A Study to Evaluating the Pharmacokinetics, Safety, and Efficacy of ATG 016 Monotherapy in IPSS-R Intermediate Risk and Above Myelodysplastic Syndrome (MDS)

Study Overview
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Brief Summary
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This is a Phase Ⅰ/II, Open-label Study to Investigate the Pharmacokinetics, Safety, and Efficacyof ATG 016 Monotherapy in IPSS-R Intermediate Risk and above Myelodysplastic Syndrome (MDS) Patients after Failure of Hypomethylating Agent (HMA)-based Therapy.

Detailed Description
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This is a Phase Ⅰ/II, Open-label Study to Investigate the Pharmacokinetics, Safety, and Efficacyof ATG 016 Monotherapy in IPSS-R Intermediate Risk and above Myelodysplastic Syndrome (MDS) Patients after Failure of Hypomethylating Agent (HMA)-based Therapy. In Phase I: approximately 15 to 21 subjects and Phase II: approximately 44 subjects; approximately 59 to 65 subjects will be enrolled totally in this study.

Official Title
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A Phase I/II, Open-label Study to Investigate the Pharmacokinetics, Safety, and Efficacyof ATG 016 Monotherapy in IPSS-R Intermediate Risk and Above Myelodysplastic Syndrome (MDS) Patients After Failure of Hypomethylating Agent (HMA)-Based Therapy

Conditions
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Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: ATG-016


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted. ≥18 years of age, males or females. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. A life expectancy longer than 3 months in the opinion of the investigator at the screening. Male subjects (Including those who have received vasectomy) must agree to use condoms during sex with a woman of childbearing age and have no plans to impregnate the woman throughout the study and for 3 months following the last dose after the date of signing the ICF. Exclusion Criteria: History of central nervous system (CNS) involvement. Toxicity from prior antitumor therapy did not return to Grade 1 or baseline (Except for alopecia, neutropenia, anemia, and thrombocytopenia. For neutrophils, hemoglobin, and platelets, please follow Exclusion Criteria No. 5). History of human immunodeficiency virus (HIV) infection. History of severe bleeding disorder, such as hemophilia A, hemophilia B, and vascular hemophilia. History of allogeneic stem-cell transplantation. Serious psychiatric or medical conditions that, in the opinion of the investigator, could interfere with treatment, compliance, or the ability to give consent. Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATG-016<br>5 mg QD×Days 1-5/week will be the initial dose of this study. | Drug: ATG-016<br>* 59 patients enrolled will be treated with ATG-016, orally, each 4 week (28-day) a cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD in Phase I | MTD will be evaluated using the NCI-CTCAE, Version 5.0 | 16 months | 
| RP2D in Phase I | RP2D will be determined under the guidance of the SRC. | 16 months | 
| AEs/SAEs | Toxicity will be graded according to the NCI CTCAE, Version 5.0. | 25 months | 
| ORR in Phase II | Based on 2006 IWG Response Criteria, evaluated by IRC: ORR (CR + PR + mCR) | 25 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) in Phase I/II | DCR (CR + PR + mCR + HI + SD) | 12 months | 
| Duration of Response (DOR) in Phase I/II | To evaluate duration of response | 12 months | 
| Progression-Free Survival (PFS) in Phase I/II | To evaluate progression-free survival | 12 months | 
| Overall Survival (OS) | The estimates of Kaplan-Meier | 12 months |