The drug being tested in this study is called brigatinib. Brigatinib has been demonstrated to
benefit people with ALK-positive NSCLC.
The comparator drug is called alectinib. Alectinib has been demonstrated to benefit people
with ALK-positive NSCLC. Both drugs belong to a class of drugs called ALK inhibitors. Both
drugs are taken by mouth. Both drugs are approved by the US FDA.
The study will enroll approximately 246 patients. Participants will be randomly assigned (by
chance, like flipping a coin) in 1:1 ratio to one of the two treatment groups:
All participants will be asked to take brigatinib or alectinib at the same time each day
throughout the study.
This multi-center trial will be conducted worldwide. The overall time to participate in this
study is 5 years. Participants will make multiple visits to the clinic, and 30 days after
last dose of study drug for a follow-up assessment.
1. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
2. Have histologically or cytologically confirmed stage IIIB (locally advanced or
recurrent) or stage IV non-small cell lung cancer (NSCLC).
3. Must meet one of the following criteria:
1. Have documentation of anaplastic lymphoma kinase (ALK) rearrangement by a
positive result from the Vysis ALK Break-Apart fluorescence in situ hybridization
(FISH) Probe Kit or the Ventana ALK (D5F3) CDx Assay or Foundation Medicine's
2. Have documented ALK rearrangement by a different test and be able to provide
tumor sample to the central laboratory. (Note: central laboratory ALK
rearrangement testing results are not required to be obtained before
4. Had progressive disease (PD) while on crizotinib, as assessed by the investigator or
treating physician. (Note: crizotinib does not need to be the last therapy a
participant received. The participant may have received chemotherapy as his/her last
5. Treatment with crizotinib for at least 4 weeks before progression.
6. Have had no other ALK inhibitor other than crizotinib.
7. Have had no more than 2 prior regimens of systemic anticancer therapy in the locally
advanced or metastatic setting. Note: a systemic anticancer therapy regimen will be
counted if it is administered over at least 1 cycle. A new antineoplastic agent used
as maintenance therapy will be counted as a new regimen. Neoadjuvant or adjuvant
systemic anticancer therapy will be counted as a prior regimen if disease
progression/recurrence occurred within 12 months upon completion of this neoadjuvant
or adjuvant therapy.
8. Have at least 1 measurable (ie, target) lesion per response evaluation criteria in
solid tumors (RECIST) v1.1.
9. Have recovered from toxicities related to prior anticancer therapy to national cancer
institute common terminology criteria for adverse events (NCI CTCAE) v4.03 grade ≤1.
(Note: treatment-related alopecia or peripheral neuropathy that are grade >1 are
allowed, if deemed irreversible).
10. Have adequate organ function, as determined by:
1. Total bilirubin ≤1.5 times the upper limit of normal (ULN).
2. Estimated glomerular filtration rate ≥30 mL/minute/1.73 m2, using the
modification of diet in renal disease equation.
3. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 × ULN; ≤5 ×
ULN is acceptable if liver metastases are present.
4. Serum lipase ≤1.5 × ULN.
5. Platelet count ≥75 ×109/L.
6. Hemoglobin ≥9 g/dL.
7. Absolute neutrophil count ≥1.5 × 109/L.
11. Suitable venous access for study-required blood sampling (ie, including PK and
laboratory safety tests).
1. Had participated in the control (crizotinib) arm of Study AP26113-13-301 (ALTA 1L).
2. Had received crizotinib within 7 days of randomization.
3. Have a history or presence at baseline of pulmonary interstitial disease, drug related
pneumonitis, or radiation pneumonitis.
4. Have uncontrolled hypertension. Participants with hypertension should be under
treatment for control of blood pressure upon study entry.
5. Had Received systemic treatment with strong cytochrome P-450 (CYP) 3A inhibitors,
strong CYP3A inducers, or moderate CYP3A inducers within 14 days before randomization.
6. Treatment with any investigational systemic anticancer agents within 14 days or 5
half-lives, whichever is longer, before randomization.
7. Had received chemotherapy or radiation therapy within 14 days of randomization except
for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy.
8. Had received antineoplastic monoclonal antibodies within 30 days of randomization.
9. Had major surgery within 30 days of randomization. Minor surgical procedures, such as
catheter placement or minimally invasive biopsies, are allowed.
10. Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening
(participants with asymptomatic brain metastases or participants who have stable
symptoms and did not require an increased dose of corticosteroids to control symptoms
within 7 days before randomization will be enrolled). Note: If a participant has
worsening neurological symptoms or signs due to CNS metastasis, the participant needs
to complete local therapy and be neurologically stable (with no requirement for an
increasing dose of corticosteroids or use of anticonvulsants) for 7 days before
11. Have current spinal cord compression (symptomatic or asymptomatic and detected by
radiographic imaging). Participants with leptomeningeal disease and without cord
compression are allowed.
12. Have significant, uncontrolled, or active cardiovascular disease, specifically
including, but not restricted to the following:
1. Myocardial infarction within 6 months before randomization.
2. Unstable angina within 6 months before randomization.
3. New York Heart Association Class III or IV heart failure within 6 months before
4. History of clinically significant atrial arrhythmia (including clinically
significant bradyarrhythmia), as determined by the treating physician.
5. Any history of clinically significant ventricular arrhythmia.
13. Had cerebrovascular accident or transient ischemic attack within 6 months before first
dose of study drug.
14. Have malabsorption syndrome or other gastrointestinal illness or condition that could
affect oral absorption of the study drug.
15. Have an ongoing or active infection, including but not limited to, the requirement for
16. Have a known history of HIV infection. Testing is not required in the absence of
17. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C
18. Have a known or suspected hypersensitivity to brigatinib or alectinib or their
19. Life-threatening illness unrelated to cancer.