A Study to Evaluate the Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Profiles of CGT9486 in subjects with Advanced Systemic Mastocytosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cogent Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Jan 2022 → ongoing

Decision date (initial)

2024-06-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-511407-42-00

EudraCT number

2021-001010-10

ClinicalTrials.gov

NCT04996875

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy, Pharmacokinetic, Pharmacodynamic

Part 1: To identify a clinically active and tolerable systemic exposure range of bezuclastinib in subjects with AdvSM.
Part 2 Stage 1: To confirm the optimal dose of bezuclastinib in subjects with AdvSM.
Part 2 Stage 2: To determine the efficacy of bezuclastinib at the selected optimal dose in subjects with AdvSM.

Secondary objectives 8

1. Part 1 and Part 2: To characterize the safety and tolerability of bezuclastinib in subjects with AdvSM
2. Part 1 and Part 2: To evaluate additional efficacy parameters with bezuclastinib in subjects with AdvSM
3. Part 1 and Part 2: To determine the effects of bezuclastinib on serum tryptase
4. Part 1 and Part 2: To determine the effects of bezuclastinib on KIT D816V mutation allele burden
5. Part 1 and Part 2: To evaluate histopathologic response in the blood and bone marrow
6. Part 1 and Part 2: To assess the PK of bezuclastinib in subjects with AdvSM
7. Part 1 and Part 2: To assess patient-reported outcomes in subjects with AdvSM
8. Part 1 and Part 2: To explore the effect of bezuclastinib in subjects with AdvSM who are nonevaluable based on the modified IWG-MRT-ECNM response criteria

Conditions and MedDRA coding

Advanced Systemic Mastocytosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Diagnosed with 1 of the following advanced mastocytosis diagnoses: 1. Aggressive Systemic Mastocytosis (ASM) 2. Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN) 3. Mast Cell Leukemia (MCL)
2. Measurable disease according to modified IWG-MRT-ECNM criteria
3. ECOG Status 0 to 3
4. Have clinically acceptable laboratory screening results (clinical chemistry, hematology) within certain limits
5. Other protocol-defined inclusion criteria apply.

Exclusion criteria 11

1. Persistent toxicity from previous therapy for Advanced Systemic Mastocytosis that has not resolved to ≤ Grade 1
2. Associated hematologic neoplasm requiring immediate antineoplastic therapy
3. Clinically significant cardiac disease
4. Known positivity for the FIP1L1 PDGFRA fusion (patients with eosinophilia without detectable KIT D816V mutation must also lack the PDGFRA fusion mutation prior to enrolment)
5. Seropositive for human immunodeficiency virus (HIV) 1 or 2, positive for hepatitis B surface antigen, or positive for hepatitis C virus (HCV) antibody
6. History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
7. Diagnosed with or treated for malignancy other than the disease under study within the prior 3 years before enrollment
8. Received any cytoreductive therapy or any investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon, and any antibody therapy less than 28 days, before screening bone marrow biopsy
9. Received hematopoietic growth factor support within 14 days before the first dose of study drug.
10. Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives, whichever is longer, before the first dose of study drug.
11. Need for treatment with high dose steroids

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part 1: Dose Optimization - Safety assessments and dose modifications; - PK and pharmacodynamic assessments; - Overall response rate (ORR)
2. Part 2 Stage 1: Dose Confirmation - Safety assessments and dose modifications - PK and pharmacodynamic assessments - Overall response rate (ORR)
3. Part 2 Stage 2: Expansion - Overall response rate (ORR)

Secondary endpoints 7

1. Part 1 and Part 2: Incidence of AEs, SAEs, AEs leading to dose modifications, and changes from baseline in laboratory results
2. Part 1 and Part 2: Duration Of Response (DOR), Time to Response (TTR), Progression Free Survival (PFS), Overall Survival (OS), Pure Pathologic Response (PPR)
3. Part 1 and Part 2: Changes in the levels of serum tryptase
4. Part 1 and Part 2: Changes in the levels of KIT D816V mutation allele burden in blood and bone marrow
5. Part 1 and Part 2: Change in pathologic findings in the blood and bone marrow including mast cell infiltration, monocytosis, and eosinophilia
6. Part 1 and Part 2: Plasma concentrations of bezuclastinib
7. Part 1 and Part 2: Change from baseline in PGIS, PGIC, MC-QoL and MAS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cogent Biosciences Inc.

Sponsor organisation

Cogent Biosciences Inc.

Address

275 Wyman Street

City

Waltham

Postcode

02451-1200

Country

United States

Scientific contact point

Organisation

Cogent Biosciences Inc.

Contact name

Apex Clinical Trial Information

Public contact point

Organisation

Cogent Biosciences Inc.

Contact name

Apex Clinical Trial Information

Third parties 15

Locations

9 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 81 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications