IDRX-42 for GIST

Recruiting in Palo Alto (17 mi)

+27 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: IDRx, Inc.

Must be taking: Imatinib

Disqualifiers: Brain metastases, Cardiovascular disease, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests IDRX-42, an oral drug designed to block proteins that help cancer grow, in adults with advanced GIST who haven't responded to other treatments. The goal is to see if the drug is safe and effective.

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.

What data supports the effectiveness of the drug IDRX-42 for treating GIST?

Research shows that IDRX-42 is a new drug that effectively targets specific mutations in GIST, which are common in these tumors and often lead to drug resistance. This suggests that IDRX-42 could be a promising option for patients whose tumors have become resistant to other treatments. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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.

I am 18 years old or older.

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.

Trial Timeline

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

Treatment Details

Interventions

• IDRX-42 (Other)

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.

Participant Groups

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.

Lead Sponsor

Trials

1

Recruited

270+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States 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). [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Revolutions in treatment options in gastrointestinal stromal tumours (GISTs): the latest updates [2021]

4. United States 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. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Increased KIT inhibition enhances therapeutic efficacy in gastrointestinal stromal tumor. [2021]