Local Consolidative Therapy and Brigatinib in Treating Patients with Stage IV or Recurrent Non-small Cell Lung Cancer, The BRIGHTSTAR Trial

Inclusion Criteria

• Histologically or cytologically confirmed diagnosis of stage IV non-small cell lung cancer (NSCLC) (or recurrent NSCLC not a candidate for definitive multimodality therapy)
• Documented ALK re-arrangement as detected by: (1) Fluorescence in situ hybridization (FISH), (2) immunohistochemistry (IHC), (3) tissue next generation sequencing (NGS), or (4) cfDNA NGS
• Subjects can be enrolled as (1) tyrosine kinase inhibitor (TKI) naive or (2) after =< 8 weeks of first-line brigatinib treatment without disease progression
• Candidate for local consolidative therapy to at least one site of residual disease
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Males or females aged at least 18 years
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L or at least 1500/cubic millimeters or at least 1.5 x 10^9/L
• Platelet count at least 75,000/cubic millimeters or at least 75 x 10^9/L
• Hemoglobin (Hb) at least 9 g/dL (or 5.69 mmol/L) at baseline
• Serum creatinine =< 1.5 x upper limit of normal (ULN) or >= 60 mL/minute for subjects with creatinine levels > 1.5 x the institutional ULN
• Serum total bilirubin less than or equal to =< 1.5 x ULN or direct bilirubin =< ULN or direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN except for subjects with liver metastases (mets) for whom ALT and AST should be =< 5 x ULN
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated PTT (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulant
• Female patients of childbearing potential must have a negative pregnancy test documented at time of screening
• Female patients who: * Are postmenopausal for at least 1 year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
• Male patients, even if surgically sterilized (i.e., status post-vasectomy), who: * Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or * Agree to completely abstain from heterosexual intercourse
• Have normal QT interval on screening electrocardiography (ECG) evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ·450 milliseconds (msec) in males or =< 470 msec in females
• Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

Exclusion Criteria

• Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 2 years elapsed since the diagnosis of the other primary malignancy
• Previously received any prior TKI, including ALK-targeted TKIs * Note: on-going first-line brigatinib use as specified in the Inclusion criteria is allowed
• Previously received more than 1 regimen of chemotherapy or immunotherapy for locally advanced or metastatic disease; Note that history of consolidative immunotherapy after concurrent chemoradiotherapy (for locally advanced disease) is allowed
• Symptomatic central nervous system (CNS) metastasis. Asymptomatic CNS disease requiring increasing dose of corticosteroids within 7 days prior to study enrollment is also not permitted
• Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression are allowed
• The presence of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis at screening
• Have a known or suspected hypersensitivity to brigatinib or its excipients
• Have malabsorption syndrome or other gastrointestinal (GI) illness or condition that could affect oral absorption of the study drug
• Be pregnant, planning a pregnancy, or breastfeeding
• 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 study drug * Unstable angina within 6 months prior to first dose of study drug * Decompensated congestive heart failure (CHF) within 6 months prior to first dose of study drug * History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician * Any history of ventricular arrhythmia * Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose of study drug
• Have uncontrolled hypertension. Patients with hypertension should be under treatment on study entry to control blood pressure
• Have an ongoing or active infection, including, but not limited to, the requirement for intravenous (IV) antibiotics
• Have a known history of human immunodeficiency virus (HIV) infection. Testing is not required in the absence of history
• Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the study drug