A Phase I/II, Multicenter, Open-Label, Nonrandomized Study to Evaluate the Tolerability and Safety of ASTX660 and the Efficacy at the Recommended Dose of ASTX660 in Patients With Relapsed or Refractory T-Cell Lymphoma
Phase: PHASE1
Conditions: Relapsed or Refractory Peripheral T-cell Lymphoma(PTCL),Cutaneous T-cell Lymphoma(CTCL),Adult T-cell Leukemia/Lymphoma(ATLL)
Sponsor: Otsuka Pharmaceutical Co., Ltd.

 
 
CLINICAL STUDY PROTOCOL 
 
 
 
A Phase 1/2, Multicenter, Open-label, Uncontrolled Trial to Evaluate the Tolerability 
and Safety of ASTX660 and the Efficacy at the Recommended Dose in Patients with 
Relapsed/Refractory T-cell Lymphoma 
 
 
 
 
NCT Number: NCT04362007 
Protocol No. 401-102-00001  
Version Date: 5 Dec 2022  

Protocol 401-102-00001 
 
1 
Confidential - Proprietary Information 
 
Amendment 4 Approval: 5 Dec 2022 
Otsuka Pharmaceutical Co., Ltd. 
 
Investigational Medicinal Product 
 
ASTX660 
 
CLINICAL PROTOCOL 
 
A Phase 1/2, Multicenter, Open-label, Uncontrolled Trial to Evaluate the Tolerability and 
Safety of ASTX660 and the Efficacy at the Recommended Dose in Patients with 
Relapsed/Refractory T-cell Lymphoma 
 
A Phase 1/2 Trial of ASTX660 in Patients with Relapsed/Refractory T-cell Lymphoma 
 
Protocol No. 401-102-00001 
 
 
 
 
CONFIDENTIAL ⎯ PROPRIETARY INFORMATION 
 
Clinical Development Phase: 
1/2 
Sponsor: 
Otsuka Pharmaceutical Co., Ltd. 
Immediately Reportable Event  
  
 
 
 
Amendment 4 Approval: 
5 Dec 2022 
Amendment 3 Approval: 
28 Jan 2021 
Amendment 2 Approval: 
15 Sep 2020 
Amendment 1 Approval: 
28 Feb 2020 
Approval: 
25 Dec 2019 
 
 
 

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Table of Contents 
Table of Contents ........................................................................................... 2 
List of In-text Tables ..................................................................................... 8 
List of In-text Figures .................................................................................... 9 
1 
Protocol Summary .............................................................................. 10 
1.1 
Synopsis............................................................................................................ 10 
1.2 
Schema ............................................................................................................. 20 
1.3 
Schedule of Assessments.................................................................................. 21 
1.3.1 
Screening Period ............................................................................................ 33 
1.3.2 
Treatment and Observation Period ................................................................ 35 
1.3.3 
Withdrawal Examination ............................................................................... 35 
1.3.4 
Follow-up Period ........................................................................................... 36 
1.3.5 
Investigation of Survival Status ..................................................................... 36 
2 
Introduction ........................................................................................ 36 
2.1 
Trial Rationale .................................................................................................. 39 
2.2 
Background ...................................................................................................... 39 
2.3 
Known and Potential Risks and Benefits ......................................................... 40 
3 
Objectives and Endpoints .................................................................. 41 
4 
Trial Design ......................................................................................... 43 
4.1 
Type/Design of Trial ........................................................................................ 43 
4.2 
Scientific Rationale for Trial Design ................................................................ 45 
4.2.1 
Phase 1 (Dose Escalation Part) ...................................................................... 45 
4.2.2 
Phase 1 (ATLL Expansion Part) .................................................................... 47 
4.2.3 
Phase 2 ........................................................................................................... 47 
4.3 
Dosing Rationale .............................................................................................. 48 
4.4 
End of Trial Definition ..................................................................................... 49 
5 
Trial Population .................................................................................. 49 
 
 .................................................................... 49 
5.2 
Eligibility Criteria ............................................................................................. 49 
5.2.1 
Inclusion Criteria ........................................................................................... 49 
5.2.2 
Exclusion Criteria .......................................................................................... 52 

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5.4 
Screen Failures ................................................................................................. 55 
6 
Trial Treatments ................................................................................. 56 
6.1 
Trial Treatments Administered ........................................................................ 56 
6.1.1 
Dose and Regimen and Treatment Duration ................................................. 56 
6.1.2 
Treatment Interruption Criteria ...................................................................... 56 
6.1.3 
Criteria for Starting the Next Cycle ............................................................... 57 
6.1.4 
Medical Devices ............................................................................................ 58 
6.2 
Management of Investigational Medicinal Product ......................................... 58 
6.2.1 
Packaging and Labeling ................................................................................. 58 
6.2.2 
Storage ........................................................................................................... 58 
6.2.3 
Accountability ................................................................................................ 58 
6.2.4 
Returns and Destruction ................................................................................ 59 
6.2.5 
Reporting of Product Quality Complaints ..................................................... 59 
6.2.5.1 
Eliciting and Reporting Product Quality Complaints ................................ 59 
6.2.5.2 
Information Required for Reporting Product Quality Complaints ............ 59 
6.2.5.3 
Return Process for Product Quality Complaints ........................................ 60 
6.2.5.4 
Assessment/Evaluation .............................................................................. 60 
6.3 
Measures to Minimize/Avoid Bias ................................................................... 60 
6.4 
Subject Compliance .......................................................................................... 60 
6.5 
Prior Medications and Concomitant Medications or Therapies ....................... 60 
6.5.1 
Prohibited Medications .................................................................................. 61 
6.5.2 
Permitted Supportive and Preventive Therapies ............................................ 61 
6.5.3 
Rescue Medications ....................................................................................... 62 
6.6 
Intervention After the End of the Trial ............................................................. 62 
7 
Stopping Rules, Withdrawal Criteria, and Procedures .................. 62 
7.1 
Entire Trial or Treatment .................................................................................. 62 
7.2 
Individual Site .................................................................................................. 62 
7.3 
Individual Subject Discontinuation .................................................................. 62 

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7.3.1 
Treatment Interruption ................................................................................... 62 
7.3.2 
Treatment Discontinuation ............................................................................ 62 
7.3.3 
Documenting Reasons for Treatment Interruption or Discontinuation ......... 63 
7.3.4 
Withdrawal of Consent .................................................................................. 64 
7.3.5 
Procedures to Encourage Continued Trial Participation ............................... 65 
7.4 
Definition of Subjects Lost to Follow-up ......................................................... 65 
8 
Trial Procedures ................................................................................. 65 
8.1 
Efficacy Assessments ....................................................................................... 66 
8.1.1 
Response ........................................................................................................ 66 
8.1.1.1 
Peripheral T-cell Lymphoma ..................................................................... 66 
8.1.1.1.1 
Assessment of Diagnostic Images .......................................................... 66 
8.1.1.1.2 
Central Image Review Committee ......................................................... 66 
8.1.1.1.3 
Definition of Measurable and Evaluable Lesions .................................. 66 
8.1.1.1.4 
Efficacy Assessment Criteria ................................................................. 67 
8.1.1.2 
Cutaneous T-cell Lymphoma ..................................................................... 70 
8.1.1.2.1 
Assessment of Skin Lesions ................................................................... 70 
8.1.1.2.2 
Efficacy Assessment Criteria ................................................................. 71 
8.1.1.3 
Adult T-cell Leukemia/Lymphoma............................................................ 71 
8.1.1.3.1 
Assessment of Diagnostic Images .......................................................... 71 
8.1.1.3.2 
Definition of Measurable and Evaluable Lesions .................................. 71 
8.1.1.3.3 
Efficacy Assessment Criteria ................................................................. 72 
8.1.2 
Best Overall Response ................................................................................... 73 
8.2 
Pharmacokinetic Assessments .......................................................................... 74 
8.2.1 
Pharmacokinetic Plasma Samples ................................................................. 74 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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8.7 
Safety Assessments .......................................................................................... 79 
8.7.1 
Dose Limiting Toxicity .................................................................................. 79 
8.7.2 
Clinical Laboratory Assessments .................................................................. 79 
8.7.3 
Physical Examination .................................................................................... 80 
8.7.4 
Vital Signs ..................................................................................................... 80 
8.7.5 
12-Lead Electrocardiogram (Local) .............................................................. 80 
 
 
8.7.7 
Other Safety Variables ................................................................................... 82 
8.7.7.1 
Body Weight .............................................................................................. 82 
8.7.7.2 
Eastern Cooperative Oncology Group Performance Status ....................... 82 
8.7.7.3 
Echocardiogram ......................................................................................... 82 
8.7.7.4 
Lung Field Assessment by PET-CT or CT Scans ...................................... 82 
8.7.7.5 
Chest X-Ray ............................................................................................... 82 
8.8 
Adverse Events ................................................................................................. 83 
8.8.1 
Definitions ..................................................................................................... 83 
8.8.2 
Eliciting and Reporting Adverse Events ........................................................ 85 
8.8.3 
Immediately Reportable Events ..................................................................... 85 
8.8.4 
Medical Device Incidents (Including Malfunctions) ..................................... 85 
8.8.5 
Adverse Events of Special Interest ................................................................ 86 
8.8.6 
Potential Serious Hepatotoxicity ................................................................... 86 
8.8.7 
Procedure for Breaking the Blind .................................................................. 86 
8.8.8 
Follow-up of Adverse Events ........................................................................ 86 
8.8.8.1 
Follow-up of Nonserious Adverse Events ................................................. 86 
8.8.8.2 
Follow-up of Immediately Reportable Events ........................................... 86 
8.8.8.3 
Follow-up and Reporting of Immediately Reportable Events 
Occurring After the Last Day of the Follow-up Period ............................. 87 
8.9 
Treatment of Overdose ..................................................................................... 87 
8.10 
Subject Assessment Recording ........................................................................ 87 
8.11 
Other Assessments ........................................................................................... 88 

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8.11.1 
Efficacy and Safety Data Review Committee ............................................... 88 
8.11.2 
Central Pathological Diagnosis Committee ................................................... 88 
9 
Statistical Considerations .................................................................. 88 
9.1 
Sample Size ...................................................................................................... 88 
9.2 
Datasets for Analysis ........................................................................................ 88 
9.3 
Handling of Missing Data for Primary and Secondary Endpoint Analysis ..... 89 
9.4 
Statistical Analyses........................................................................................... 89 
9.4.1 
Efficacy Analyses .......................................................................................... 89 
9.4.1.1 
Primary Efficacy Endpoint Analysis .......................................................... 89 
9.4.1.2 
Key Secondary Efficacy Endpoint Analysis .............................................. 89 
9.4.1.3 
Secondary Efficacy Endpoint Analysis ...................................................... 89 
9.4.1.4 
Control of Experiment-wise Type 1 Error ................................................. 90 
9.4.1.5 
Other Efficacy Endpoint Analysis ............................................................. 90 
9.4.2 
Safety Analysis .............................................................................................. 90 
9.4.2.1 
Adverse Events .......................................................................................... 91 
9.4.2.2 
Clinical Laboratory Data ............................................................................ 91 
9.4.2.3 
Vital Signs Data ......................................................................................... 91 
9.4.2.4 
Electrocardiogram Data ............................................................................. 91 
9.4.2.5 
Other Safety Data ....................................................................................... 92 
9.4.3 
Other Analyses ............................................................................................... 92 
9.4.3.1 
Analysis of Demographic and Baseline Characteristics ............................ 92 
9.4.3.2 
Pharmacokinetic Analysis .......................................................................... 92 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.5 
Interim Analysis ............................................................................................... 94 
9.5.1 
Data Monitoring Committee .......................................................................... 94 
10 
Supporting Documentation and Operational Considerations ....... 95 

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10.1 
Appendix 1: Regulatory, Ethical, and Trial Oversight Considerations ............ 95 
10.1.1 
Ethics and Responsibility .............................................................................. 95 
10.1.2 
Informed Consent .......................................................................................... 95 
10.1.3 
Confidentiality ............................................................................................... 96 
10.1.4 
Quality Control and Quality Assurance ......................................................... 96 
10.1.4.1 
Monitoring ................................................................................................. 97 
10.1.4.2 
Auditing ..................................................................................................... 97 
10.1.5 
Protocol Deviations ....................................................................................... 97 
10.1.6 
Records Management .................................................................................... 98 
10.1.6.1 
Source Documents ..................................................................................... 98 
10.1.6.2 
Data Collection .......................................................................................... 98 
10.1.6.3 
File Management at the Trial Site .............................................................. 99 
10.1.6.4 
Records Retention at the Trial Site ............................................................ 99 
10.1.6.5 
Publication Authorship Requirements ..................................................... 100 
10.2 
Appendix 2: Clinical Laboratory Tests .......................................................... 101 
10.3 
Appendix 3: Contraceptive Guidance and Collection of Pregnancy 
Information ..................................................................................................... 102 
10.4 
Appendix 4: Abbreviations ............................................................................ 104 
10.5 
Appendix 5: Protocol Amendments ............................................................... 107 
10.5.1 
Protocol Amendment(s)/Administrative Change(s) .................................... 108 
11 
References ..........................................................................................122 
 
 
 
 

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List of In-text Tables 
Table 1.3-1 
Schedule of Assessments, Phase 1 (Dose Escalation Part), 
Cycles 1 and 2 ............................................................................... 21 
Table 1.3-2 
Schedule of Assessments, Phase 1 (Dose Escalation Part), 
From Cycle 3 Onward, Withdrawal Examination, Follow-up 
Period, Investigation of Survival Status ........................................ 24 
Table 1.3-3 
Schedule of Assessments, Phase 1 (ATLL Expansion Part) ......... 27 
Table 1.3-4 
Schedule of Assessments, Phase 2 ................................................ 30 
Table 1.3-5 
Disease Stage (Lugano Classification) ......................................... 33 
Table 1.3-6 
Disease Stage (TNMB Classification of Mycosis 
Fungoides/Sézary Syndrome) ....................................................... 34 
Table 1.3-7 
International Prognostic Index (IPI) ............................................. 35 
Table 3-1 
Trial Objectives and Endpoints ..................................................... 41 
Table 4.1-1 
Dose Levels in Phase 1 (Dose Escalation Part) ............................ 43 
Table 4.1-2 
Dose Escalation Plan for the Dose Escalation Part ....................... 44 
Table 8.1.1.1.4-1 
Lugano Response Criteria for Non-Hodgkin’s Lymphoma 
(2014) by the IWG ........................................................................ 68 
Table 8.1.1.2.1-1 
mSWAT Percentage Total Body Surface Area of Body 
Regions ......................................................................................... 70 
Table 8.1.1.2.2-1 
Assessment of Overall Skin Lesions Using mSWAT................... 71 
Table 8.1.1.3.3-1 
JCOG Response Criteria for Adult T-Cell Leukemia-
Lymphoma (2009) ........................................................................ 73 
Table 8.2.1-1 
Time Points of Blood Sampling for Pharmacokinetics and 
Allowable Windows (Phase 1 [Dose Escalation Part and 
ATLL Expansion Part]) ................................................................ 74 
Table 8.2.1-2 
Time Points of Blood Sampling for Pharmacokinetics and 
Allowable Windows (Phase 2) ...................................................... 75 
 
 
Table 8.7.7.2-1 
ECOG PS ...................................................................................... 82 
Table 10.2-1 
Clinical Laboratory Assessments ................................................ 101 
 
 

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List of In-text Figures 
Figure 1.2-1 
Trial Design Schematic ................................................................. 20 

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1 
Protocol Summary 
1.1 
Synopsis 
Name of Sponsor: 
Otsuka Pharmaceutical Co., Ltd. 
Name of Investigational Medicinal Product: 
ASTX660 
Protocol No.: 
401-102-00001 
Protocol Title: 
A phase 1/2, multicenter, open-label, uncontrolled trial to evaluate the tolerability and 
safety of ASTX660 and the efficacy at the recommended dose in patients with 
relapsed/refractory T-cell lymphoma 
Protocol Lay Person Short Title: 
A phase 1/2 trial of ASTX660 in patients with relapsed/refractory T-cell lymphoma 
Clinical Phase/Trial Type: 
Phase 1/2 trial/clinical pharmacology trial 
Treatment/Indication: 
Patients with relapsed/refractory peripheral T-cell lymphoma (r/r PTCL), patients with 
relapsed/refractory cutaneous T-cell lymphoma (r/r CTCL), and patients with 
relapsed/refractory adult T-cell leukemia/lymphoma (r/r ATLL) 
Objectives and Endpoints: 
Primary Objectives: 
Phase 1 (dose escalation part): To evaluate the tolerability and safety of ASTX660 in 
patients with r/r PTCL and patients with r/r CTCL and determine the recommended dose 
(RD) for phase 2 
Phase 1 (ATLL expansion part): To evaluate the safety of ASTX660 at the RD in patients 
with r/r ATLL 
Phase 2: To evaluate the efficacy of ASTX660 at the RD in patients with r/r PTCL 

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Secondary Objectives: 
Phase 1 (dose escalation and ATLL expansion parts): 
• To evaluate the pharmacokinetics (PK) of ASTX660 
• To evaluate the efficacy of ASTX660 
Phase 2: 
• To evaluate the safety of ASTX660 
• To evaluate the PK of ASTX660 
 
 
 
 
 
Primary Endpoints: 
Phase 1 (dose escalation part): Dose-limiting toxicity (DLT) and safety (adverse events 
[AEs], clinical laboratory values, vital signs, body weight, Eastern Cooperative Oncology 
Group [ECOG] Performance Status [PS], 12-lead ECGs, and left ventricular ejection 
fraction (LVEF) 
Phase 1 (ATLL expansion part): Safety (AEs, clinical laboratory values, vital signs, body 
weight, ECOG PS, 12-lead ECGs, and LVEF) 
Phase 2: Overall response rate (ORR) as assessed by the Central Efficacy Evaluation 
Committee based on Lugano response criteria for non-Hodgkin lymphoma (2014) 
proposed by the International Working Group (IWG). 
Secondary Endpoints: 
Phase 1 (dose escalation and ATLL expansion parts): 
[Pharmacokinetic endpoints] 
• Plasma ASTX660 concentrations over time and PK parameters. Dose 
proportionality will only be assessed in the dose escalation part. 
[Efficacy endpoints] 
• ORR as assessed by the investigator or subinvestigator 
• Duration of response (DOR) 
• Progression free survival (PFS) 
• Overall survival (OS) 
• Time to response (TTR) 

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• Time to progression (TTP) 
• Proportion of subjects who proceed to transplantation 
Phase 2: 
[Efficacy endpoints] 
• DOR 
• PFS 
• OS 
• TTR 
• TTP 
• Proportion of subjects who proceed to transplantation 
• ORR as assessed by the investigator or subinvestigator 
[Safety endpoints] 
AEs, clinical laboratory values, vital signs, body weight, ECOG PS, 12-lead ECGs, and 
LVEF 
[Pharmacokinetic endpoints] 
• Plasma ASTX660 concentrations over time 
 
 
 
 
Trial Design: 
Multicenter, open-label, uncontrolled 
Trial Population: 
The following male or female patients, 20 years of age or older, will be enrolled: a 
maximum of 18 patients with r/r PTCL or r/r CTCL combined (3 to 6 subjects/cohort) in 
phase 1 (dose escalation part); 6 to 10 patients with r/r ATLL in phase 1 (ATLL 
expansion part); and 33 patients with r/r PTCL as efficacy-evaluable subjects in phase 2. 

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Inclusion/Exclusion Criteria: 
Inclusion Criteria: 
1) Patients 20 years of age or older at the time of informed consent and who provide 
written consent to participate in the trial using the informed consent form 
approved by the institutional review board. 
2) Patients with T-cell lymphoma with a histopathologic diagnosis of any of the 
following based on the World Health Organization (WHO) Classification (2017): 
<Peripheral T-cell lymphoma>: Phase 1 (dose escalation part) and phase 2 
For the purpose of this trial, peripheral T-cell lymphoma is defined as mature T- or 
natural killer (NK) cell neoplasms listed in the WHO Classification that fall under 
any of the following subtypes (for phase 2, submission of specimens is required for 
central pathological diagnosis): 
• Extranodal NK/T-cell lymphoma, nasal type 
• Enteropathy-associated T-cell lymphoma 
• Monomorphic epitheliotropic intestinal T-cell lymphoma 
• Hepatosplenic T-cell lymphoma 
• Subcutaneous panniculitis-like T-cell lymphoma 
• Peripheral T-cell lymphoma, not otherwise specified (NOS) 
• Angioimmunoblastic T-cell lymphoma 
• Follicular T-cell lymphoma 
• Nodal peripheral T-cell lymphoma with T-follicular helper cells phenotype 
• Anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK) positive 
• Anaplastic large cell lymphoma, ALK negative 
<Cutaneous T-cell lymphoma>: Phase 1 (dose escalation part) 
For the purpose of this trial, cutaneous T-cell lymphoma is defined as mature T- or 
NK cell neoplasms listed in the WHO Classification that fall under any of the 
following subtypes: 
• Mycosis fungoides 
• Sézary syndrome 
• Primary cutaneous CD30 positive T-cell lymphoproliferative disorders 
• Primary cutaneous peripheral T-cell lymphoma, rare subtypes 
<Adult T-cell leukemia/lymphoma>: Phase 1 (ATLL expansion part) 
Patients with a diagnosis of ATLL classified into acute, lymphoma, or chronic type 
with unfavorable prognostic factors who are positive for serum anti-human T-cell 
leukemia virus type 1 antibody. 

