Study of Repotrectinib and CYP450 probe Cocktail in Patients with locally advanced or Metastatic Tyrosine Kinase Inhibitors (TKI)-Pretreated ROS1-Positive Non-small Cell Lung Cancer (NSCLC)

Phase 1

Completed

• Conditions: Non-small Cell Lung Cancer (NSCLC)
• Interventions: Drug: TPX-0005; Drug: Metformin Hydrochloride; Drug: Digoxin; Drug: Rosuvastatin Calcium

• Registration Number: 2024-511030-12-00
• Lead Sponsor: Bristol-Myers Squibb Services Unlimited Company

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.

Study Timeline

• Study First Posted: 2024-11-27
• Last Update Posted: 2025-01-29

Recruitment & Eligibility

• Status: Ended
• Sex: All
• Target Recruitment: 17

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Repotrectinib (TPX-0005)	TPX-0005	Phase 1 Oral repotrectinib (TPX-0005) + cocktail drugs (metformin hydrochloride, digoxin, rosuvastatin calcium)
Repotrectinib (TPX-0005)	Digoxin	Phase 1 Oral repotrectinib (TPX-0005) + cocktail drugs (metformin hydrochloride, digoxin, rosuvastatin calcium)
Repotrectinib (TPX-0005)	Rosuvastatin Calcium	Phase 1 Oral repotrectinib (TPX-0005) + cocktail drugs (metformin hydrochloride, digoxin, rosuvastatin calcium)
Repotrectinib (TPX-0005)	Metformin Hydrochloride	Phase 1 Oral repotrectinib (TPX-0005) + cocktail drugs (metformin hydrochloride, digoxin, rosuvastatin calcium)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (21)

Institut Bergonie; 🇫🇷 Bordeaux, France

Centre Hospitalier Universitaire De Rennes; 🇫🇷 Rennes, France

Centre Hospitalier Regional De Marseille; 🇫🇷 Marseille, France

Centre Hospitalier Universitaire Grenoble Alpes; 🇫🇷 Grenoble Cedex 9, France

Centre Hospitalier Universitaire De Poitiers; 🇫🇷 Poitiers, France

Centre Hospitalier Universitaire De Nantes; 🇫🇷 Saint Herblain, France

Institut De Cancerologie De L Ouest; 🇫🇷 Angers, France

Centro Di Riferimento Oncologico Di Aviano; 🇮🇹 Aviano, Italy

Ospedale Santa Maria Della Misericordia - Azienda Ospedaliera di Perugia; 🇮🇹 Perugia, Italy

Humanitas Mirasole S.p.A.; 🇮🇹 Rozzano, Italy

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Institut Bergonie

🇫🇷Bordeaux, France

Sophie Cousin

Site contact

+33556333333

s.cousin@bordeaux.unicancer.fr