Clinical trial • Phase II • Oncology
3,4-DIMETHYL-N-(2-PHENYL-1H-PYRROLO[2,3-B]PYRIDIN-5-YL)-1H-PYRAZOLE-5-CARBOXAMIDE for Advanced systemic mastocytosis
Phase II trial of 3,4-DIMETHYL-N-(2-PHENYL-1H-PYRROLO[2,3-B]PYRIDIN-5-YL)-1H-PYRAZOLE-5-CARBOXAMIDE for Advanced systemic mastocytosis.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Advanced systemic mastocytosis
- Trial Stage
- Phase II
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 30-04-2024
- First CTIS Authorization Date
- 06-06-2024
Trial design
open-label, none/not specified-controlled, adaptive Phase II trial in Spain, Belgium, Poland and others.
- Open Label
- Yes
- Comparator
- None/Not specified
- Adaptive
- True, Part 1 is dose optimization (adaptive dose-finding) with dose modifications based on safety/PK/PD; Part 2 includes dose confirmation and an expansion stage—stage-based design with dose optimization/confirmation elements.
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 80
Eligibility
Recruits 80 Vulnerable population selected. Subject information and informed consent forms (main ICFs and pregnant partner ICFs) and data processing consent forms are included in the provided documents in multiple country-specific versions (e.g., Spanish, Dutch, French, German, Italian, Polish, Norwegian, English). No specific assent process for minors is described in the available records..
- Vulnerable Population
- Vulnerable population selected. Subject information and informed consent forms (main ICFs and pregnant partner ICFs) and data processing consent forms are included in the provided documents in multiple country-specific versions (e.g., Spanish, Dutch, French, German, Italian, Polish, Norwegian, English). No specific assent process for minors is described in the available records.
Inclusion criteria
- {"criterion_text":"- 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)\n- Measurable disease according to modified IWG-MRT-ECNM criteria\n- ECOG Status 0 to 3\n- Have clinically acceptable laboratory screening results (clinical chemistry, hematology) within certain limits\n- Other protocol-defined inclusion criteria apply."}
Exclusion criteria
- {"criterion_text":"- Persistent toxicity from previous therapy for Advanced Systemic Mastocytosis that has not resolved to ≤ Grade 1\n- Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives, whichever is longer, before the first dose of study drug.\n- Need for treatment with high dose steroids\n- Associated hematologic neoplasm requiring immediate antineoplastic therapy\n- Clinically significant cardiac disease\n- 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)\n- Seropositive for human immunodeficiency virus (HIV) 1 or 2, positive for hepatitis B surface antigen, or positive for hepatitis C virus (HCV) antibody\n- History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study\n- Diagnosed with or treated for malignancy other than the disease under study within the prior 3 years before enrollment\n- 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\n- Received hematopoietic growth factor support within 14 days before the first dose of study drug."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Part 1: Dose Optimization - Safety assessments and dose modifications; - PK and pharmacodynamic assessments; - Overall response rate (ORR)","definition_or_measurement_approach":"Safety assessments and dose modifications (safety/tolerability assessments), pharmacokinetic (PK) and pharmacodynamic (PD) assessments, and Overall Response Rate (ORR) as the efficacy measure."}
- {"endpoint_text":"- Part 2 Stage 1: Dose Confirmation - Safety assessments and dose modifications - PK and pharmacodynamic assessments - Overall response rate (ORR)","definition_or_measurement_approach":"Safety assessments and dose modification criteria, PK and PD assessments to confirm dose exposure, and Overall Response Rate (ORR) as efficacy endpoint."}
- {"endpoint_text":"- Part 2 Stage 2: Expansion - Overall response rate (ORR)","definition_or_measurement_approach":"Overall Response Rate (ORR) measured in the expansion cohort at the selected optimal dose."}
Secondary endpoints
- {"endpoint_text":"- Part 1 and Part 2: Incidence of AEs, SAEs, AEs leading to dose modifications, and changes from baseline in laboratory results","definition_or_measurement_approach":"Adverse events (AEs), serious adverse events (SAEs), AEs causing dose changes and laboratory value changes from baseline; standard AE/SAE reporting and laboratory monitoring."}
- {"endpoint_text":"- Part 1 and Part 2: Duration Of Response (DOR), Time to Response (TTR), Progression Free Survival (PFS), Overall Survival (OS), Pure Pathologic Response (PPR)","definition_or_measurement_approach":"Standard oncology time-to-event measures: DOR, TTR, PFS, OS; Pure Pathologic Response (PPR) per protocol-defined criteria."}
- {"endpoint_text":"- Part 1 and Part 2: Changes in the levels of serum tryptase","definition_or_measurement_approach":"Measured serum tryptase concentrations over time (central laboratory assays) to assess pharmacodynamic effect."}
- {"endpoint_text":"- Part 1 and Part 2: Changes in the levels of KIT D816V mutation allele burden in blood and bone marrow","definition_or_measurement_approach":"Quantitative assessment of KIT D816V allele burden in blood and bone marrow samples (mutational analysis) to evaluate molecular response."}
- {"endpoint_text":"- Part 1 and Part 2: Change in pathologic findings in the blood and bone marrow including mast cell infiltration, monocytosis, and eosinophilia","definition_or_measurement_approach":"Histopathologic evaluation of blood and bone marrow for mast cell infiltration, monocytosis, eosinophilia and other pathologic changes."}
- {"endpoint_text":"- Part 1 and Part 2: Plasma concentrations of bezuclastinib","definition_or_measurement_approach":"Pharmacokinetic measurement of plasma concentrations of bezuclastinib."}
- {"endpoint_text":"- Part 1 and Part 2: Change from baseline in PGIS, PGIC, MC-QoL and MAS","definition_or_measurement_approach":"Patient-reported outcomes: changes from baseline in PGIS, PGIC, MC-QoL and MAS instruments per protocol schedule."}
Recruitment
- Planned Sample Size
- 80
- Recruitment Window Months
- 66
- Consent Approach
- Informed consent is obtained using country-specific Subject Information and Informed Consent Forms (main ICFs) and associated documents; pregnant-partner ICFs and data processing consent forms are included. ICF documents are provided in multiple country/language versions (examples present for Spain, Belgium (Dutch/French/German), Italy, Poland, Austria, Norway, France, Netherlands, Germany, and English-language materials). The consent forms and supporting materials are the documented mechanism for obtaining consent; no specific assent process for minors is described in the available documents.
