140 Participants Needed

Bezuclastinib for Systemic Mastocytosis

Recruiting at 40 trial locations
HJ
Overseen ByHina Jolin, PharmD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. Specifically, you must not have received any cytoreductive therapy or investigational agents less than 14 days before the study, and certain medications like cladribine, interferon alpha, pegylated interferon, and antibody therapy must be stopped 28 days before. Additionally, you cannot take strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives before the first dose of the study drug.

What data supports the effectiveness of the drug Bezuclastinib for treating systemic mastocytosis?

While there is no direct data on Bezuclastinib, similar drugs like avapritinib, which target the same mutation (KITD816V) found in most systemic mastocytosis cases, have shown promising results. Avapritinib has demonstrated a 72% overall response rate in patients with advanced systemic mastocytosis, suggesting that targeting this mutation can be effective.12345

How is the drug Bezuclastinib different from other drugs for systemic mastocytosis?

Bezuclastinib is unique because it specifically targets the KIT D816V mutation, which is present in most patients with systemic mastocytosis, potentially offering a more targeted approach compared to other treatments like midostaurin and cladribine that have broader mechanisms of action.26789

What is the purpose of this trial?

This is an open-label, two-part Phase 2 study investigating CGT9486 for the treatment of patients with Advanced Systemic Mastocytosis (AdvSM), including patients with Aggressive SM (ASM), SM with Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL).

Research Team

RE

Rachael Easton, MD, Ph.D.

Principal Investigator

Cogent Biosciences, Inc.

Eligibility Criteria

This trial is for patients with Advanced Systemic Mastocytosis, including Aggressive SM, SM with an Associated Hematologic Neoplasm, or Mast Cell Leukemia. Participants must have measurable disease and be in a stable enough condition (ECOG 0 to 3). They can't join if they have HIV, hepatitis B/C, other recent cancers, significant heart issues or bleeding events, unresolved toxicity from past treatments or need certain medications like strong CYP3A4 inhibitors.

Inclusion Criteria

I can care for myself but may not be able to do heavy physical work.
Measurable disease according to modified IWG-MRT-ECNM criteria. (A subset of patients evaluable per mIWG-MRT-ECNM will be included in the study)
Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits
See 6 more

Exclusion Criteria

I haven't had specific cancer treatments in the last 14 to 28 days.
Seropositive for human immunodeficiency virus (HIV) 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody
I haven't taken strong CYP3A4 affecting drugs recently.
See 16 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CGT9486 for the treatment of Advanced Systemic Mastocytosis

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

  • Bezuclastinib
  • CGT9486 tablets
Trial Overview The study is testing Bezuclastinib's effectiveness on Advanced Systemic Mastocytosis. It's an open-label Phase 2 trial where all participants receive the drug. The goal is to see how well it treats different types of this mast cell cancer by monitoring changes in the disease according to specific criteria.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: bezuclastinibExperimental Treatment1 Intervention

Bezuclastinib is already approved in European Union, United States for the following indications:

🇪🇺
Approved in European Union as Bezuclastinib for:
  • Orphan designation for Gastrointestinal stromal tumours and Systemic mastocytosis
🇺🇸
Approved in United States as Bezuclastinib for:
  • Orphan designation for Gastrointestinal stromal tumours and Systemic mastocytosis

Find a Clinic Near You

Who Is Running the Clinical Trial?

Cogent Biosciences, Inc.

Lead Sponsor

Trials
11
Recruited
1,100+

Findings from Research

Avapritinib is a promising new treatment for advanced systemic mastocytosis (AdvSM), specifically designed to target the KITD816V mutation, showing potent antineoplastic activity in early Phase 1 trials, especially in patients who did not respond to midostaurin.
While avapritinib has demonstrated rapid symptom relief and reductions in bone marrow mast cells and mutant allele burden, it also has potential side effects, including myelosuppression, periorbital edema, and cognitive impairment, highlighting the need for further research on its long-term efficacy and safety.
Novel approaches to treating advanced systemic mastocytosis.Gilreath, JA., Tchertanov, L., Deininger, MW.[2020]
A new risk score called the mutation-adjusted risk score (MARS) was developed for patients with advanced systemic mastocytosis (AdvSM), based on a study of 383 patients, which helps predict overall survival by identifying key risk factors such as age, anemia, thrombocytopenia, and specific gene mutations.
The MARS score effectively categorizes patients into low, intermediate, and high-risk groups for survival outcomes, and it is independent of the WHO classification, potentially enhancing treatment strategies for this rare condition.
MARS: Mutation-Adjusted Risk Score for Advanced Systemic Mastocytosis.Jawhar, M., Schwaab, J., Álvarez-Twose, I., et al.[2020]
Mast cell disorders, particularly systemic mastocytosis (SM), can vary greatly in severity and are often linked to a specific mutation (D816V) in the c-kit gene, which affects treatment options.
Patients with indolent forms of mastocytosis are typically treated with mediator-targeting drugs, while those with aggressive forms may require cytoreductive therapy or alternative targeted treatments due to resistance against common drugs like Imatinib.
Mastocytosis: pathology, genetics, and current options for therapy.Valent, P., Akin, C., Sperr, WR., et al.[2019]

References

Novel approaches to treating advanced systemic mastocytosis. [2020]
MARS: Mutation-Adjusted Risk Score for Advanced Systemic Mastocytosis. [2020]
Mastocytosis: pathology, genetics, and current options for therapy. [2019]
Advanced systemic mastocytosis-Revised classification, new drugs and how we treat. [2023]
Rapid Responses to Avapritinib (BLU-285) in Mastocytosis. [2019]
The KIT D816V allele burden predicts survival in patients with mastocytosis and correlates with the WHO type of the disease. [2022]
Real-World Efficacy of Midostaurin in Aggressive Systemic Mastocytosis. [2021]
Cladribine therapy for advanced and indolent systemic mastocytosis: Mayo Clinic experience in 42 consecutive cases. [2022]
The Efficacy of Cladribine (2-CdA) in Advanced Systemic Mastocytosis. [2020]
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