Repotrectinib Drug Interactions for Advanced Cancer

No longer recruiting at 42 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Turning Point Therapeutics, Inc.

Must not be taking: CYP3A inhibitors, Metformin, others

Disqualifiers: Cardiovascular disease, Active infections, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how a new cancer treatment, repotrectinib (also known as TPX-0005), interacts with other medications in the body. It targets individuals with advanced cancer who have a specific gene change, ROS1 or NTRK1-3. Participants must have a confirmed diagnosis of a solid tumor with this gene change and be able to perform daily activities with minimal assistance. The trial involves taking repotrectinib alongside some common drugs to observe their combined effects. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you cannot take drugs that are moderate or strong CYP3A inhibitors or inducers, or certain other drugs like metformin, digoxin, or rosuvastatin within 14 days before the trial's drug interaction assessment period.

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

Research has shown that repotrectinib, also known as TPX-0005, has undergone safety testing in patients with advanced cancer. In a previous study involving 426 patients, 35% experienced serious side effects. This indicates some significant reactions, but researchers continue to investigate these further.

Repotrectinib has already received approval for treating a type of lung cancer, suggesting that its safety is somewhat established. However, since this current trial is in an early phase, the complete safety profile is still being developed. This phase typically focuses on how well participants tolerate the drug and identifying any potential side effects.

Participants considering this trial should consult their doctors and weigh the benefits against possible risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Repotrectinib (TPX-0005) because it targets advanced cancers in a novel way. Unlike traditional treatments that focus on one specific cancer pathway, Repotrectinib is designed to inhibit multiple pathways, potentially making it more effective against tumors that have become resistant to other treatments. This drug is taken orally, which can be more convenient than intravenous therapies. Its ability to work in concert with other drugs like metformin, digoxin, and rosuvastatin might enhance its effectiveness, offering a multifaceted approach to tackling tough cancers.

What evidence suggests that this treatment might be an effective treatment for advanced cancer?

Research has shown that repotrectinib, also known as TPX-0005, may help treat certain types of cancer. In patients with ROS1-positive non-small-cell lung cancer (NSCLC), studies found that 79% of those untreated with TKIs (tyrosine kinase inhibitors) responded well to the treatment. Among those with previous TKI treatments, 41% still showed a positive response. On average, the benefits lasted about 36.8 months, indicating prolonged improvements. Repotrectinib also proved effective for patients who had received other treatments, continuing to show positive effects. These findings suggest that repotrectinib could be effective for advanced cancers, especially those with ROS1-positive markers. Participants in this trial will receive repotrectinib alongside a combination of cocktail drugs to study potential drug interactions. ^{6 7 8 9 10}

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 advanced solid tumors, including CNS tumors, that have specific gene fusions (ROS1 or NTRK1-3). Participants must be in fairly good health based on ECOG status and lab tests. They can't join if they have symptomatic brain metastases, significant heart disease, are in another clinical trial, had major surgery recently, have active infections needing treatment, use certain other drugs or have gastrointestinal issues affecting drug absorption.

Inclusion Criteria

I am 18 or older and can do most of my daily activities.

Protocol specified baseline hematology, liver function and kidney function laboratory values

My cancer has a ROS1 or NTRK gene fusion.

Exclusion Criteria

I am taking or will take drugs that strongly affect liver enzyme activity.

I have a condition that affects how my body absorbs nutrients.

I haven't taken drugs that affect certain body transport systems within the last 14 days or 5 half-lives.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral repotrectinib and cocktail drugs (metformin, digoxin, rosuvastatin) to evaluate drug-drug interactions

4 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TPX-0005

Trial Overview The study is testing how repotrectinib (TPX-0005) affects the body's handling of metformin hydrochloride, digoxin and rosuvastatin calcium. It aims to understand potential interactions between repotrectinib and these medications when taken by patients with advanced cancer.

How Is the Trial Designed?

Group I: Repotrectinib (TPX-0005) Experimental Treatment 4 Interventions

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

Who Is Running the Clinical Trial?

Turning Point Therapeutics, Inc.

Lead Sponsor

Trials

10

Recruited

790+

Citations

1. 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- ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2302299

Repotrectinib in ROS1 Fusion–Positive Non–Small-Cell ... Repotrectinib had durable clinical activity in patients with ROS1 fusion–positive NSCLC, regardless of whether they had previously received a ROS1 TKI.

3. news.bms.com news.bms.com/news/details/2023/Updated-Data-from-TRIDENT-1-Trial-Show-Durable-Efficacy-Benefits-with-Repotrectinib-for-Patients-with-Locally-Advanced-or-Metastatic-ROS1-Positive-Non-Small-Cell-Lung-Cancer/default.aspx

Updated Data from TRIDENT-1 Trial Show Durable ... Repotrectinib continued to demonstrate high response rates and durable responses, including robust intracranial responses, in patients with ROS1-positive ...

4. cancernursingtoday.com cancernursingtoday.com/post/trident-1-follow-up-exploring-the-long-term-impact-of-repotrectinib-in-patients-with-ros1-nsclc

Exploring the Long-Term Impact of Repotrectinib in ... In the same cohort, median progression-free survival (PFS) was 31.1 months and 8.6 months, respectively, while median overall survival (OS) was ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11326972/

FDA Approval Summary: Repotrectinib for locally advanced or ... The presentation of data describing efficacy outcomes in patients who received prior crizotinib or entrectinib reflects the changing ...

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. augtyrohcp.com augtyrohcp.com/ros1/safety

Safety Profile | AUGTYRO® (repotrectinib) for ROS1+ mNSCLC The pooled safety population in TRIDENT-1 included 426 patients who were exposed to AUGTYRO. Serious adverse reactions occurred in 35% of patients who ...

8. oncologynewscentral.com oncologynewscentral.com/drugs/monograph/187829-323094/repotrectinib-oral

Repotrectinib: uses, dosing, warnings, adverse events, ... Repotrectinib is used for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose cancer is c-ros oncogene ...

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

Augtyro, INN-repotrectinib - EMA Long-term safety data are unavailable on the use of AUGTYRO in paediatric patients 12 years of age and older. Drug interactions. Co-administration of AUGTYRO ...

10. drugs.com drugs.com/cons/repotrectinib.html

Repotrectinib Advanced Patient Information Enhertu is a treatment for breast cancer, stomach cancer ... Enter medications to view a detailed interaction report using our Drug Interaction Checker.