A Phase 1 Drug-Drug Interaction Study Between Brigatinib and the CYP3A Substrate, Midazolam, in Participants With ALK-Positive or ROS1-Positive Solid Tumors

The study will enroll approximately 20 participants to achieve approximately 15 PK-evaluable participants for assessment. This study will consist of 2 parts: Part A of the study will evaluate the effect of repeat-dose administration of brigatinib on the single-dose PK of midazolam. Part B of the study is exploratory and will allow participants to continue brigatinib until disease progression (PD). All participants will receive study drug via the oral route. Participants will be assigned to: Midazolam 3 mg + Brigatinib 90 mg.

The overall time to participate in this study is 26 months. Participants will have a 28-day PK cycle in Part A and a maximum of 23 cycles in Part B, and a 30-day follow-up period after end of treatment.

Inclusion criteria

• Locally advanced or metastatic solid tumors who meet 1 of the following 4 criteria:

• With locally advanced or metastatic ALK-positive NSCLC who have progressed on or are intolerant to treatment with at least 1 other ALK inhibitor.
• With ALK-positive nonlung solid tumors that are locally advanced or metastatic and for whom no standard, nonexperimental therapy is available.
• With locally advanced or metastatic ROS1-positive NSCLC who have progressed on crizotinib therapy or are intolerant to crizotinib, or
• With ROS1-positive nonlung solid tumors that are locally advanced or metastatic and for whom no standard, nonexperimental therapy is available.
• Eastern cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have at least 1 target lesion per response evaluation criteria in solid tumors (RECIST) version 1.1.
• Have recovered from toxicities related to prior anticancer therapy to National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) version 4.03 Grade less than or equal to (<=) 1.
• Suitable venous access for study-required blood sampling (that is, including PK and laboratory safety tests).

Exclusion criteria

• Systemic treatment with strong or moderate cytochrome P450 3A (CYP3A) inhibitors or inducers within 14 days before enrollment.
• Prior therapy with brigatinib.
• Received prior ALK-inhibitor therapy within 7 days before the first dose of study drug.
• Treatment with any investigational systemic anticancer agents within 14 days or 5 half-lives, whichever is longer, before the first dose of study drug.
• Received chemotherapy or radiation therapy within 14 days before the first dose of study drug, except for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy.
• Received antineoplastic monoclonal antibodies within 30 days before the first dose of study drug.
• Had major surgery within 30 days before the first dose of study drug. Minor surgical procedures, such as catheter placement or minimally invasive biopsies, are allowed.
• Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression are allowed.