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

Cogent Biosciences

Status and phase: Enrolling; Phase 2

Conditions: ISM; Mastocytosis; Smoldering Systemic Mastocytosis; BMM; Bone Marrow Mastocytosis; Mastocytosis, Systemic; Mastocytosis, Indolent; SSM

Treatments: Drug: Bezuclastinib Tablets (Formulation A); Drug: Placebo Tablets; Drug: Bezuclastinib Tablets (Formulation B)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05186753

CGT9486-21-202

Details and patient eligibility

About

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.

Enrollment: 207 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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

Key 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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207 participants in 9 patient groups, including a placebo group

(Part 1a) Bezuclastinib Dose 1 + BSC

Experimental group

Treatment:

Drug: Bezuclastinib Tablets (Formulation A)

(Part 1a) Bezuclastinib Dose 2 + BSC

Experimental group

Treatment:

Drug: Bezuclastinib Tablets (Formulation A)

(Part 1a) Placebo + BSC

Placebo Comparator group

Treatment:

Drug: Placebo Tablets

(Part 1b) Bezuclastinib Dose 1 + BSC

Experimental group

Treatment:

Drug: Bezuclastinib Tablets (Formulation B)

(Part 1b) Bezuclastinib Dose 2 + BSC

Experimental group

Treatment:

Drug: Bezuclastinib Tablets (Formulation B)

(Part 1b) Placebo + BSC

Placebo Comparator group

Treatment:

Drug: Placebo Tablets

(Part 2) Bezuclastinib Selected Dose + BSC

Experimental group

Treatment:

Drug: Bezuclastinib Tablets (Formulation B)

(Part 2) Placebo + BSC

Placebo Comparator group

Treatment:

Drug: Placebo Tablets

(Part 3) Bezuclastinib + BSC

Experimental group

Treatment:

Drug: Bezuclastinib Tablets (Formulation B)

Drug: Bezuclastinib Tablets (Formulation A)