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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Advanced Solid Tumor, Metastatic Solid Tumor

Intervention / Treatment
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* Drug: TPX-0005
* Drug: Metformin Hydrochloride
* Drug: Digoxin
* Drug: Rosuvastatin Calcium


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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. Patient must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 (≥ 18 years). Protocol specified baseline hematology, liver function and kidney function laboratory values. Key Exclusion Criteria: Concurrent participation in another therapeutic clinical trial. Symptomatic brain metastases or leptomeningeal involvement. Major surgery within 4 weeks of start of repotrectinib treatment. Clinically significant cardiovascular disease. History of non-pharmacologically induced prolonged QTc interval Known active infections requiring ongoing treatment (bacterial, fungal, viral including human immunodeficiency virus positivity). Gastrointestinal disease or other malabsorption syndromes. Current or anticipated use of drugs that are known to be moderate or strong CYP3A inhibitors or inducers. Patients who have received, or are expected to receive metformin, digoxin or rosuvastatin within 14 days prior to beginning of the DDI assessment period. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Repotrectinib (TPX-0005)<br>Phase 1 Oral repotrectinib (TPX-0005) + cocktail drugs (metformin hydrochloride, digoxin, rosuvastatin calcium) | Drug: TPX-0005<br>* Oral TPX-0005 capsules<br>* Other names: repotrectinib;Drug: Metformin Hydrochloride<br>* oral solution<br>* Other names: Axpinet;Drug: Digoxin<br>* oral tablet<br>* Other names: Lanoxin;Drug: Rosuvastatin Calcium<br>* oral tablet<br>* Other names: Crestor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under plasma-concentration time curve | AUC0-t: area under the plasma-concentration time curve from time 0 to time of the last measurable concentration. AUC0-inf: area under the plasma-concentration time curve from time 0 to infinity (if data permit). | Within 28 days of first cocktail dose | 
| Maximum Observed Plasma Concentration | Cmax: maximum observed plasma concentration | Within 28 days of first cocktail dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety and tolerability | To evaluate the safety and tolerability of repotrectinib in patients with moderate and severe hepatic impairment and patients with normal hepatic function following single and multiple dose administration of repotrectinib assessed by CTCAE v5.0 | Within 28 days of first cocktail dose |