IDRX-42 for GIST

Recruiting at 63 trial locations

Overseen By IDRX Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: IDRx Inc. - A GSK Company

Must be taking: Imatinib

Disqualifiers: Brain metastases, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

278 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IDRX-42 for individuals with advanced gastrointestinal stromal tumors (GIST) that cannot be surgically removed or have metastasized. The goal is to determine the safety and effectiveness of IDRX-42 in combating these tumors. The trial includes different groups based on treatment history, such as those whose GIST has worsened after other cancer drugs and those who have not yet received any treatment. This trial may suit individuals with GIST whose condition has progressed despite previous treatments like imatinib and sunitinib, or who have not started any treatment and are ineligible for standard options. As a Phase 1 trial, this research aims to understand how IDRX-42 works in people, offering participants the chance to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the IDRX-42 trial?

The trial does not specify if you need to stop taking your current medications, but it does require that any side effects from previous treatments are resolved to a mild level or baseline before starting the study drug.

Is there any evidence suggesting that IDRX-42 is likely to be safe for humans?

Research shows that IDRX-42 is in the early stages of testing to determine its safety for humans. This trial marks the first time it is being tested in people, so information remains limited. The trial assesses how well participants tolerate the drug by monitoring any side effects and their severity. As an early phase trial, it primarily focuses on understanding the drug's safety and how the body processes it. This phase is crucial to establish general safety before conducting more extensive testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

IDRX-42 is unique because it offers a potential new way to treat gastrointestinal stromal tumors (GIST), especially for patients who have seen their cancer progress despite using existing treatments like imatinib, sunitinib, regorafenib, and ripretinib. Unlike these standard treatments, which often focus on blocking certain proteins involved in tumor growth, IDRX-42 may target different pathways, potentially overcoming resistance seen with current therapies. Researchers are excited about IDRX-42 because it could provide a new option for patients who have exhausted other lines of therapy, offering hope for those with few alternatives.

What evidence suggests that IDRX-42 might be an effective treatment for GIST?

Research shows that IDRX-42 holds promise for treating advanced gastrointestinal stromal tumors (GIST). This trial will enroll participants in different cohorts based on their treatment history. For instance, some participants will have experienced GIST progression after two or more lines of TKI therapy, while others may be treatment-naïve or have progressed after first-line imatinib therapy. A recent study found that about 29% of patients experienced significant tumor shrinkage, meaning nearly one-third saw positive results. This is crucial because these patients had tried several other treatments without success. IDRX-42 targets specific changes in the KIT gene, which often cause GIST to grow and resist other treatments. Early results indicate that it can effectively block these changes, offering a new option for those with few alternatives. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with advanced GIST that can't be surgically removed or has spread, who have tried other treatments like imatinib and possibly others without success. They should be in good physical condition (ECOG 0-1) and have recovered from previous treatment side effects.

Inclusion Criteria

Any side effects from my previous treatments are mild or gone.

My cancer progressed after treatment with imatinib and sunitinib, or after these plus another drug.

My GIST cannot be removed with surgery and is confirmed by lab tests.

Exclusion Criteria

Any prior exposure to the following investigational agents NB003 or THE-630 or bezuclastinib plus sunitinib combination

I have never had brain cancer or untreated brain metastases.

I have serious heart problems that are not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Phase 1)

Participants receive escalating doses of IDRX-42 to assess safety, tolerability, and pharmacologic profile

8-12 weeks

Phase 1b Expansion

Participants are enrolled in cohorts based on prior lines of therapy to assess preliminary antitumor effect and further characterize safety

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IDRX-42

Trial Overview The trial is testing IDRX-42's safety, how well it's tolerated by the body, its pharmacokinetics (how the drug moves through the body), and its initial effectiveness in treating GIST.

How Is the Trial Designed?

Group I: Dose Escalation (Phase I) Experimental Treatment 1 Intervention

Participants should have advanced (metastatic and/or surgically unresectable) GIST, following failure of at least prior imatinib therapy due to progression of GIST.

Group II: (Phase 1b): Cohort 4 Experimental Treatment 1 Intervention

Participants with GIST progression who meet the same criteria as Cohort 2 (third line or greater TKI therapy) and have had prior treatment with investigational agents NB003 or THE-630 or a line of therapy of bezuclastinib plus sunitinib combination.

Group III: (Phase 1b): Cohort 3 - Participants with GIST who are treatment naïve Experimental Treatment 1 Intervention

Participants with metastatic and/or surgically unresectable GIST who are treatment naïve (first line therapy) and refused or are ineligible for other standard of care (SOC) therapies.

Group IV: (Phase 1b): Cohort 2 - Participants with GIST progression after 2 or more lines of TKI therapy Experimental Treatment 1 Intervention

Participants with metastatic and/or surgically unresectable GIST following progression EITHER after sequential imatinib then sunitinib (third-line therapy setting) OR after imatinib, sunitinib, and then an additional TKI agent (i.e., regorafenib or ripretinib) (fourth-line therapy setting) OR after imatinib, sunitinib, regorafenib, and ripretinib (5th line or greater therapy).

Group V: (Phase 1b) Cohort 1 - Participants with GIST progression after first-line imatinib therapy Experimental Treatment 1 Intervention

Participants with advanced GIST who have had GIST progression after first-line imatinib only (second line therapy setting) and refused or are ineligible for other standard of care (SOC) therapies.

