Phase 1
Completed N=24
A Phase 1 Drug-Drug Interaction Study Between Brigatinib and the CYP3A Substrate, Midazolam, in Participants With ALK-Positive or ROS1-Positive Solid Tumors
Carcinoma, Advanced ALK+ or ROS1+Non-Small-Cell Lung, Neoplasm, Advanced ALK+ or ROS1+Solid Tumors
Source: ClinicalTrials.gov NCT03420742 ↗
Enrolled (actual)
24
Serious AEs
70.8%
Results posted
Jan 2023
Primary outcomePrimary: Part A, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam — 57.2; 42.1 hour*nanogram per milliliter (h*ng/mL)
Summary
The purpose of this study is to characterize the effect of repeat-dose administration of brigatinib 180 milligram (mg) once daily (QD) on the single-dose pharmacokinetics (PK) of midazolam.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam |
57.2; 42.1 | — |
| PRIMARY Part A, Cmax: Maximum Observed Plasma Concentration for Midazolam |
19.7; 16.5 | — |
| PRIMARY Part A, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Midazolam |
0.500; 0.500 | — |
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT03420742). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.