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3) Patients who previously received systemic antineoplastics to treat the primary 
disease as indicated below. 
<Peripheral T-cell lymphoma>: Phase 1 (dose escalation part) 
Relapsed or refractory patients who previously received at least 1 regimen of 
antineoplastics (oral corticosteroid monotherapy is not included in this category). 
Patients with CD30-positive anaplastic large cell lymphoma must have a history of 
treatment with brentuximab vedotin.a 
<Peripheral T-cell lymphoma>: Phase 2 
Relapsed or refractory patients who previously received at least 2 regimens of 
antineoplastics (oral corticosteroid monotherapy is not included in this category). 
Patients with CD30-positive anaplastic large cell lymphoma must have a history of 
treatment with brentuximab vedotin.a 
<Cutaneous T-cell lymphoma> 
Relapsed or refractory patients who previously received at least 1 regimen of 
systemic antineoplastics (oral corticosteroid monotherapy is not included in this 
category). Patients with mycosis fungoides or Sézary syndrome must have a history 
of treatment with mogamulizumab.a 
<Adult T-cell leukemia/lymphoma> 
Relapsed or refractory patients who previously received at least 1 regimen of 
antineoplastics. Patients who are positive for CCR4 must have a history of treatment 
with mogamulizumab.a 
aThis criterion does not apply to patients for whom treatment has been judged to be inappropriate or 
those who refused to receive the treatment. 
4) Patients with the following lesion(s) at screening: 
<Peripheral T-cell lymphoma>: Phase 1 (dose escalation part) 
Swollen lymph nodes or extranodal lesions identified by positron emission 
tomography-computed tomography (PET-CT) or computed tomography (CT) during 
screening or within 28 days prior to the first dose of trial treatment. 
<Peripheral T-cell lymphoma>: Phase 2 
Swollen lymph nodes or extranodal lesions measurable in 2 perpendicular diameters 
by CT scan during screening or within 28 days prior to the first dose of trial 
treatment, with the longest diameter exceeding 1.5 cm (swollen lymph nodes) or 
1.0 cm (extranodal lesions). 

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<Cutaneous T-cell lymphoma> 
Lesions that can be considered skin lesions during screening. 
<Adult T-cell leukemia/lymphoma> 
At least one of measurable lesions identified by CT scan during screening or within 
28 days prior to the first dose of trial treatment or skin lesions identified during 
screening. 
5) Patients with an ECOG PS score of 0 or 1. For phase 2, patients with a PS score 
of 2 are eligible to be enrolled in the trial only if their physical activities are 
restricted by symptoms associated with the primary disease such as accumulation 
of pleural or ascitic fluid. 
6) Patients with acceptable organ function as indicated below. 
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
≤ 2.0 × institutional upper limit of normal (ULN) (≤ 3.0 × institutional ULN for 
subjects with hepatic involvement). 
• Total bilirubin ≤ 1.5 × institutional ULN. 
• Absolute neutrophil count (ANC) ≥ 1,000/mm3 (≥ 750/mm3 for subjects with 
bone marrow involvement) (Administration of granulocyte colony-stimulating 
factor [G-CSF] within 14 days prior to the test is not allowed). 
• Platelet count ≥ 50,000/mm3 (≥ 25,000/mm3 for subjects with bone marrow 
involvement) (Platelet transfusion within 14 days prior to the test is not allowed). 
• Serum creatinine ≤ 1.5 × institutional ULN or creatinine clearance (calculated by 
Cockcroft & Gault formula) ≥ 50 mL/min. 
• Amylase and lipase ≤ 1.0 × institutional ULN. 
7) Patients who are able to orally receive the investigational medicinal product 
(IMP). 
8) Patients who are expected to live for at least 3 months. 
9) Fertile, sexually active male patients (excluding those who have had a bilateral 
orchiectomy) or sexually active female patients of childbearing potential, who 
agree to practice 2 different contraceptive measures during the trial and for 
3 months after the last dose of IMP. If birth control is employed, 2 of the 
following methods must be used: vasectomy, tubal ligation, intrauterine device, 
oral contraceptive, and condom (all methods approved or certified in Japan). 
Exclusion Criteria: 
All phase 1 and 2 of the trial 
1) Patients with hypersensitivity to ASTX660 or excipients of the drug product. 
2) Patients with active infection(s) requiring antibacterial, antifungal, or antiviral 
therapies. 
3) Patients with cardiac disease that meets any of the following criteria: 

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a) Left ventricular ejection fraction (LVEF) < 50% by echocardiography or 
multiple-gated acquisition (MUGA) scan. 
b) Congestive cardiac failure (Grade 3 or 4 according to New York Heart 
Association [NYHA] functional classification). 
c) Inadequately controlled cardiac disease including unstable angina or 
hypertension requiring hospitalization within the past 3 months (90 days). 
d) History or presence of complete left bundle branch block, third-degree 
(complete) atrioventricular block, cardiac pacemaker, or inadequately 
controlled arrhythmia requiring treatment. 
e) History or presence of long QT syndrome. 
f) History or presence of ventricular arrhythmia requiring aggressive treatment. 
g) Screening 12-lead ECG with QTc interval of ≥ 470 msec. 
h) Any other condition that is medically considered to have the potential to put 
the subject at increased cardiac risk. 
4) Patients who are positive for human immunodeficiency virus (HIV) antibody, 
hepatitis B virus (HBV)-deoxyribonucleic acid (DNA), or hepatitis C virus 
(HCV) antibody. 
5) Patients with Grade 2 or greater neuropathy. 
6) Patients with significant mental illness or other condition (alcohol or other 
substance abuse/addiction) that, in the opinion of the investigator or 
subinvestigator, predisposes the subject to high risk of noncompliance with the 
protocol. 
7) Patients who received any of the following treatments for the primary disease 
prior to the first dose of trial treatment: 
a) Chemotherapy or radiotherapy within 3 weeks (6 weeks if nitrosoureas) prior 
to trial treatment. 
b) Skin directed therapy including topicals or radiation within 3 weeks prior to 
trial treatment. 
c) Monoclonal antibody therapy within 4 weeks prior to trial treatment. 
d) Other investigational drugs (small molecules or biologics) or investigational 
therapies (including cell-based therapies such as chimeric antigen receptor 
[CAR] T-cell therapy) within the longer of 3 weeks or 5 half-lives prior to 
trial treatment. 
8) Patients with adverse reactions (except for alopecia) to the prior treatment that has 
not resolved to Grade 2. 
9) Patients with concurrent malignancies, except appropriately treated squamous 
carcinoma or basal cell carcinoma of skin or carcinoma in situ of uterine cervix, 
breast or prostate cancer stable on endocrine therapy, and other previous cancers 
that have not relapsed for at least 5 years. 
10) Patients with central nervous system involvement of lymphoma. 

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11) Patients with a history of allogenic hematopoietic stem cell transplantation, or 
those who underwent autologous stem cell transplantation within 14 weeks prior 
to the first dose of trial treatment. 
12) Patients who received corticosteroids > 10 mg/day prednisone equivalent within 3 
weeks prior to the first dose of trial treatment. However, patients without tumor 
decrease on stable corticosteroid therapy at low doses (≤ 10 mg/day prednisone 
equivalent) for more than 3 weeks prior to the first dose of trial treatment can be 
included. In that case, the corticosteroid therapy can be continued without dose 
increase until trial treatment is discontinued. 
13) Patients with a history of gastrectomy. 
14) Patients with a history or presence of pneumonitis (interstitial pneumonia) or 
pulmonary fibrosis. If screening CT scan suggests abnormal shadow of the 
pulmonary interstitium (eg, bilateral ground glass opacity), the investigator or 
subinvestigator should consult with a pulmonologist or a radiologist, as needed, to 
determine whether the patient has pneumonitis (interstitial pneumonia) or 
pulmonary fibrosis. 
15) Patients with inadequately controlled diabetes mellitus. 
16) Pregnant or nursing female patients or female patients with a positive pregnancy 
test at screening. Nursing patients cannot participate in the trial even if they 
discontinue breastfeeding. Female patients must undergo a pregnancy test to 
confirm that they are not pregnant at screening. However, a pregnancy test is not 
necessary for female patients without childbearing potential (ie, patients with a 
history of bilateral oophorectomy or hysterectomy or who have been 
postmenopausal for at least 12 months except for cases where menopause could 
be due to the effect of antineoplastic treatment). 
17) Patients who, in the opinion of the investigator or subinvestigator, are otherwise 
ineligible to participate in the trial. 
Trial Site(s): 
Approximately 25 trial sites in Japan 
Investigational Medicinal Product(s), Dose, Dosage Regimen, Treatment Duration, 
Formulation, Mode of Administration: 
Investigational medicinal product and formulations: 
ASTX660 capsules 30 mg and 90 mg (1 capsule contains 30 or 90 mg of ASTX660) 
Dose, dosage regimen, and mode of administration: 
Trial treatment will be conducted in repeated 28-day cycles comprising 7 days of IMP 
administration (Days 1 - 7 and Days 15 - 21) and 7 days of rest (Days 8 - 14 and Days 22 
- 28). 
After the dosing time is determined, the IMP will be orally administered once daily at 
approximately the same clock time on Days 1 to 7 and Days 15 to 21 of each cycle 

Protocol 401-102-00001 
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Amendment 4 Approval: 5 Dec 2022 
throughout the trial period. On scheduled visit days, subjects will return to the trial site 
without taking the IMP and receive the IMP after the scheduled examinations. Subjects 
will, in principle, fast for 2 hours before and 2 hours after IMP administration. In phase 1 
(dose escalation and ATLL expansion parts), subjects will fast for at least 10 hours before 
IMP administration on Cycle 1 Day 1 and Cycle 1 Day 7. During fasting, consumption of 
tea, coffee, and water is permitted but other beverages must not be consumed. In cases 
where a delay of 6 hours or longer has elapsed from the scheduled dosing time, IMP 
administration scheduled on that day will be skipped. 
In phase 1 (dose escalation part), treatment will begin with a daily dose of 120 mg, which 
will then be increased to 150 mg and 180 mg according to the dose escalation plan. Dose 
increase in the same subject is prohibited. Phase 1 (ATLL expansion part) and phase 2 
will use the RD determined based on the results of phase 1 (dose escalation part). 
Treatment duration: 
Trial treatment can be continued until the withdrawal criteria are met. 
Trial Assessments: 
Assessments for Efficacy: Hematology, CT scan (PTCL subjects, CTCL subjects, and 
ATLL subjects), PET-CT scan (PTCL subjects), bone marrow aspiration or biopsy 
(PTCL subjects and ATLL subjects), modified severity weighted assessment tool 
(mSWAT) assessment (CTCL subjects), response review, investigation of new treatment 
for the primary disease, investigation of disease progression, and investigation of survival 
status 
Assessments for Pharmacokinetics and 
: Blood sampling 
for plasma drug concentrations and 
 
Assessments for Safety: AEs, clinical laboratory tests, vital signs, body weight, ECOG 
PS, 12-lead ECG (local), echocardiography, and lung field assessment by PET-CT and 
CT scans 
 
Screening/Other: Subject demographics (prior treatment, disease stage [Lugano 
classification will be used for PTCL and ATLL and TNMB classification of mycosis 
fungoides and Sézary syndrome will be used for CTCL], and International Prognostic 
Index [IPI] [PTCL and ATLL]), medical history, viral tests, pregnancy test, and height 

Protocol 401-102-00001 
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Amendment 4 Approval: 5 Dec 2022 
Efficacy and Safety Data Review Committee: 
The Efficacy and Safety Data Review Committee will consist of individuals who are 
independent of the parties involved in the trial (eg, sponsor, medical expert, investigators, 
and subinvestigators) and are not directly involved in the trial. The committee will review 
the trial-related safety, serious or unexpected AEs, and efficacy from a third party 
standpoint, and will make recommendations, based on the obtained results of assessment, 
regarding the conduct and results of the trial, including continuation, modification, or 
discontinuation of the trial. For phase 1 (dose escalation part), the committee will also 
make recommendations about DLT assessment, dose, and whether to advance to phase 2. 
For phase 2, the committee will also serve as the Central Efficacy Evaluation Committee. 
Statistical Methods: 
For phase 2 efficacy analysis set, the ORR as assessed by the Central Efficacy Evaluation 
Committee and its two-sided 95% confidence interval (by Clopper-Pearson method) will 
be calculated and the frequency of the best overall response as assessed by the Central 
Efficacy Evaluation Committee will be summarized. 
Trial Duration: 
Each subject in this trial is expected to participate in the following periods of the trial 
(approximate durations listed): 
• Screening period: Days −21 to −1 
• IMP treatment period: Trial treatment can be continued until the withdrawal criteria 
are met. 
• Follow-up period: 30 days after trial treatment discontinuation or the start of new 
treatment for the primary disease, whichever comes first. 
• Investigation of survival status: Every 3 months following the end of the follow-up 
period. 
Overall, the trial duration from signing of the first informed consent form to the final 
subject assessment is expected to be approximately 4 years and 6 months, including 
phase 1 (dose escalation part), phase 1 (ATLL expansion part), and phase 2. 
 

 
 
Protocol 401-102-00001 
 
20 
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Amendment 4 Approval: 5 Dec 2022 
1.2 
Schema 
 
Figure 1.2-1 
Trial Design Schematic 
 
aPhase 2 will enroll 33 subjects as efficacy-evaluable subjects. 
 

Protocol 401-102-00001 
 
21 
Confidential - Proprietary Information 
Amendment 4 Approval: 5 Dec 2022 
1.3 
Schedule of Assessments 
Table 1.3-1 
Schedule of Assessments, Phase 1 (Dose Escalation Part), Cycles 1 and 2 
 
Week 4
Week 4
1a
2
3
7
8
9
10
15
16
21
22
1b
7
15
21
22
-
-
-
-
-
-
-
-
-
-
-
-4
-
-2
-
±7
 
Trial Procedure
Screening Period (D-21 to D-1)
Informed consentf
X
X
Demographics
X
Viral testsg
X
X
Eligibility assessment
X
Physical examination
X
X
X
Height
X
Body weight
X
X
X
Vital signs (blood pressure, pulse rate, SpO2, body temperature)
X
X
X
Performance status (ECOG PS)
X
X
12-Lead ECG (local)h
X
X
X
X
Echocardiography or MUGA scanj
X
AEs
Concomitant medications/therapies
Hematologyk
X
X
X
X
X
X
Serum chemistryk,l
X
X
X
X
X
X
X
X
X
X
Urinalysisk
X
X
X
X
X
Pregnancy testm
X
X
Blood sampling for PK analysiso
X
X
X
X
X
X
X
X
X
X
X
CT scan (PTCL subjects, CTCL subjects)r
X
Xr
PET-CT scan (PTCL subjects)s
X
Xs
Lung field assessment on CT imagest
X
Xt
Identification of lesions
X
Bone marrow aspiration or biopsy (PTCL subjects)u
X
Xu
mSWAT assessment (CTCL subjects)v
X
Xv
Response revieww
Xw
Chest X rayx
X
X
Cycle Day
IMP administrationd
Hospitalizatione
Allowable Windowc
Cycle 1
Cycle 2
Week
Week 1
Week 3
Week 1
Week 2
Week 3

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Amendment 4 Approval: 5 Dec 2022 
SpO2 = percutaneous oxygen saturation. 
aEach scheduled test/assessment will be performed prior to IMP administration. Physical examination, body weight, hematology, serum chemistry, urinalysis, 
and chest X ray can be omitted on Cycle 1 Day 1 if they were performed within 4 days before Cycle 1 Day 1. 
bEach test/assessment will be performed prior to IMP administration. Physical examination, body weight, 12-lead ECG (local), hematology, serum chemistry, 
urinalysis, and pregnancy test can be omitted on Cycle 2 Day 1 if they were performed within 4 days before Cycle 2 Day 1. 
cThis allowable window is only for tests, observations, and assessments. The IMP must be administered on the scheduled days. 
dThe IMP will be orally administered once daily at approximately the same clock time on Days 1 to 7 and Days 15 to 21 of each cycle throughout the trial 
period. On scheduled visit days, subjects will return to the trial site without taking the IMP and receive the IMP after scheduled examinations. Subjects will 
fast for 2 hours before and 2 hours after IMP administration. In cases where a delay of 6 hours or longer has elapsed from the scheduled dosing time, IMP 
administration scheduled on that day will be skipped. 
eSubjects will be hospitalized during Cycle 1. 
fWritten informed consent will be obtained from potential subjects themselves prior to all trial-related procedures. Subjects who wish to continue their 
participation in Cycle 2 onward will provide additional written informed consent, no earlier than Cycle 1 Day 22 and prior to the start of Cycle 2, to 
continue participation. 
gSubjects will undergo viral tests (HBV-DNA quantification) from Cycle 2 onward only if they tested positive for HBc or HBs antibody at screening. 
h12-Lead ECGs (local) will be performed at screening, predose and 2 hours postdose on Day 15 and Day 21 of Cycle 1, and from Cycle 2 Day 1 onward, 
predose on Day 1 of each cycle. 
 
 
jEchocardiography or MUGA scan will be performed at screening, on Cycle 3 Day 1 (within −7 days), and thereafter, Day 1 (within −7 days) of each odd-
numbered cycle. 
kSee Table 10.2-1 Clinical Laboratory Assessments for test items. 
lKL-6 will be measured at screening and from Cycle 1 Day 1 onward, predose on Day 1 of each cycle. 
mFor females of childbearing potential (FOCBP) only. 
 
oSee Table 8.2.1-1 for the timing of blood sampling. 
 
 

Protocol 401-102-00001 
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Amendment 4 Approval: 5 Dec 2022 
rCT scan will be performed at screening, Week 4 of Cycles 2, 4, and 6, and thereafter, Week 4 of every 3 cycles (Cycles 9, 12, 15…). The allowable window 
for Cycle ≥ 2 is ±7 days. Scan results obtained within 28 days before Cycle 1 Day 1 can be used as screening results if the subject agrees. 
sPET-CT scan will be performed at screening and thereafter, at the earliest possible timing after complete response (CR) is confirmed by CT scan for efficacy 
evaluation. Scan results obtained within 28 days before Cycle 1 Day 1 can be used if the subject agrees. 
tLung field on CT images by PET-CT or CT scan will be reviewed for safety evaluation. 
uBone marrow aspiration or biopsy will be performed at screening and thereafter, as needed, such as when confirming CR at the time of efficacy evaluation. 
Results obtained within 28 days before Cycle 1 Day 1 can be used if the subject agrees. 
vSkin lesions will be assessed using an mSWAT at screening, Week 4 of Cycles 2, 4, and 6, and thereafter, Week 4 of every 3 cycles (Cycles 9, 12, 15…). 
The allowable window is ±7 days. 
wFor PTCL, assessment is based on Lugano response criteria for non-Hodgkin lymphoma (2014)1 by the IWG, and for CTCL, assessment is based on 
mSWAT. 
xIf the lung field was assessed on CT images within 7 days, its results can substitute for chest X ray. 
 

Protocol 401-102-00001 
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Confidential - Proprietary Information 
 
Amendment 4 Approval: 5 Dec 2022 
Table 1.3-2 
Schedule of Assessments, Phase 1 (Dose Escalation Part), From Cycle 3 Onward, Withdrawal 
Examination, Follow-up Period, Investigation of Survival Status 
 
aWithdrawal examination will be performed within 7 days after trial treatment discontinuation is determined. Efficacy endpoints will be evaluated in 
consideration of the subject’s general condition. 
Week
4
4
Cycle Day
1c
7
15
21
1c
7
15
21
22
1c
7
15
21
22
Allowable Windowd
-4
-
-4
-
-4
-
-4
-
±7
-4
-
-4
-
±7
+14
±14
IMP administratione
Trial Procedure
Viral testsf
X
X
X
X
Physical examination
X
X
X
X
X
Body weight
X
X
X
Vital signs (blood pressure, pulse rate, SpO2, body temperature)
X
X
X
X
X
X
X
X
Performance status (ECOG PS)
X
X
 
X
X
12-Lead ECG (local)
X
X
X
X
X
Echocardiography or MUGA scang
Xg
Xg
Xg
X
AEs
Concomitant medications/therapies
Hematologyh
X
X
X
X
X
X
X
X
Serum chemistryh,i
X
X
X
X
X
X
X
X
Urinalysish
X
X
X
X
X
X
X
Pregnancy testj
X
X
X
X
CT scan (PTCL subjects, CTCL subjects)k
Xk
Xk
X
PET-CT scan (PTCL subjects)l
Xl
Xl
Lung field assessment on CT imagesm
Xm
Xm
X
Bone marrow aspiration or biopsy (PTCL subjects)n
Xn
Xn
Xn
mSWAT assessment (CTCL subjects)o
Xo
Xo
X
Response reviewp
X
X
X
Chest X rayq
X
X
X
Investigation of new treatment for the primary diseaser
X
Investigation of disease progressions
X
Investigation of survival statust
X
Cycle 3
Cycles 4–6
Cycle ≥7
Withdrawal
Examinationa
Follow-up Periodb
Survival
Status
1
3
1
3
1
3
Within 7 days after
discontinuation
Within 30 days after last
dose of treatment
Every 3
months

Protocol 401-102-00001 
25 
Confidential - Proprietary Information 
 
Amendment 4 Approval: 5 Dec 2022 
bThe scheduled tests/assessments will be performed 30 days after trial treatment discontinuation or just before new treatment for the primary disease begins, 
whichever comes first. If withdrawal examination or scheduled tests/assessments were performed within 7 days, repeated tests/assessments can be omitted, 
and information on AEs and concomitant medications/therapies will be collected. 
cEach test/assessment will be performed prior to IMP administration. Scheduled tests/assessments can be omitted on Day 1 if they were performed within 
4 days before Day 1. 
dThis allowable window is only for tests, observations, and assessments. The IMP must be administered on the scheduled days. 
eThe IMP will be orally administered once daily at approximately the same clock time on Days 1 to 7 and Days 15 to 21 of each cycle throughout the trial 
period. On scheduled visit days, subjects will return to the trial site without taking the IMP and receive the IMP after scheduled examinations. Subjects will 
fast for 2 hours before and 2 hours after IMP administration. In cases where a delay of 6 hours or longer has elapsed from the scheduled dosing time, IMP 
administration scheduled on that day will be skipped. 
fSubjects will undergo viral tests (HBV-DNA quantification) from Cycle 2 onward only if they tested positive for HBc or HBs antibody at screening. 
gEchocardiography or MUGA scan will be performed at screening, on Cycle 3 Day 1 (within −7 days), and thereafter, Day 1 (within −7 days) of each odd-
numbered cycle. 
hSee Table 10.2-1 Clinical Laboratory Assessments for test items. 
iKL-6 will be measured at screening and from Cycle 1 Day 1 onward, predose on Day 1 of each cycle. 
jFor FOCBP only. 
kCT scan will be performed at screening, Week 4 of Cycles 2, 4, and 6, and thereafter, Week 4 of every 3 cycles (Cycles 9, 12, 15…). The allowable window 
for Cycle ≥ 2 is ±7 days. Scan results obtained within 28 days before Cycle 1 Day 1 can be used if the subject agrees. 
lPET-CT scan will be performed at screening and thereafter, at the earliest possible timing after CR is confirmed by CT scan for efficacy evaluation. Scan 
results obtained within 28 days before Cycle 1 Day 1 can be used if the subject agrees. 
mLung field on CT images by PET-CT or CT scan will be reviewed for safety evaluation. 
nBone marrow aspiration or biopsy will be performed at screening and thereafter, as needed, such as when confirming CR at the time of efficacy evaluation. 
Results obtained within 28 days before Cycle 1 Day 1 can be used if the subject agrees. 
oSkin lesions will be assessed using an mSWAT at Week 4 of Cycles 2, 4, and 6 and thereafter, Week 4 of every 3 cycles (Cycles 9, 12, 15…). The allowable 
window is ±7 days. 
pFor PTCL, assessment is based on Lugano response criteria for non-Hodgkin lymphoma (2014)1 by the IWG, and for CTCL, assessment is based on 
mSWAT. 
qIf the lung field was assessed on CT images within 7 days, its results can substitute for chest X ray. 
rInvestigation will be performed every 3 months following the end of the follow-up period. Only for subjects who have no disease progression at trial 
discontinuation, the investigation will be performed after trial discontinuation until the start of new treatment or the end of the trial. For subjects whose new 

Protocol 401-102-00001 
26 
Confidential - Proprietary Information 
 
Amendment 4 Approval: 5 Dec 2022 
treatment for the primary disease is being investigated at the date of approval of protocol amendment 4, the investigation will be completed after the final 
investigation has been conducted, and for subjects receiving trial treatment at that time, the investigation will be performed and completed following the 
end of the follow-up period. 
sInvestigation will be performed every 3 months following the end of the follow-up period. Only for subjects who have no disease progression at trial 
discontinuation, progression of the primary disease will be investigated after trial discontinuation until disease progression (including the start of new 
treatment) or the end of the trial. For subjects whose disease progression is being investigated at the date of approval of protocol amendment 4, the 
investigation will be completed after the final investigation has been conducted, and for subjects receiving trial treatment at that time, the investigation will 
be performed and completed following the end of the follow-up period. 
tInvestigation will be performed every 3 months following the end of the follow-up period. For subjects whose survival status is being investigated at the date 
of approval of protocol amendment 4, the investigation of survival status will be completed after the final investigation has been conducted, and for 
subjects receiving trial treatment at that time, the investigation will be performed and completed following the end of the follow-up period. 
 

