Advanced Solid Tumor, Metastatic Solid Tumor
Conditions
Brief summary
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
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.
Interventions
DRUGTPX-0005
Oral TPX-0005 capsules
DRUGMetformin Hydrochloride
oral solution
DRUGDigoxin
oral tablet
oral tablet
Sponsors
Turning Point Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under plasma-concentration time curve | Within 28 days of first cocktail dose | 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). |
| Maximum Observed Plasma Concentration | Within 28 days of first cocktail dose | Cmax: maximum observed plasma concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate safety and tolerability | Within 28 days of first cocktail dose | 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 |
Countries
Australia, Brazil, France, Italy, Spain, United States
Outcome results
None listed