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

NCT05828303 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: CA127-1027
• Study Type: interventional
• Target: N/A
• Locations: 6 countries
• Sites: 33

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.

Conditions

Advanced Solid Tumor; Metastatic Solid Tumor

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Evaluate safety and tolerability

  Within 28 days of first cocktail dose

Study Arms (1)

Repotrectinib (TPX-0005)

EXPERIMENTAL

Phase 1 Oral repotrectinib (TPX-0005) + cocktail drugs (metformin hydrochloride, digoxin, rosuvastatin calcium)

Drug: TPX-0005; Drug: Metformin Hydrochloride; Drug: Digoxin; Drug: Rosuvastatin Calcium

Interventions

TPX-0005 DRUG

Oral TPX-0005 capsules

Also known as: repotrectinib

Repotrectinib (TPX-0005)

Metformin Hydrochloride DRUG

oral solution

Also known as: Glucophage, Metabet, Glucient, Diagemet, Axpinet

Repotrectinib (TPX-0005)

Digoxin DRUG

oral tablet

Also known as: Lanoxin

Repotrectinib (TPX-0005)

Rosuvastatin Calcium DRUG

oral tablet

Also known as: Crestor

Repotrectinib (TPX-0005)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Turning Point Therapeutics, Inc.: lead

Study Sites (33)

Gabrail Cancer Research Center

Canton, Ohio, 44718, United States

Location

Local Institution - 2101

Canton, Ohio, 44718, United States

Location

Local Institution - 2119

Westmead, New South Wales, 2145, Australia

Location

Local Institution - 2126

Botafogo, Rio de Janeiro, 22281100, Brazil

Location

Local Institution - 2132

Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

Location

Local Institution - 2134

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Local Institution - 2130

São Paulo, São Paulo, 1308050, Brazil

Location

Local Institution - 2108

São Paulo, 01246-000, Brazil

Location

Local Institution - 2123

Bordeaux, 33076, France

Location

Local Institution - 2122

La Tronche, 38700, France

Location

Local Institution - 2117

Marseille, 13915, France

Location

Local Institution - 2115

Nantes, 44093, France

Location

Local Institution - 2121

Poitiers, 86021, France

Location

Local Institution - 2136

Rennes, 35000, France

Location

Local Institution - 2120

Saint-Herblain, 44805, France

Location

Local Institution - 2135

Milan, MI, 20132, Italy

Location

Local Institution - 2116

Rozzano, MI, 20089, Italy

Location

Local Institution - 2111

Perugia, PG, 06129, Italy

Location

Local Institution - 2104

Aviano, PN, 33081, Italy

Location

Local Institution - 2103

Verona, VR, 37134, Italy

Location

Local Institution - 2114

Naples, 80131, Italy

Location

Local Institution - 2124

Barcelona, B, 08003, Spain

Location

Local Institution - 2113

Barcelona, B, 08025, Spain

Location

Local Institution - 2105

Barcelona, B, 8035, Spain

Location

Local Institution - 2129

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Local Institution - 2138

Madrid, M, 28027, Spain

Location

Local Institution - 2110

Madrid, M, 28034, Spain

Location

Local Institution - 2128

Madrid, M, 28040, Spain

Location

Local Institution - 2109

Barcelona, 8950, Spain

Location

Local Institution - 2127

Madrid, 28033, Spain

Location

Local Institution - 2106

Madrid, 28040, Spain

Location

Local Institution - 2112

Pamplona, 31008, Spain

Location

Local Institution - 2125

Valencia, 46009, Spain

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

repotrectinib; Metformin; Digoxin; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 28, 2023
• First Posted: April 25, 2023
• Study Start: November 15, 2024
• Primary Completion: July 31, 2025
• Study Completion: November 30, 2025
• Last Updated: April 1, 2025

Record last verified: 2025-03

Locations

US (2); IT (6); AU (1); ES (12); BR (5); FR (7)