Protocol 401-102-00001 
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Confidential - Proprietary Information 
 
Amendment 4 Approval: 5 Dec 2022 
Table 1.3-3 
Schedule of Assessments, Phase 1 (ATLL Expansion Part) 
 
aEach test/assessment will be performed prior to IMP administration. Scheduled tests/assessments can be omitted on Day 1 if they were performed within 
4 days before Cycle 1 Day 1 and from Cycle 2 onward, within 4 days before Day 1 of the relevant cycle. 
Week 4
Week 4
Week 4
1a
2
3
7
8
9
10
15
16
21
22
1a
7
15
21
22
1a
7
15
21
22
-
-
-
-
-
-
-
-
-
-
-
-4
-
-4
-
±7
-4
-
-4
-
±7
+14
±14
IMP administratione
Hospitalizationf
Trial Procedure
Screening Period
(D-21 to D-1)
Informed consent
X
Demographics
X
Viral testsg
X
X
X
X
Eligibility assessment
X
Physical examination
X
X
X
X
X
X
Height
X
Body weight
X
X
X
X
Vital signs (blood pressure, pulse rate, SpO2, body
temperature)
X
X
X
X
X
X
X
X
X
Performance status (ECOG PS)
X
X
X
X
X
X
12-Lead ECG (local)h
X
X
X
X
X
X
X
X
X
Echocardiography or MUGA scani
X
Xi
X
AEs
Concomitant medications/therapies
Hematologyj
X
X
X
X
X
X
X
X
X
X
Serum chemistryj,k
X
X
X
X
X
X
X
X
X
X
X
Urinalysisj
X
X
X
X
X
X
X
X
X
Pregnancy testl
X
X
X
X
Blood sampling for PK analysism
X
X
X
X
X
X
X
X
X
X
X
CT scano
X
Xo
Xo
X
Lung field assessment on CT imagesp
X
Xp
Xp
X
Identification of lesions
X
Bone marrow aspiration or biopsyq
Xq
Xq
Xq
Xq
Response reviewr
Xr
Xr
X
Chest X rays
X
X
X
Investigation of new treatment for the primary
diseaset
X
Investigation of disease progressionu
X
Investigation of survival statusv
X
Cycle 1
Cycle 2
Cycle ≥3
Withdrawal
Examination
Follow-up
Periodc
Survival
Status
Week
Week 1
Week 2
Week 3
Week 1
Week 3
Week 1
Week 3
Within 7 days
after
discontin-
uationb
Within 30 days
after last dose of
treatment
Every 3
months
Cycle Day
Allowable Windowd

Protocol 401-102-00001 
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Amendment 4 Approval: 5 Dec 2022 
bWithdrawal examination will be performed within 7 days after trial treatment discontinuation is determined. Efficacy endpoints will be evaluated in 
consideration of the subject’s general condition. 
cThe scheduled tests/assessments will be performed 30 days after trial treatment discontinuation or just before new treatment for the primary disease begins, 
whichever comes first. If withdrawal examination or scheduled tests/assessments were performed within 7 days, repeated tests/assessments can be omitted, 
and information on AEs and concomitant medications/therapies will be collected. 
dThis allowable window is only for tests, observations, and assessments. The IMP must be administered on the scheduled days. 
eThe IMP will be orally administered once daily at approximately the same clock time on Days 1 to 7 and Days 15 to 21 of each cycle throughout the trial 
period. On scheduled visit days, subjects will return to the trial site without taking the IMP and receive the IMP after scheduled examinations. Subjects will 
fast for 2 hours before and 2 hours after IMP administration. In cases where a delay of 6 hours or longer has elapsed from the scheduled dosing time, IMP 
administration scheduled on that day will be skipped. 
fSubjects will be hospitalized during Cycle 1. 
gSubjects will undergo viral tests (HBV-DNA quantification) from Cycle 2 onward only if they tested positive for HBc or HBs antibody at screening. 
h12-Lead ECGs (local) will be performed at screening, predose and 2 hours postdose on Day 1, Day 7, Day 15, and Day 21 of Cycle 1, and from 
Cycle 2 Day 1 onward, predose on Day 1 of each cycle. 12-Lead ECG on Cycle 1 Day 1 must not be omitted even if it was performed within 4 days. 
iEchocardiography or MUGA scan will be performed at screening, on Cycle 3 Day 1 (within −7 days), and thereafter, Day 1 (within −7 days) of each odd-
numbered cycle. 
jSee Table 10.2-1 Clinical Laboratory Assessments for test items. 
kKL-6 will be measured at screening and from Cycle 1 Day 1 onward, predose on Day 1 of each cycle. 
lFor FOCBP only. 
mSee Table 8.2.1-1 for the timing of blood sampling. 
 
oCT scan will be performed at screening, Week 4 of Cycles 2, 4, and 6, and thereafter, Week 4 of every 3 cycles (Cycles 9, 12, 15…). The allowable window 
for Cycle ≥ 2 is ±7 days. Scan results obtained within 28 days before Cycle 1 Day 1 can be used if the subject agrees. 
pLung field on CT images by CT scan will be reviewed for safety evaluation. 
qBone marrow aspiration or biopsy will be performed at screening and thereafter, as needed, such as when confirming CR at the time of efficacy evaluation. 
Bone marrow involvement identified during prior treatment of the primary disease can be used as screening results only if the subject agrees. 
rAssessment is based on the Japan Clinical Oncology Group (JCOG) response criteria for ATLL (2009). 
sIf the lung field was assessed on CT images within 7 days, its results can substitute for chest X ray. 

Protocol 401-102-00001 
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Amendment 4 Approval: 5 Dec 2022 
tInvestigation will be performed every 3 months following the end of the follow-up period. Only for subjects who have no disease progression at trial 
discontinuation, investigation will be performed after trial discontinuation until the start of new treatment or the end of the trial. 
uInvestigation will be performed every 3 months following the end of the follow-up period. Only for subjects who have no disease progression at trial 
discontinuation, progression of the primary disease will be investigated after trial discontinuation until disease progression (including the start of new 
treatment) or the end of the trial. 
vInvestigation will be performed every 3 months following the end of the follow-up period. 
 

Protocol 401-102-00001 
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Amendment 4 Approval: 5 Dec 2022 
Table 1.3-4 
Schedule of Assessments, Phase 2 
 
Withdrawal
Examination
Follow-up periodc
Survival
status
Week 2
Week 4
Week 4
Week 4
1a
7
8
15
21
22
1a
7
15
21
22
1a
7
15
21
22
-
-
-
-4
-
-
-4
-
-4
-
±7
-4
-
-4
-
±7
+14
±14
IMP administratione
Hospitalizationf
Trial Procedure
Screening Period (D-21 to D-1)
Informed consent
X
Demographics
X
Viral testsg
X
X
X
X
Eligibility assessment
X
Physical examination
X
X
X
X
X
X
Height
X
Body weight
X
X
X
X
Vital signs (blood pressure, pulse rate, SpO2, body
temperature)
X
X
X
X
X
X
X
X
X
Performance status (ECOG PS)
X
X
X
X
X
X
12-Lead ECG (local)h
X
X
X
X
X
X
Echocardiography or MUGA scani
X
Xi
X
AEs
Concomitant medications/therapies
Hematologyj
X
X
X
X
X
X
X
X
X
X
Serum chemistryj,k
X
X
X
X
X
X
X
X
X
X
X
Urinalysisj
X
X
X
X
X
X
X
X
X
Pregnancy testl
X
X
X
X
Blood sampling for PK analysism
X
X
X
X
X
Submission of samples for central pathological
diagnosiso
X
CT scanp
X
Xp
Xp
X
PET-CT scanq
X
Xq
Xq
Lung field assessment on CT imagesr
X
Xr
Xr
X
Identification of lesions
X
Bone marrow aspiration or biopsys
X
Xs
Xs
Xs
Response reviewt
Xt
Xt
X
Chest X rayu
X
X
X
Investigation of new treatment for the primary
diseasev
X
Investigation of disease progressionw
X
Investigation of survival statusx
X
Week
Week 1
Cycle Day
Allowable Windowd
Within 7 days
after
discontinuationb
Week 1
Week 3
Week 1
Week 3
Every 3
months
Within 30 days after last
dose of treatment
Week 3
Cycle 2
Cycle ≥3
Cycle 1

Protocol 401-102-00001 
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Amendment 4 Approval: 5 Dec 2022 
aEach test/assessment will be performed prior to IMP administration. Scheduled tests/assessments can be omitted on Day 1 if they were performed within 
4 days before Cycle 1 Day 1 and from Cycle 2 onward, within 4 days before Day 1 of the relevant cycle. 
bWithdrawal examination will be performed within 7 days after trial treatment discontinuation is determined. Efficacy endpoints will be evaluated in 
consideration of the subject’s general condition. 
cThe scheduled tests/assessments will be performed 30 days after trial treatment discontinuation or just before new treatment for the primary disease begins, 
whichever comes first. If withdrawal examination or scheduled tests/assessments were performed within 7 days, repeated tests/assessments can be omitted, 
and information on AEs and concomitant medications/therapies will be collected. 
dThis allowable window is only for tests, observations, and assessments. The IMP must be administered on the scheduled days. 
eThe IMP will be orally administered once daily at approximately the same clock time on Days 1 to 7 and Days 15 to 21 of each cycle throughout the trial 
period. On scheduled visit days, subjects will return to the trial site without taking the IMP and receive the IMP after scheduled examinations. Subjects will 
fast for 2 hours before and 2 hours after IMP administration. In cases where a delay of 6 hours or longer has elapsed from the scheduled dosing time, IMP 
administration scheduled on that day will be skipped. 
fSubjects will be hospitalized from Cycle 1 Day 1 through Cycle 1 Day 7. 
gSubjects will undergo viral tests (HBV-DNA quantification) from Cycle 2 onward only if they tested positive for HBc or HBs antibody at screening. 
h12-Lead ECGs (local) will be performed at screening, predose and 2 hours postdose on Cycle 1 Day 7, and from Cycle 2 Day 1 onward, predose on Day 1 of 
each cycle. 
iEchocardiography or MUGA scan will be performed at screening, on Cycle 3 Day 1 (within −7 days), and thereafter, Day 1 (within −7 days) of each odd-
numbered cycle. 
jSee Table 10.2-1 Clinical Laboratory Assessments for test items. 
kKL-6 will be measured at screening and from Cycle 1 Day 1 onward, predose on Day 1 of each cycle. 
lFor FOCBP only. 
mSee Table 8.2.1-2 for the timing of blood sampling. 
. 
oTumor samples will be submitted by the end of Cycle 1 according to a separately prepared procedure for central pathological diagnosis. 
pCT scan will be performed at screening, Week 4 of Cycles 2, 4, and 6, and thereafter, Week 4 of every 3 cycles (Cycles 9, 12, 15…). The allowable window 
for Cycle ≥ 2 is ±7 days. Scan results obtained within 28 days before Cycle 1 Day 1 can be used as screening results if the subject agrees. 
qPET-CT scan will be performed at screening and thereafter, at the earliest possible timing after CR is confirmed by CT scan for efficacy evaluation. Scan 
results obtained within 28 days before Cycle 1 Day 1 can be used if the subject agrees. 
rLung field on CT images by PET-CT or CT scan will be reviewed for safety evaluation. 

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sBone marrow aspiration or biopsy will be performed at screening and thereafter, as needed, such as when confirming CR at the time of efficacy evaluation. 
Results obtained within 28 days before Cycle 1 Day 1 can be used if the subject agrees. 
tAssessment is based on Lugano response criteria for non-Hodgkin lymphoma (2014)1 by the IWG. 
uIf the lung field was assessed on CT images within 7 days, its results can substitute for chest X ray. 
vInvestigation will be performed every 3 months following the end of the follow-up period. Only for subjects who have no disease progression at trial 
discontinuation, investigation will be performed after trial discontinuation until the start of new treatment or the end of the trial. 
wInvestigation will be performed every 3 months following the end of the follow-up period. Only for subjects who have no disease progression at trial 
discontinuation, progression of the primary disease will be investigated after trial discontinuation until disease progression (including the start of new 
treatment) or the end of the trial. 
xInvestigation will be performed every 3 months following the end of the follow-up period. 

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1.3.1 
Screening Period 
The investigator or subinvestigator will obtain written informed consent from each 
subject him/herself prior to the screening procedure. Following acquisition of informed 
consent, the subject identifier and the date of signed informed consent will be recorded in 
the subject screening log. 
The investigator or subinvestigator will then screen consented subjects and select those 
who meet all the inclusion criteria and do not fall under any of the exclusion criteria. The 
investigations and examinations specified in Section 1.3, Schedule of Assessments will 
be conducted, and the result of eligibility assessment will be recorded in the case report 
form (CRF). 
At the screening visit, the following information will be recorded in the CRF: subject 
demographics (collection date, date of birth, sex, childbearing potential, race, ethnicity, 
country, disease type, date of initial diagnosis, prior chemotherapy for the primary 
disease [names of regimens or medications, treatment period, and best overall response], 
prior hematopoietic stem cell transplantation [if yes, date of treatment], prior 
radiotherapy for the primary disease [if yes, date of treatment and location of treatment], 
other prior treatment for the primary disease [if yes, medications/therapies, treatment 
period, and best overall response], disease stage [Lugano classification1 for PTCL and 
ATLL and TNMB classification2 of mycosis fungoides/Sézary syndrome for CTCL], IPI3 
[PTCL and ATLL]), and medical history (prior diseases within 5 years before informed 
consent and concurrent diseases). 
Table 1.3-5 
Disease Stage (Lugano Classification) 
Disease Stage 
Involvement 
Extranodal Status 
Limited 
I 
One node or a group of adjacent nodes 
Single extranodal lesions without 
nodal involvement 
II 
Two or more nodal groups on the same 
side of the diaphragm 
Stage I or II by nodal extent with 
limited contiguous extranodal 
involvement 
II 
bulkya 
II as above with “bulky” disease 
Not applicable 
Advanced 
III 
Nodes on both sides of the diaphragm; 
nodes above the diaphragm with spleen 
involvement 
Not applicable 
IV 
Additional noncontiguous 
extralymphatic involvement 
Not applicable 
Tonsils, Waldeyer’s ring, and spleen are considered nodal tissue. 
aWhether stage II bulky is treated as limited or advanced disease may be determined by histology and 
a number of prognostic factors. Since the definition of bulky disease differs depending on histology, 
the longest diameter, instead of “X,” should be recorded. 
 

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Table 1.3-6 
Disease Stage (TNMB Classification of Mycosis 
Fungoides/Sézary Syndrome) 
Skin: T 
T1 
Limited patches, papules, and/or plaques covering < 10% of the skin 
surface 
(Patch is a lesion without significant elevation or induration. Plaque is 
a lesion that is elevated or indurated.) 
T1a (patch only), T1b (plaque ± patch) 
T2 
Patches, papules, or plaques covering ≥ 10% of the skin surface 
T2a (patch only), T2b (plaque ± patch) 
T3 
One or more tumors (≥ 1 cm diameter) 
T4 
Confluence of erythema covering ≥ 80% of the body surface area 
Node: N 
N0 
No clinically abnormal lymph nodes; biopsy not required 
N1 
 
N1a 
N1b 
Clinically abnormal lymph nodes; 
histopathology Dutch grade 1 or NCI LN0-2a 
Clone negative 
Clone positive 
N2 
 
N2a 
N2b 
Clinically abnormal lymph nodes; 
histopathology Dutch grade 2 or NCI LN3a 
 
Clone negative 
Clone positive 
N3 
 
Nx 
Clinically abnormal lymph nodes; 
histopathology Dutch grade 3-4 or NCI LN4a 
Clone positive or negative 
 
Clinically abnormal lymph nodes; no histologic confirmation or strict 
N grading impossible 
Visceral: M 
M0 
No visceral organ involvement 
M1 
Visceral involvement 
(must have pathology confirmation and organ involved should be 
specified) 
Blood: B 
B0 
 
 
B0a 
B0b 
Absence of significant blood involvement: 
≤ 5% of peripheral blood lymphocytes are atypical (Sézary) cells 
Clone negative 
Clone positive 
B1 
 
B1a 
B1b 
> 5% of peripheral blood lymphocytes are atypical (Sézary) cells but 
does not meet the criteria of B2  
Clone negative 
Clone positive 
B2 
≥ 1000/μL Sézary cells (clone positive) in peripheral blood leukocytes 
plus one of the following: CD4/CD8 ≥ 10, CD4 + CD7– cells ≥ 40%, 
or CD4+ CD26– cells ≥ 30% 
aNCI classification for lymph node 
NCI LN0 
No atypical lymphocytes 
NCI LN1 
Occasional and isolated atypical lymphocytes not arranged in clusters 
NCI LN2 
Many atypical lymphocytes or in 3 to 6 cell clusters 
NCI LN3 
Aggregates of atypical lymphocytes: nodal architecture preserved 
NCI LN4 
Partial/complete effacement of nodal architecture by atypical lymphocytes or frankly 
neoplastic cells 

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Stage 
T 
N 
M 
B 
I A 
1 
0 
0 
0, 1 
I B 
2 
0 
0 
0, 1 
II A 
1, 2 
1, 2, X 
0 
0, 1 
II B 
3 
0-2, X 
0 
0, 1 
III A 
III B 
4 
4 
0-2, X 
0-2, X 
0 
0 
0 
1 
IV A1 
IV A2 
IV B 
1-4 
1-4 
1-4 
0-2, X 
3 
0-3, X 
0 
0 
1 
2 
0-2 
0-2 
X: Clinically abnormal enlargement of lymph nodes is not histologically confirmed, or strict N grading 
is impossible. 
 
Table 1.3-7 
International Prognostic Index (IPI) 
Prognostic Factor 
Adverse Prognostic Factor 
Age 
Serum lactate dehydrogenase (LDH) level 
Performance Status 
Disease stage 
Number of extranodal sites of involvement 
> 60 years 
Above normal 
2 - 4 
III or IV 
≥ 2 
Prognostic factor score of 0 or 1: Low risk 
Prognostic factor score of 2: Low-Intermediate risk 
Prognostic factor score of 3: High-Intermediate risk 
Prognostic factor score of 4 or 5: High risk 
 
1.3.2 
Treatment and Observation Period 
The treatment and observation period will be from Cycle 1 Day 1 through determination 
of trial treatment discontinuation. On treatment days, the scheduled tests/assessments will 
be performed prior to IMP administration as specified in Section 1.3, Schedule of 
Assessments. Subjects with suspected interstitial lung disease based on percutaneous 
oxygen saturation (SpO2), auscultation, chest X ray, or lung field assessment on CT 
images will undergo additional examinations at the discretion of the investigator or 
subinvestigator and receive appropriate treatment as necessary. Likewise, subjects with 
suspected pancreatitis based on elevated amylase or lipase levels identified by serum 
chemistry and objective/subjective symptoms will also undergo additional examinations 
at the discretion of the investigator or subinvestigator and receive appropriate treatment 
as necessary. 
1.3.3 
Withdrawal Examination 
Withdrawal examination will be performed within 7 days after trial treatment 
discontinuation is determined. Efficacy endpoints will be evaluated in consideration of 
the subject’s general condition. 

