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NCT Number: NCT05186753

(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis

This is a multi-part, randomized, double-blind, placebo-controlled Phase 2 clinical study comparing the safety and efficacy of bezuclastinib (CGT9486) plus best supportive care (BSC) with placebo plus BSC in patients with nonadvanced systemic mastocytosis (NonAdvSM), including indolent systemic mastocytosis and smoldering systemic mastocytosis, whose symptoms are not adequately controlled by BSC. This study will be conducted in three parts. Patients in Parts 1a, 1b and 2 will receive bezuclastinib or placebo, and may roll over onto Part 3 to receive treatment with bezuclastinib. Additionally, a substudy of subjects will investigate the efficacy, safety, and tolerability of bezuclastinib in patients who are experiencing inadequate symptom control with avapritinib.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

SSM BMM Bone Marrow Mastocytosis Hematologic Diseases Hemic and Lymphatic Diseases Hypersensitivity ISM Immune Complex Diseases Immune System Diseases Mast Cell Activation Disorders Mastocytosis Mastocytosis, Indolent Mastocytosis, Systemic Neoplasms Neoplasms by Histologic Type Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Smoldering Systemic Mastocytosis

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Diagnosed with 1 of the following diagnoses according to the 2016 World Health Organization (WHO) classification for systemic mastocytosis (SM):
  • Indolent systemic mastocytosis (ISM),
  • Bone marrow mastocytosis (BMM)
  • Smoldering systemic mastocytosis (SSM)
  • Moderate-to-severe symptoms based on a minimum total symptom scoew (TSS) of the Mastocytosis Activity Score (MAS) and after establishing a stable regimen of at least 2 antimediator therapies over a 14-day eligibility period
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
  • For patients receiving corticosteroids, the dose must be ≤10 mg/day of prednisone or equivalent

Key Exclusion Criteria:

  • Persistent toxicity from previous therapy for NonAdvSM that has not resolved to ≤ Grade 1
  • Diagnosed with any of the following WHO SM classifications: bone marrow mastocytosis, advanced systemic mastocytosis including SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia; or mast cell sarcoma
  • Diagnosed with mastocytosis of the skin without systemic involvement
  • Received prior treatment with any targeted KIT inhibitor with the exception of approved agents for the treatment of SM
  • Received prior cytoreductive therapy or investigational agent for <14 days or 5 half- lives of the drug and for cladribine, interferon alpha, pegylated interferon, or antibody therapy <28 days or 5 half-lives of the drug (whichever is longer), before starting screening assessments
  • Received radiotherapy or psoralen and ultraviolet A therapy <14 days before starting screening assessments
  • Received any hematopoietic growth factor support <14 days or 5 half lives of the drug before starting screening assessments
  • History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
  • Need for treatment of corticosteroids at >10 mg/day of prednisone or equivalent
  • Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives before the first dose of study drug

Treatment and study plan

Bezuclastinib Tablets (Formulation A)

Drug

Bezuclastinib will be administered orally, once daily continuously for 28-day cycles

Other names: CGT9486, PLX9486

Bezuclastinib Tablets (Formulation B)

Drug

Bezuclastinib will be administered orally, once daily continuously for 28-day cycles

Other names: CGT9486, PLX9486

Placebo tablets

Drug

Placebo will be administered orally, once daily continuously for 28-day cycles

Primary outcomes

  1. Part 1: Determine recommended dose of bezuclastinib (CGT9486) in subjects with NonAdvSM

    Time frame: 3 months

    Selection of the recommended dose to be used in subsequent parts of the study.

  2. Part 2: Efficacy of bezuclastinib at the selected dose versus placebo

    Time frame: 24 Weeks

    Mean absolute change on the Mastocytosis Symptom Severity Daily Diary (MS2D2)

  3. Part 3: Safety and tolerability of bezuclastinib as assessed by number of adverse events

    Time frame: Up to 5 years

    CTCAE v5

Secondary outcomes

  1. Part 2: Proportion of subjects who had at least 50% reduction in serum tryptase

    Time frame: 24 weeks

  2. Part 2: Proportion of subjects who had at least a 50% reduction in peripheral blood D816V allele fraction

    Time frame: 24 weeks

  3. Part 2: Determine responder rates of subjects treated with bezuclastinib at the selected dose versus placebo

    Time frame: 24 weeks

    Proportion of subjects with at least a 30% reduction of the total symptom score (TSS) on the MS2D2.

    Proportion of subjects with at least a 50% reduction of the total symptom score (TSS) on the MS2D2.

  4. Part 2: Proportion of subjects who had at least 50% reduction in mast cell burden

    Time frame: 24 weeks

  5. Parts 1 & 2: Safety and tolerability of bezuclastinib as assessed by number of adverse events

    Time frame: Up to 24 weeks

    CTCAE v5

  6. Parts 1, 2, & 3: Change and percent change in patient reported outcome (PRO) measures

    Time frame: Up to 5 years

  7. Parts 1 & 3: Change and percent change in serum tryptase

    Time frame: Up to 12 months

  8. Parts 1 & 3: Change and percent change in bone marrow mast cells

    Time frame: Up to 18 months

  9. Part 1: Assess the pharmacokinetics (PK) of bezuclastinib in subjects with NonAdvSM

    Time frame: 3 months

    Plasma concentrations of CGT9846

  10. Part 2: Determine mean change from baseline in predetermined PRO sub-domain and individual item scores

    Time frame: 24 weeks

  11. Parts 2 & 3: Determine change of the lead (most severe) symptom and lead (most severe) subdomain of the MS2D2 in subjects treated with bezuclastinib versus placebo

    Time frame: Up to 5 years

    Change and percent change from baseline in the symptom score of the subject's most severe symptom.

    Change and percent change from baseline in the MS2D2 subdomain score of the subject's most severe subdomain.

  12. Part 3: Change and percent change in the levels of KIT D816V mutation allele burden

    Time frame: Up to 12 months

  13. Part 3: To determine the efficacy of bezuclastinib at the selected dose

    Time frame: Up to 2 years

    Proportion of subjects with at least a 50% reduction in MS2D2 TSS from baseline at 1 year and 2 years from start of bezuclastinib

    Change and percent change from baseline in the MS2D2 TSS, subdomain, and individual item scores

  14. Part 3: Usage of concomitant medications as rescue therapy for NonAdvSM and changes from baseline in rescue therapy and best supportive care medications regimen

    Time frame: Up to 5 years

Other outcomes

  1. Substudy: Efficacy of bezuclastinib at selected dose in subjects whose symptoms are not adequately controlled by avapritinib

    Time frame: Up to 2 years

    Mean absolute change on the Mastocytosis Symptom Severity Daily Diary (MS2D2)

Sponsors and collaborators

Lead sponsor

Cogent Biosciences, Inc.

Industry

Registry information

Official study title

A Multi-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study of The Safety and Efficacy of CGT9486 in Subjects With Nonadvanced Systemic Mastocytosis

Important dates

Study start
2022
Primary completion
2025
Study completion
2030
First posted
Jan 11, 2022
Registry last updated
May 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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