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
- Conditions
- Advanced Systemic Mastocytosis (AdvSM)MedDRA version: 20.0Level: LLTClassification code 10056453Term: Aggressive systemic mastocytosisSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-001010-10-ES
- Lead Sponsor
- Cogent Biosciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 140
1. Diagnosed with 1 of the following advanced mastocytosis diagnoses based on WHO diagnostic criteria (Appendix A of the protocol):
• ASM
• SM-AHN (The associated hematologic neoplasm must be myeloid, with the following diagnoses excluded from study entry: acute myeloid leukemia, myelodysplastic syndrome that is very high- or high-risk as defined by the Revised International Prognostic Scoring System for Myelodysplastic Syndromes, Philadelphia Chromosome positive malignancies, and patients with =10% blast cells in bone marrow)
• MCL
2. Measurable disease according to modified IWG-MRT-ECNM consensus eligibility and response criteria for CI (Appendix A of the protocol)
NOTE: Diagnosis and evidence of measurable disease must be evaluable according to response criteria and confirmed by the Eligibility Committee prior to the first dose of study drug.
NOTE: Approximately 20 patients with AdvSM may be enrolled in Part 2 who are inevaluable per modified IWG-MRT-ECNM response criteria based on lack of evaluable organ damage per modified IWG-MRT-ECNM.
3. Able to provide written informed consent
4. Able and willing to commit to study assessments and visit schedule
5. Age =18 years of age
6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 3
7. Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits specified below:
a. Absolute neutrophil count >500/µL (subjects enrolled in Part 1 only)
b. Platelet count =50,000/µL for 2 weeks prior to the first dose of study drug
Note: Platelet transfusion to meet enrollment criteria is not allowed.
c. AST and ALT =2.5× upper limit of normal (ULN) or =5×ULN if there is liver involvement by AdvSM
d. Direct bilirubin =1.5×ULN; if related to AdvSM may be =3×ULN
e. Calculated creatinine clearance (Cockcroft-Gault) >40 mL/min
f. Serum tryptase =20 ng/mL
8. For women of childbearing potential (defined as physiologically and anatomically capable of becoming pregnant), confirmation of a negative serum pregnancy test and agreement to the use of a highly effective method of contraception or at least 2 effective methods at the same time during the study treatment period and for up to 6 months after the last dose of CGT9486; for male subjects, agreement to use effective barrier contraception (ie, condoms) during the study treatment period and for up to 6 months after the last dose of CGT9486
9. Able to swallow pills
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70
1. Persistent toxicity from previous therapy for AdvSM that has not resolved to = Grade 1.
2. Patients presenting with an associated hematologic neoplasm who require immediate antineoplastic therapy.
3. Clinically significant cardiac disease, defined by any of the following:
g. Clinically significant cardiac arrhythmias, and/or the need for anti-arrhythmic therapy (excluding beta blockers or digoxin). (Subjects with controlled atrial fibrillation are not excluded.)
h. Congenital long QT syndrome or concomitant medications known to prolong the QT interval except those required for infections that carry a low risk of QTc prolongation.
i. A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTcF interval >480 ms).
j. History of clinically significant cardiac disease or congestive heart failure > New York Heart Association Class II. (Patients must not have unstable angina [anginal symptoms at rest] or new-onset angina within the last 3 months or myocardial infarction within the past 6 months.)
k. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 6 months before study drug initiation (except for adequately treated catheter-related venous thrombosis occurring more than 1 month before the first dose of study drug).
4. Known positivity for the FIP1L1 PDGFRA fusion (except for patients who demonstrated relapse or disease progression on prior imatinib therapy). Patients with eosinophilia (eosinophil count >1.5 × 109/L) who do not have a detectable KIT D816V mutation must provide documentation of the lack of a PDGFRA fusion mutation by fluorescence in situ hybridization or polymerase chain reaction prior to enrollment.
5. Any other concurrent severe known disease or concurrent severe and/or uncontrolled medical condition (eg, uncontrolled diabetes or active uncontrolled infection), either of which could compromise participation in the study.
6. Seropositive for human immunodeficiency virus (HIV) 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody. (Subjects with a positive HCV antibody may be eligible if HCV RNA is undetectable on a quantitative HCV RNA assay, following discussion with the Medical Monitor.)
7. Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening.
NOTE: Oral antibiotics for a controlled infection are permitted with Medical Monitor approval. Patients on antimicrobial, antifungal, or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met.
8. History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study.
9. Diagnosed with or treated for malignancy other than the disease under study within the prior 3 years before enrollment, or expected to need treatment for an active malignancy. (The following are allowed within 3 years of study enrollment if the subject has received definitive local therapy [eg, surgical excision, external beam radiation, or other local therapy with curative intent]: non-melanoma skin cancers, localized prostate cancer, or carcinoma in situ.)
10. Any condition that could hamper compliance with the study protocol in the judgment of the Investigator.
11. Pregnant or currently breastfeeding.
12. Received any cytoreductive therapy (including midostaurin and other tyrosi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method