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1.3.4 
Follow-up Period 
The scheduled tests/assessments will be performed 30 days after trial treatment 
discontinuation or just before new treatment for the primary disease begins, whichever 
comes first. If withdrawal examination or scheduled tests/assessments were performed 
within 7 days of the last day of the follow-up period, repeated tests/assessments can be 
omitted, and information on AEs and concomitant medications/therapies will be 
collected. 
1.3.5 
Investigation of Survival Status 
The subject’s survival status will be investigated every 3 months following the end of the 
follow-up period. Only for subjects who have no disease progression at trial 
discontinuation, new treatment for the primary disease and disease progression will be 
investigated. The results will be recorded in the CRF.  These visits may be conducted by 
telephone. In phase 1 (dose escalation part), for subjects whose survival status is being 
investigated at the date of approval of protocol amendment 4, the investigation will be 
completed after the final investigation of survival status has been conducted (including 
investigation of new treatment for the primary disease and investigation of disease 
progression), and for subjects receiving trial treatment at that time, the investigation of 
survival status (including investigation of new treatment for the primary disease and 
investigation of disease progression) will be performed and completed following the end 
of the follow-up period. 
2 
Introduction 
ASTX660 is a synthetic small molecule that was developed using the fragment-based 
drug discovery platform of Astex Pharmaceuticals Inc. (hereinafter referred to as 
“ASTEX”). It is known that the inhibitor of the apoptosis protein (IAP) family, which 
engages in evasion of apoptosis, includes the X-linked inhibitor of apoptosis protein 
(XIAP) and the cellular inhibitor of apoptosis protein (cIAP), and overexpression of these 
IAPs in numerous tumors has been reported.4 The XIAP suppresses the apoptosis 
pathway by directly inhibiting caspases primarily through the intrinsic pathway, while 
cIAP suppresses the extracellular ligand-mediated extrinsic apoptosis pathway through 
binding to tumor necrosis factor (TNF) receptor-associated factor-2 (TRAF2) or other 
factors thereby forming complexes. It have been reported that overexpression of IAPs in 
cells inhibits apoptosis and is associated with resistance to chemotherapy and 
radiotherapy.4,5 ASTX660 represents a novel structural class of nonpeptidomimetic IAP 
antagonists. ASTX660 has been shown to have tumour growth inhibitory activity and 

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potent proapoptotic activity in nonclinical studies.6 ASTX660 has an inhibitory profile 
for both cIAP1 and XIAP and therefore is expected to be effective in blocking the 
pathways that circumvent apoptosis. ASTEX has been conducting a phase 1/2 clinical 
trial (hereinafter referred to as “ASTX660-01 trial”) since 2015 in the United States and 
other foreign countries. After a recommended dose (RD) of 180 mg was identified in 
phase 1, the trial proceeded to phase 2 for solid tumor and lymphoma. Phase 2 has 
demonstrated that ASTX660 has promising efficacy in the treatment of relapsed or 
refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL), 
and further efficacy evaluation is ongoing in additionally enrolled patients with PTCL 
and CTCL. Against this backdrop, Otsuka Pharmaceutical Co., Ltd. (hereinafter referred 
to as “Otsuka”) embarked on the development of ASTX660 for patients with PTCL in 
Japan, where the prevalence of this illness is comparable to that in the United States7 and 
has planned a phase 1/2 trial to evaluate the tolerability, safety, efficacy, and 
pharmacokinetics (PK) of ASTX660 in Japanese patients. In patients with adult T-cell 
leukemia/lymphoma [ATLL] as well, a disease that affects a relatively large number of 
individuals in Japan7 but is not included in the overseas trial, phase 1 (ATLL expansion 
part) of this trial is designed to evaluate the safety of ASTX660 at the RD. 
PTCL, CTCL, and ATLL, which are derived from mature T-cells and natural killer (NK) 
cells, are categorized as “mature T- and NK cell neoplasms” by the World Health 
Organization (WHO) Classification (2017) and are associated with a variety of symptoms 
including systemic lymphadenopathy, hepatosplenomegaly, weight loss, fever, and night 
sweats.8 
“Mature T- and NK cell neoplasms” are rare illnesses, and the number of patients in 
Japan is estimated to be approximately 2000 according to Portal Site of Official Statistics 
of Japan 2017 (https://www.e-stat.go.jp/). 
The WHO Classification divides “mature T- and NK cell neoplasms” into approximately 
30 subtypes, and the relative frequency of the subtypes varies among regions across the 
world. A comparative study of the incidence of hematopoietic malignancies between 
Japan and the United States has found that the proportion of “mature T- and NK cell 
neoplasms” in diagnosed malignant lymphomas between 2003 and 2008 is 18.1% in 
Japan and 6.8% in the United States.7 This difference is due to ATLL caused by human 
T-cell leukemia virus type 1 (HTLV-1), which affects individuals predominantly in the 
southwest area of Japan. Excluding ATLL, the proportion of “mature T- and NK cell 
neoplasms” was 9.8% in Japan and 6.6% in the United States. 

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Among “mature T- and NK cell neoplasms,” the most frequent of all lymphoma subtypes 
(including B-cell lymphoma and Hodgkin’s lymphoma) in Japan is ATLL (10.00%), 
followed by angioimmunoblastic T-cell lymphoma (5.13%), peripheral T-cell lymphoma, 
not otherwise specified (NOS) (4.51%), anaplastic large-cell lymphoma, anaplastic 
lymphoma kinase (ALK) negative (1.59%), and extranodal NK/T-cell lymphoma, nasal 
type (1.55%).9 
Regarding the prognosis of PTCL, a study by the International T-Cell Lymphoma 
Project10 reported a 5-year survival rate of 70% for anaplastic large-cell lymphoma, ALK 
positive (ALK-positive ALCL), 49% for anaplastic large-cell lymphoma, ALK negative 
(ALK-negative ALCL), 32% for both angioimmunoblastic T-cell lymphoma (AITL) and 
peripheral T-cell lymphoma, NOS (PTCL NOS), and prognosis varies substantially 
among subtypes. Peripheral T-cell lymphoma is classified as aggressive lymphoma 
(intermediate-grade lymphoma) that progresses monthly without treatment, and a 
multinational retrospective study designed to evaluate clinical utility of Revised 
European American Lymphoma (REAL) Classification prior to introduction of rituximab 
revealed that all PTCL subtypes combined excluding ALCL had a poorer prognosis 
compared with diffuse large B-cell lymphoma (DLBCL).11,12 
Concerning treatment for PTCL, the Practical Guidelines for Hematological 
Malignancies (2018) presents separate therapeutic strategies for ALK-positive ALCL and 
other PTCL subtypes. For ALK-positive ALCL, the guidelines recommend the CHOP 
protocol as the primary treatment based on treatment outcomes in patients with ALK-
positive ALCL being comparable to that in patients with DLBCL. For other subtypes 
including PTCL NOS, AITL, and ALK-negative ALCL, the guidelines also recommend, 
as the primary treatment, combination chemotherapy such as the CHOP protocol, the 
treatment outcomes of which have been widely reported. For patients with partial or no 
response to the primary treatment, salvage therapy or clinical trials are recommended, 
and subsequent recommended treatment regimens include salvage therapy, clinical trials, 
and autologous or allogeneic transplantation, as well as palliative therapy and best 
supportive care. The guidelines do not specify regimens or drugs for salvage therapy to 
be used as secondary or subsequent treatments. 
With regard to the prognosis of ATLL, a study of the above International T-Cell 
Lymphoma Project reported a 5-year survival rate of 14%.10 As treatment for ATLL, the 
Practical Guidelines for Hematological Malignancies (2018) recommend VCAP-AMP-
VECP-based combination chemotherapy for acute subtype, lymphoma subtype, and 
chronic subtype with unfavorable prognostic factors (abnormal values of at least 1 of 
lactate dehydrogenase [LDH], albumin, and blood urea nitrogen [BUN]), all categorized 

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as aggressive ATLL. For patients responsive to treatment without issues of age, general 
condition, or major organ function, allogeneic hematopoietic stem cell transplantation is 
considered if an appropriate donor is available. For patients unresponsive to treatment, 
the guidelines recommend salvage therapy, clinical trials, allogeneic transplantation, 
palliative radiotherapy, and best supportive care. The guidelines13 do not specify 
regimens or drugs for salvage therapy to be used as secondary or subsequent treatments. 
Various chemotherapy regimens have been tried to date in the treatment of relapsed or 
refractory aggressive ATLL, often resulting in a brief response followed by the rapid 
progression of the disease. 
For the smoldering subtype and chronic subtype without unfavorable prognostic factors, 
both categorized as indolent ATLL, the guidelines recommend observation without 
treatment until progression to aggressive ATLL and, after exacerbation of the disease, 
introduction of similar treatment regimens to those for initial aggressive ATLL. 
Although multiple approved agents are available for relapsed or refractory PTCL in 
Japan, there is no established standard of care with evidence of prolonged survival. Some 
patients respond to the existing therapies but their progression free survival (PFS) is as 
short as approximately 1 to 4 months.14 Given that ASTX660 has a novel mechanism of 
action that differs from that of the existing drugs and that the interim results of an 
overseas trial suggest that ASTX660 monotherapy has a certain level of efficacy in 
patients with PTCL, Otsuka believes that ASTX660 may represent a new treatment 
option for relapsed or refractory PTCL. 
Please refer to the ASTX660 Investigator’s Brochure (IB) for more detailed information. 
2.1 
Trial Rationale 
Encouraged by the interim results of an ongoing foreign phase 1/2 clinical trial 
(ASTX660-01 trial) suggesting that ASTX660 is effective in patients with PTCL and 
CTCL, Otsuka has designed this trial protocol with the aim of evaluating the tolerability, 
safety, efficacy, and PK of ASTX660 in Japanese patients. This trial has been designed 
with due consideration given to subject safety, and Otsuka has determined that provided 
the trial is conducted in accordance with the protocol, it is appropriate from scientific and 
ethical perspectives. See Section 4.2 for scientific rationale for the trial design. 
2.2 
Background 
At the present time, the ASTX660-01 trial, an ongoing phase 1/2 first-in-human trial, is 
the only clinical trial of ASTX660. The primary objectives of phase 1 of the ASTX660-
01 trial are to evaluate safety and identify the maximum tolerated dose (MTD), the 

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recommended phase 2 dose (RP2D), and the recommended dosing regimen of ASTX660 
in subjects with advanced solid tumors or lymphoma for whom standard life-prolonging 
measures are not available and who receive ASTX660 on Days 1 to 7 and Days 15 to 21 
in repeated 28-day cycles. Subject enrollment in phase 1 has been completed and all 
subjects have completed trial treatment. Phase 1 has identified 210 mg/day as the MTD 
and 180 mg/day as the RP2D. 
The primary objectives of phase 2 of the ASTX660-01 trial are to explore the single-
agent antitumor activity of ASTX660 in selected tumor types that are characterized by a 
molecular feature that may confer sensitivity to ASTX660. Phase 2 is designed to enroll 
patients with head and neck squamous cell carcinoma (HNSCC), DLBCL, PTCL, CTCL, 
and cervical carcinoma, as well as other tumor types that are characterized by a molecular 
feature that may confer sensitivity to ASTX660 (eg, oncogenic activation of the NF-κB 
pathway or documented amplification of the gene loci encoding cIAP1 or cIAP2), 
pending confirmation by the Astex medical monitor. It is designed to initially enroll 14 
subjects in each of 6 patient populations (6 tumor types) (the first stage) and then if 1 or 
more responses are observed in any cohort, the cohort could be expanded to a total of 
30 subjects (the second stage). Responses have been observed in the PTCL and CTCL 
cohorts in the first stage, and only these 2 cohorts have entered the second stage and 
enrollment of additional subjects in these cohorts is under way. 
As mentioned earlier, PTCL comprises a variety of tumor types and prognosis varies 
greatly among them. The 5-year survival rate of PTCL NOS and AITL, which are both 
relatively common in Japan, is approximately 30% and the median overall survival (OS) 
is approximately 2 to 3 years. The prognosis of relapsed or refractory PTCL is worse than 
that. Lately, multiple agents have been approved in Japan for the treatment of relapsed or 
refractory PTCL. Although all these drugs achieve a certain overall response rate (ORR), 
which has been used as the primary endpoint in clinical trials, none of them are 
recommended as established standard of care, and there remains limited treatment options 
for relapsed or refractory PTCL. Based on the convenience of an oral formulation and a 
novel mechanism of action that differs from that of the existing agents, ASTX660 has the 
potential to become a new therapeutic option for patients with relapsed or refractory 
PTCL. 
2.3 
Known and Potential Risks and Benefits 
As of data cutoff date (04 Jun 2019), 152 subjects were exposed to ASTX660 in phase 1 
and 2 of the ASTX660-01 trial. Frequently reported investigational medicinal product 
(IMP)-related adverse events (AEs) (incidence of ≥ 10%) included lipase increased 
(23%), amylase increased (22%), nausea (16%), fatigue (14%), rash/rash maculo-papular 

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(12%/14%), diarrhoea (13%), pruritis (12%), anaemia (11%), and alanine 
aminotransferase increased (11%). Frequently reported IMP-related AEs of ≥ Grade 3 
(incidence of ≥ 5%) included lipase increased (11%), amylase increased (7%), and rash 
maculo-papular (7%). IMP-related serious AEs (SAEs) that occurred in more than 
1 subject included pneumonitis (5 subjects, 3.3%), rash maculo-papular (3 subjects, 
2.0%), and pancreatitis (2 subjects, 1.3%). These events represent potential risks of 
exposure to ASTX660 in the present trial. 
Exposure to ASTX660 and participation in the present trial are expected to provide 
clinical benefits including tumor decrease and suppression of primary disease 
exacerbation. 
3 
Objectives and Endpoints 
Table 3-1 
Trial Objectives and Endpoints 
Objectives 
Endpoints 
Primary: 
Phase 1 (dose escalation part): To evaluate the 
tolerability and safety of ASTX660 in patients with 
relapsed/refractory peripheral T-cell lymphoma 
(r/r PTCL) and patients with relapsed/refractory 
cutaneous T-cell lymphoma (r/r CTCL) and 
determine the recommended dose (RD) for phase 2 
Phase 1 (ATLL expansion part): To evaluate the 
safety of ASTX660 at the RD in patients with 
relapsed/refractory adult T-cell 
leukemia/lymphoma (r/r ATLL) 
Phase 2: To evaluate the efficacy of ASTX660 at 
the RD in patients with r/r PTCL 
Primary: 
Phase 1 (dose escalation part): Dose-limiting 
toxicity (DLT) and safety 
Phase 1 (ATLL expansion part): Safety 
Phase 2: ORR as assessed by the Central Efficacy 
Evaluation Committee based on Lugano response 
criteria for non-Hodgkin lymphoma (2014)1 
proposed by the International Working Group 
(IWG) 
 
Phase 2: 
Secondary efficacy: 
• 
Duration of response (DOR) 
• 
PFS 
• 
OS 
• 
Time to response (TTR) 
• 
Time to progression (TTP) 
• 
Proportion of subjects who proceed to 
transplantation 
• 
ORR as assessed by the investigator or 
subinvestigator 

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Table 3-1 
Trial Objectives and Endpoints 
Objectives 
Endpoints 
Secondary: 
Phase 1 (dose escalation and ATLL expansion 
parts): 
• 
To evaluate the PK of ASTX660 
• 
To evaluate the efficacy of ASTX660 
Phase 2: 
• 
To evaluate the safety of ASTX660 
• 
To evaluate the PK of ASTX660 
Pharmacokinetics: Plasma ASTX660 
concentrations over time, PK parametersa (see 
below for details), and dose proportionalityb,c 
• 
Day 1: Cmax, AUC∞, AUCt, tmax, λz, 
AUC_%Extrap, t1/2,z, CL/F, CL/F/BW, 
tlast, Cmax/D,b AUC∞/D,b AUCt/Db 
• 
Day 7: Cmax, AUC24h, tmax, λz, t1/2,z, 
CL/F, CL/F/BW, tlast, Cmax/D,b 
AUC24h/D,b Rac(AUC24h), Rac(Cmax), 
Rac(Ctrough) 
 
aFor phase 1 only, bFor the dose escalation part 
only, cOnly when dosing is performed at 3 or 
more dose levels. 
 
Secondary efficacy: 
• 
ORR as assessed by the investigator or 
subinvestigator 
• 
DOR 
• 
PFS 
• 
OS 
• 
TTR 
• 
TTP 
• 
Proportion of subjects who proceed to 
transplantation 
 
Safety:  
AEs, clinical laboratory values, vital signs, body 
weight, Eastern Cooperative Oncology Group 
Performance Status (ECOG PS), 12-lead 
electrocardiograms (ECGs), and left ventricular 
ejection fraction (LVEF) 
 
 
 
 
 
 
 
 
 
 
 
Section 9.4 describes the statistical analysis of the endpoints. 

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4 
Trial Design 
4.1 
Type/Design of Trial 
This is a phase 1/2, multicenter, open-label, uncontrolled trial of ASTX660 in Japanese 
patients with relapsed/refractory (r/r) PTCL, r/r CTCL, and r/r ATLL. This trial 
comprises the following 3 parts: phase 1 (dose escalation part) for subjects with r/r PTCL 
and r/r  CTCL, phase 1 (ATLL expansion part) for subjects with r/r ATLL, and phase 2 
for subjects with r/r PTCL. 
Phase 1 (dose escalation part) will assign 3 to 6 subjects to each dose cohort (see 
Table 4.1-1) to evaluate the tolerability and safety of ASTX660 and then determine the 
recommended dose (RD) based on the dose-limiting toxicity (DLT) observed during the 
DLT assessment period of Cycle 1 and its incidence. Once a tested dose is considered the 
RD of ASTX660 in a particular cohort, this cohort will be expanded to 6 subjects to 
evaluate safety, even if the initial 3 subjects in the cohort have not experienced DLT. 
Table 4.1-1 
Dose Levels in Phase 1 (Dose Escalation Part) 
Dose Level 
Daily Dose 
Dose level 1 
120 mg 
Dose level 2 
150 mg 
Dose level 3 
180 mg 
 
Phase 1 (ATLL expansion part) will enroll 6 to 10 subjects with r/r ATLL to evaluate the 
safety of ASTX660 at the RD and explore efficacy. 
Phase 2 is designed to evaluate the efficacy of ASTX660 in a single arm of subjects with 
r/r PTCL in consideration of the prevalence of PTCL in Japan. The primary endpoint is 
ORR (as assessed by the Central Efficacy Evaluation Committee) and secondary 
endpoints are duration of response (DOR), PFS, OS, time to response (TTR), time to 
progression (TTP), proportion of subjects who proceed to transplantation, and ORR as 
assessed by the investigator or subinvestigator. A total of 33 efficacy-evaluable subjects 
will be enrolled. 
The DLT assessment period of phase 1 (dose escalation part) will begin on Cycle 1 Day 1 
(when trial treatment begins) and end just before the start of Cycle 2 (or before 
withdrawal examination if the subject discontinued the trial before Cycle 2). Subjects can 
continue trial treatment if they do not meet any of the withdrawal criteria and wish to 
continue participation in the trial. Subjects will be hospitalized during Cycle 1 of phase 1 
(dose escalation part) and of phase 1 (ATLL expansion part) and between Cycle 1 Day 1 
and Cycle 1 Day 7 of phase 2. 

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Advancement to the next dose cohort in phase 1 (dose escalation part) will be determined 
according to the dose escalation plan as shown in Table 4.1-2. If the initial 3 subjects 
have not experienced DLT during the DLT assessment period of each dose cohort, then 
the next dose cohort will begin. If 1 of 3 subjects have experienced DLT, an additional 3 
subjects will be enrolled in the current dose cohort to further investigate DLT in 
6 subjects. Thereafter, advancement to the next dose cohort will be permitted only if DLT 
has occurred in no more than 1 of 6 subjects. If DLT has occurred in 2 or more of 
3 subjects or 2 or more of 6 subjects, further dose increase will not be permitted. 
Table 4.1-2 
Dose Escalation Plan for the Dose Escalation Part 
Number of 
Subjects With 
DLT 
Dose Escalation Plan 
0/3 
Advance to the next dose cohorta 
1/3 
Expand the current dose cohort to a total of 6 subjects by enrolling additional 
subjects 
1/6 
Advance to the next dose cohorta 
2/6 
Judge the treatment to be intolerable and identify the one-level lower dose as the 
RDb 
≥ 2/3 
Discontinue subject enrollment in the current dose cohort and identify the one-
level lower dose as the RDb 
aThe sponsor will consult with the medical expert and/or members of the Efficacy and Safety Data 
Review Committee and determine, as appropriate, dose increase and/or a next dose level to be tested 
in consideration of safety observed at the dose levels that have been tested. 
bIf the initial dose level is judged to be intolerable due to the occurrence of DLT, the sponsor will 
consult with the medical expert and/or members of the Efficacy and Safety Data Review Committee 
and consider assessment at the one-level lower dose. 
 
