Ziftomenib + Imatinib for GIST

Recruiting at 26 trial locations

Overseen By Kura MedInfo 844-KURAONC

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kura Oncology, Inc.

Must be taking: Imatinib

Must not be taking: Investigational therapy

Disqualifiers: Non-KIT mutation, CNS metastases, others

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

Compensation: Varies

Number of Visits: 1

157 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for gastrointestinal stromal tumors (GIST), a type of cancer in the digestive tract. The trial aims to determine if the drugs ziftomenib (a new potential drug) and imatinib are safe and can reduce tumors in patients previously treated with imatinib. Different groups in the trial will help identify the best dose and assess the treatment's effectiveness. Individuals with advanced GIST, whose disease progressed after imatinib treatment, might be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive a potentially groundbreaking new drug.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot have taken any prohibited medications, including investigational therapies, less than 14 days before starting the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ziftomenib, when combined with imatinib, has strong and lasting effects against gastrointestinal stromal tumors (GIST), even when these tumors do not respond to imatinib alone. Studies have found that this combination lowers levels of the KIT protein, which often promotes tumor growth.

While researchers continue to study this combination for safety, it is important to note that ziftomenib is currently in a Phase 1 trial. The primary goal is to assess its safety and tolerability in people. Although this is an early stage of testing, it provides initial information about possible side effects. Researchers closely monitor participants for any unwanted effects from the treatment, ensuring careful collection of safety data.

Overall, ziftomenib plus imatinib appears promising, but more information is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for GIST?

Researchers are excited about Ziftomenib for treating gastrointestinal stromal tumors (GIST) because it offers a novel approach compared to standard treatments like imatinib. Unlike existing therapies that primarily target specific tyrosine kinases, Ziftomenib works differently by potentially addressing resistance mechanisms that reduce the effectiveness of current drugs. This unique mechanism could provide new hope for patients who have become resistant to other treatments, offering a fresh strategy to combat the disease.

What evidence suggests that ziftomenib in combination with imatinib could be an effective treatment for GIST?

Research has shown that combining ziftomenib with imatinib can effectively combat gastrointestinal stromal tumors (GIST). This trial will explore this combination, especially for tumors that no longer respond to imatinib alone. Previous studies demonstrated that ziftomenib reduced levels of the protein KIT, which is often elevated in GIST patients. These early findings suggest that ziftomenib could be a promising option for patients whose tumors have become resistant to standard treatments like imatinib. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced GIST who have a specific mutation (KIT mutant) and whose disease got worse despite being treated with imatinib. They should be relatively active (ECOG ≤2), not pregnant, have at least one tumor that can be measured, good organ function, and recovered from previous treatments.

Inclusion Criteria

I can understand and sign the consent form myself or have someone legally allowed to do it for me.

I have at least one tumor that can be measured.

My organs are functioning well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of ziftomenib in combination with imatinib to determine the dose limiting toxicity

28 days

Cycle 1 (first 28 day cycle)

Recommended Phase 2 Dose Determination

Determination of the recommended phase 2 dose based on safety, pharmacokinetics, and preliminary antitumor activity

Up to 1 year

Dose Expansion

Participants receive the recommended phase 2 dose to evaluate antitumor activity and overall survival

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year following end of treatment

What Are the Treatments Tested in This Trial?

Interventions

• Imatinib
• Ziftomenib

Trial Overview The trial tests the combination of ziftomenib, an oral drug that inhibits a protein called menin, with imatinib to see if it's safe and effective against GIST tumors in patients who've already tried imatinib alone.

How Is the Trial Designed?

Group I: Recommended Phase 2 Dose Determination Experimental Treatment 2 Interventions

Group II: Dose Expansion Experimental Treatment 2 Interventions

Group III: Dose Escalation Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Kura Oncology, Inc.

Lead Sponsor

Trials

19

Recruited

1,700+

Published Research Related to This Trial

Imatinib mesylate is the standard first-line treatment for chronic myeloid leukaemia (CML) and gastrointestinal stromal tumour (GIST), effectively targeting specific tyrosine kinases and significantly improving patient prognosis.

The treatment is generally well tolerated with a low risk of severe side effects, and long-term use shows excellent tolerability, with concerns like cardiotoxicity being largely exaggerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety profile of imatinib in CML and GIST: long-term considerations. Thanopoulou, E., Judson, I.[2015]

Imatinib mesylate has shown a high clinical response rate of 81.6% in patients with gastrointestinal stromal tumors (GIST), with 53.7% achieving a partial response and 27.9% having stable disease.

While most patients experienced only mild toxicities (grade 1 or 2), 21.1% had more severe side effects (grade 3 or higher), indicating that imatinib is relatively safe but can still cause significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of imatinib for gastrointestinal tumor]. Mizunuma, N.[2015]

Imatinib, a tyrosine kinase inhibitor, has significantly improved the prognosis for patients with chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GIST), showing high rates of cytogenetic and molecular responses across all phases of CML.

The drug is well tolerated, with only mild adverse effects such as joint pain and gastrointestinal symptoms, primarily occurring in the first two years of treatment, making it a safe and effective oral option for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A benefit-risk assessment of imatinib in chronic myeloid leukaemia and gastrointestinal stromal tumours. Wolf, D., Rumpold, H.[2021]

In a study of 12 cases of gastric mesenchymal tumors, 67% were identified as GISTs, with gastrointestinal bleeding being the most common symptom and a significant number presenting with palpable abdominal masses.

Imatinib Mesylate showed a good response in a case of metastatic GIST, highlighting its potential as a palliative treatment option, especially when combined with surgical resection for advanced lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastric GISTs. Personal experience. Mingolla, GP., Riccio, PA., Linguerri, R., et al.[2015]

Citations

1. ir.kuraoncology.com ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-reports-preclinical-data-supporting-opportunity

Press Release The combination of ziftomenib and imatinib unexpectedly showed robust and durable antitumor activity in both imatinib-sensitive and imatinib- ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS11578

Phase 1a/1b study of the safety, pharmacokinetics, and ... Ziftomenib plus imatinib has demonstrated synergistic antitumor activity in imatinib-sensitive and -resistant GIST models, with reduced KIT protein levels and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06655246

NCT06655246 | A Study of Ziftomenib, an Oral Menin ... In this clinical trial, the safety, tolerability, and preliminary antitumor activity of ziftomenib in combination with imatinib will be evaluated in adults ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12416134/

Gastrointestinal Stromal Tumor: Current Approaches and ... Imatinib is the standard first-line treatment for advanced GIST, with sunitinib, regorafenib, and ripretinib approved for subsequent lines. Avapritinib ...

5. ir.kuraoncology.com ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-announces-first-patients-dosed-phase-1-combination

Kura Oncology Announces First Patients Dosed in Phase 1 ... Sixty percent of patients develop resistance to imatinib, the frontline standard of care for GIST, within two years, and ziftomenib has the ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/548818

A Study of Ziftomenib, an Oral Menin Inhibitor, in ... In this clinical trial, the safety, tolerability, and preliminary antitumor activity of ziftomenib in combination with imatinib will be ...

7. clinicaltrialsarena.com clinicaltrialsarena.com/news/kura-first-subjects-ziftomenib-advanced-gist/

Kura doses first subjects in trial of ziftomenib for advanced ... Kura doses first subjects in trial of ziftomenib for advanced GIST. The trial's primary goal is to assess the tolerability and safety and to ...