Inclusion Criteria:

        Locally advanced or metastatic NSCLC that has been cytologically or histologically
        confirmed

        ALK rearrangement based on FDA approved test (e.g. Vysis breakapart FISH or IHC using
        Ventana)

        ECOG PS ≤2

        Age of ≥ 18 years

        Brain lesions may be used as target lesions if progressing, ≥10mm in longest diameter and
        if they were not previously treated with any of the following:

          -  Whole brain radiation therapy (WBRT) within 3 months

          -  Stereotactic radiosurgery (SRS)

          -  Surgical resection Availability of core biopsy of progressive lesion taken within 60
             days prior to D1 of treatment under study therapy or willing to undergo tumor biopsy:
             NOTE:. All subjects must consent to provide tumor blocks or slides.

          -  If archival tissue is not available and biopsies to obtain fresh tumor tissue cannot
             be performed with minimal risk to the subject, subjects may be permitted to enroll on
             the study with prior approval of the Study PI.

          -  In the situation the patient undergoes biopsy within 60 days prior to D1. and there is
             insufficient tumor tissue subjects for the correlative science part of the protocol
             patient will be permitted to enroll on the study with prior approval of the study PI

          -  In the situation the patient undergoes molecular testing or next-generation sequencing
             as part of standard care there must be sufficient tumor sample available for
             participation in the study (i.e. a next generation sequencing report is not sufficient
             for enrollment)

        Recovered from toxicities related to prior anticancer treatment to ≤Grade 2 or baseline
        with the exception of alopecia

        Have normal QT interval on ECG evaluation QT corrected Fridericia (QTcF) of ≤ 450 ms in
        males or ≤ 470 ms in females

        Adequate organ function defined as:

        Absolute neutrophil count (ANC) ≥1500/µL Platelets ≥75,000/µL Hemoglobin≥ 10g/dL AST /ALT ≤
        2.5 x upper limit of normal (ULN); ≤ 5 x ULN if liver metastasis Total serum bilirubin ≤
        1.5 x ULN Serum creatinine ≤ 1.5 x UNL Serum amylase ≤ 1.5 x UNL

        At least 1 measurable lesion per RECIST version 1.1

        Negative serum pregnancy test within 7 days of D1 of treatment in women of child bearing
        potential (WOCBP)

        If fertile, willing to use highly effective form of contraception (defined as a combination
        of at least two of the following methods: condom or other barrier methods, oral
        contraceptives, implantable contraceptives, intrauterine devices) during the dosing period
        and for at least 4 months after

        Ability to provide signed informed consent and willing and able to comply with all study
        requirements

        Inclusion criteria for cohort assignment:

        Cohort A: Progressive disease on any next generation ALK inhibitor except first line
        alectinib or brigatinib (any line)

        Cohort B: Progressive disease on first-line therapy with alectinib, and no other ALK
        inhibitors

        Cohort C: Previous treatment brigatinib at 180 mg daily for ≥4 weeks without > grade 2
        drug-related toxicities and with radiographic evidence of progressive disease and no
        intervening systemic therapies such as chemotherapy, immunotherapy or another ALK inhibitor
        (radiation therapy allowed as intervening therapy). Patients who are treated on cohorts A
        and B will be allowed to enroll in cohort C if the meet the inclusion and exclusion
        criteria

        Exclusion Criteria for cohorts A, B, and C:

        Patients meeting any of the following exclusion criteria will not be able to participate in
        this study:

        History or the presence of pulmonary interstitial disease, drug-related or immune-related
        pneumonitis, or radiation pneumonitis requiring medical management within 6 months of trial
        enrollment

        Prior treatment with brigatinib for cohorts A and B

        History of or active significant gastrointestinal (GI) bleeding within 3 months

        Malabsorption syndrome or other GI illness that could affect oral absorption of the study
        drug

        Received cytotoxic chemotherapy, investigational agents or radiation within 7 days prior to
        D1 of study treatment

        Received prior ALK TKI therapy within 7 days prior to D1 of treatment under study drug. 7
        day wash out period is required after prior ALK inhibitor treatment.

        Have significant, uncontrolled, or active cardiovascular disease, specifically including,
        but not restricted to:

          -  Myocardial infarction (MI) within 6 months of trial enrollment

          -  Unstable angina within 6 months of trial enrollment

          -  Congestive heart failure (CHF) with 6 months prior to trial enrollment

          -  Any history of ventricular arrhythmia

          -  Cerebrovascular accident or transient ischemic attack within 6 months of D1 of study
             treatment

          -  Clinically significant atrial arrhythmia or severe baseline bradycardia defined as
             resting heart rate < 60 beat per minute

          -  Uncontrolled hypertension defined as baseline SBP> 160 and DBP > 100 on 3 separate
             clinic visits or past history of hypertensive urgency, emergency or encephalopathy

        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 which require an increasing dose of corticosteroids within
        the last 2 weeks to remain asymptomatic.

        Have active infection requiring intravenous antibiotics

        Pregnant or breastfeeding

        Have any condition or illness that, in the opinion of the investigator, would compromise
        patient safety or interfere with evaluation of the study drug.