Dose-limiting toxicities in this trial are defined as shown below. Advancement to the next 
dose cohort will be determined based on the occurrence of DLTs during the DLT 
assessment period of each cohort in consideration of recommendations of the Efficacy 
and Safety Data Review Committee. 
<Definition of dose-limiting toxicities> 
The DLT assessment period of phase 1 (dose escalation part) will begin on Cycle 1 Day 1 
(when trial treatment begins) and end just before the start of Cycle 2 (or before 
withdrawal examination if the subjects discontinued the trial before Cycle 2). Dose-
limiting toxicities are defined as AEs occurring during this period that meet any of the 
following criteria, are not related to the primary disease, complication(s), or concomitant 
medication(s), and has a reasonable relationship with ASTX660. The Common 

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Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) will be used to 
determine severity. 
1) Grade 4 thrombocytopenia, Grade 3 or higher clinically significant bleeding, or 
anemia requiring a new erythrocyte transfusion 
2) Febrile neutropenia that does not resolve within 3 days or Grade 4 neutropenia 
that lasts for more than 7 days under appropriate treatment 
3) Liver-associated abnormalities as listed below: 
• Grade 3 or higher alanine aminotransferase (ALT) or aspartate aminotransferase 
(AST) elevation except ALT or AST elevation < 8 × upper limit of normal (ULN) 
for less than 7 days 
• ALT or AST > 3 × ULN and either total bilirubin > 2 × ULN or international 
normalized ratio (INR) > 1.5 
• ALT or AST > 3 × ULN with clinical indications of liver toxicity (symptoms [eg, 
jaundice] or other clinical findings) 
4) Excepting the above AEs, any other Grade 3 or higher nonhematologic or Grade 4 
hematologic toxicity except Grade 3 nausea, vomiting, or diarrhea lasting less 
than 48 hours 
Among Grade 3 nonhematologic toxicities, transient laboratory abnormalities, laboratory 
abnormalities in laboratory test items not specified in the protocol, symptoms and signs 
that can be controlled by symptomatic treatments, and so on will be discussed with the 
Efficacy and Safety Data Review Committee to determine whether or not these events are 
DLTs. Subjects with an ASTX660 compliance of < 85% (ie, less than 12 days of 
completed dosing in a cycle of 14 days of scheduled dosing) during the DLT assessment 
period for reasons other than AEs will be excluded from the DLT-evaluable population in 
the trial. 
During the screening period of phase 2, tumor samples will be collected from subjects 
with r/r PTCL, and central pathological diagnoses will be made according to a separately 
prepared procedure during the trial. The central image review committee will read the 
computed tomography (CT) and positron emission tomography-computed tomography 
(PET-CT) images obtained during the screening period and the treatment and observation 
period and at the withdrawal examination based on the Lugano response criteria for non-
Hodgkin lymphoma (2014)1 proposed by the International Working Group (IWG), and 
then the Central Efficacy Evaluation Committee will centrally assess the reading results. 
4.2 
Scientific Rationale for Trial Design 
4.2.1 
Phase 1 (Dose Escalation Part) 
Phase 1 (dose escalation part) is designed to evaluate the tolerability and safety of 
ASTX660 in patients with r/r PTCL and r/r CTCL and determine the RD for phase 2. As 

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mentioned earlier, the initial dose is 120 mg/day, and 3 to 6 subjects will be enrolled in 
each cohort with a 3 + 3 dose escalation design. The RD will be determined based on the 
DLT observed during the DLT assessment period of Cycle 1 of each cohort and its 
incidence. The tolerability of ASTX660 will be carefully assessed in each cohort with 
due consideration given to subject safety, and advancement to the next cohort will be 
determined according to the dose escalation plan. Hospitalization during Cycle 1 is 
mandatory so that the trial will be conducted with close monitoring of the subject’s 
condition. Treatment interruption criteria and criteria for starting the next cycle are in 
place for possible occurrences of toxicities of ASTX660 to ensure subject safety. 
Target subjects are r/r PTCL and r/r CTCL patients who were previously treated with 
antineoplastics. Both PTCL and CTCL are lymphomas derived from mature T-cells and 
NK cells, and the interim results of an overseas trial suggest that ASTX660 has a certain 
level of efficacy at the RD in subjects with PTCL and CTCL. Considering that the safety 
of ASTX660 has been studied at the same dose level in a few patients with PTCL and 
CTCL in an overseas trial, Otsuka has decided that evaluating the tolerability, safety, and 
PK of ASTX660 in PTCL and CTCL patients is appropriate. 
For PTCL, as mentioned earlier, the Practical Guidelines for Hematological 
Malignancies13 lists salvage therapy, clinical trials, and autologous or allogeneic 
transplantation, as well as palliative therapy and best supportive care as secondary and 
subsequent treatments for PTCL but does not specify regimens or drugs for salvage 
therapy to be used as secondary or subsequent treatments. For CTCL, the Evidence-based 
Clinical Guidelines for Skin Malignancies Version 2 (2015)15 has no description of 
secondary and subsequent treatments. Under such circumstances, Otsuka believes that the 
eligibility criteria defined in this protocol will ensure appropriate selection of subjects 
who meet the target patient criteria as specified in the Guidelines for Clinical Evaluation 
of Antimalignant Tumor Drugs (PFSB/ELD Notification No. 1101001 dated 01 Nov 
2005).16 
Subjects who experience neither AEs that make it difficult to continue the trial nor 
exacerbation of the primary disease during Cycle 1, which is in the DLT assessment 
period of the trial, and are expected to benefit from continued treatment with ASTX660 
will be allowed from an ethical point of view to continue trial treatment after the DLT 
assessment period if they wish to carry on the treatment. Safety and efficacy will also 
continue to be evaluated in these subjects. 
In conclusion, the conduct of phase 1 (dose escalation part) in r/r PTCL and r/r CTCL 
patients is justified scientifically and ethically. 

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4.2.2 
Phase 1 (ATLL Expansion Part) 
Phase 1 (ATLL expansion part) is designed to evaluate the safety of ASTX660 at the RD 
in patients with r/r ATLL and explore efficacy. Aggressive ATLL, the target disease in 
this part of the trial, often follows the rapid progression. Relapsed patients after 
chemotherapy or refractory patients, the target population of the trial, have an even worse 
prognosis. For this reason, Otsuka has decided to conduct an ATLL expansion part for 
ATLL patients after the RD is determined, in addition to a dose escalation part for PTCL 
and CTCL patients. 
Adult T-cell leukemia/lymphoma, listed in “mature T- and NK cell neoplasms” 
categorized by the WHO Classification, is more prevalent in the southwest area of Japan 
compared with other regions in the world. In view of the current lack of adequate 
response of r/r ATLL to the existing treatments, the ATLL expansion part has been 
designed to evaluate the safety of ASTX660 monotherapy, the efficacy of which has been 
shown in PTCL and CTCL patients, in Japanese patients and explore the efficacy as well. 
As in phase 1 (dose escalation part), hospitalization during Cycle 1 is mandatory, 
treatment interruption criteria and criteria for starting the next cycle are in place to ensure 
subject safety, and each examination will be required before advancing to the next cycle. 
In conclusion, the conduct of phase 1 (ATLL expansion part) in r/r ATLL patients is 
justified scientifically and ethically. 
4.2.3 
Phase 2 
Phase 2 is designed to evaluate the efficacy of ASTX660 at the RD in patients with 
r/r PTCL who were previously treated with at least 2 regimens of antineoplastics. For the 
purpose of minimizing interinstitutional differences in tumor type classification and 
efficacy evaluation and ensuring coherent objective evaluation across trial sites, a central 
pathological diagnosis committee and a central image review committee will be 
organized to conduct central assessments. The primary endpoint is ORR as assessed by 
the Central Efficacy Evaluation Committee based on assessments by the central image 
review committee according to the Lugano response criteria for non-Hodgkin lymphoma 
(2014)1 by the IWG. The threshold response rate and the expected response rate are set at 
10% and 30%, respectively, and the target sample size is set at 33 subjects as evaluable 
subjects (see Section 9.1, Sample Size). Given that no standard of care has been 
established for the target disease and the unavailability of trial results for ASTX660 
monotherapy in PTCL patients who previously received secondary treatment, 10% is 
selected as a threshold response rate that could represent a certain level of efficacy. The 
expected response rate is selected based on ORRs observed in patients who previously 

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received at least 1 regimen of antineoplastic therapies in Japanese trials conducted for 
gaining approval of antineoplastics that are currently approved for the indication of 
r/r PTCL17,18,19,20, as well as on the expectation that ASTX660 may also yield a similar 
response rate in r/r PTCL patients who previously received at least 2 regimens of 
antineoplastics. 
The eligibility criteria have been determined in consultation with the Guidelines for 
Clinical Evaluation of Antimalignant Tumor Drugs (PFSB/ELD Notification 
No. 1101001 dated 01 Nov 2005)16 to ensure that the patients selected for the trial are 
appropriate. 
As in phase 1 (dose escalation part), hospitalization during Cycle 1 is mandatory, 
treatment interruption criteria and criteria for starting the next cycle are in place to ensure 
subject safety, and each examination will be required before advancing to the next cycle. 
Hospitalization for 7 days from the first IMP administration through Cycle 1 Day 7 is 
mandatory. 
In conclusion, the conduct of phase 2 in r/r PTCL patients is justified scientifically and 
ethically. 
4.3 
Dosing Rationale 
 
 
 
 
 

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4.4 
End of Trial Definition 
The end of trial date is defined as the last date of contact or the date of final contact 
attempt from the end of trial electronic case report form (eCRF) page for the last subject 
completing or withdrawing from the trial. 
5 
Trial Population 
Patients with r/r PTCL, patients with r/r CTCL, and patients with r/r ATLL 
• Phase 1 (dose escalation part): A maximum of 18 subjects with r/r PTCL or 
r/r CTCL (3 to 6 subjects/cohort) 
• Phase 1 (ATLL expansion part): 6 to 10 subjects with r/r ATLL 
• Phase 2: 33 subjects with r/r PTCL (as efficacy-evaluable subjects) 
 
 
 
 
5.2 
Eligibility Criteria 
5.2.1 
Inclusion Criteria 
Exceptions for eligibility criteria will not be permitted during the trial by the investigator 
or subinvestigator. 
Subjects are required to meet the following inclusion criteria during the screening period 
as specified in the schedule of assessments (see Table 1.3-1, Table 1.3-3, and 
Table 1.3-4): 
1) Patients 20 years of age or older at the time of informed consent and who provide 
written consent to participate in the trial using the informed consent form (ICF) 
approved by the institutional review board (IRB). 
2) Patients with T-cell lymphoma with a histopathologic diagnosis of any of the 
following based on the WHO Classification (2017): 
<Peripheral T-cell lymphoma>: Phase 1 (dose escalation part) and phase 2 
For the purpose of this trial, peripheral T-cell lymphoma is defined as mature T- or 
NK cell neoplasms listed in the WHO Classification that fall under any of the 
following subtypes (for phase 2, submission of specimens is required for central 
pathological diagnosis): 

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• Extranodal NK/T-cell lymphoma, nasal type 
• Enteropathy-associated T-cell lymphoma 
• Monomorphic epitheliotropic intestinal T-cell lymphoma 
• Hepatosplenic T-cell lymphoma 
• Subcutaneous panniculitis-like T-cell lymphoma 
• Peripheral T-cell lymphoma, NOS 
• Angioimmunoblastic T-cell lymphoma 
• Follicular T-cell lymphoma 
• Nodal peripheral T-cell lymphoma with T-follicular helper cells phenotype 
• Anaplastic large cell lymphoma, ALK positive 
• Anaplastic large cell lymphoma, ALK negative 
<Cutaneous T-cell lymphoma>: Phase 1 (dose escalation part) 
For the purpose of this trial, cutaneous T-cell lymphoma is defined as mature T- or 
NK cell neoplasms listed in the WHO Classification that fall under any of the 
following subtypes: 
• Mycosis fungoides 
• Sézary syndrome 
• Primary cutaneous CD30 positive T-cell lymphoproliferative disorders 
• Primary cutaneous peripheral T-cell lymphoma, rare subtypes 
<Adult T-cell leukemia/lymphoma>: Phase 1 (ATLL expansion part) 
Patients with a diagnosis of ATLL classified into acute, lymphoma, or chronic type 
with unfavorable prognostic factors who are positive for serum anti-human T-cell 
leukemia virus type 1 antibody. 
3) Patients who previously received systemic antineoplastics to treat the primary 
disease as indicated below. 
<Peripheral T-cell lymphoma>: Phase 1 (dose escalation part) 
Relapsed or refractory patients who previously received at least 1 regimen of 
antineoplastics (oral corticosteroid monotherapy is not included in this category). 
Patients with CD30-positive anaplastic large cell lymphoma must have a history of 
treatment with brentuximab vedotin.a 
<Peripheral T-cell lymphoma>: Phase 2 
Relapsed or refractory patients who previously received at least 2 regimens of 
antineoplastics (oral corticosteroid monotherapy is not included in this category). 

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Patients with CD30-positive anaplastic large cell lymphoma must have a history of 
treatment with brentuximab vedotin.a 
<Cutaneous T-cell lymphoma> 
Relapsed or refractory patients who previously received at least 1 regimen of 
systemic antineoplastics (oral corticosteroid monotherapy is not included in this 
category). Patients with mycosis fungoides or Sézary syndrome must have a history 
of treatment with mogamulizumab.a 
<Adult T-cell leukemia/lymphoma> 
Relapsed or refractory patients who previously received at least 1 regimen of 
antineoplastics. Patients who are positive for CCR4 must have a history of treatment 
with mogamulizumab.a 
aThis criterion does not apply to patients for whom treatment has been judged to be inappropriate or 
those who refused to receive the treatment. 
4) Patients with the following lesion(s) at screening: 
<Peripheral T-cell lymphoma>: Phase 1 (dose escalation part) 
Swollen lymph nodes or extranodal lesions identified by PET-CT or CT during 
screening or within 28 days prior to the first dose of trial treatment. 
<Peripheral T-cell lymphoma>: Phase 2 
Swollen lymph nodes or extranodal lesions measurable in 2 perpendicular diameters 
by CT scan during screening or within 28 days prior to the first dose of trial 
treatment, with the longest diameter exceeding 1.5 cm (swollen lymph nodes) or 
1.0 cm (extranodal lesions). 
<Cutaneous T-cell lymphoma> 
Lesions that can be considered skin lesions during screening. 
<Adult T-cell leukemia/lymphoma> 
At least one of measurable lesions identified by CT scan during screening or within 
28 days prior to the first dose of trial treatment or skin lesions identified during 
screening. 
5) Patients with an Eastern Cooperative Oncology Group (ECOG) Performance 
Status (PS) score of 0 or 1. For phase 2, patients with a PS score of 2 are eligible 
to be enrolled in the trial only if their physical activities are restricted by 
symptoms associated with the primary disease such as accumulation of pleural or 
ascitic fluid. 

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6) Patients with acceptable organ function as indicated below. 
• AST and ALT ≤ 2.0 × ULN (≤ 3.0 × institutional ULN for subjects with hepatic 
involvement). 
• Total bilirubin ≤ 1.5 × institutional ULN. 
• ANC ≥ 1,000/mm3 (≥ 750/mm3 for subjects with bone marrow involvement) 
(Administration of granulocyte colony-stimulating factor [G-CSF] within 14 days 
prior to the test is not allowed). 
• Platelet count ≥ 50,000/mm3 (≥ 25,000/mm3 for subjects with bone marrow 
involvement) (Platelet transfusion within 14 days prior to the test is not allowed). 
• Serum creatinine ≤ 1.5 × institutional ULN or creatinine clearance (calculated by 
Cockcroft & Gault formula) ≥ 50 mL/min. 
• Amylase and lipase ≤ 1.0 × institutional ULN. 
7) Patients who are able to orally receive the IMP. 
8) Patients who are expected to live for at least 3 months. 
9) Fertile, sexually active male patients (excluding those who have had a bilateral 
orchiectomy) or sexually active female patients of childbearing potential, who 
agree to practice 2 different contraceptive measures during the trial and for 
3 months after the last dose of IMP. If birth control is employed, 2 of the 
following methods must be used: vasectomy, tubal ligation, intrauterine device, 
oral contraceptive, and condom (all methods approved or certified in Japan). 
A definition of childbearing potential can be found in Section 10.3. 
[Rationale for Inclusion Criteria] 
1) The age of 20 years was selected as the lower limit because individuals at this age can 
give consent by themselves, and due to ethical considerations based on Good Clinical 
Practice (GCP). 
2), 3), 5), and 6) These criteria were set to define the target population of the trial with 
reference to the Guidelines for Clinical Evaluation of Antimalignant Tumor Drugs 
(PFSB/ELD Notification No. 1101001 dated 01 Nov 2005).16 
4) This criterion was set to evaluate tumor response. 
7) This criterion was set because ASTX660 is an oral formulation. 
8) This criterion was set in consideration of the expected length of time to complete the 
safety evaluation. 
9) This criterion was set in consideration of the safety of subjects and their partners 
5.2.2 
Exclusion Criteria 
Subjects will be excluded if they meet any of the following exclusion criteria at screening 
as specified in the schedule of assessments (Table 1.3-1, Table 1.3-3, and Table 1.3-4): 

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All phase 1 and 2 of the trial 
1) Patients with hypersensitivity to ASTX660 or excipients of the drug product. 
2) Patients with active infection(s) requiring antibacterial, antifungal, or antiviral 
therapies. 
3) Patients with cardiac disease that meets any of the following criteria: 
a) Left ventricular ejection fraction (LVEF) < 50% by echocardiography or 
multiple-gated acquisition (MUGA) scan. 
b) Congestive cardiac failure (Grade 3 or 4 according to New York Heart 
Association [NYHA] functional classification). 
c) Inadequately controlled cardiac disease including unstable angina or 
hypertension requiring hospitalization within the past 3 months (90 days). 
d) History or presence of complete left bundle branch block, third-degree 
(complete) atrioventricular block, cardiac pacemaker, or inadequately 
controlled arrhythmia requiring treatment. 
e) History or presence of long QT syndrome. 
f) History or presence of ventricular arrhythmia requiring aggressive treatment. 
g) Screening 12-lead electrocardiogram (ECG) with QTc interval of ≥ 470 msec. 
h) Any other condition that is medically considered to have the potential to put 
the subject at increased cardiac risk. 
4) Patients who are positive for human immunodeficiency virus (HIV) antibody, 
hepatitis B virus (HBV)-DNA, or hepatitis C virus (HCV) antibody. 
5) Patients with Grade 2 or greater neuropathy. 
6) Patients with significant mental illness or other condition (alcohol or other 
substance abuse/addiction) that, in the opinion of the investigator or 
subinvestigator, predisposes the subject to high risk of noncompliance with the 
protocol. 
7) Patients who received any of the following treatments for the primary disease 
prior to the first dose of trial treatment: 
a) Chemotherapy or radiotherapy within 3 weeks (6 weeks if nitrosoureas) prior 
to trial treatment. 
b) Skin directed therapy including topicals or radiation within 3 weeks prior to 
trial treatment. 
c) Monoclonal antibody therapy within 4 weeks prior to trial treatment. 
d) Other investigational drugs (small molecules or biologics) or investigational 
therapies (including cell-based therapies such as chimeric antigen receptor 
[CAR] T-cell therapy) within the longer of 3 weeks or 5 half-lives prior to 
trial treatment. 
8) Patients with adverse reactions (except for alopecia) to the prior treatment that has 
not resolved to Grade 2. 
9) Patients with concurrent malignancies, except appropriately treated squamous 
carcinoma or basal cell carcinoma of skin or carcinoma in situ of uterine cervix, 

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breast or prostate cancer stable on endocrine therapy, and other previous cancers 
that have not relapsed for at least 5 years. 
10) Patients with central nervous system involvement of lymphoma. 
11) Patients with a history of allogenic hematopoietic stem cell transplantation, or 
those who underwent autologous stem cell transplantation within 14 weeks prior 
to the first dose of trial treatment. 
12) Patients who received corticosteroids > 10 mg/day prednisone equivalent within 
3 weeks prior to the first dose of trial treatment. However, patients without tumor 
decrease on stable corticosteroid therapy at low doses (≤ 10 mg/day prednisone 
equivalent) for more than 3 weeks prior to the first dose of trial treatment can be 
included. In that case, the corticosteroid therapy can be continued without dose 
increase until trial treatment is discontinued. 
13) Patients with a history of gastrectomy. 
14) Patients with a history or presence of pneumonitis (interstitial pneumonia) or 
pulmonary fibrosis. If screening CT scan suggests abnormal shadow of the 
pulmonary interstitium (eg, bilateral ground glass opacity), the investigator or 
subinvestigator should consult with a pulmonologist or a radiologist, as need, to 
determine whether the patient has pneumonitis (interstitial pneumonia) or 
pulmonary fibrosis. 
15) Patients with inadequately controlled diabetes mellitus. 
16) Pregnant or nursing female patients or female patients with a positive pregnancy 
test at screening. Nursing patients cannot participate in the trial even if they 
discontinue breastfeeding. Female patients must undergo a pregnancy test to 
confirm that they are not pregnant at screening. However, a pregnancy test is not 
necessary for female patients without childbearing potential (ie, patients with a 
history of bilateral oophorectomy or hysterectomy or who have been 
postmenopausal for at least 12 months except for cases where menopause could 
be due to the effect of antineoplastic treatment). 
17) Patients who, in the opinion of the investigator or subinvestigator, are otherwise 
ineligible to participate in the trial 
Subjects must agree to restrictions to medications and lifestyle described in Section 6.4 
and Section 5.3, respectively. 
 
[Rationale for Exclusion Criteria] 
1), 2), 3), 4), 5), 8), 14), 15), and 16) These criteria were set in consideration of subject 
safety. 
6), 7), 9), 10), 11), and 13) These criteria were set in consideration of the possible effects 
on safety and efficacy evaluations of ASTX660. 
12) This criterion was set to ensure appropriate efficacy evaluation of ASTX660. 

