A Study of Brigatinib in Participants With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib
Condition: ALK-positive Advanced NSCLC
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Brigatinib
Intervention description: Brigatinib Tablets
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 103.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      The primary purpose of this study is to determine the efficacy of brigatinib by confirmed
      objective response rate (ORR) by response evaluation criteria in solid tumors (Response
      Evaluation Criteria in Solid Tumors [RECIST]), in participants with ALK+ locally advanced or
      metastatic NSCLC whose disease has progressed on therapy with alectinib or ceritinib.
    

Eligibility criteria:

        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.