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

March 26, 2025 updated by: Turning Point Therapeutics, Inc.

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Local Institution - 2119
  • Brazil
      • Sao Paulo, Brazil, 01246-000
        • Local Institution - 2108
    • RJ
      • Botafogo, RJ, Brazil, 22281100
        • Local Institution - 2126
    • RS
      • Porto Alegre, RS, Brazil, 90050-170
        • Local Institution - 2132
      • Porto Alegre, RS, Brazil, 90610-000
        • Local Institution - 2134
    • SP
      • Sao Paulo, SP, Brazil, 1308050
        • Local Institution - 2130
  • France
      • Bordeaux, France, 33076
        • Local Institution - 2123
      • La Tronche, France, 38700
        • Local Institution - 2122
      • Marseille, France, 13915
        • Local Institution - 2117
      • Nantes, France, 44093
        • Local Institution - 2115
      • Poitiers, France, 86021
        • Local Institution - 2121
      • Rennes, France, 35000
        • Local Institution - 2136
      • Saint-Herblain, France, 44805
        • Local Institution - 2120
  • Italy
      • Naples, Italy, 80131
        • Local Institution - 2114
    • MI
      • Milan, MI, Italy, 20132
        • Local Institution - 2135
      • Rozzano, MI, Italy, 20089
        • Local Institution - 2116
    • PG
      • Perugia, PG, Italy, 06129
        • Local Institution - 2111
    • PN
      • Aviano, PN, Italy, 33081
        • Local Institution - 2104
    • VR
      • Verona, VR, Italy, 37134
        • Local Institution - 2103
  • Spain
      • Barcelona, Spain, 8950
        • Local Institution - 2109
      • Madrid, Spain, 28033
        • Local Institution - 2127
      • Madrid, Spain, 28040
        • Local Institution - 2106
      • Pamplona, Spain, 31008
        • Local Institution - 2112
      • Valencia, Spain, 46009
        • Local Institution - 2125
    • B
      • Barcelona, B, Spain, 08003
        • Local Institution - 2124
      • Barcelona, B, Spain, 08025
        • Local Institution - 2113
      • Barcelona, B, Spain, 8035
        • Local Institution - 2105
    • M
      • Madrid, M, Spain, 28034
        • Local Institution - 2110
      • Madrid, M, Spain, 28040
        • Local Institution - 2128
      • Madrid, M, Spain, 28027
        • Local Institution - 2138
    • Madrid
      • Pozuelo de Alarcon, Madrid, Spain, 28223
        • Local Institution - 2129
  • United States
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Research Center
      • Canton, Ohio, United States, 44718
        • Local Institution - 2101

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Repotrectinib (TPX-0005)
Phase 1 Oral repotrectinib (TPX-0005) + cocktail drugs (metformin hydrochloride, digoxin, rosuvastatin calcium)
Drug: TPX-0005
Oral TPX-0005 capsules
Other Names:
  • repotrectinib
Drug: Metformin Hydrochloride
oral solution
Other Names:
  • Glucophage
  • Metabet
  • Glucient
  • Diagemet
  • Axpinet
Drug: Digoxin
oral tablet
Other Names:
  • Lanoxin
Drug: Rosuvastatin Calcium
oral tablet
Other Names:
  • Crestor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under plasma-concentration time curve
Time Frame: 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).
Within 28 days of first cocktail dose
Maximum Observed Plasma Concentration
Time Frame: Within 28 days of first cocktail dose
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
Time Frame: 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
Within 28 days of first cocktail dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Turning Point Therapeutics, Inc.

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 15, 2024

Primary Completion (Estimated)

July 31, 2025

Study Completion (Estimated)

November 30, 2025

Study Registration Dates

First Submitted

March 28, 2023

First Submitted That Met QC Criteria

April 12, 2023

First Posted (Actual)

April 25, 2023

Study Record Updates

Last Update Posted (Actual)

April 1, 2025

Last Update Submitted That Met QC Criteria

March 26, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA127-1027 (BMS Protocol ID)
  • TPX-0005-16 (Other Identifier: Turning Point Therapeutics Protocol ID)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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