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17) This criterion was set to allow the investigator or subinvestigator to exercise his/her 
discretion in judging if subjects are ineligible for trial participation. 
5.4 
Screen Failures 
A screen failure is a subject from whom informed consent is obtained and is documented 
in writing (ie, subject signs an ICF), but who is not administered the IMP. 
Subjects who fail to meet the eligibility criteria at screening may be rescreened for the 
test item(s) that did not meet the eligibility criteria at the first screening, and those who 
meet the eligibility criteria at rescreening can be enrolled. New consent is not required if 
rescreening takes place during the allowable window of the screening period, and only 
test item(s) for which variables have changed will be retested. Screening failures due to 
inability to be rescreened within the allowable window of the screening period must 
provide new written consent prior to rescreening and will be assigned a new subject ID. 
If the subject meets the definition of a screen failure in this trial, the following 
information will be recorded in the CRF: 
• Date of informed consent 
• Visit date (screening visit) 
• Demographics (collection date, birth date, sex, race, ethnicity, country) 
• Result of eligibility assessment 
• Screen failure date 
• Reason for screen failure 
 

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6 
Trial Treatments 
6.1 
Trial Treatments Administered 
For information regarding the dose regimen and treatment period, including the follow-up 
period, for each treatment group of the trial, see Section 1.3 and Section 4.1. 
6.1.1 
Dose and Regimen and Treatment Duration 
1) Investigational Medicinal Product 
ASTX660 capsules: 30 mg and 90 mg (1 capsule contains 30 or 90 mg of ASTX660) 
2) Dose and Regimen 
Trial treatment will be conducted in repeated 28-day cycles comprising 7 days of IMP 
administration (Days 1 - 7 and Days 15 - 21) and 7 days of rest (Days 8 - 14 and 
Days 22 - 28). 
After the dosing time is determined, the IMP will be orally administered once daily at 
approximately the same clock time on Days 1 to 7 and Days 15 to 21 of each cycle 
throughout the trial period. On scheduled visit days, subjects will return to the trial 
site without taking the IMP and receive the IMP after the scheduled examinations. 
Subjects will, in principle, fast for 2 hours before and 2  hours after IMP 
administration. In phase 1 (dose escalation and ATLL expansion parts), subjects will 
fast for at least 10 hours before IMP administration on Cycle 1 Day 1 and 
Cycle 1 Day 7. During fasting, consumption of tea, coffee, and water is permitted but 
other foods or beverages must not be consumed. In cases where a delay of 6 hours or 
longer has elapsed from the scheduled dosing time, IMP administration scheduled on 
that day will be skipped. 
In phase 1 (dose escalation part), treatment will begin with a daily dose of 120 mg, 
which will then be increased to 150  mg and 180 mg according to the dose escalation 
plan. Dose increase in the same subject is prohibited. Phase 1 (ATLL expansion part) 
and phase 2 will adopt the RD determined based on the results of phase 1 (dose 
escalation part). 
3) Treatment Duration 
Trial treatment can be continued until the withdrawal criteria are met. 
6.1.2 
Treatment Interruption Criteria 
In phase 1 (dose escalation part), if a DLT occurs in Cycle 1, trial treatment will be 
discontinued. If any AE corresponding to a DLT occurs in and after Cycle 2, trial 
treatment will be suspended, and if the event fails to improve by 1 or more grades (eg, 

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from Grade 3 to Grade 2) within 3 weeks following the onset of the event, trial treatment 
will be discontinued. If the event improves to the point where it no longer meets the DLT 
criteria and satisfies the criteria for starting the next cycle as described in Section 6.1.3, 
trial treatment will be resumed with the next cycle at a one-level lower dose (30-mg 
reduction per level). The dose may be reduced down to 60 mg (eg, a maximum reduction 
equivalent to 3 dose levels is permitted for subjects assigned to 150 mg [dose level 2]), 
and the dose must not be increased following dose reduction. 
In phase 1 (ATLL expansion part) and phase 2, if any AE corresponding to a DLT 
occurs, trial treatment will be suspended, and if the event fails to improve by 1 or more 
grades within 3 weeks following the onset of the event, trial treatment will be 
discontinued. If the event improves to the point where it no longer meets the DLT criteria 
and satisfies the criteria for starting the next cycle as described in Section 6.1.3, trial 
treatment will be resumed with the next cycle at a one-level lower dose. The dose may be 
reduced down to 60 mg, and the dose may be increased up to the RD following dose 
reduction at the discretion of the investigator or subinvestigator (the dose should be 
decreased or re-increased cycle by cycle, not within a cycle). 
In addition, in phase 1 (ATLL expansion part) and phase 2, trial treatment can be 
suspended if the investigator or subinvestigator decides that treatment interruption is 
necessary, but adjustment of the dosing schedule to compensate for missed doses (eg, 
administering the IMP on Day 16 to compensate a missed dose on Day 8) is prohibited. 
The dose may be reduced by 1 dose level to 60 mg cycle by cycle with close monitoring 
for subject’s general condition and AEs. Following dose reduction, the dose may be 
increased up to the RD at the discretion of the investigator or subinvestigator (the dose 
should be decreased or re-increased cycle by cycle, not within a cycle). 
The dose may be reduced down to 60 mg. In the event that an unacceptable adverse 
reaction occurs after dose reduction to 60 mg, trial treatment will be discontinued. 
6.1.3 
Criteria for Starting the Next Cycle 
The following criteria will be confirmed to be met within 7 days before start of the next 
cycle. 
• AST and ALT ≤ 5 × institutional ULN 
• Total bilirubin ≤ 2 × institutional ULN 
• Lipase and amylase ≤ 2 × institutional ULN 
• Confirmed or suspected cytokine release syndrome, pneumonitis, and interstitial 
pneumonia: Disappeared 

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• Nonhematologic toxicities (including skin rash, facial nerve disorder and facial 
weakness, and left ventricular ejection fraction decreased) other than the above: 
Grade 2 or less 
If the above criteria are not satisfied, the next cycle may be postponed up to Day 50. If 
the above criteria are still not satisfied on Day 50, then subsequent treatment will be 
discontinued. 
For information regarding the dose regimen and treatment period (including the follow-
up period) for each treatment group of the trial, see Section 1.3 and Section 4.1. 
6.1.4 
Medical Devices 
Not applicable. 
6.2 
Management of Investigational Medicinal Product 
For full details on IMP management, please refer to the ASTX660 IB and a separate 
procedure. 
6.2.1 
Packaging and Labeling 
Investigational medicinal product will be provided by the sponsor or designated agent to 
the IMP manager. 
 
 
will be labeled to clearly disclose the compound ID, trial number, 
sponsor’s name and address, a statement that the product is for trial use, lot number, 
expiration date, storage method, route of administration, appropriate precautionary 
statements, and other information required by local regulatory authorities. 
6.2.2 
Storage 
The IMP will be stored in a securely locked cabinet or enclosure. Access will be limited 
to the IMP manager. 
The IMP will be stored according to the conditions indicated on the IMP label. 
The trial site staff will maintain a temperature log in the IMP storage area to record the 
temperature. 
6.2.3 
Accountability 
The IMP manager must maintain an inventory record of IMP received, dispensed, 
administered, destroyed, and returned. The IMP manager must not provide IMP to any 
patient not participating in this protocol. 

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6.2.4 
Returns and Destruction 
Upon completion or termination of the trial, all used IMP containers, unused IMP, and 
partially used IMP must be returned to the sponsor or a designated agent. All IMP 
returned to the sponsor must be accompanied by the appropriate documentation and be 
clearly identified by protocol number and trial site number on the outermost shipping 
container. Returned supplies should be in the original containers (eg, subject kits). The 
assigned trial monitor will facilitate the return of used IMP containers, unused IMP, and 
partially-used IMP. 
6.2.5 
Reporting of Product Quality Complaints 
A Product Quality Complaint (PQC) is any written, electronic, or oral communication 
provided by a healthcare professional, consumer, subject, medical representative, 
competent authority, regulatory agency, partner, affiliate, or other third party that alleges 
deficiencies or dissatisfaction related to the identity, quality, labeling, packaging, 
reliability, safety, durability, tampering, counterfeiting, theft, effectiveness, or 
performance of a medicinal product or medical device after it is released for distribution. 
Examples include, but are not limited to, communications involving: 
• Failure/malfunction of a product to meet any of its specifications  
• Incorrect or missing labeling 
• Packaging issues (eg, damaged, dirty, crushed, missing product) 
• Bottle defects (eg, under-fill, over-fill, no safety seal) 
• Vial defects 
• Loss or theft of product 
 
6.2.5.1 
Eliciting and Reporting Product Quality Complaints 
The investigator/subinvestigator or designee must record all PQCs identified through any 
means from the receipt of the IMP from the sponsor or sponsor’s designee, through and 
including reconciliation and up to destruction, including subject IMP dosing. The 
investigator/subinvestigator or designee must notify the sponsor or sponsor’s designee 
 of the information specified in Section 6.2.5.2 
by email immediately after becoming aware of the PQC. 
Identification of a PQC by the subject should be reported to the site investigator or 
subinvestigator, who should then follow the reporting mechanism above. 
6.2.5.2 
Information Required for Reporting Product Quality Complaints 
• Description of a PQC 

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• Reporter identification (eg, subject, investigator or subinvestigator, site, etc) 
• Reporter contact information (eg, address, phone number, e-mail address) 
• ID of material (product/compound name, kit number) 
• Clinical protocol reference (number and/or trial name) 
• Dosage form/strength (if known) 
• Photos (if available) 
• Availability of complaint sample for return 
 
6.2.5.3 
Return Process for Product Quality Complaints 
Indicate during the report of the PQC if the complaint sample is available for return. The 
sponsor may provide sample return instructions, when applicable. 
It must be documented in the site accountability record that the complaint sample for a 
dispensed kit has been forwarded to the sponsor for complaint investigation. 
6.2.5.4 
Assessment/Evaluation 
Assessment and evaluation of PQCs of the IMP will be handled by the sponsor. 
6.3 
Measures to Minimize/Avoid Bias 
Not applicable because this is an open-label trial. 
6.4 
Subject Compliance 
Subjects will be under the supervision of the investigator or subinvestigator during the 
trial. The investigator or subinvestigator will instruct subjects to comply with the 
following: 
• Adhere to the specified dose and regimen when taking the IMP. 
• Adhere to the specified schedule during the trial. 
• Do not take any prohibited concomitant medications (see Section 6.5.1, Prohibited 
Medications). 
• Do not undergo any prohibited concomitant therapies (see Section 6.5.1, Prohibited 
Medications). 
• Do not communicate to third parties any information obtained through participating 
in the trial. 
 
6.5 
Prior Medications and Concomitant Medications or Therapies 
The investigator or subinvestigator will record all regimens or medications used and 
therapies performed for the primary disease prior to the start of trial treatment in the CRF. 

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The investigator or subinvestigator will also record all concomitant medications and 
therapies taken by the subject from the date of signing the ICF through the withdrawal 
examination in the CRF. The investigator or subinvestigator will also record all 
medications and therapies taken by the subject for treatment of an AE or which caused an 
AE up to 30 days after the last dose of IMP or the start date of new therapy, including 
new exploratory therapy, for the primary disease, whichever is earlier, in the CRF. For 
concomitant medications, the following will be recorded in the CRF: medication, 
indication, dose, frequency, route, start date and end date. For concomitant therapy, the 
following will be recorded in the CRF: therapy, indication, start date and end date. 
6.5.1 
Prohibited Medications 
The following medications or therapies must not be used from informed consent until the 
withdrawal examination. 
• Treatments (including chemotherapy, radiotherapy, hematopoietic stem cell 
transplantation, ultraviolet therapy, extracorporeal photochemotherapy, and total skin 
electron beam therapy) for the primary disease 
• Commencement of systemic administration of corticosteroids > 10 mg/day 
prednisone equivalent or dose increase of oral corticosteroids that the subject has 
been taking at a low dose since before participation in the trial. However, the use of 
such medications for the treatment of an AE is permitted. 
• Live vaccines 
• Other IMPs 
During the DLT assessment period, the use of G-CSF or other hematopoietic growth 
factors for a primary preventive purpose is prohibited. 
6.5.2 
Permitted Supportive and Preventive Therapies 
Medications or treatments except for prohibited concomitant medications and therapies 
may be used. Supportive therapies to ameliorate primary disease-related symptoms, 
transfusion, and treatments required for management of general conditions may also be 
used at the discretion of the investigator or subinvestigator. Preventive administration of 
antibiotics (eg, sulfamethoxazole-trimethoprim [ST]) for bacterial, fungal, viral, and 
opportunistic infections associated with the primary disease is recommended. All 
supportive and preventative therapies will be recorded in the CRF. 
 
 

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Drugs with the potential to induce torsades de pointes ventricular 
tachycardia must also be used carefully. 
6.5.3 
Rescue Medications 
Not applicable. 
6.6 
Intervention After the End of the Trial 
Not applicable. 
7 
Stopping Rules, Withdrawal Criteria, and Procedures 
7.1 
Entire Trial or Treatment 
If the sponsor terminates or suspends the trial for any reason, prompt notification will be 
given to the heads of the trial sites and regulatory authorities in accordance with 
regulatory requirements. 
7.2 
Individual Site 
Individual trial site participation may be discontinued by the sponsor, the investigator, or 
the IRB if judged to be necessary for medical, safety, regulatory, ethical, or other reasons 
consistent with applicable laws, regulations, and GCP. The head of a trial site will notify 
the sponsor promptly if the trial is terminated by the investigator or the IRB at the site. 
7.3 
Individual Subject Discontinuation 
7.3.1 
Treatment Interruption 
See Section 6.1.2, Treatment Interruption Criteria. 
7.3.2 
Treatment Discontinuation 
After trial treatment begins, a subject may stop treatment permanently for a variety of 
reasons. Treatment discontinuations may be initiated by a subject who is not satisfied 
with treatment or may become medically necessary due to AEs, required treatment with a 
disallowed medication or therapy, or other issues, as determined by the investigator or 
subinvestigator. However, each investigator or subinvestigator must comprehensively 
review the circumstances and offer the subject options for continued treatment to the 
degree possible as described in Section 7.3.5, Procedures to Encourage Continued Trial 
Participation. 

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7.3.3 
Documenting Reasons for Treatment Interruption or 
Discontinuation 
All subjects have the right to discontinue the trial, and the investigator or subinvestigator 
can discontinue a subject’s participation in the trial if medically necessary. In addition, 
subjects must discontinue the trial if they meet any of the following criteria. Only 1 
reason (main reason) for discontinuation will be recorded in the CRF. 
• AE 
− A DLT occurred in phase 1 (dose escalation part) 
− An AE corresponding to a DLT occurred in and after Cycle 2 of phase 1 (dose 
escalation part), or in phase 1 (ATLL expansion part) or phase 2, and the event 
has not improved based on the DLT criteria despite 3-week treatment interruption, 
or an adverse reaction occurred after dose reduction to 60 mg 
− The criteria for starting the next cycle are not satisfied even after the next cycle 
has been postponed to Day 50. 
− Grade > 3 interstitial pneumonia developed 
− Continuing IMP places the subject at undue risk as determined by the investigator 
or subinvestigator (eg, a safety concern that is possibly, probably, or likely related 
to IMP) 
• Obvious exacerbation or relapse of the primary disease requiring an alternative 
therapy 
• Pregnancy of the subject (see Section 10.3) 
• Significant protocol deviation 
• The subject’s request to discontinue trial treatment for reasons not related to safety or 
efficacy 
• Withdrawal of consent by subject 
• Lost to follow-up 
• Death 
• The investigator decides that trial continuation is not in the best interests of the 
subject (for reasons other than AEs) 
• Other 
 
If the subject discontinues IMP due to an AE, the investigator/subinvestigator, or other 
trial personnel, will make every effort to follow the event until it has resolved or 
stabilized. Follow-up procedures in Section 7.3.2, Treatment Discontinuation, must be 
followed. Subjects who discontinue trial treatment will remain under observation after the 
withdrawal examination. 

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7.3.4 
Withdrawal of Consent 
All subjects have the right to withdraw their consent from further participation in the trial 
at any time without prejudice. Subjects cannot withdraw consent for use of data already 
collected as part of the trial but can withdraw consent only for future participation. The 
investigator or subinvestigator can also discontinue a subject’s participation in the trial at 
any time if medically necessary. Unless the subject provides their written withdrawal of 
consent or there is other written documentation by the investigator or subinvestigator 
confirming the subject’s verbal intent to completely withdraw from the trial, subjects 
should be followed for all protocol-specified evaluations and assessments, if possible. 
Complete withdrawal of consent requires a subject’s refusal of ALL of the following 
methods of follow-up: 
• Participation in all follow-up procedures specified in the protocol (whether in-clinic, 
by telephone, or by a home visit). 
• Participation in a subset of protocol specified follow-up procedures (by a frequency 
schedule and method, as agreed by subject and trial personnel). 
• Contact of the subject by trial personnel, even if only by telephone, to assess current 
medical condition, and obtain necessary medical or laboratory reports relevant to the 
trial’s objectives. 
• Contact of alternative person(s) who have been designated in source records as being 
available to discuss the subject’s medical condition, even if only by telephone, mail, 
or e-mail (eg, family, spouse, partner, legal representative, friend, neighbor, or 
physician). 
• Access to medical information from alternative sources (eg, hospital/clinic medical 
records, referring doctor’s notes, public records, dialysis, transplantation or vital 
registries, social media sources). 
 
Withdrawal of consent is a critical trial event and, therefore, should be approached with 
the same degree of importance and care as is used in initially obtaining informed consent. 
The reasons for a subject’s intended withdrawal need to be completely understood, 
documented, and managed to protect the rights of the subject and the integrity of the trial. 
A subject may initially express their desire to discontinue IMP administration, which is 
not equivalent to a complete withdrawal of consent for further participation (see 
Section 7.3.1, Treatment Interruption, and Section 7.3.2, Treatment Discontinuation, 
respectively). A subject may, however, indicate that further trial participation is creating 
a burden on their work, school, or social schedule. Therefore, the investigator or 
subinvestigator should follow the procedures outlined in Section 7.3.3, Documenting 
Reasons for Treatment Interruption or Discontinuation, to determine if the subject can 

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continue participation in the trial if modifications to his/her treatment and/or schedule of 
assessments can be accommodated. Only subjects who withdraw their permission for all 
of the above methods of follow-up are considered to have completely withdrawn their 
consent to participate in the trial. 
 
7.3.5 
Procedures to Encourage Continued Trial Participation 
In all cases of impending IMP discontinuation or consent withdrawal, investigators or 
subinvestigators will be instructed to meet and discuss (without undue coercion) with the 
subject their options of continuing in the trial, preferably on therapy. The investigator or 
subinvestigator should ensure understanding and documentation of the reasons for the 
subject’s desire to withdraw consent. 
7.4 
Definition of Subjects Lost to Follow-up 
Subjects who cannot be contacted during or before the investigation of survival status in 
the treatment period, who do not have a known reason for discontinuation (eg, withdrew 
consent or AE), and for whom a survival status at the end of the trial cannot be 
determined will be classified as “lost to follow-up.” Survival status can be determined 
from a variety of sources, either by obtaining acceptable documentation for death (ie, 
death certificate, medical records, public records, statement by a family member or 
primary care physician) or acceptable documentation for life (ie, direct contact with the 
subject, medical records, successful telephone contact with the subject, statement by a 
family member or primary care physician, or public records). 
The site will make 3 documented attempts to contact the subject by telephone and in the 
event the site is unable to reach the subject by telephone, the site will attempt to contact 
the subject via certified mail or an alternative similar method, where appropriate, before 
assigning a “lost to follow-up” status. 
If the subject was classified as “lost to follow-up,” “Were you able to contact the 
subject?,” “Date of contact/Date of final contact attempt,” and “Contact method” will be 
recorded in the source documents and CRF. 
8 
Trial Procedures 
The assessments to be conducted during the trial are summarized in Section 1.3, Schedule 
of Assessments. 

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8.1 
Efficacy Assessments 
In phase 1 (dose escalation part and ATLL expansion part), ORR as assessed by the 
investigator or subinvestigator, DOR, PFS, OS, TTR, TTP, and proportion of subjects 
who proceed to transplantation will be assessed as the secondary endpoints. 
In phase 2, ORR as assessed by the Central Efficacy Evaluation Committee based on 
Lugano response criteria for non-Hodgkin lymphoma (2014)1 proposed by the IWG will 
be assessed as the primary endpoint. In addition, DOR, PFS, OS, TTR, TTP, proportion 
of subjects who proceed to transplantation, and ORR as assessed by the investigator or 
subinvestigator will be assessed as the secondary endpoints. 
8.1.1 
Response 
8.1.1.1 
Peripheral T-cell Lymphoma 
8.1.1.1.1 
Assessment of Diagnostic Images 
Assessment of CT and PET-CT images in phase 1 (dose escalation part) will be 
performed according to institutional procedures. However, CT scans with contrast will be 
performed. For phase 2, in order to obtain consistent high-quality imaging data from all 
trial sites, scanning will be performed under the same conditions throughout the trial 
period, according to the procedure prepared separately. The date of imaging, and 
response assessment results for target and nontarget lesions will be recorded in the 
medical record and CRF. 
For phase 2, in order to have the imaging diagnosis assessed by an independent imaging 
diagnosis institute, all imaging data obtained during this trial will be provided to the 
sponsor, according to the procedure prepared separately. 
8.1.1.1.2 
Central Image Review Committee 
Phase 2 will include the central image review committee, which is an imaging diagnosis 
institute independent of the parties involved in the trial (eg, sponsor, medical expert, 
investigators, and subinvestigators). The central image review committee will assess the 
imaging data obtained from trial sites, according to the procedure prepared separately. 
Based on the assessment by the central image review committee, the best overall 
response will be determined by the Central Efficacy Evaluation Committee. 
8.1.1.1.3 
Definition of Measurable and Evaluable Lesions 
Subjects eligible for this trial should have at least 1 measurable lesion. 
Measurable lesions are defined as swollen lymph nodes or extranodal lesions measurable 
in 2 perpendicular diameters by CT scan with the longest diameter exceeding 1.5 cm 

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(swollen lymph nodes) or 1.0 cm (extranodal lesions). All other lesions will be 
considered to be evaluable lesions. Measurement will be performed by imaging 
diagnosis. 
Evaluable lesions are defined as lesions that are difficult to follow quantitatively with 
imaging, including pleural effusions and ascites, bone lesions, leptomeningeal disease, 
abdominal masses, and other lesions that cannot be confirmed and followed with 
imaging. 
From measurable lesions, up to 6 of the largest nodal/extranodal lesions as the product of 
the perpendicular diameters will be identified as target lesions. Nodal lesions should be 
from different body regions, where should include, where applicable, mediastinal and 
retroperitoneal areas. Extranodal lesions include those in solid organs (eg, liver, spleen, 
kidneys, and lungs), those with gastrointestinal involvement, and skin lesions noted on 
palpation. 
For disease selected as target lesions, from cranial to caudal, the lesion site, examination 
method, date of examination, long and short diameters (cm) of each lesion, product of 
both diameters (ie, product of the perpendicular diameters), and sum of the product of the 
perpendicular diameters for multiple lesions (SPD) will be recorded in the medical record 
and CRF. 
All measurable and evaluable lesions not selected as target lesions will be identified as 
nontarget lesions, and the lesion site, examination method, and date of examination will 
be recorded in the medical record and CRF. Nontarget lesions include any measurable 
nodal and extranodal lesions not selected as target lesions, and those that are measurable 
but considered abnormal. Bone marrow involvement will be assessed using the result of 
bone marrow aspiration or biopsy. The date of bone marrow aspiration or biopsy and 
examination results will be recorded in the medical record and CRF. 
8.1.1.1.4 
Efficacy Assessment Criteria 
Assessment of the efficacy against PTCL will be based on Lugano response criteria for 
non-Hodgkin lymphoma (2014)1 by the IWG, and the date of CT/PET-CT imaging and 
5-point scale scores and response assessment results for target and nontarget lesions will 
be recorded in the medical record and CRF. The assessment criteria for each response 
category are shown below in Table 8.1.1.1.4-1. 

