Bezuclastinib for Systemic Mastocytosis

Recruiting at 71 trial locations

Overseen By Hina Jolin, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cogent Biosciences, Inc.

Must be taking: Antimediator therapies

Must not be taking: Strong CYP3A4 inhibitors

Disqualifiers: Advanced systemic mastocytosis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

207 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new drug called bezuclastinib, given with usual care, in patients with nonadvanced systemic mastocytosis whose symptoms are not well-managed. The drug aims to reduce the activity of cells that cause symptoms, potentially leading to better symptom control.

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.

What safety data is available for Bezuclastinib in treating systemic mastocytosis?

The provided research does not contain specific safety data for Bezuclastinib (CGT9486) or its placebo in the treatment of systemic mastocytosis. The articles focus on other treatments like midostaurin and general management of mastocytosis, but do not mention Bezuclastinib or its safety profile. ^{1 2 3 4 5}

Is the drug Bezuclastinib a promising treatment for systemic mastocytosis?

The drug Bezuclastinib is considered promising for treating systemic mastocytosis because it targets the KITD816V mutation, which is a key driver of the disease. This mutation is common in patients with advanced forms of systemic mastocytosis, and targeting it can help reduce symptoms and disease burden. Other drugs like midostaurin and avapritinib have shown success in targeting this mutation, suggesting that Bezuclastinib could also be effective. ^{3 6 7 8 9}

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

Bezuclastinib is unique because it targets the KITD816V mutation, which is a common driver in systemic mastocytosis, potentially offering a more specific and potent treatment option compared to existing drugs like midostaurin, which have partial and unsustained responses. ^{3 6 7 8 9}

What data supports the idea that Bezuclastinib for Systemic Mastocytosis is an effective drug?

The available research does not provide specific data on the effectiveness of Bezuclastinib for Systemic Mastocytosis. Instead, it highlights the effectiveness of another drug, Midostaurin, which has shown positive results in treating aggressive systemic mastocytosis. For example, in a study, 77% of patients showed clinical improvement by the second month of therapy, and 50% of evaluated patients had an objective response, including a significant decrease in disease markers. This suggests that while Bezuclastinib's effectiveness is not detailed here, Midostaurin is a proven alternative treatment. ^{1 3 5 6 8}

What data supports the effectiveness of the drug Bezuclastinib (CGT9486) for treating systemic mastocytosis?

While there is no direct data on Bezuclastinib (CGT9486) for systemic mastocytosis, similar drugs like midostaurin have shown effectiveness in treating aggressive systemic mastocytosis by reducing disease symptoms and improving patient outcomes. ^{1 3 5 6 8}

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

I am taking 10 mg or less of prednisone daily or its equivalent.

I can take care of myself and am up and about more than half of my waking hours.

I have moderate-to-severe symptoms despite taking at least 2 treatments for 14 days.

Exclusion Criteria

I haven't had radiotherapy or PUVA therapy in the last 14 days.

I have been treated with a KIT inhibitor, but not for systemic mastocytosis.

I have been diagnosed with mastocytosis that affects only my skin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive bezuclastinib or placebo to determine the recommended dose

3 months

Treatment Part 2

Participants receive bezuclastinib at the selected dose or placebo to assess efficacy and safety

24 weeks

Treatment Part 3

Participants may roll over to receive bezuclastinib for long-term efficacy and safety assessment

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bezuclastinib (CGT9486)
• Placebo Tablets

Trial Overview The study tests bezuclastinib tablets against placebo tablets to see which is better at managing systemic mastocytosis when added to standard care. It's randomized and double-blind meaning neither doctors nor patients know who gets the real drug versus placebo. The trial has three parts; after completing Parts 1a/1b/2 with either drug or placebo, participants may move on to Part 3 for bezuclastinib treatment.

How Is the Trial Designed?

Group I: (Part 3) Bezuclastinib + BSC Experimental Treatment 2 Interventions

Group II: (Part 2) Bezuclastinib Selected Dose + BSC Experimental Treatment 1 Intervention

Group III: (Part 1b) Bezuclastinib Dose 2 + BSC Experimental Treatment 1 Intervention

Group IV: (Part 1b) Bezuclastinib Dose 1 + BSC Experimental Treatment 1 Intervention

Group V: (Part 1a) Bezuclastinib Dose 2 + BSC Experimental Treatment 1 Intervention

Group VI: (Part 1a) Bezuclastinib Dose 1 + BSC Experimental Treatment 1 Intervention

Group VII: (Part 2) Placebo + BSC Placebo Group 1 Intervention

Group VIII: (Part 1a) Placebo + BSC Placebo Group 1 Intervention

Group IX: (Part 1b) Placebo + BSC Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Cogent Biosciences, Inc.

