Repotrectinib for Liver Disease

No longer recruiting at 6 trial locations

Overseen By Eric Lawitz, Site 0002

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bristol-Myers Squibb

Disqualifiers: Major surgery, Drug abuse, Alcohol abuse, Smoking, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called repotrectinib (also known as Augtyro or TPX-0005) to observe its behavior in individuals with liver disease. The researchers aim to understand how a single dose of the drug is processed in those with moderate or severe liver impairment compared to healthy individuals. People with long-term liver disease, especially from alcohol use, might be suitable if they have noticeable liver issues. Healthy participants without significant medical conditions are also needed for comparison. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that repotrectinib is likely to be safe for humans?

Research has shown that repotrectinib is usually well-tolerated. Since its approval, no reports of serious liver damage caused by the drug have emerged. This indicates it is generally safe for the liver under normal conditions. However, in individuals with moderate or severe liver problems, repotrectinib might lead to higher drug levels in the body and an increased risk of side effects. Caution is essential when considering this treatment for those with liver issues. Discuss the risks and benefits with a healthcare professional before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Repotrectinib is unique because it targets specific genetic mutations in liver disease, potentially offering a more personalized treatment approach. Unlike traditional treatments, such as antiviral medications or liver transplants, repotrectinib focuses on inhibiting the activity of certain tyrosine kinases, which are enzymes that contribute to the progression of liver disease. Researchers are excited about this treatment because it could offer a new way to manage liver disease more effectively, especially in patients whose conditions are linked to these genetic factors. This targeted mechanism of action represents a significant advancement in the quest for more precise and effective liver disease therapies.

What evidence suggests that repotrectinib might be an effective treatment for liver disease?

Research shows that repotrectinib may help treat certain cancers. One study with patients who have ROS1-positive non-small cell lung cancer demonstrated that the drug worked well for 79% of those who hadn't taken tyrosine kinase inhibitors before, with many patients experiencing significant tumor shrinkage. However, repotrectinib hasn't been fully studied in people with moderate or severe liver problems. This trial will explore how repotrectinib affects individuals with different levels of liver function. Participants will be divided into groups based on their hepatic function: moderate hepatic impairment, severe hepatic impairment, and normal hepatic function. While repotrectinib has been effective in treating cancer, its impact on liver disease remains under investigation. ^{1 3 4 6 7}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with moderate to severe liver impairment and healthy individuals with normal liver function. Participants will be matched based on certain characteristics like age, weight, and gender.

Inclusion Criteria

Matched healthy participants (Group 3) must have liver-related laboratory test results within the respective reference ranges or with clinically insignificant excursions therefrom as agreed by the investigator

I am healthy with no significant diseases affecting study participation.

Matched healthy participants (Group 3) must be in good health as determined by past medical history, physical examination, vital signs, ECG, and clinical laboratory safety tests. Clinical laboratory safety tests (eg, hematology, chemistry, and urinalysis) and 12-lead ECGs must be within normal limits or clinically acceptable as judged by the investigator

Exclusion Criteria

History of drug abuse within 1 year of study intervention administration

Participants who currently smoke, as well as those who have stopped smoking less than 6 months prior to dosing on Day 1

History of alcohol abuse within 1 year of study intervention administration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single oral dose of repotrectinib

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Repotrectinib

Trial Overview The study is testing how a single oral dose of the drug Repotrectinib behaves in the body in people with different levels of liver health compared to those who are healthy.

How Is the Trial Designed?

Group I: Group 3: Normal Hepatic Function Experimental Treatment 1 Intervention

Group II: Group 2: Severe Hepatic Impairment Experimental Treatment 1 Intervention

Group III: Group 1: Moderate Hepatic Impairment Experimental Treatment 1 Intervention

Repotrectinib is already approved in United States for the following indications:

Approved in United States as Augtyro for:

• ROS1-positive non-small cell lung cancer (NSCLC)
• Solid tumors caused by certain abnormal NTRK genes

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK613921/

Repotrectinib - LiverTox - NCBI Bookshelf - NIH In a large, open label study of repotrectinib in patients with ROS1 positive NSCLC, the objective response rate was 79% in tyrosine kinase naïve ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05828277

A Phase 1 Study to Assess the Effect of Hepatic Impairment ... This is a Phase 1 study to evaluate the effect of moderate or severe hepatic impairment on the PK of repotrectinib in patients with advanced cancer. Detailed ...

3. ema.europa.eu ema.europa.eu/en/documents/product-information/augtyro-epar-product-information_en.pdf

Augtyro, INN-repotrectinib - EMA Hepatic impairment. AUGTYRO has not been studied in patients with moderate or severe hepatic impairment. AUGTYRO should not be used in patients with moderate ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/218213Orig1s001.pdf

CENTER FOR DRUG EVALUATION AND RESEARCH A sufficient number of patients will be evaluated to more precisely characterize response and durability of response for a spectrum of patients ...

5. packageinserts.bms.com packageinserts.bms.com/pi/pi_augtyro.pdf

AUGTYRO U.S. Prescribing Information Fatal adverse reactions occurred in 3.5% of patients who received AUGTYRO, including pneumonia, pneumonia aspiration, cardiac arrest, sudden cardiac death, ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/218213s001lbl.pdf

augtyro - accessdata.fda.gov This includes data demonstrating that the exposure of repotrectinib in pediatric patients 12 years of age and older is expected to result in similar safety and ...

7. onclive.com onclive.com/view/repotrectinib-demonstrates-durable-efficacy-in-tki-naive-and--pretreated-ros1-nsclc

Repotrectinib Demonstrates Durable Efficacy in TKI-Naive ... Repotrectinib showed a cORR of 79% in TKI-naive and 41% in TKI-pretreated ROS1-positive NSCLC patients. · The median DOR was 36.8 months for TKI- ...