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Table 8.1.1.1.4-1 
Lugano Response Criteria for Non-Hodgkin’s Lymphoma 
(2014) by the IWG 
Response and 
Site 
PET-CT-Based Response 
CT-Based Response 
Complete 
Response (CR)  
Complete Metabolic Response 
(CMR) 
Complete Radiologic Response 
Nodal and 
extranodal lesions 
5-PSa Score 1, 2, or 3 with or without 
residual massb 
Target lesions must regress to ≤ 1.5 cm 
in LDi. 
No extralymphatic sites of disease 
Nontarget lesions 
Not applicable 
Absent 
Organ 
enlargement 
Not applicable 
Regress to normal 
New lesions 
None 
None 
Bone marrow 
involvement 
No evidence of FDG-avid disease in 
marrow. If bone marrow involvement 
positive is confirmed at screening by 
bone marrow aspiration or biopsy, 
bone marrow involvement negative 
should be confirmed by the same 
method. 
Normal by morphology; if 
indeterminate, flow cytometry or 
immunohistochemistry negative 
Partial Response 
(PR) 
Partial Metabolic Response (PMR) 
Partial Remission 
Nodal and 
extranodal lesions 
5-PSa Score 4 or 5 with reduced 
uptake compared with baseline and 
residual mass(es) of any size 
≥ 50% decrease in SPD of target lesions 
(up to 6 of the largest measurable 
lesions)c 
Nontarget lesions 
Not applicable 
No increase (Absent/normal, or 
regressed) 
Organ 
enlargement 
Not applicable 
Spleen must have regressed by > 50% in 
length beyond normal. 
New lesions 
None 
None 
Bone marrow 
involvement 
Residual uptake higher than uptake in 
normal marrow, but reduced compared 
with baseline (diffuse uptake 
compatible with reactive changes from 
chemotherapy is allowed). If there are 
persistent focal changes in the marrow 
in the context of a nodal response, 
consideration should be given to 
further evaluation with MRI or biopsy, 
or an interval PET scan. 
Not applicable 
No Response or 
Stable Disease 
(NR/SD)  
No Metabolic Response 
Stable Disease 
Target lesions 
Extranodal lesions 
5-PSa Score 4 or 5 with no significant 
change in FDG uptake from baseline at 
any time during treatment or the end of 
treatment 
< 50% decrease from baseline in SPD of 
target lesions (up to 6 of the largest 
measurable lesions); no criteria for 
progressive disease are met. 
Nontarget lesions 
Not applicable 
No increase consistent with progression 
Organ 
enlargement 
Not applicable 
No increase consistent with progression 
New lesions 
None 
None 

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Table 8.1.1.1.4-1 
Lugano Response Criteria for Non-Hodgkin’s Lymphoma 
(2014) by the IWG 
Response and 
Site 
PET-CT-Based Response 
CT-Based Response 
Bone marrow 
involvement 
No change from baseline 
Not applicable 
Progressive 
Disease (PD) 
Progressive Metabolic Disease 
Progressive Disease 
Individual target 
lesions 
Extranodal lesions 
5-PSa Score 4 or 5 with an increase in 
intensity of FDG uptake from baseline 
and/or 
New FDG-avid foci consistent with 
lymphoma during treatment or at the 
end of treatment. 
At least 1 of the following is met:  
PPD progression: 
≥ 1 individual nodal lesion is abnormal 
with all of the following: 
LDi > 1.5 cm and 
Increase by ≥ 50% from PPD nadir and 
Increase in LDi or SDi from nadir 
0.5 cm (for lesion ≤ 2 cm) 
1.0 cm (for lesion > 2 cm) 
In the setting of splenomegaly, the 
splenic length must increase by > 50% 
of the extent of its prior increase beyond 
baseline. 
If no prior splenomegaly, must increase 
by at least 2 cm from baseline. 
New or recurrent splenomegaly. 
Nontarget lesions 
None 
New nontarget lesions or clear 
progression of preexisting nontarget 
lesions 
New lesions 
New FDG-avid foci consistent with 
lymphoma. False positives are 
unlikely. If etiology of new lesions is 
uncertain, a biopsy or interval PET 
scan may be considered. 
Regrowth of previously resolved lesions. 
New node > 1.5 cm in any axis. 
New extranodal site > 1.0 cm in any 
axis; if < 1.0 cm, it should be 
unequivocal and attributable to 
lymphoma. 
Assessable disease of any size 
unequivocally attributable to lymphoma. 
Bone marrow 
involvement 
New or recurrent FDG-avid foci. 
New or recurrent involvement. 
5-PS = 5-point scale; FDG = fluorodeoxyglucose; LDi = longest transverse diameter of a lesion; 
PPD = cross product of the LDi and perpendicular diameter; SDi = shortest axis perpendicular to the 
LDi; SPD = sum of the product of the perpendicular diameters for multiple lesions. 
a5-PS: 1 = no uptake above background; 2 = uptake ≤ mediastinal blood pool; 3 = uptake > mediastinal 
blood pool, but ≤ liver; 4 = uptake moderately > liver; 5 = markedly increased uptake at any site 
involved at baseline compared with liver and/or new lesions estimated to represent lymphoma; 
X = new areas of uptake unlikely to be related to lymphoma. 
bIt is recognized that in Waldeyer's ring or extranodal sites with high physiologic uptake or with 
activation within spleen or marrow (eg, as a result of chemotherapy or G-CSF), uptake may be greater 
than normally seen in the mediastinum and/or liver. In this circumstance, complete metabolic 
response may be inferred if uptake at sites of initial involvement is no greater than the surrounding 
normal tissue, even if the tissue has high physiologic uptake. 
cWhen a lesion is too small to measure on CT, assign 5 mm × 5 mm as the default value. When no 
longer visible, assign 0 × 0 mm. For a node > 5 mm × 5 mm, but smaller than normal, use actual 
measurements for calculation. 

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8.1.1.2 
Cutaneous T-cell Lymphoma 
8.1.1.2.1 
Assessment of Skin Lesions 
Assessment of CTCL skin lesions will be based on the modified severity weighted 
assessment tool (mSWAT).2 From the prespecified percentage total body surface area 
(%TBSA), as shown in Table 8.1.1.2.1-1, for each region where the whole body is 
divided into 12, the surface area of each type of skin lesion in each of the 12 body regions 
will be measured using the surface area of the patient's palm. The area of involvement 
(%TBSA) will be measured for each region of skin patch, plaque, and tumor. For the 
measurement, the area of one hand with the thumb bent inward and the other fingers 
extended can be used as approximately 1%. Subsequently, the total area of involvement 
for each of patch, plaque, and tumor will be calculated, and then multiplied by a 
weighting factor (ie, patch = 1, plaque = 2, and tumor = 4), and these products will be 
summed to calculate the mSWAT skin assessment score. 
Patch is defined as skin lesions of any size without significant elevation or induration, 
and plaque is defined as skin lesions of any size with elevation or induration. Tumor is 
defined as at least 1 solid or nodal lesion ≥ 1 cm diameter with evidence of deep 
infiltration in the skin and/or vertical growth. 
Table 8.1.1.2.1-1 
mSWAT Percentage Total Body Surface Area of Body 
Regions 
Body Region  
%TBSA in 
Body Region 
Patch %TBSA 
(or erythroderma 
without elevation) 
Plaque %TBSA  
(or erythroderma with 
elevation/induration) 
Tumor %TBSA 
(or erythroderma 
with ulceration 
including fissuring) 
Head 
7 
 
 
 
Neck 
2 
 
 
 
Anterior Trunk 
13 
 
 
 
Arms 
8 
 
 
 
Forearms 
6 
 
 
 
Hands 
5 
 
 
 
Posterior Trunk 
13 
 
 
 
Buttocks 
5 
 
 
 
Thighs 
19 
 
 
 
Legs 
14 
 
 
 
Feet 
7 
 
 
 
Groin 
1 
 
 
 
Subtotal 
lesion %TBSA 
 
 
 
 
Weighting factor 
 
×1 
×2 
×4 
Subtotal mSWAT 
skin assessment score 
 
 
 
 
Total mSWAT skin 
assessment score 

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8.1.1.2.2 
Efficacy Assessment Criteria 
Assessment of the efficacy for CTCL skin lesions will be based on the mSWAT, and the 
date of assessment and %TBSA in each body region and responses for each of patch, 
plaque, and tumor will be recorded in the medical record and CRF. Responses will be 
assessed based on the percent change from baseline in the mSWAT skin assessment 
score. The assessment criteria for overall skin lesions using mSWAT are described in 
Table 8.1.1.2.2-1. 
Table 8.1.1.2.2-1 
Assessment of Overall Skin Lesions Using mSWAT 
Response 
Criteria 
Complete response 
(CR) 
No disease evidence: 100% clearance of skin lesions, maintained for at least 4 weeks. No 
disease subsequently confirmed by CT scan 
Partial response (PR) 
≥ 50% decrease in the mSWAT skin assessment score from baseline, maintained for at 
least 4 weeks 
Stable disease (SD) 
< 50% decrease in the mSWAT skin assessment score from baseline 
Progressive disease 
(PD) 
At least a 25% increase in the mSWAT skin assessment score from baseline during the 
trial treatment period 
 
8.1.1.3 
Adult T-cell Leukemia/Lymphoma 
8.1.1.3.1 
Assessment of Diagnostic Images 
Assessment of CT images will be performed according to institutional procedures, and 
the date of CT and response assessment of target and nontarget lesions will be recorded 
in the medical record and CRF. 
8.1.1.3.2 
Definition of Measurable and Evaluable Lesions 
Measurable lesions are defined as swollen lymph nodes or extranodal lesions measurable 
in 2 perpendicular diameters by CT scan with the longest diameter exceeding 1.5 cm 
(swollen lymph nodes) or 1.0 cm (extranodal lesions). All other lesions will be 
considered to be evaluable lesions. Measurement will be performed by imaging 
diagnosis. 
Evaluable lesions are defined as lesions that are difficult to follow quantitatively followed 
with imaging, including pleural effusions and ascites, bone lesions, leptomeningeal 
disease, abdominal masses, and other lesions that cannot be confirmed and followed with 
imaging. 
From measurable lesions, up to 6 of the largest nodal/extranodal lesions as the product of 
the perpendicular diameters will be identified as target lesions. Nodal lesions should be 
from different body regions, where should include, where applicable, mediastinal and 
retroperitoneal areas. Extranodal lesions include those in solid organs (eg, liver, spleen, 

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kidneys, and lungs), those with gastrointestinal involvement, and skin lesions noted on 
palpation. 
For disease selected as target lesions, from cranial to caudal, the lesion site, examination 
method, date of examination, long and short diameters (cm) of each lesion, product of 
both diameters (ie, product of the perpendicular diameters), and SPD will be recorded in 
the medical record and CRF. 
All measurable and evaluable lesions not selected as target lesions will be identified as 
nontarget lesions, and the lesion site, examination method, and date of examination will 
be recorded in the medical record and CRF. Nontarget lesions include any measurable 
nodal and extranodal lesions not selected as target lesions, and those that are measurable 
but considered abnormal. 
8.1.1.3.3 
Efficacy Assessment Criteria 
Assessment of the efficacy for ATLL will be based on Japan Clinical Oncology Group 
(JCOG) Response Criteria for ATLL (2009),21 and the date of assessment, response 
assessment results for each variable, and overall response will be recorded in the medical 
record and CRF. The assessment criteria for each response category are shown below in 
Table 8.1.1.3.3-1. 

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Table 8.1.1.3.3-1 
JCOG Response Criteria for Adult T-Cell Leukemia-Lymphoma 
(2009) 
Overall 
Response 
Variable 
Target Lesions 
Nontarget Lesions 
Bone 
Marrow 
Involve-
ment 
Peripheral 
Blood 
Lesionsd 
Skin 
Lesions 
Hepatomegaly, 
Splenomegaly 
New 
Lesions 
Nodal Extra-
nodal 
Nodal 
Extra-
nodal 
(Abnormal 
Lymphocytes) 
Complete  
response 
(CR) 
Normal Absent 
Normal 
Absent 
Negative 
Normal 
Normal 
Absent 
No 
Partial  
response 
(PR) 
≥ 50% decrease 
in SPDa 
Normal  
or 
no 
increaseb 
Absent 
or 
no 
increaseb 
Irrelevant 
(untested is 
acceptable) 
Normal 
or 
decrease 
Normal  
or 
decreasec 
Absent or 
no increase 
No 
Stable 
disease 
(SD) 
Fails to attain CR, PR, or PD. 
Progressive 
disease 
(PD) 
PD is assessed if any one of the following is met. 
≥ 50% increaseb 
in SPDa 
Increaseb 
or 
re-
enlargement 
Increaseb 
or 
re-
appearance 
Positive 
conversion 
Increase 
or 
reappearance 
Increasec 
  
Increasee  
or 
reappearance 
Yes 
 
or 
 
Nodal target 
 
lesion re-
enlargement 
 
or 
 
extranodal 
 
 target lesion 
reappearance 
Inevaluable 
Any variable is “inevaluable.” 
(NE) 
aSum of the product of the perpendicular diameters for multiple lesions. 
bIncreased target/nontarget lesions: ≥ 50% increase from nadir. 
cSkin lesions: PR, ≥ 50% decrease from baseline; and PD, ≥ 50% increase from baseline. 
dPeripheral blood lesions: CR, abnormal lymphocytes < 5% AND lymphocyte count < 4000/mm3; PR, 
≥ 50% decrease from baseline; and PD, ≥ 50% increase from nadir AND lymphocyte count 
≥ 4000/mm3. 
e≥ 50% increase from baseline 
 
8.1.2 
Best Overall Response 
At trial treatment discontinuation, the best overall response after treatment with 
ASTX660 for each subject will be recorded in the medical record and CRF. 

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8.2 
Pharmacokinetic Assessments 
8.2.1 
Pharmacokinetic Plasma Samples 
Blood samples (3 mL) will be collected in vacutainers containing 
ethylenediaminetetraacetic acid (EDTA) and processed into plasma to determine the 
concentrations of ASTX660. Additional metabolites that are not identified in the protocol 
may also be analyzed, if needed. In addition, PK samples may be used for the 
investigation of a bioanalytical method, if needed. 
Blood samples for PK analysis will be collected at the time points as shown in 
Table 1.3-1 (schedule of assessments). Each blood sampling time point has an allowable 
window as shown in Table 8.2.1-1 and Table 8.2.1-2. 
Table 8.2.1-1 
Time Points of Blood Sampling for Pharmacokinetics and 
Allowable Windows (Phase 1 [Dose Escalation Part and 
ATLL Expansion Part]) 
Time Point 
Allowable 
Window 
Cycle 1 
Cycle 2 
Day 1 
Day 7 
Day 15 
Day 21 
Day 1 
Predose 
 
Xa 
Xb 
Xa 
Xc 
− 
0.5 h postdose 
± 5 min 
X 
X 
− 
− 
− 
1 h postdose 
± 5 min 
X 
X 
− 
− 
− 
2 h postdose 
± 10 min 
X 
X 
− 
− 
− 
1 - 2 h postdose 
− 
− 
− 
X 
X 
X 
3 h postdose 
± 10 min 
X 
X 
− 
− 
− 
4 h postdose 
± 20 min 
− 
− 
X 
X 
− 
5 h postdose 
± 10 min 
X 
X 
− 
− 
− 
6 h postdose 
± 10 min 
X 
X 
− 
− 
− 
8 h postdose 
± 20 min 
X 
X 
X 
X 
− 
24 h postdose 
± 60 min 
Xe (Day 2) 
X (Day 8) 
Xf (Day 16) 
X (Day 22) 
− 
48 h postdose 
± 120 min 
− 
X (Day 9) 
− 
− 
− 
72 h postdose 
± 120 min 
− 
X (Day 10 
− 
− 
− 
Allowable windows are as follows: 
a3 h before administration 
bPredose, AND 24 ± 2 h postdose on Day 6 
cPredose, AND 24 ± 2 h postdose on Day 20 
ePredose on Day 2 
fPredose on Day 16 
 

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Table 8.2.1-2 
Time Points of Blood Sampling for Pharmacokinetics 
and Allowable Windows (Phase 2) 
Time Point 
Allowable Window 
Cycle 1 
Day 1 
Day 7 
Day 21 
Predose 
 
Xa 
Xb 
Xc 
1 - 2 h postdose 
− 
X 
X 
X 
3 - 4 h postdose 
− 
X 
X 
− 
4 h postdose 
± 20 min 
− 
− 
X 
8 h postdose 
± 20 min 
X 
X 
X 
24 h postdose 
± 60 min 
− 
X (Day 8) 
X (Day 22) 
Allowable windows are as follows: 
a3 h before administration 
bPredose, AND 24 ± 2 h postdose on Day 6 
cPredose, AND 24 ± 2 h postdose on Day 20 
 
When vital signs or ECGs are scheduled at the same nominal time as PK sample 
collections, vital signs should be measured and ECGs should be performed before PK 
samples are collected. 
The actual date and time of the PK sample collection will be recorded in the CRF. 
After processing into plasma, aliquots will be placed into appropriately labeled tubes and 
will be placed in a freezer set at −70°C or −20°C, unless otherwise instructed in the 
Operations. 
All plasma samples will be shipped to the bioanalytical laboratory for analysis. 
Additional information will be provided in the Operations. 
 
 
 
 
 

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8.4 
Pharmacogenomic Assessments 
Not applicable. 
8.5 
Biomarker Assessments 
Not applicable. 
 
 
 
 
 
 
 
 

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. 

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8.7 
Safety Assessments 
Details pertaining to the definitions, collection, reporting, and follow-up of AEs are 
described in Section 8.8. 
8.7.1 
Dose Limiting Toxicity 
The definition of DLT and details regarding the DLT assessment period are described in 
Section 4.1, Type/Design of Trial. 
8.7.2 
Clinical Laboratory Assessments 
The clinical laboratory assessments described in Section 10.2 will be performed 
according to the procedures established by the trial site. Blood and urine samples will be 
collected, and the date of blood collection, date of urine collection, and test results will be 
recorded in the CRF. Urine or serum pregnancy test (human chorionic gonadotropin 
[hCG] test) will be performed for females of childbearing potential (FOCBP). 

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The level of HBV-DNA will be monitored in subjects who are positive for HBc antibody 
or HBs antibody at screening, in accordance with the “Guidelines for the prevention of 
hepatitis B virus reactivation in patients receiving immunosuppressive therapy or 
chemotherapy.24” Virus test (HBV-DNA quantification) and serum chemistry will be 
performed from Cycle 2 onward, according to Section 1.3, Schedule of Assessments. 
8.7.3 
Physical Examination 
The investigator or subinvestigator will check physical findings by examining each of the 
following sites: head, ears, eyes, nose, laryngopharynx, chest, abdomen, urogenital 
system, limbs, nerves, skin, and mucosa. The assessment date and results will be recorded 
in the CRF. The same investigator or subinvestigator should perform observations, 
whenever possible. Any clinically significant physical finding that detected after 
screening examination will be recorded as an AE in the CRF. 
8.7.4 
Vital Signs 
After at least a 3-minute rest, blood pressure (systolic/diastolic), pulse rate, SpO2, and 
body temperature will be measured in a sitting position. The date of measurement and 
measurement results will be recorded in the CRF. 
8.7.5 
12-Lead Electrocardiogram (Local) 
According to the procedures established by the trial site, 12-lead ECGs will be performed 
using a 12-lead electrocardiograph. 
In phase 1 (dose escalation part), 12-lead ECGs will be performed at screening, predose 
and 2 hours postdose on Day 15 and Day 21 of Cycle 1, and from Cycle 2 Day 1 onward, 
predose on Day 1 of each cycle. In phase 1 (ATLL expansion part), 12-lead ECGs will be 
performed at screening, predose and 2 hours postdose on Day 1, Day 7, Day 15, and 
Day 21 of Cycle 1, and from Cycle 2 Day 1 onward, predose on Day 1 of each cycle. In 
phase 2, 12-lead ECGs will be performed at screening, predose and 2 hours postdose on 
Cycle 1 Day 7, and from Cycle 2 Day 1 onward, predose on Day 1 of each cycle. 
The investigator or subinvestigator will check each ECG chart and determine whether the 
ECG is normal (within the normal range) or abnormal, and date and sign the chart. The 
date and time of measurement, measured 12-lead ECG data (heart rate, RR interval, PR 
interval, QRS width, QT interval, and QT corrected for heart rate by Fridericia’s formula 
[QTcF] interval), assessment of normality/abnormality, and abnormal findings (if any) 
will be recorded in the CRF. The same investigator or subinvestigator should perform 
assessment, whenever possible. 

