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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. 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) 2. 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 3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2 4. For patients receiving corticosteroids, the dose must be ≤10 mg/day of prednisone or equivalent

Exclusion Criteria

  1. Persistent toxicity from previous therapy for NonAdvSM that has not resolved to ≤ Grade 1 2. 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 3. Diagnosed with mastocytosis of the skin without systemic involvement 4. Received prior treatment with any targeted KIT inhibitor with the exception of approved agents for the treatment of SM 5. 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 6. Received radiotherapy or psoralen and ultraviolet A therapy <14 days before starting screening assessments 7. Received any hematopoietic growth factor support <14 days or 5 half lives of the drug before starting screening assessments 8. History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study 9. Need for treatment of corticosteroids at >10 mg/day of prednisone or equivalent 10. Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives before the first dose of study drug

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
In Part 1a and 1b of the study, patients with NonAdvSM will be randomly assigned to 1 of 2 dose levels of bezuclastinib plus BSC, or to placebo plus BSC. Upon analysis of the Part 1 data, a dose will be selected for Part 2. In Part 2, patients with NonAdvSM will be randomly assigned to the selected dose of bezuclastinib plus BSC, or to placebo plus BSC. Patients who complete Part 1 or Part 2 may participate in Part 3 in which all patients will receive bezuclastinib plus BSC.
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
(Part 1a) Bezuclastinib Dose 1 + BSC
  • Drug: Bezuclastinib Tablets (Formulation A)
    Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
    Other names:
    • CGT9486
    • PLX9486
Experimental
(Part 1a) Bezuclastinib Dose 2 + BSC
  • Drug: Bezuclastinib Tablets (Formulation A)
    Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
    Other names:
    • CGT9486
    • PLX9486
Placebo Comparator
(Part 1a) Placebo + BSC
  • Drug: Placebo Tablets
    Placebo will be administered orally, once daily continuously for 28-day cycles
Experimental
(Part 1b) Bezuclastinib Dose 1 + BSC
  • Drug: Bezuclastinib Tablets (Formulation B)
    Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
    Other names:
    • CGT9486
    • PLX9486
Experimental
(Part 1b) Bezuclastinib Dose 2 + BSC
  • Drug: Bezuclastinib Tablets (Formulation B)
    Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
    Other names:
    • CGT9486
    • PLX9486
Placebo Comparator
(Part 1b) Placebo + BSC
  • Drug: Placebo Tablets
    Placebo will be administered orally, once daily continuously for 28-day cycles
Experimental
(Part 2) Bezuclastinib Selected Dose + BSC
  • Drug: Bezuclastinib Tablets (Formulation B)
    Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
    Other names:
    • CGT9486
    • PLX9486
Placebo Comparator
(Part 2) Placebo + BSC
  • Drug: Placebo Tablets
    Placebo will be administered orally, once daily continuously for 28-day cycles
Experimental
(Part 3) Bezuclastinib + BSC
  • Drug: Bezuclastinib Tablets (Formulation A)
    Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
    Other names:
    • CGT9486
    • PLX9486
  • Drug: Bezuclastinib Tablets (Formulation B)
    Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
    Other names:
    • CGT9486
    • PLX9486

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35233

More Details

Status
Recruiting
Sponsor
Cogent Biosciences, Inc.

Study Contact

Hina Jolin, PharmD
+1 (833) 411-6976
SummitInfo@cogentbio.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.