A Phase 1 Study to Evaluate the Potential Drug Interactions Between Repotrectinib and Metformin, Digoxin, and Rosuvastatin in Patients With Advanced Solid Tumors

A Phase 1, Open-Label, Fixed-Sequence Study to Evaluate the Potential Drug Interactions Between Repotrectinib and Metformin, Digoxin, and Rosuvastatin in Patients With Advanced Solid Tumors Harboring ROS1 or NTRK1-3 Rearrangements

This is a Phase 1 study to evaluate the potential drug-drug interaction (DDI) effect of repotrectinib on certain drug transporters in patients with advanced cancer.

This is a Phase 1, open-label, fixed-sequence study to evaluate the potential drug-drug interaction (DDI) effect of repotrectinib on drug transporters (metformin, digoxin and rosuvastatin) following multiple dose administration of repotrectinib in patients with advanced cancer harboring ROS1 and NTRK1 Rearrangements.

Key Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary central nervous system [CNS] tumors) that harbors a ROS1 or NTRK1-3 gene fusion.
2. Patient must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing.
3. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 (≥ 18 years).
4. Protocol specified baseline hematology, liver function and kidney function laboratory values.

Key Exclusion Criteria:

1. Concurrent participation in another therapeutic clinical trial.
2. Symptomatic brain metastases or leptomeningeal involvement.
3. Major surgery within 4 weeks of start of repotrectinib treatment.
4. Clinically significant cardiovascular disease.
5. History of non-pharmacologically induced prolonged QTc interval
6. Known active infections requiring ongoing treatment (bacterial, fungal, viral including human immunodeficiency virus positivity).
7. Gastrointestinal disease or other malabsorption syndromes.
8. Current or anticipated use of drugs that are known to be moderate or strong CYP3A inhibitors or inducers.
9. Patients who have received, or are expected to receive metformin, digoxin or rosuvastatin within 14 days prior to beginning of the DDI assessment period.
10. Patients who have received or are expected to receive drugs that are inhibitors of P-gp, OATP1B1, BCRP, and MATE2-K within 14 days or 5 half-lives (whichever is longer) prior to beginning of the DDI assessment period until the DDI assessment period is completed.