Bezuclastinib for Systemic Mastocytosis
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial investigates a new treatment called bezuclastinib for individuals with nonadvanced systemic mastocytosis (NonAdvSM), a condition characterized by an excess of mast cells in the body, leading to symptoms like itching, flushing, and abdominal pain. The study aims to determine if bezuclastinib, combined with standard care, can better control these symptoms compared to a placebo (a pill with no active medicine). Participants will be randomly assigned to receive either the active treatment or a placebo, with some potentially switching to the active treatment later. This trial suits those diagnosed with indolent or smoldering systemic mastocytosis who experience moderate-to-severe symptoms not well-managed by current medications. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering a chance to contribute to important findings.
Do I have to stop taking my current medications for this trial?
The trial protocol does not specify if you must stop all current medications. However, you cannot take strong CYP3A4 inhibitors or inducers within 14 days before the first dose. If you're on corticosteroids, the dose must be 10 mg/day or less of prednisone or equivalent. You also need to have a stable regimen of at least 2 antimediator therapies for 14 days before joining.
Will I have to stop taking my current medications?
The trial does not specify if you must stop all current medications, but you cannot take strong CYP3A4 inhibitors or inducers within 14 days before starting the study. If you are on corticosteroids, the dose must be 10 mg/day or less of prednisone or equivalent.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that bezuclastinib is generally safe for people with systemic mastocytosis. In earlier studies, most participants did not experience serious side effects. Some individuals reported mild to moderate issues, such as headaches or stomach upset, but these were not severe. Solid information on long-term effects is not yet available, but current evidence suggests bezuclastinib is safe for most people in the short term. As this is a Phase 2 trial, the treatment has already demonstrated some safety in earlier research, which is a positive sign.12345
Why do researchers think this study treatment might be promising for systemic mastocytosis?
Most treatments for systemic mastocytosis focus on managing symptoms rather than addressing the underlying cause. However, bezuclastinib stands out because it targets the KIT D816V mutation, which is a key driver of the disease. This specific inhibition can potentially reduce mast cell proliferation directly. Researchers are excited because this approach could offer a more effective way to control the disease progression compared to current options, which often include symptom management with antihistamines or corticosteroids.
What evidence suggests that bezuclastinib could be an effective treatment for systemic mastocytosis?
Research has shown that bezuclastinib holds promise for treating systemic mastocytosis. In studies, 94% of patients experienced at least a 50% reduction in serum tryptase, a disease marker. Additionally, 100% of patients showed a similar reduction in KIT D816V, another important marker. These decreases suggest that bezuclastinib effectively targets and reduces the activity of abnormal cells in systemic mastocytosis. In this trial, participants may receive bezuclastinib in various dosages or a placebo, alongside best supportive care (BSC). This early evidence supports the potential of bezuclastinib to improve symptoms in patients whose conditions are not well-managed with current treatments.25678
Who Is on the Research Team?
Rachael Easton, MD, PhD
Principal Investigator
Cogent Biosciences
Are You a Good Fit for This Trial?
This trial is for patients with a condition called systemic mastocytosis, specifically the indolent or smoldering types. Participants should have moderate-to-severe symptoms despite current treatments and be in fairly good health overall (ECOG 0-2). They can't join if they've had significant bleeding recently, need blood thinners, have certain advanced forms of the disease, skin-only mastocytosis, previous KIT inhibitor therapy (except approved ones), recent cytoreductive therapy or radiation.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment Part 1
Participants receive bezuclastinib or placebo to determine the recommended dose
Treatment Part 2
Participants receive bezuclastinib at the selected dose or placebo to assess efficacy and safety
Treatment Part 3
Participants may roll over to receive bezuclastinib for long-term efficacy and safety assessment
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Bezuclastinib (CGT9486)
- Placebo Tablets
Find a Clinic Near You
Who Is Running the Clinical Trial?
Cogent Biosciences, Inc.
Lead Sponsor