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

Sponsor

Cogent Biosciences, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05186753

Collaborator

(none)

138

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multi-part, randomized, double-blind, placebo-controlled Phase 2 clinical study comparing the safety and efficacy of 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 1 and 2 will receive CGT9486 or placebo, and may roll over onto Part 3 to receive treatment with CGT9486.

Condition or Disease	Intervention/Treatment	Phase
SSM Mastocytosis, Indolent Mastocytosis, Systemic Mastocytosis	Drug: CGT9486 Tablets Drug: Placebo Tablets	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

138 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

In Part 1 of the study, patients with NonAdvSM will be randomly assigned to 1 of 3 dose levels of CGT9486 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 CGT9486 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 CGT9486 plus BSC.In Part 1 of the study, patients with NonAdvSM will be randomly assigned to 1 of 3 dose levels of CGT9486 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 CGT9486 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 CGT9486 plus BSC.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official 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

Anticipated Study Start Date :

Apr 1, 2022

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Nov 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: (Part 1) CGT9486 Dose 1 + BSC	Drug: CGT9486 Tablets CGT9486 will be administered orally, once daily continuously for 28-day cycles Other Names: Bezuclastinib PLX9486
Experimental: (Part 1) CGT9486 Dose 2 + BSC	Drug: CGT9486 Tablets CGT9486 will be administered orally, once daily continuously for 28-day cycles Other Names: Bezuclastinib PLX9486
Experimental: (Part 1) CGT9486 Dose 3 + BSC	Drug: CGT9486 Tablets CGT9486 will be administered orally, once daily continuously for 28-day cycles Other Names: Bezuclastinib PLX9486
Placebo Comparator: (Part 1) Placebo + BSC	Drug: Placebo Tablets Placebo will be administered orally, once daily continuously for 28-day cycles
Experimental: (Part 2) CGT9486 Selected Dose + BSC	Drug: CGT9486 Tablets CGT9486 will be administered orally, once daily continuously for 28-day cycles Other Names: Bezuclastinib 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) CGT9486 + BSC	Drug: CGT9486 Tablets CGT9486 will be administered orally, once daily continuously for 28-day cycles Other Names: Bezuclastinib PLX9486

Outcome Measures

Primary Outcome Measures

Part 1: Recommended dose of CGT9486 in subjects with NonAdvSM [3 months]
Selection of the recommended dose to be used in subsequent parts of the study.
Part 2: Proportion of responders based on reduction in a disease-specific patient reported outcome (PRO) [6 months]

Secondary Outcome Measures

Safety and tolerability of CGT9486 as assessed by number of adverse events [Up to 24 months]
CTCAE v5
Change and percent change in patient reported outcome (PRO) measures [Up to 24 months]
Change and percent change in serum tryptase [Up to 24 months]
Change and percent change in bone marrow mast cells [Up to 24 months]
Determine the effects of CGT9486 on KIT D816V mutation allele burden [Up to 24 months]
Change and percent change in the levels of KIT D816V mutation allele burden
Assess the pharmacokinetics (PK) of CGT9486 in subjects with NonAdvSM [Up to 24 months]
Plasma concentrations of CGT9846
Determine the efficacy of CGT9486 at the selected dose [Up to 24 months]
Percent change from baseline in the disease specific PRO
Mean Change in the Mast Cell Quality of Life (MC-QOL) Score [up to 24 months]
Scale of 0-100, higher numbers represent more severe impairment to quality of life.
Mean Change in 12-item Short Form Health Survey (SF-12) [up to 24 months]
Scale of 0-100, higher numbers represent better symptom outcomes
Mean Change in EuroQol 5 Dimensions 5 Levels (EQ 5D-5L [up to 24 months]
Scale of 0-100, higher numbers represent better symptom outcomes

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)
Smoldering systemic mastocytosis (SSM)

Moderate-to-severe symptoms based on a disease-specific PRO 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:

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
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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Innovative Research of West Florida	Clearwater	Florida	United States	33756
2	Mid Florida Hematology and Oncology Center	Orange City	Florida	United States	32763
3	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
4	University of Michigan	Ann Arbor	Michigan	United States	48109
5	Washington University at St. Louis	Saint Louis	Missouri	United States	63110
6	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030