A Study to Evaluate the Efficacy of Brigatinib (AP26113) in Participants With Anaplastic Lymphoma Kinase (ALK)-Positive, Non-small Cell Lung Cancer (NSCLC) Previously Treated With Crizotinib
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Brigatinib
Intervention description: Brigatinib tablets
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 222.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      The purpose of this study is to evaluate the efficacy and safety of two different dosing
      regimens of brigatinib (AP26113) in participants with ALK-positive locally advanced or
      metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on therapy with
      crizotinib.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have histologically or cytologically confirmed locally advanced or metastatic
             Non-small Cell Lung Cancer (NSCLC) that is anaplastic lymphoma kinase (ALK+).

          2. Must meet one of the following two criteria:

               1. Have documented ALK rearrangement by a positive result from the Vysis® ALK
                  Break-Apart fluorescence in situ hybridization (FISH) Probe Kit; or

               2. Have documented ALK positivity by a different test and tissue available for the
                  Vysis® FISH test. Tissue should be derived preferably from a biopsy taken after
                  progression with crizotinib. If such a sample is not available, testing may be
                  performed with archived tumor tissue.

          3. Had progressive disease while on crizotinib, as assessed by the investigator or
             treating physician.

          4. Have at least 1 measurable lesion per RECIST v1.1. Note: Previously irradiated lesions
             may not be used for target lesions, unless there is unambiguous radiological
             progression after radiotherapy. Brain lesions may not be used as target lesions if
             they were: 1) previously treated with whole brain radiation therapy (WBRT) within 3
             months, or 2) previously treated by stereotactic radiosurgery (SRS) or surgical
             resection.

          5. Recovered from toxicities related to prior anticancer therapy to National Cancer
             Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0) grade ≤2.

          6. Are a male or female participants ≥18 years old.

          7. Have a life expectancy ≥3 months.

          8. Have adequate organ and hematologic function, as determined by:

               1. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x upper
                  limit of normal (ULN; ≤5 x ULN is acceptable if liver metastases are present)

               2. Total serum bilirubin ≤1.5 x ULN (<3.0 x ULN for participants with Gilbert
                  syndrome)

               3. Serum creatinine ≤1.5 x ULN

               4. Serum lipase/amylase ≤1.5 x ULN

               5. Absolute neutrophil count (ANC) ≥1500/µL

               6. Platelets ≥75000/µL

               7. Hemoglobin ≥10 g/dL

          9. Have Eastern Cooperative Oncology Group (ECOG) performance status ≤2.

         10. Have normal QT interval on screening electrocardiogram (ECG) evaluation, defined as QT
             interval corrected (Fridericia) (QTcF) of ≤450 ms in males or ≤470 ms in females.

         11. For female participants of childbearing potential, a negative pregnancy test must be
             documented prior to enrollment.

         12. Female and male participants who are fertile must agree to use a highly effective form
             of contraception with their sexual partners throughout study participation.

         13. Must provide a signed and dated informed consent indicating that the participants has
             been informed of all pertinent aspects of the study, including the potential risks,
             and is willingly participating.

         14. Have the willingness and ability to comply with scheduled visits and study procedures.

        Exclusion Criteria:

          1. Received any prior ALK-targeted TKI other than crizotinib.

          2. Received crizotinib within 3 days of the first dose of brigatinib (Day 1, Cycle 1).

          3. Received cytotoxic chemotherapy, investigational agents, or radiation within 14 days,
             except SRS or stereotactic body radiosurgery.

          4. Received monoclonal antibodies or had major surgery within 30 days of the first dose
             of brigatinib (Day 1, Cycle 1).

          5. 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).

          6. Have symptomatic CNS metastases that are neurologically unstable or require an
             increasing dose of corticosteroids.

          7. Have current spinal cord compression.

          8. Have significant, uncontrolled, or active cardiovascular disease, specifically
             including, but not restricted to:

               1. Myocardial infarction (MI) within 6 months prior to the first dose of brigatinib

               2. Unstable angina within 6 months prior to first dose

               3. Congestive heart failure (CHF) within 6 months prior to first dose

               4. History of clinically significant (as determined by the treating physician)
                  atrial arrhythmia

               5. Any history of ventricular arrhythmia

               6. Cerebrovascular accident or transient ischemic attack within 6 months prior to
                  first dose

          9. Have a history or the presence of pulmonary interstitial disease or drug-related
             pneumonitis.

         10. Have an ongoing or active infection. The requirement for intravenous (IV) antibiotics
             is considered active infection.

         11. Have a known history of human immunodeficiency virus (HIV). Testing is not required in
             the absence of history.

         12. Have a history of or active significant gastrointestinal (GI) bleeding within 3 months
             of the first dose of brigatinib.

         13. Have a known or suspected hypersensitivity to brigatinib or its excipients.

         14. Have malabsorption syndrome or other GI illness that could affect oral absorption of
             the study drug.

         15. Have any condition or illness that, in the opinion of the investigator, would
             compromise participants safety or interfere with evaluation of the drug study.

         16. Be pregnant or breastfeeding.