#1 Clinical Trials Search in Europe

[4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL]-(6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A]PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE

This article discusses a Phase 3 clinical trial investigating [4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL]-(6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A]PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE (also known as IDRX-42 or GSK6042981) for patients with metastatic or unresectable gastrointestinal stromal tumors (GIST) who have not responded to imatinib treatment. The trial aims to evaluate whether this investigational drug is more effective than sunitinib in preventing disease progression.

Table of Contents

Trial Overview

A Phase 3 clinical trial has been authorized to investigate [4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL]-(6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A]PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE (known by the development codes IDRX-42 and GSK6042981) as a potential treatment for patients with gastrointestinal stromal tumors (GIST)[1]. This trial, identified by the number 2025-522229-37-00, represents a significant step in developing new treatment options for patients whose cancer has not responded to standard therapy[1].

The study is designed as an interventional trial, meaning that participants will actively receive treatment with either the investigational drug or a comparison drug[1]. The trial plans to enroll approximately 450 participants, making it a large-scale study that will provide substantial data about the effectiveness and safety of this new treatment approach[1].

Understanding GIST and Current Treatment Challenges

Gastrointestinal stromal tumors are a specific type of cancer that develops in the digestive system, most commonly affecting the stomach or small intestine[1]. These tumors arise from specialized cells called interstitial cells of Cajal, which are part of the nervous system of the digestive tract. While GIST is considered rare compared to other cancers, it is the most common type of sarcoma (connective tissue cancer) found in the gastrointestinal tract.

The current standard first-line treatment for GIST is imatinib, a targeted therapy drug that has dramatically improved outcomes for GIST patients since its introduction. However, not all patients respond to imatinib, and many who initially respond eventually experience disease progression, meaning their cancer begins to grow again despite treatment. This phenomenon is known as imatinib failure or resistance[1].

When imatinib stops working, patients typically move to second-line therapy with sunitinib, another targeted drug that works through a different mechanism[1]. While sunitinib provides benefit for many patients, there remains a significant need for additional effective treatment options, particularly for patients with metastatic (cancer that has spread to other parts of the body) or unresectable (cannot be surgically removed) disease[1].

About [4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL]-(6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A]PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE

The investigational drug being studied in this trial is [4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL]-(6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A]PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE, which is also referred to by its development names IDRX-42 and GSK6042981[1]. These alternative names are used by the pharmaceutical companies developing the drug and in scientific communications.

This compound represents a potential new treatment option for GIST patients who have experienced failure with imatinib therapy. The trial will evaluate whether this investigational agent offers advantages over the current standard second-line treatment, sunitinib[1].

Trial Design and Methodology

This is a Phase 3 clinical trial, which is an advanced stage of drug development[1]. Phase 3 trials are conducted after earlier phases (Phase 1 and Phase 2) have established basic safety and provided initial evidence of effectiveness. These large-scale trials are designed to definitively determine whether a new treatment is better than, equal to, or worse than existing standard treatments.

The trial uses a comparative design, meaning that participants will be assigned to receive either [4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL]-(6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A]PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE or sunitinib[1]. This head-to-head comparison allows researchers to directly evaluate whether the new drug offers advantages over the current standard of care. The specific method of assignment (whether randomized or not) and whether the study is blinded (where participants and/or doctors don’t know which treatment is being given) are important design features that would be detailed in the full trial protocol.

With a planned enrollment of approximately 450 participants, this trial will generate substantial data to support regulatory decision-making[1]. The large sample size increases the statistical power of the study, meaning it is better able to detect true differences in effectiveness between the two treatments.

Patient Eligibility and Target Population

The trial is specifically designed for patients with GIST who meet certain criteria related to their disease status and treatment history[1]. Understanding these eligibility criteria helps patients and their healthcare providers determine whether participation in this trial might be appropriate.

Disease Characteristics

Eligible participants must have GIST that is either metastatic or unresectable, or both[1]. Metastatic disease means the cancer has spread beyond its original location to other parts of the body, such as the liver, lungs, or peritoneum (lining of the abdominal cavity). Unresectable disease refers to tumors that cannot be completely removed by surgery, either because of their size, location, involvement with critical blood vessels or organs, or the extent of spread.

Prior Treatment Requirements

A critical eligibility criterion is that participants must have experienced failure of imatinib therapy[1]. This means patients must have previously received imatinib and either:

  • Did not respond to the treatment initially (primary resistance)
  • Responded initially but then experienced disease progression while taking imatinib (acquired resistance)
  • Were unable to tolerate imatinib due to side effects (intolerance)

This requirement ensures that the trial enrolls patients who are appropriate candidates for second-line therapy and for whom new treatment options are most needed[1].

Primary and Secondary Endpoints

Clinical trials measure specific outcomes to determine whether a treatment is effective. These outcomes are called endpoints, and they are defined before the trial begins.

Primary Endpoint: Progression-Free Survival

The primary endpoint of this trial is progression-free survival (PFS)[1]. PFS is defined as the length of time from when a patient starts treatment until their cancer gets worse (progresses) or they die from any cause. This is a standard and clinically meaningful endpoint in cancer trials because it directly measures how well a treatment controls the disease.

By comparing PFS between patients receiving [4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL]-(6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A]PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE and those receiving sunitinib, researchers can determine whether the investigational drug provides superior disease control[1]. A longer PFS with [4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL]-(6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A]PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE would suggest it is more effective at keeping the cancer under control.

PFS is assessed through regular imaging studies (such as CT or MRI scans) performed at scheduled intervals throughout the trial. Independent radiologists typically review these scans using standardized criteria to determine whether the cancer has progressed.

Clinical Significance

This Phase 3 trial represents an important development in the treatment landscape for GIST patients who have experienced imatinib failure[1]. The need for new treatment options in this setting is significant, as current second-line and later-line therapies have limitations in terms of effectiveness and tolerability.

Addressing an Unmet Medical Need

While sunitinib is an established second-line treatment for GIST, not all patients respond to it, and those who do respond eventually experience disease progression. Additional treatment options with different mechanisms of action could provide alternatives for patients who don’t respond to or cannot tolerate sunitinib, or could offer improved outcomes compared to current standards[1].

Potential Impact on Treatment Guidelines

If [4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL]-(6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A]PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE demonstrates superior progression-free survival compared to sunitinib, it could potentially become a new standard second-line treatment for GIST[1]. This would represent a significant advancement in the management of this disease and could improve outcomes for patients worldwide.

Contribution to Scientific Knowledge

Beyond the potential direct benefit to participants, this trial will contribute valuable data about GIST biology, treatment resistance mechanisms, and optimal management strategies[1]. The results will inform future research directions and drug development efforts in this field.

Trial Status and Participation

The trial has received authorization to proceed, indicating that regulatory authorities have reviewed the trial design and determined it is scientifically sound and ethically appropriate[1]. Patients with metastatic or unresectable GIST who have experienced imatinib failure may wish to discuss with their oncologists whether participation in this trial might be appropriate for their individual situation.

Trial ID Phase Condition Intervention Comparator Status Enrollment Primary Endpoint
2025-522229-37-00 Phase 3 Metastatic and/or Unresectable GIST after Imatinib Failure [4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL]-(6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A]PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE (IDRX-42/GSK6042981) Sunitinib Authorised 450 Progression-Free Survival

FAQ

  • What is the trial studying? The trial is comparing [4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL]-(6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A]PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE (IDRX-42/GSK6042981) to sunitinib in patients with GIST that has spread or cannot be surgically removed. The main goal is to see which treatment better prevents the cancer from getting worse.
  • Who can participate in this trial? Participants must have metastatic or unresectable GIST and must have previously tried imatinib therapy that either stopped working or did not work. The trial plans to enroll approximately 450 participants.
  • What phase is this clinical trial? This is a Phase 3 trial, which is an advanced stage of clinical research. Phase 3 trials typically involve larger numbers of patients and compare the new treatment to standard treatments already in use.
  • What is the main outcome the trial is measuring? The primary outcome is progression-free survival (PFS), which measures how long patients live without their cancer getting worse. This helps determine if [4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL]-(6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A]PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE is more effective than the current standard treatment.
  • What is the current status of this trial? The trial has been authorized and is an interventional study, meaning participants will receive active treatment. The trial identifier is 2025-522229-37-00.

Ongoing Clinical Trials on [4-(METHYL-1H-PYRAZOL-4-YL)-BENZYL]-(6[7-(3-PYRROLIDIN-1-YL-PROPOXY)-IMIDAZO[1,2-A]PYRIDIN-3-YL]-PYRIMIDIN-4-YL]-AMINE

Unfortunately, we did not find any clinical trials matching the selected criteria. Try changing the filter settings or broadening the search criteria to see more available research participation opportunities.

Glossary

  • GIST (Gastrointestinal Stromal Tumor): A type of cancer that starts in the digestive tract, most commonly in the stomach or small intestine. These tumors develop from special cells in the wall of the digestive system.
  • Metastatic: Cancer that has spread from where it started to other parts of the body. Metastatic disease is more difficult to treat than cancer that remains in one location.
  • Unresectable: A tumor that cannot be completely removed by surgery, either because of its size, location, or because it has spread too extensively.
  • Imatinib: A targeted therapy drug commonly used as the first-line treatment for GIST. It works by blocking specific proteins that help cancer cells grow.
  • Sunitinib: A targeted therapy drug used to treat GIST when imatinib stops working. It is currently a standard second-line treatment option for GIST patients.
  • Progression-Free Survival (PFS): The length of time during and after treatment that a patient lives with the disease without it getting worse. This is a key measure of how well a cancer treatment works.
  • Phase 3 Trial: A large-scale clinical trial that compares a new treatment to the current standard treatment. These trials typically involve hundreds to thousands of participants and help determine if a new drug should be approved.
  • Interventional Study: A type of clinical trial where researchers actively give participants a specific treatment or intervention and then measure the outcomes.
  • Second-Line Therapy: Treatment given when the first treatment (first-line therapy) does not work or stops working. For GIST, this occurs after imatinib failure.
  • Efficacy: How well a treatment works in producing a desired effect, such as shrinking tumors or preventing disease progression in a clinical trial setting.

References

  1. https://clinicaltrials.gov/study/2025-522229-37-00