemotherapy, investigational agents, or radiation within 14 days, except SRS or stereotactic body radiosurgery.
• Received monoclonal antibodies or had major surgery within 30 days of the first dose of brigatinib (Day 1, Cycle 1).
• Have been diagnosed with another primary malignancy within the past 3 years (except for adequately treated non-melanoma skin cancer, cervical cancer in situ, or prostate cancer, which are allowed within 3 years).
• Have symptomatic CNS metastases that are neurologically unstable or require an increasing dose of corticosteroids.
• Have current spinal cord compression.
• Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
• Myocardial infarction (MI) within 6 months prior to the first dose of brigatinib
• Unstable angina within 6 months prior to first dose
• Congestive heart failure (CHF) within 6 months prior to first dose
• History of clinically significant (as determined by the treating physician) atrial arrhythmia
• Any history of ventricular arrhythmia
• Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose
• Have a history or the presence of pulmonary interstitial disease or drug-related pneumonitis.
• Have an ongoing or active infection. The requirement for intravenous (IV) antibiotics is considered active infection.
• Have a known history of human immunodeficiency virus (HIV). Testing is not required in the absence of history.
• Have a history of or active significant gastrointestinal (GI) bleeding within 3 months of the first dose of brigatinib.
• Have a known or suspected hypersensitivity to brigatinib or its excipients.
• Have malabsorption syndrome or other GI illness that could affect oral absorption of the study drug.
• Have any condition or illness that, in the opinion of the investigator, would compromise participants safety or interfere with evaluation of the drug study.
• Be pregnant or breastfeeding.