Phase 1 Trial of ASTX727 in Subjects With Lower-risk Myelodysplastic Syndromes

Study Overview
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Brief Summary
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To investigate the tolerability and safety of ASTX727 in Japanese subjects with lower-risk MDS.

Official Title
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A Multicenter, Open-label, Dose-escalation, Phase 1 Trial to Investigate the Tolerability and Safety of ASTX727 in Subjects With Lower-risk Myelodysplastic Syndromes

Conditions
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Lower-risk Myelodysplastic

Intervention / Treatment
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* Drug: ASTX727
* Drug: ASTX727
* Drug: ASTX727
* Drug: ASTX727
* Drug: ASTX727


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subjects with a definitive diagnosis of MDS and classified as low or Intermediate-1 risk by the International Prognostic Scoring System (IPSS) risk category Subjects meeting at least one of the disease-related criteria for Red blood cell (RBC) transfusion, hemoglobin (Hb) ,Absolute neutrophil count,Platelet count within 8 weeks prior to initial administration of IMP Subjects with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 Adequate hepatic and renal function Sexually active men with reproductive capacity (except those who have undergone bilateral orchidectomy) must agree to use 2 effective contraceptive measures or remain abstinent during the trial and for 3 months after final administration of IMP. Sexually active women of child-bearing potential must agree to use 2 effective contraceptive measures or remain abstinent during the trial and for 6 months after final administration of IMP. Subjects who have provided written informed consent using the form approved by the institutional review board Key Exclusion Criteria: Subjects who have received cytokine therapy, immunosuppressant therapy, or chemotherapy within 4 weeks prior to initial investigational medicinal product (IMP) administration Subjects who have received any other IMP or privately-imported medicine within 2 weeks prior to initial IMP administration Subjects with deletion 5q who are to be treated with lenalidomide Subjects with current or previous bone marrow blast percentage of >10% Subjects with a diagnosis of chronic myelomonocytic leukemia Subjects with heart disease of New York Heart Association (NYHA) Functional Class 3 or 4 Subjects with an uncontrolled systemic disease or active uncontrolled infection Subjects with diabetes mellitus requiring medical treatment Subjects with a life-threatening illness, medical condition or multiple organ dysfunction, or other reason, including laboratory abnormalities, which in the investigator's or subinvestigator's opinion could compromise the subject's safety, interfere with the absorption or metabolism of IMP, or compromise the integrity of the trial outcome Subjects with prior malignancy Subjects who test positive for human immunodeficiency virus antibody, hepatitis B virus DNA, or hepatitis C virus antibody Subjects with a history of surgical gastrectomy Subjects with previous organ transplantation Subjects with a ≥Grade 2 AE attributable to treatment of underlying disease, excluding the AEs Subjects who have undergone an invasive and extensive operation within 2 weeks prior to initial IMP administration Subjects with hypersensitivity to the IMPs or their excipients Subjects with known significant mental illness or other condition, such as active alcohol or other substance abuse or addiction, that in the opinion of the investigator or subinvestigator predisposes the subject to high risk of noncompliance with the protocol Female subjects who are pregnant, breast-feeding, or who test positive for pregnancy at screening

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10-Day Schedule<br>10-Day Schedule Investigational Medicinal Products (IMP) will be administered for 10 days in total per 4 weeks, i.e. a 28-day cycle. | Drug: ASTX727<br>* oral decitabine 5mg + cedazuridine<br>|
| Experimental: 5-Day Schedule A<br>5-Day Schedule A IMP will be administered for 5 days in total per 4 weeks, i.e. a 28-day cycle. | Drug: ASTX727<br>* oral decitabine 5mg + cedazuridine<br>|
| Experimental: 5-Day Schedule B<br>5-Day Schedule B IMP will be administered for 5 days in total per 4 weeks, i.e. a 28-day cycle. | Drug: ASTX727<br>* oral decitabine 10mg + cedazuridine<br>|
| Experimental: 5-Day Schedule C<br>5-Day Schedule C IMP will be administered for 5 days in total per 4 weeks, i.e. a 28-day cycle. | Drug: ASTX727<br>* oral decitabine 20mg + cedazuridine<br>|
| Experimental: 7-Day Schedule<br>7-Day Schedule IMP will be administered for 7 days in total per 4 weeks, i.e. a 28-day cycle. | Drug: ASTX727<br>* oral decitabine 10mg + cedazuridine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity |  | 28days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC) | pharmacokinetics parameter | Pre-dose, 15 min, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h after dosing | 
| Maximum plasma concentration (Cmax) | pharmacokinetics parameter | Pre-dose, 15 min, 30 min, 60 min, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, 24 h after dosing |