Lead Sponsor

Trials

11

Recruited

1,100+

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MARS: Mutation-Adjusted Risk Score for Advanced Systemic Mastocytosis. Jawhar, M., Schwaab, J., Álvarez-Twose, I., et al.[2020]

Midostaurin is effective in rapidly reducing the disease burden in patients with systemic mastocytosis, even in cases that are resistant to cladribine treatment.

The management of systemic mastocytosis requires a comprehensive diagnostic approach and tailored treatment strategies, highlighting the complexity of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of aggressive systemic mastocytosis with bulky lymphadenopathy showing response to midostaurin. Sciumè, M., Serpenti, F., Muratori, S., et al.[2021]

The Italian Mastocytosis Registry included data from 600 patients diagnosed with mastocytosis, revealing that 38.9% of adults had systemic mastocytosis, often diagnosed without bone marrow studies, particularly in non-hematologic centers.

Most patients with systemic mastocytosis had elevated serum tryptase levels (>20 ng/ml) and detectable KIT D816V mutations, indicating specific biomarkers that can aid in diagnosis and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Italian Mastocytosis Registry: 6-year experience from a hospital-based registry. Merante, S., Ferretti, VV., Elena, C., et al.[2019]

In a study of 116 patients with advanced systemic mastocytosis, midostaurin demonstrated a 60% overall response rate, with 45% achieving a major response, indicating significant efficacy in treating this challenging condition.

Despite its effectiveness, midostaurin was associated with notable side effects, leading to dose reductions in 56% of patients, highlighting the need for careful monitoring and management of adverse events during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. Gotlib, J., Kluin-Nelemans, HC., George, TI., et al.[2022]

In a study of 13 patients with aggressive systemic mastocytosis (ASM) treated with midostaurin, 77% showed clinical improvement within two months, indicating its efficacy in this patient population.

Among the eight patients evaluated, 50% had an objective response, with significant reductions in serum tryptase levels and bone marrow mast cell infiltration, suggesting that midostaurin effectively targets the underlying disease mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Efficacy of Midostaurin in Aggressive Systemic Mastocytosis. Szudy-Szczyrek, A., Bachanek-Mitura, O., Gromek, T., et al.[2021]

In a study of 101 patients with mastocytosis, 50% of childhood cases began before age 2, with many showing improvement over time, challenging the belief that childhood mastocytosis is often temporary.

In contrast, adult onset mastocytosis was found to have less severe symptoms, with 21 out of 36 adults experiencing no mast cell-mediated symptoms, indicating a potentially milder course than previously thought.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of mastocytosis with onset in children and adults. Middelkamp Hup, MA., Heide, R., Tank, B., et al.[2019]

Midostaurin, an oral multikinase/KIT inhibitor, has been approved for the treatment of advanced systemic mastocytosis (advSM) based on phase 2 clinical studies, showing its efficacy in managing this condition characterized by neoplastic mast cell accumulation.

Adverse events (AEs) from midostaurin can be challenging to differentiate from symptoms of the disease itself, which may lead to unnecessary treatment discontinuation; therefore, effective management strategies for AEs are crucial to ensure patients can continue benefiting from the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical management of adverse events in patients with advanced systemic mastocytosis receiving midostaurin. Gotlib, J., Kluin-Nelemans, HC., Akin, C., et al.[2021]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel approaches to treating advanced systemic mastocytosis. Gilreath, JA., Tchertanov, L., Deininger, MW.[2020]

A survey of 56 adults with systemic mastocytosis (SM) revealed a significant symptom burden, with 93% experiencing at least 10 symptoms, including severe issues like anaphylaxis and abdominal pain, leading to reduced work hours and quality of life.

The mean symptom score of 52.7 indicates a high level of symptom severity, well above the threshold for moderate-to-severe symptoms, highlighting the urgent need for improved care and management strategies for patients with SM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes among patients with systemic mastocytosis in routine clinical practice: Results of the TouchStone SM Patient Survey. Mesa, RA., Sullivan, EM., Dubinski, D., et al.[2023]

Citations

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

MARS: Mutation-Adjusted Risk Score for Advanced Systemic Mastocytosis. [2020]

2. England pubmed.ncbi.nlm.nih.gov

A case of aggressive systemic mastocytosis with bulky lymphadenopathy showing response to midostaurin. [2021]

3. England pubmed.ncbi.nlm.nih.gov

The Italian Mastocytosis Registry: 6-year experience from a hospital-based registry. [2019]

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

Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Efficacy of Midostaurin in Aggressive Systemic Mastocytosis. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Comparison of mastocytosis with onset in children and adults. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Practical management of adverse events in patients with advanced systemic mastocytosis receiving midostaurin. [2021]

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

Novel approaches to treating advanced systemic mastocytosis. [2020]

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

Patient-reported outcomes among patients with systemic mastocytosis in routine clinical practice: Results of the TouchStone SM Patient Survey. [2023]