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Antigen-Antibody Complex

Bezuclastinib is administered as tablets to be taken orally, continuously in 28-day cycles.

bezuclastinib

Hina Jolin, PharmD

Rachael Easton, MD, Ph.D.

This is an open-label, two-part Phase 2 study investigating CGT9486 for the treatment of patients with Advanced Systemic Mastocytosis (AdvSM), including patients with Aggressive SM (ASM), SM with Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL).

There are two parts to this study, including Part I, Dose Optimization, and Part II Expansion. Part II is separated into two stages.

(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis

A Phase 2 Open-Label, Multicenter Clinical Study of the Safety, Efficacy, Pharmacokinetic, and Pharmacodynamic Profiles of CGT9486 as a Single Agent in Patients With Advanced Systemic Mastocytosis

Incidence of AEs according to CTCAE version 5.0 or higher

Percentage change in plasma concentrations of bezuclastinib

Percentage change in mast cell infiltration in the bone marrow and percentage change in eosinophilia and monocytosis in the blood

0 -10 points (higher values represent worse symptom outcomes)

0 - 7 points (higher values represent better symptom outcomes)

0 - 100 (higher values represent better symptom outcomes)

0 - 252 (higher values represent worse symptom outcomes)

Cogent Biosciences, Inc.

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

Bezuclastinib Tablets (Formulation A)

Bezuclastinib Tablets (Formulation B)

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

Placebo Tablets

Rachael Easton, MD, PhD

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.

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.

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

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

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

Mean absolute change in a disease-specific patient reported outcome (PRO)

Scale of 0-100, higher numbers represent more severe impairment to quality of life.

Scale of 0-100, higher numbers represent better symptom outcomes

Response rate based on reduction in disease specific PRO

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis	NCT04996875	Advanced System... SM With an Asso... Mast Cell Leuke... Aggressive Syst...	bezuclastinib	18 Years -	Cogent Biosciences, Inc.
(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis	NCT05186753	SSM Mastocytosis, I... Mastocytosis, S... Mastocytosis	Bezuclastinib T... Bezuclastinib T... Placebo Tablets	18 Years -	Cogent Biosciences, Inc.

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