A Study of Brigatinib in Participants With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib

The drug being tested in this study is called brigatinib (AP26113). Brigatinib is being
tested to treat people who have anaplastic lymphoma kinase-positive (ALK+), advanced
non-small-cell lung cancer (NSCLC).

The study will enroll approximately 103 patients. Participants will be assigned to the
treatment group:

• Brigatinib

All participants will be asked to take brigatinib 90 mg tablet in lead-in period for 7 days,
followed by brigatinib 180 mg at the same time each day throughout the study.

This multicenter trial will be conducted worldwide. The overall time to participate in this
study is approximately 5 years, but the total sample size and study duration may be adjusted
according to preliminary data from interim analysis. Participants will make multiple visits
to the clinic, and 30 days after last dose of study drug for a follow-up assessment.

Inclusion Criteria:

1. Have histologically or cytologically confirmed stage IIIB (locally advanced or
recurrent and not a participant for curative therapy) or stage IV non-small-cell lung
cancer (NSCLC).

2. Must meet both of the following 2 criteria:

1. Have documentation of anaplastic lymphoma kinase (ALK) rearrangement by a
positive result from any laboratory test® approved by the food and drug
administration (FDA) or Have documented ALK rearrangement by a different test
(non-FDA-approved local lab tests) and have provided tumor sample to the central
laboratory. (Note: Central laboratory ALK rearrangement testing results are not
required to be obtained before randomization.)

2. Had been on any one of the ALK tyrosine kinase inhibitor (TKIs) (alectinib,
ceritinib, crizotinib) for at least 12 weeks before progression.

3. Had progressive disease (PD) while on alectinib or ceritinib

4. Had alectinib or ceritinib as the most recent ALK inhibitor therapy.

5. Have at least 1 measurable lesion per response evaluation criteria in solid tumors
(RECIST) version 1.1 as assessed by the investigator.

6. Had recovered from toxicities related to prior anticancer therapy to national cancer
institute common terminology criteria for adverse events (NCI CTCAE), version 4.03,
Grade =1. (Note: Treatment-related alopecia or peripheral neuropathy that are Grade >1
are allowed if deemed irreversible.) and have adequate major organ functions.

7. Have a life expectancy of ≥3 months.

Exclusion Criteria:

1. Had received any prior ALK-targeted TKI other than crizotinib, alectinib, or
ceritinib.

2. Had received both alectinib and ceritinib.

3. Had previously received more than 3 regimens of systemic anticancer therapy for
locally advanced or metastatic disease.

4. Had symptomatic brain metastasis (parenchymal or leptomeningeal). Participants with
asymptomatic brain metastasis or who have stable symptoms that did not require an
increased dose of corticosteroids to control symptoms in the past 7 days before the
first dose of brigatinib may be enrolled.

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

6. Had a cerebrovascular accident or transient ischemic attack within 6 months before
first dose of brigatinib.

7. Had an ongoing or active infection, including, but not limited to, the requirement for
intravenous antibiotics.

8. Had malabsorption syndrome or other gastrointestinal (GI) illness that could affect
oral absorption of brigatinib.