Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 2
Cogent Biosciences, Inc. (Voir sur ClinicalTrials)
novembre 2021
juillet 2026
31 mai 2025
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).
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Necker-Enfants Malades | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Hospitalier Universitaire (CHU) de Poitiers - 86000 - Poitiers - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Universitaire (CHU) de Toulouse - 31300 - Toulouse - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Key Inclusion Criteria for Main Study:
1. Diagnosed with one of the following advanced mastocytosis diagnoses by Eligibility
Committee
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. (A subset of
patients inevaluble per mIWG-MRT-ECNM will be included in the study).
3. ECOG (0 to 3)
4. Have clinically acceptable local laboratory screening results (clinical chemistry,
hematology) within certain limits
Key Exclusion Criteria for Main Study:
1. Persistent toxicity from previous therapy for AdvSM 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 demonstrate lack of PDGFRA fusion mutation prior
to enrollment
5. Seropositive for human immunodeficiency virus (HIV) 1 or 2, or positive for
hepatitis B surface antigen or 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
Key Inclusion Criteria for Substudy Population:
Rollover Cohort
1. Demonstrate AHN progression requiring immediate AHN-directed therapy while receiving
bezuclastinib
2. Demonstrated clinical benefit from bezuclastinib therapy
3. Have clinically acceptable local laboratory screening results (clinical chemistry,
hematology) within certain limits
High-Risk Cohort
1. Receiving or indicated for AHN-directed therapy.
2. Diagnosed with one of the following pathologic diagnoses of SM-AHN:
1. Myelodysplastic syndrome (MDS) that is high- or very high-risk
2. Accelerated phase myeloproliferative neoplasm (MPN)
3. MDS with excessive blasts in bone marrow or peripheral blood
4. Chronic myelomonocytic leukemia-2 (CMML-2)
3. Have clinically acceptable local laboratory screening results (clinical chemistry,
hematology) within certain limits.
Key Exclusion Criteria for Substudy Population:
1. Diagnosis of Philadelphia chromosome-positive malignancy
2. Diagnosis of acute myeloid leukemia (AML)
3. Appropriate for allogenic hematopoietic stem cell transplantation
4. Any contraindication to selected concomitant therapy
5. Rollover Cohort: Have not demonstrated acceptable tolerability of previous
bezuclastinib therapy
6. High-Risk Cohort: Previously treated with investigational therapy for AdvSM
7. High-Risk Cohort: Previously treated with cytoreductive therapy and discontinued due
to treatment-related toxicity
8. High-Risk Cohort: 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 or archival bone marrow
biopsy
1. Diagnosed with one of the following advanced mastocytosis diagnoses by Eligibility
Committee
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. (A subset of
patients inevaluble per mIWG-MRT-ECNM will be included in the study).
3. ECOG (0 to 3)
4. Have clinically acceptable local laboratory screening results (clinical chemistry,
hematology) within certain limits
Key Exclusion Criteria for Main Study:
1. Persistent toxicity from previous therapy for AdvSM 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 demonstrate lack of PDGFRA fusion mutation prior
to enrollment
5. Seropositive for human immunodeficiency virus (HIV) 1 or 2, or positive for
hepatitis B surface antigen or 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
Key Inclusion Criteria for Substudy Population:
Rollover Cohort
1. Demonstrate AHN progression requiring immediate AHN-directed therapy while receiving
bezuclastinib
2. Demonstrated clinical benefit from bezuclastinib therapy
3. Have clinically acceptable local laboratory screening results (clinical chemistry,
hematology) within certain limits
High-Risk Cohort
1. Receiving or indicated for AHN-directed therapy.
2. Diagnosed with one of the following pathologic diagnoses of SM-AHN:
1. Myelodysplastic syndrome (MDS) that is high- or very high-risk
2. Accelerated phase myeloproliferative neoplasm (MPN)
3. MDS with excessive blasts in bone marrow or peripheral blood
4. Chronic myelomonocytic leukemia-2 (CMML-2)
3. Have clinically acceptable local laboratory screening results (clinical chemistry,
hematology) within certain limits.
Key Exclusion Criteria for Substudy Population:
1. Diagnosis of Philadelphia chromosome-positive malignancy
2. Diagnosis of acute myeloid leukemia (AML)
3. Appropriate for allogenic hematopoietic stem cell transplantation
4. Any contraindication to selected concomitant therapy
5. Rollover Cohort: Have not demonstrated acceptable tolerability of previous
bezuclastinib therapy
6. High-Risk Cohort: Previously treated with investigational therapy for AdvSM
7. High-Risk Cohort: Previously treated with cytoreductive therapy and discontinued due
to treatment-related toxicity
8. High-Risk Cohort: 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 or archival bone marrow
biopsy