Who Is Running the Clinical Trial?

IDRx Inc. - A GSK Company

Lead Sponsor

IDRx, Inc.

Lead Sponsor

Trials

1

Recruited

270+

Published Research Related to This Trial

A recent clinical trial (SSGXVIII/AIO) demonstrated that patients with high-risk gastrointestinal stromal tumors (GIST) have improved recurrence-free survival (RFS) and overall survival (OS) when treated with adjuvant imatinib for 3 years compared to 1 year.

The findings highlight the need for further research to better understand the risk factors associated with GIST recurrence, which could help optimize treatment duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The SSG XVIII/AIO trial: results change the current adjuvant treatment recommendations for gastrointestinal stromal tumors. Eisenberg, BL.[2022]

Avapritinib is set to become the first-line treatment for GIST patients with the D842V mutation in PDGFRA exon 18, showcasing its efficacy in this specific subgroup, while imatinib remains the primary treatment for most patients.

The evolving landscape of GIST treatment includes over five lines of therapy, with promising results from novel compounds like avapritinib and ripretinib, suggesting a shift towards personalized treatment approaches and the potential for combination therapies to address challenges like secondary resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revolutions in treatment options in gastrointestinal stromal tumours (GISTs): the latest updates Farag, S., Smith, MJ., Fotiadis, N., et al.[2021]

In preclinical models of gastrointestinal stromal tumors (GIST), PLX3397 was found to be more effective than imatinib in reducing tumor weight and cellularity, suggesting it could be a better treatment option.

The enhanced efficacy of PLX3397 is attributed to its stronger inhibition of the KIT signaling pathway, rather than its effect on tumor-associated macrophages, although it also caused significant intratumoral fibrosis that may hinder complete tumor eradication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased KIT inhibition enhances therapeutic efficacy in gastrointestinal stromal tumor. Kim, TS., Cavnar, MJ., Cohen, NA., et al.[2021]

GDC-0941, when used alone, stabilized tumor growth in gastrointestinal stromal tumors (GIST) but did not cause cell death; however, when combined with imatinib, it led to significant tumor regression and increased apoptosis, showing greater efficacy than either drug alone.

The combination treatment of GDC-0941 and imatinib not only resulted in a more substantial reduction in tumor size but also maintained this effect even after treatment stopped, suggesting a durable response, particularly in tumors with PTEN loss, which may serve as a predictive biomarker for treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A potent combination of the novel PI3K Inhibitor, GDC-0941, with imatinib in gastrointestinal stromal tumor xenografts: long-lasting responses after treatment withdrawal. Floris, G., Wozniak, A., Sciot, R., et al.[2021]

IDRX-42, a novel selective KIT inhibitor, demonstrated significant antitumor activity in various gastrointestinal stromal tumor (GIST) xenograft models, leading to substantial tumor volume shrinkage and delayed growth compared to control treatments.

The treatment with IDRX-42 resulted in decreased mitotic activity and characteristic histological changes, such as myxoid degeneration, particularly in tumors with specific KIT mutations, indicating its potential as an effective therapy for drug-resistant GISTs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor Efficacy of the Novel KIT Inhibitor IDRX-42 (Formerly M4205) in Patient- and Cell Line-Derived Xenograft Models of Gastrointestinal Stromal Tumor (GIST). De Sutter, L., Wozniak, A., Verreet, J., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.11501

StrateGIST 1: A first-in-human (FIH), phase 1 study of IDRX ... Results: As of January 2, 2024, 42 pts received IDRX-42 in the ph 1a portion of the study with median treatment duration of 19+ (range 2-73+) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12214875/

M4205 (IDRX-42) Is a Highly Selective and Potent Inhibitor ... M4205, a kinome-selective KIT inhibitor, was designed to address this high unmet medical need by inhibiting all relevant KIT driver and resistance mutations.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05489237

NCT05489237 | First-in-human Study of IDRX-42 ... The study is designed to evaluate the safety, tolerability, PK, and preliminary antitumor activity of IDRX-42 in adult participants with advanced (metastatic ...

4. biospace.com biospace.com/press-releases/idrx-announces-updated-phase-1-data-from-ongoing-phase-1-1b-strategist-1-trial-of-idrx-42-in-advanced-gastrointestinal-stromal-tumors-gist-at-ctos-2024

IDRx Announces Updated Phase 1 Data from Ongoing ... IDRX-42 continues to demonstrate promising anti-tumor activity with a 29% ORR across all patients (median four prior lines of therapy) and a ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.11524

In vitro profiling of IDRX-42 against secondary and tertiary ... Recently, IDRX-42 has demonstrated promising activity in a phase 1/1b study of patients with TKI-resistant GIST. However, the cellular potency ...

6. oncodaily.com oncodaily.com/drugs/idrx186962

IDRx Announces Updated Phase 1 Data from Ongoing ... IDRX-42 continues to demonstrate promising anti-tumor activity with a 29% ORR across all patients (median four prior lines of therapy) and a ...

7. gisttrials.org gisttrials.org/iLRG/details.php?Trial=386

trial detail - GIST clinical trials A first-in-human (FIH) study of IDRX-42 in participants with metastatic and/or unresectable gastrointestinal stromal tumors (GIST).