Ziftomenib + Imatinib for GIST

Recruiting at 1 trial location

Overseen By Clinical Operations

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

Trial Summary

What is the purpose of this trial?

In this clinical trial, the safety, tolerability, and preliminary antitumor activity of ziftomenib in combination with imatinib will be evaluated in adults with gastrointestinal stromal tumors (GIST) who have been treated previously with imatinib.

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.

What data supports the effectiveness of the drug combination Ziftomenib + Imatinib for GIST?

Imatinib has been shown to significantly change the treatment and prognosis of gastrointestinal stromal tumors (GISTs) by effectively targeting the disease, especially in cases that are intermediate- and high-risk, as well as locally advanced and metastatic. This suggests that combining it with another drug like Ziftomenib could potentially enhance its effectiveness. ^{1 2 3 4 5}

Is the combination of Ziftomenib and Imatinib safe for treating GIST?

Imatinib, used for treating gastrointestinal stromal tumors (GIST), is generally well tolerated with most side effects being mild, such as muscle cramps and gastrointestinal symptoms. Severe side effects are rare and usually occur early in treatment. There is no specific safety data available for Ziftomenib in this context. ^{1 6 7 8 9}

What makes the drug Ziftomenib + Imatinib unique for treating GIST?

Ziftomenib + Imatinib is unique because it combines two drugs that target different pathways involved in gastrointestinal stromal tumor (GIST) growth, potentially overcoming resistance seen with Imatinib alone. This combination may enhance the effectiveness of treatment by addressing multiple mechanisms that tumors use to survive. ^{2 3 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

The analysis of 3-year adjuvant therapy with imatinib in patients with high-risk molecular profiled gastrointestinal stromal tumors (GIST) treated in routine practice. [2021]

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

Combining targeted therapy with immunotherapy (interferon-α): Rational, efficacy in gastrointestinal stromal tumor model and implications in other malignancies. [2021]

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

Controversies in the surgical management of GIST in the era of imatinib. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Delayed adjuvant imatinib in patients with high risk of recurrence of gastrointestinal stromal tumor after radical surgery: a retrospective cohort study. [2022]

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

The Landmark Series: Systemic Therapy for Resectable Gastrointestinal Stromal Tumors. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

A benefit-risk assessment of imatinib in chronic myeloid leukaemia and gastrointestinal stromal tumours. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

The safety profile of imatinib in CML and GIST: long-term considerations. [2015]

8. Ireland pubmed.ncbi.nlm.nih.gov

Repurposing cabozantinib to GISTs: Overcoming multiple imatinib-resistant cKIT mutations including gatekeeper and activation loop mutants in GISTs preclinical models. [2019]

9. Japan pubmed.ncbi.nlm.nih.gov

[The effect of imatinib for gastrointestinal tumor]. [2015]

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

Phase II Trial of Imatinib Plus Binimetinib in Patients With Treatment-Naive Advanced Gastrointestinal Stromal Tumor. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Combined Inhibition of AKT and KIT Restores Expression of Programmed Cell Death 4 (PDCD4) in Gastrointestinal Stromal Tumor. [2022]

12. Italy pubmed.ncbi.nlm.nih.gov

Gastric GISTs. Personal experience. [2015]