Local Consolidative Therapy and Brigatinib in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of stage IV NSCLC (or recurrent
NSCLC not a candidate for definitive multimodality therapy)

2. Documented ALK re-arrangement as detected by: (1) FISH, (2) IHC, (3) tissue NGS, or
(4) cfDNA NGS

3. Subjects can be enrolled as (1) TKI naive or (2) after brigatinib treatment without disease progression

4. Measurable disease according to RECIST 1.1. At least one lesion of at least 1.0 cm in
the long-axis diameter for a non-lymph node or at least 1.5 cm in the short-axis
diameter for a lymph node which is serially measurable according to RECIST 1.1. If
there is only one target lesion and it is a non-lymph node, it should have a longest
diameter of at least 1.5 cm

5. Candidate for local consolidative therapy to at least one site of residual disease

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

7. Males or females aged at least 18 years

8. Adequate organ function laboratory values, defined as: a.) 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 b.)
Platelet count at least 75,000/cubic millimeters or at least 75 x 10^9/L c.)
Hemoglobin (Hb) at least 9 g/dL (or 5.69 mmol/L) at baseline d.) Serum creatinine 1.5 x ULN or >/= 60 mL/minute for subjects with creatine levels > 1.5 x the
institutional ULN e.) Serum total bilirubin less than or equal to direct bilirubin levels > 1.5 ULN Inclusion 8) continues on next line

9. Continuation from Inclusion 8) f.) Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) and AST should be time (PT) PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of
anticoagulants h.) Activated PTT (aPTT) anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
of anticoagulant

10. Female patients of childbearing potential must have a negative pregnancy test
documented at time of screening.

11. Female patients who: a.) Are postmenopausal for at least 1 year before the screening
visit, OR b.) Are surgically sterile, OR c.) 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

12. Male patients, even if surgically sterilized (i.e., status post-vasectomy), who: a.)
Agree to practice effective barrier contraception during the entire study treatment
period and through 4 months after the last dose of study drug, or b.)Agree to
completely abstain from heterosexual intercourse

13. Have normal QT interval on screening ECG evaluation, defined as QT interval corrected
(Fridericia) (QTcF) of ≤450 milliseconds (msec) in males or
14. Voluntary agreement to provide written informed consent and the willingness and
ability to comply with all aspects of the protocol.

Exclusion Criteria:

1. 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.

2. Previously received any prior TKI, including ALK-targeted TKIs. Note: on-going
first-line brigatinib use as specified in the Inclusion criteria is allowed.

3. Previously received more than 1 regimen of chemotherapy or immunotherapy for locally
advanced or metastatic disease.

4. Symptomatic CNS metastasis. Asymptomatic CNS disease requiring increasing dose of
corticosteroids within 7 days prior to study enrollment is also not permitted.

5. Have current spinal cord compression (symptomatic or asymptomatic and detected by
radiographic imaging). Patients with leptomeningeal disease and without cord
compression are allowed.

6. The presence of pulmonary interstitial disease, drug-related pneumonitis, or radiation
pneumonitis at screening.

7. Have a known or suspected hypersensitivity to brigatinib or its excipients.

8. Have malabsorption syndrome or other gastrointestinal (GI) illness or condition that
could affect oral absorption of the study drug.

9. Be pregnant, planning a pregnancy, or breastfeeding.

10. Have significant, uncontrolled, or active cardiovascular disease, specifically
including, but not restricted to: a.) Myocardial infarction (MI) within 6 months prior
to the first dose of study drug b.) Unstable angina within 6 months prior to first
dose of study drug c.) Decompensated congestive heart failure (CHF) within 6 months
prior to first dose of study drug d.)History of clinically significant atrial
arrhythmia (including clinically significant bradyarrhythmia), as determined by the
treating physician e.) Any history of ventricular arrhythmia f.) Cerebrovascular
accident or transient ischemic attack within 6 months prior to first dose of study
drug

11. Have uncontrolled hypertension. Patients with hypertension should be under treatment
on study entry to control blood pressure

12. Have an ongoing or active infection, including, but not limited to, the requirement
for intravenous (IV) antibiotics.

13. Have a known history of human immunodeficiency virus (HIV) infection. Testing is not
required in the absence of history.

14. 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.