Geography
- Total Number Of Sites
- 21
- Total Number Of Participants
- 60
Spain
- Earliest CTIS Part Ii Submission Date
- 17-05-2024
- Latest Decision Or Authorization Date
- 14-04-2025
- Processing Time Days
- 332
- Number Of Sites
- 3
- Number Of Participants
- 7
Sites
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Hematology
- Contact Person Name
- Olga Salamero Garcia
- Contact Person Email
- osalamero@vhebron.net
- Site Name
- Institut Catala D'oncologia
- Department Name
- Hematology
- Contact Person Name
- Helena Pomares Marin
- Contact Person Email
- hpomares@iconcologia.net
- Site Name
- Hospital Universitario Ramon Y Cajal
- Department Name
- Hematology
- Contact Person Name
- Miguel Piris Villaespesa
- Contact Person Email
- miguel.piris@salud.madrid.org
Belgium
- Earliest CTIS Part Ii Submission Date
- 17-05-2024
- Latest Decision Or Authorization Date
- 11-04-2025
- Processing Time Days
- 329
- Number Of Sites
- 1
- Number Of Participants
- 7
Sites
- Site Name
- Centre hospitalier universitaire de Liege
- Department Name
- Oncology
- Contact Person Name
- Aurelie Jaspers
- Contact Person Email
- aurelie.jaspers@chuliege.be
Poland
- Earliest CTIS Part Ii Submission Date
- 17-05-2024
- Latest Decision Or Authorization Date
- 15-04-2025
- Processing Time Days
- 333
- Number Of Sites
- 1
- Number Of Participants
- 7
Sites
- Site Name
- Uniwersytecki Szpital Kliniczny Nr 1 W Lublinie
- Department Name
- Hematology
- Contact Person Name
- Marek Hus
- Contact Person Email
- marek.hus@umlub.pl
Austria
- Earliest CTIS Part Ii Submission Date
- 17-05-2024
- Latest Decision Or Authorization Date
- 16-04-2025
- Processing Time Days
- 334
- Number Of Sites
- 1
- Number Of Participants
- 6
Sites
- Site Name
- Medical University Of Vienna
- Department Name
- Department of Medicine I Clinical Division of Hematology and Hemostaseology
- Contact Person Name
- Wolfgang Sperr
- Contact Person Email
- wolfgang.r.sperr@meduniwien.ac.at
Norway
- Earliest CTIS Part Ii Submission Date
- 17-05-2024
- Latest Decision Or Authorization Date
- 14-04-2025
- Processing Time Days
- 332
- Number Of Sites
- 1
- Number Of Participants
- 6
Sites
- Site Name
- Oslo University Hospital HF
- Department Name
- Hematology
- Contact Person Name
- Ingunn Dybedal
- Contact Person Email
- idybedal@ous-hf.no
France
- Earliest CTIS Part Ii Submission Date
- 17-05-2024
- Latest Decision Or Authorization Date
- 16-04-2025
- Processing Time Days
- 334
- Number Of Sites
- 3
- Number Of Participants
- 7
Sites
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- Service de Dermatologie
- Contact Person Name
- Cristina Livideanu
- Contact Person Email
- livideanu.c@chu-toulouse.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service Hematologie Adultes
- Contact Person Name
- Olivier Hermine
- Contact Person Email
- olivier.hermine@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Poitiers
- Department Name
- Dermatology and Oncology department
- Contact Person Name
- Ewa Wierzbicka- Hainaut
- Contact Person Email
- ewa.hainaut@chu-poitiers.fr
Italy
- Earliest CTIS Part Ii Submission Date
- 17-05-2024
- Latest Decision Or Authorization Date
- 16-04-2025
- Processing Time Days
- 334
- Number Of Sites
- 6
- Number Of Participants
- 6
Sites
- Site Name
- Fondazione IRCCS Policlinico San Matteo
- Department Name
- UOC Hematology I
- Contact Person Name
- Chiara Elena
- Contact Person Email
- c.elena@smatteo.pv.it
- Site Name
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
- Department Name
- Hematology
- Contact Person Name
- Cristina Papayannidis
- Contact Person Email
- cristina.papayannidis@unibo.it
- Site Name
- Centro Ricerche Cliniche Di Verona S.r.l.
- Department Name
- Hematology
- Contact Person Name
- Massimiliano Bonifacio
- Contact Person Email
- massimiliano.bonifacio@univr.it
- Site Name
- Careggi University Hospital
- Department Name
- Hematology
- Contact Person Name
- Francesco Mannelli
- Contact Person Email
- francesco.mannelli@unifi.it
- Site Name
- Azienda Ospedaliera Universitaria San Giovanni Di Dio E Ruggi d'Aragona
- Department Name
- Division of Allergy and Clinical Immunology
- Contact Person Name
- Massimo Triggiani
- Contact Person Email
- mtriggiani@unisa.it
- Site Name
- Universita' Degli Studi Di Roma La Sapienza
- Department Name
- Hematology
- Contact Person Name
- Massimo Breccia
- Contact Person Email
- breccia@bce.uniroma1.it
Netherlands
- Earliest CTIS Part Ii Submission Date
- 17-05-2024
- Latest Decision Or Authorization Date
- 14-04-2025
- Processing Time Days
- 332
- Number Of Sites
- 1
- Number Of Participants
- 7
Sites
- Site Name
- Universitair Medisch Centrum Groningen
- Department Name
- Hematology
- Contact Person Name
- Saskia Karina Klein
- Contact Person Email
- s.k.klein@umcg.nl
Germany
- Earliest CTIS Part Ii Submission Date
- 17-05-2024
- Latest Decision Or Authorization Date
- 16-04-2025
- Processing Time Days
- 334
- Number Of Sites
- 4
- Number Of Participants
- 7
Sites
- Site Name
- Universitaetsklinikum Aachen AöR
- Department Name
- Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation (Med. Klinik IV)
- Contact Person Name
- Jens Panse
- Contact Person Email
- jpanse@ukaachen.de
- Site Name
- Universitaetsklinikum Mannheim GmbH
- Department Name
- III. Medizinische Klinik, Universität heidelberg Medizinische Fakultät Mannheim
- Contact Person Name
- Juliana Schwaab
- Contact Person Email
- juliana.schwaab@medma.uni-heidelberg.de
- Site Name
- Universitaetsklinikum Schleswig-Holstein AöR
- Department Name
- Hematology and Oncology
- Contact Person Name
- Nikolas von Bubnoff
- Contact Person Email
- Nikolas.vonBubnoff@uksh.de
- Site Name
- Medical Center - University Of Freiburg
- Department Name
- Dept. of Medicine, Hematology, Oncology and Stem Cell Transplantation
- Contact Person Name
- Khalid Shoumariyeh
- Contact Person Email
- khalid.shoumariyeh@uniklinik-freiburg.de
Sponsor
Primary sponsor
- Full Name
- Cogent Biosciences Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Icon Clinical Research Limited
- Name
- Ppd Inc.
- Responsibilities
- Bioanalytics
- Name
- Icon Laboratory Services Inc.
- Responsibilities
- Laboratory - Shipment and Storage of Clinical Samples
- Name
- Advanced Clinical GmbH
Third parties
- {"country":"United States","full_name":"Verasafe LLC","duties_or_roles":"Data Protection Officer and Data Protection Representative services","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Laboratory - Shipment and Storage of Clinical Samples","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Germany","full_name":"Advanced Clinical GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Eclinical Solutions LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Njs Associates Company","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Arup Laboratories Inc.","duties_or_roles":"Laboratory -Serum Tryptase (centrally) and mutational analysis","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"QoL licensing, translations, and system","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"IVRS","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Gene By Gene Ltd.","duties_or_roles":"hereditary alpha tryptasemia (HAT) testing","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Block Clinical Inc.","duties_or_roles":"Patient Concierge Service. Travel and Reimbursement Services","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"Bioanalytics","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"Switzerland","full_name":"United BioSource (Suisse) S.A.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, etc","organisation_type":"Laboratory/Research/Testing facility"}
Investigational products
- Investigational Product Name
- CGT9486
- Active Substance
- 3,4-DIMETHYL-N-(2-PHENYL-1H-PYRROLO[2,3-B]PYRIDIN-5-YL)-1H-PYRAZOLE-5-CARBOXAMIDE
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Maximum Dose
- 300 mg
- Investigational Product Name
- CGT9486
- Active Substance
- 3,4-DIMETHYL-N-(2-PHENYL-1H-PYRROLO[2,3-B]PYRIDIN-5-YL)-1H-PYRAZOLE-5-CARBOXAMIDE
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Maximum Dose
- 400 mg
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