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8.7.7 
Other Safety Variables 
8.7.7.1 
Body Weight 
Body weight will be measured according to the procedures established by the trial site, 
and the date of measurement and measurement result will be recorded in the CRF. 
8.7.7.2 
Eastern Cooperative Oncology Group Performance Status 
The investigator or subinvestigator will assess the subject’s PS according to the ECOG 
criteria (see Table 8.7.7.2-1), and the date of assessment and results will be recorded in 
the CRF. 
Table 8.7.7.2-1 
ECOG PS 
Score 
Definition 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light housework, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities; up and 
about more than 50% of waking hours 
3 
Capable of only limited self-care; confined to bed or chair more than 50% of waking hours 
4 
Completely disabled; cannot carry on any self-care; totally confined to bed or chair 
5 
Dead 
Source: ECOG PS (https://ecog-acrin.org/resources/ecog-performance-status [accessed August 2019]) 
 
8.7.7.3 
Echocardiogram 
Echocardiography or MUGA scan will be performed according to the procedures 
established by the trial site, and the LVEF will be measured. The date of measurement, 
measurement method, and measurement result will be recorded in the CRF. 
8.7.7.4 
Lung Field Assessment by PET-CT or CT Scans 
Lung field on CT images by PET-CT or CT scan will be reviewed as part of the safety 
evaluation, and the date of examination, assessment of normality/abnormality (normal, 
abnormal), and abnormal findings (if any) will be recorded in the medical record and 
CRF. Any clinically significant finding will be assessed as an AE. 
8.7.7.5 
Chest X-Ray 
Chest x-ray will be performed according to the procedures established by the trial site, 
and the date of examination, assessment of normality/abnormality (normal, abnormal), 
and abnormal findings (if any) will be recorded in the medical record and CRF. Any 
clinically significant finding will be assessed as an AE. However, if the lung field was 
assessed on CT images within 7 days, its results can substitute for chest x-ray. 

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8.8 
Adverse Events 
8.8.1 
Definitions 
An AE is defined as any untoward medical occurrence in a patients or clinical trial 
subject administered an IMP and which does not necessarily have a causal relationship 
with this treatment. Adverse events would not include information recorded as medical 
history at screening for pre-planned procedures for which the underlying condition was 
known and no worsening occurred. An adverse drug reaction is any untoward and 
unintended response to an IMP related to any dose administered. 
A suspected adverse reaction is any AE for which there is a reasonable possibility that the 
IMP caused the AE. 
Treatment-emergent AEs (TEAEs) are defined as AEs with an onset date on or after the 
start of open-label treatment. In more detail, TEAEs are all AEs which started after the 
start of open-label IMP treatment; or if the event was continuous from baseline and was 
worsening after the start of open-label IMP treatment. However, AEs will not include 
worsening of the primary disease in this trial 
An SAE includes any event that results in any of the following outcomes: 
• Death 
• Life-threatening; ie, the subject was, in the opinion of the investigator or 
subinvestigator, at immediate risk of death from the event as it occurred. It does not 
include an event that, had it occurred in a more severe form, might have caused death. 
• Persistent or significant incapacity/disability or substantial disruption of the ability to 
conduct normal life functions. 
• Requires inpatient hospitalization or prolongs hospitalization. 
− Hospitalization itself should not be reported as an SAE; whenever possible the 
reason for the hospitalization should be reported. 
− Hospitalizations or prolonged hospitalizations for social admissions (ie, those 
required for reasons of convenience or other nonmedical need) are not considered 
SAEs. 
− Prescheduled hospitalization to address a condition that has existed prior to the 
signing of the ICF should not be considered an SAE. 
• Congenital anomaly/birth defect. 
• Other medically significant events that, based upon appropriate medical judgment, 
may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed above; eg, allergic bronchospasm requiring 
intensive treatment in an emergency room or home, blood dyscrasias or convulsions 
that do not result in hospitalization, or the development of drug dependency or drug 
abuse. 

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Nonserious AEs are all AEs that do not meet the criteria for a “serious” AE. 
Immediately Reportable Event (IRE):  
• Any SAE. 
• Any DLT. 
• Any AE related to occupational exposure. 
• Potential serious hepatotoxicity (see Section 8.8.6). 
• Pregnancies are also defined as IREs. Although normal pregnancy is not an AE, it 
will mandate IMP discontinuation and must be reported on an IRE form and the 
Pregnancy Surveillance Form(s) to the sponsor. Pregnancy will only be documented 
on the AE CRF if there is an abnormality or complication. This includes pregnancy of 
the subject or the partner of the subject. 
 
Clinical Laboratory Test Value Changes: It is the investigator/subinvestigator’s 
responsibility to review the results of laboratory tests for each individual subject as they 
become available. The investigator or subinvestigator may repeat the laboratory test or 
request additional tests to verify the results of the original laboratory tests. If this 
laboratory value is considered medically relevant (ie, clinically significant) by the 
investigator or subinvestigator (subject is symptomatic, requiring corrective treatment or 
further evaluation), or if the laboratory value leads to discontinuation, and/or fulfills a 
seriousness criterion, this is considered an AE. 
Severity:  
Severity of AEs will be graded according to CTCAE version 4.03, on a 5-point scale of 
Grades 1 through 5 as follows: 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention 
not indicated. 
Grade 2 
Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living.a 
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self care activities of daily 
living.b 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE. 
A Semi-colon indicates ‘or’ within the description of the grade. 
aInstrumental activities of daily living refer to preparing meals, shopping for groceries or clothes, using 
the telephone, managing money, etc. 
bSelf care activities of daily living refer to bathing, dressing and undressing, feeding self, using the 
toilet, taking medications, and not bedridden. 
 

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IMP Causality: Assessment of causal relationship of an AE to the use of the IMP is 
defined as follows: 
Related:  
There is a reasonable possibility of a temporal and causal 
relationship between the IMP and the AE. 
Not Related:  
There is no temporal or causal relationship between the IMP and 
the AE. 
8.8.2 
Eliciting and Reporting Adverse Events 
The investigator or subinvestigator will regularly assess subjects for the occurrence of 
AEs. To avoid bias in eliciting AEs, subjects should be asked the nonleading question: 
“How have you felt since your last visit?” All AEs (serious and nonserious) reported by 
the subject must be recorded on the source documents and CRF provided by the sponsor. 
Adverse event collection will begin after a subject signs the ICF. 
Medical terminology should be used for AE reporting. Adverse events should be reported 
as a single unifying diagnosis whenever possible or, in the absence of a unifying 
diagnosis, as individual signs or symptoms. 
In addition, the sponsor must be notified immediately by e-mail, in principle, of any IREs 
according to the procedure in Section 8.8.3. Special attention should be paid to recording 
hospitalization and concomitant medications. 
The AE, start date (including start time, in the event vomiting occurs on the scheduled 
date of blood sampling for PK analysis. At a minimum, the hour should be identified in 
the event the exact time is unknown), end date, seriousness, severity, relationship to trial 
treatment (IMP causality), action taken with trial treatment, and outcome will be recorded 
on the source documents and in the CRF. 
8.8.3 
Immediately Reportable Events 
The investigator or subinvestigator must immediately report (within 24 hours), using an 
IRE form, etc, after he/she or site personnel become aware of any IRE (SAE, DLT, AE 
related to occupational exposure, potential serious hepatotoxicity, and confirmed 
pregnancy), in principle, by e-mail to the sponsor or designee using the contact 
information on the cover page of this protocol (please note that the IRE form is NOT the 
AE CRF). The utmost consideration should be given to the protection of subjects' privacy 
when forwarding IRE forms, etc. If reporting by e-mail is not available, communication 
by fax may be used. 
8.8.4 
Medical Device Incidents (Including Malfunctions) 
Not applicable. 

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8.8.5 
Adverse Events of Special Interest 
Not applicable. 
8.8.6 
Potential Serious Hepatotoxicity 
For a subject who experiences an elevation in AST or ALT that is  3 times the ULN, a 
total bilirubin level should also be evaluated. If the total bilirubin is  2 times the ULN, 
complete an IRE form, etc, with all values listed and also report as an AE in the CRF. 
8.8.7 
Procedure for Breaking the Blind 
This trial does not use blinding procedures. 
8.8.8 
Follow-up of Adverse Events 
The follow-up period is defined as 30 days after trial treatment discontinuation or the 
start of new treatment for the primary disease, whichever comes first. 
8.8.8.1 
Follow-up of Nonserious Adverse Events 
Nonserious AEs that are identified at any time from the date on which the subject signs 
the ICF through the last day of the follow-up period must be recorded on the AE CRF 
with the current status (ongoing or resolved/recovered) noted. All nonserious events (that 
are not IREs) that are ongoing on the last day of the follow-up period will be recorded as 
ongoing in the CRF. For any AE having been identified throughout the trial, during 
analysis, additional relevant medical history information may be requested by the sponsor 
to further ascertain causality (including, but not limited to, information such as risk-
related behavior, family history, and occupation). 
8.8.8.2 
Follow-up of Immediately Reportable Events 
This trial requires that subjects be actively monitored for IREs up to the last day of the 
follow-up period. 
Immediately reportable events that are identified or ongoing on the last day of the follow-
up period must be recorded as such on the AE CRF page and the IRE form, etc. If 
updated information (eg, resolved status) on IRE status becomes available after the last 
day of the follow-up period for the subject (up to the last day of the follow-up period for 
the final subject in the entire trial), this must be reported to the sponsor and recorded on 
the AE CRF page and the IRE form, etc, according to the appropriate reporting 
procedures described in Section 8.8.3. 

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It is expected that the investigator or subinvestigator will provide or arrange appropriate 
supportive care for the subject and will provide prompt updates on the subject’s status to 
the sponsor. The investigator or subinvestigator will follow IREs until the events are: 
• Resolved, 
• Stabilized, 
• The subject is lost to follow-up, or 
• Has died. 
 
Resolution means that the subject has returned to the baseline state of health and 
stabilized means that the investigator or subinvestigator does not expect any further 
improvement or worsening of the subject’s condition. The investigator or subinvestigator 
will continue to report any significant follow-up information to the sponsor up to the 
point the event has resolved or stabilized, or the subject is lost to follow-up, or has died. 
Refer to Section 10.3 for additional information regarding the follow-up period for 
subjects that become pregnant or for pregnant partners of male subjects. 
8.8.8.3 
Follow-up and Reporting of Immediately Reportable Events 
Occurring After the Last Day of the Follow-up Period 
Any new IREs reported to the investigator or subinvestigator which occur after the last 
day of the follow-up period and are determined by the investigator or subinvestigator to 
be reasonably associated with the use of the IMP, should be reported to the sponsor 
according to the procedures outlined in Section 8.8.3. This may include IREs that are 
captured on follow-up telephone contact or at any other time point after the defined trial 
period and continue to report any significant follow-up information to the sponsor until 
the events are resolved or stabilized, or the subject is lost to follow-up or has died. 
8.9 
Treatment of Overdose 
For treatment of overdoses, please refer to the IB Section 6.4 for overdose. If the signs 
and symptoms due to overdose meet the criteria for an SAE, the actual dose and clinical 
signs and symptoms associated with an overdose will be recorded on the source 
document and in the CRF, and the sponsor must be notified within 24 hours by e-mail, 
according to the procedure in Section 8.8.3, Immediately Reportable Events. 
8.10 
Subject Assessment Recording 
Not applicable. 

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8.11 
Other Assessments 
8.11.1 
Efficacy and Safety Data Review Committee 
The Efficacy and Safety Data Review Committee will consist of individuals who are 
independent of the parties involved in the trial (eg, sponsor, medical expert, investigators, 
and subinvestigators) and are not directly involved in the trial. The committee will review 
the trial-related safety, serious or unexpected AEs, and efficacy from a third party 
standpoint, and will make recommendations, based on the obtained results of assessment, 
regarding the conduct and results of the trial, including continuation, modification, or 
discontinuation of the trial. For phase 1 (dose escalation part), the committee will also 
make recommendations about DLT assessment, dose, and whether to advance to phase 2. 
For phase 2, the committee will also serve as the Central Efficacy Evaluation Committee. 
8.11.2 
Central Pathological Diagnosis Committee 
Phase 2 will include the central pathological diagnosis committee, which is a pathological 
diagnosis institution independent of the parties involved in the trial (eg, sponsor, medical 
expert, investigators, and subinvestigators). The central pathological diagnosis committee 
will assess the disease type using pathological samples collected from the trial site, 
according to the procedure prepared separately. 
9 
Statistical Considerations 
9.1 
Sample Size 
For phase 1, the sample size was not calculated statistically. In phase 1 (dose escalation 
part), DLT will be evaluated, with reference to section IV., Phase 1 Studies, of 
“Guidelines for Clinical Evaluation of Antimalignant Tumor Drugs (PFSB/ELD 
Notification No. 1101001 dated 01 Nov 2005),16” in 3 to 6 subjects per cohort. In phase 1 
(ATLL expansion part), the sample size will be 6 to 10 subjects to confirm the safety of 
ASTX660 at the RD for phase 2 study in patients with r/r ATLL. 
For phase 2, a threshold response rate (P0) of 10%, an ASTX660 expected response rate 
of 30%, and at one-sided 2.5% level of significance will be used to test the null 
hypothesis H0 of P = P0 against the alternative hypothesis H1 of P > P0 (where, P is the 
response rate of ASTX660) by a proportion test (by Clopper-Pearson method). Under 
these conditions, the sample size needed to achieve a power of 80% was determined to be 
≥ 33 efficacy-evaluable subjects. 
9.2 
Datasets for Analysis 
The safety analysis set includes all subjects that were administered at least 1 dose of IMP. 

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The DLT analysis set include all subjects who received at least 1 dose of IMP and have 
available data necessary for DLT assessment during the DLT assessment period. 
The efficacy analysis set includes all subjects that were administered at least 1 dose of 
IMP. If subjects enrolled in phase 2 are not diagnosed with PTCL by central pathological 
diagnosis, the subjects will not be included in the efficacy analysis set. 
The PK analysis set includes all subjects who received at least 1 dose of IMP and have 
available ASTX660 concentration measurement data for at least 1 time point. 
9.3 
Handling of Missing Data for Primary and Secondary Endpoint 
Analysis 
For primary, secondary, or PK endpoint analysis, missing data will not be imputed. 
9.4 
Statistical Analyses 
Tabulations will be performed for each of phase 1 (dose escalation part), phase 1 (ATLL 
expansion part), and phase 2, and the tabulation for phase 1 (dose escalation part) will be 
performed by cohort. 
9.4.1 
Efficacy Analyses 
For the efficacy analysis set, the analysis of efficacy will be summarized as follows. 
9.4.1.1 
Primary Efficacy Endpoint Analysis 
Regarding the ORR as assessed by the Central Efficacy Evaluation Committee, the ORR 
and its two-sided 95% confidence interval (CI) (by Clopper-Pearson method) will be 
calculated. The response rate is defined as the proportion of responders (subjects who 
have a best overall response of CR or PR) over the analysis set. The frequency of the best 
overall response as assessed by the Central Efficacy Evaluation Committee will be 
summarized. 
9.4.1.2 
Key Secondary Efficacy Endpoint Analysis 
Regarding the ORR as assessed by the investigator or subinvestigator, the ORR and its 
two-sided 95% CI (by Clopper-Pearson method) will be calculated. The frequency of the 
best overall response as assessed by the investigator or subinvestigator will be 
summarized. 
9.4.1.3 
Secondary Efficacy Endpoint Analysis 
Kaplan-Meier plots will be provided for the DOR, PFS, OS, TTR, and TTP, and the 
median and 95% CI will be estimated using the Kaplan-Meier method. The CI will be 
calculated based on Greenwood’s formula. 

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• Duration of response is defined as the period from the date of documented CR or PR 
as the overall response to the date of documented PD as the overall response, date of 
the start of new treatment for the primary disease, or date of death due to any cause, 
whichever occurs earlier. Subjects without a documented PD or death date will be 
censored on the last date of overall response assessment, or responders who undergo 
transplantation will be censored on the date of transplant. 
• Progression free survival is defined as the period from the date of the start of 
ASTX660 treatment to the date of documented PD as the overall response, date of the 
start of new treatment for the primary disease, or date of death due to any cause, 
whichever occurs earlier. Subjects without a documented PD or death date will be 
censored on the last date of overall response assessment, or responders who undergo 
transplantation will be censored on the date of transplant. 
• Overall survival is defined as the period from the date of the start of ASTX660 
treatment to the date of death due to any cause. Subjects without a documented death 
date will be censored on the last date they were known to be alive. 
• Time to response is defined as the period from the date of the start of ASTX660 
treatment to the date of the earliest documented CR or PR as the overall response. 
• Time to progression is defined as the period from the date of the start of ASTX660 
treatment to the date of documented PD as the overall response or date of the start of 
new treatment for the primary disease, whichever occurs earlier. Subjects without a 
documented PD date will be censored on the last date of overall response assessment, 
or responders who undergo transplantation will be censored on the date of transplant. 
Overall response for the definitions of DOR, PFS, TTR, and TTP will be based on 
assessment by the investigator or subinvestigator. 
In addition, the proportion of subjects who proceed to transplantation (proportion of 
subjects who undergo transplantation) will be calculated. 
9.4.1.4 
Control of Experiment-wise Type 1 Error 
The primary efficacy analysis is the ORR and its two-sided 95% CI (by Clopper-Pearson 
method) in phase 2. No multiplicity adjustment will be applied for the primary or other 
efficacy analyses. 
9.4.1.5 
Other Efficacy Endpoint Analysis 
Not applicable. 
9.4.2 
Safety Analysis 
For the safety analysis set unless otherwise indicated, the analysis of safety will be 
summarized as follows. 

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9.4.2.1 
Adverse Events 
All AEs will be coded by system organ class and Medical Dictionary for Regulatory 
Activities (MedDRA) preferred term. The incidence of the following events will be 
summarized: 
• TEAEs 
• TEAEs by CTCAE grade 
• TEAEs potentially causally related to the IMP 
• TEAEs with an outcome of death 
• Serious TEAEs 
• TEAEs leading to discontinuation of the IMP 
 
For phase 1 (dose escalation part), the frequencies of DLTs (number and proportion of 
subjects with DLT) will be summarized in the DLT analysis set. 
9.4.2.2 
Clinical Laboratory Data 
Hematology, serum chemistry, coagulation, and urinalysis (excluding qualitative tests) at 
each time point will be summarized using the following. 
• Descriptive statistics of measured value 
• Descriptive statistics of change from baseline 
• Shift tables from baseline by CTCAE Grade 
 
Urinalysis (qualitative tests) at each time point will be summarized using the following. 
• Shift tables of measured values from baseline 
 
9.4.2.3 
Vital Signs Data 
Vital signs (blood pressure, pulse rate, SpO2, and body temperature) at each time point 
will be summarized using the following. 
• Descriptive statistics of measured value 
• Descriptive statistics of change from baseline 
 
9.4.2.4 
Electrocardiogram Data 
Heart rate, RR interval, PR interval, QRS width, QT interval, and QTcF interval at each 
time point after the start of trial treatment will be summarized using the following. 

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• Descriptive statistics of measured value 
• Descriptive statistics of change from baseline 
 
For QTcF interval, the following will be summarized. 
• Number and proportion of subjects who showed a measured value of “> 450 msec,” 
“> 480 msec,” and “> 500 msec” 
• Number and proportion of subjects who had a change from baseline: > 30 msec and 
> 60 msec 
 
At each time point, ECG assessment of normality/abnormality will be summarized using 
the following. 
• Shift tables from baseline 
 
9.4.2.5 
Other Safety Data 
At each time point, ECOG PS will be summarized using the following. 
• Shift tables from baseline 
 
Body weight and LVEF at each time point will be summarized using the following. 
• Descriptive statistics of measured value 
• Descriptive statistics of change from baseline 
 
9.4.3 
Other Analyses 
9.4.3.1 
Analysis of Demographic and Baseline Characteristics 
Based on the safety analysis set, for demographic and baseline characteristics, including 
age, gender, race, ethnicity, height, body weight (screening period), and ECOG PS 
(screening period), calculation of descriptive statistics or tabulation of frequencies will be 
performed according to the characteristics of each parameter. 
9.4.3.2 
Pharmacokinetic Analysis 
1) Calculation of Descriptive Statistics 
In the PK analysis set, descriptive statistics will be calculated for the parameters for 
which numerical data were obtained from the majority of subjects. 

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• Plasma drug concentration: to be summarized for each blood sampling point by 
period and by dose. 
• PK parameters: to be summarized for each parameter by period and by dose. 
 
2) Dose Proportionality 
If ASTX660 have been administered at 3 or more dose levels in phase 1 (dose 
escalation part), the parameters after multiple-dose will be analyzed using the 
regression equation expressed by (I) to determine the estimate of b with a two-sided 
95% CI. 
 
ln Y = a + b∙ln X···· (I) 
 
X: dose 
 
Y: parameter (Cmax, AUC24h) 
Dose proportionality is considered to be statistically demonstrated, when the two-sided 
95% CI of the estimate of b includes 1. 
9.4.3.3 
Pharmacodynamic Analysis 
See Section 9.4.3.6. 
9.4.3.4 
Pharmacokinetic/Pharmacodynamic Analysis 
No PK/PD analysis is planned. 
9.4.3.5 
Pharmacogenomic Analysis 
No pharmacogenomic analysis is planned. 
 
 
 
 
 
 
 
 

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9.5 
Interim Analysis 
No interim analysis is applicable. 
9.5.1 
Data Monitoring Committee 
Not applicable. 

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10 
Supporting Documentation and Operational Considerations 
10.1 
Appendix 1: Regulatory, Ethical, and Trial Oversight 
Considerations 
10.1.1 
Ethics and Responsibility 
This trial must be conducted in compliance with the protocol, ICH-GCP Guideline (E6) 
25, international ethical principles derived from the Declaration of Helsinki and Council 
for International Organizations of Medical Science (CIOMS) guidelines, and applicable 
local laws and regulations. Each trial site will seek approval by an IRB according to 
regional requirements, and the trial site will provide that documentation to the sponsor. 
The IRB will evaluate the ethical, scientific, and medical appropriateness of the trial. 
Further, in preparing and handling the CRF, IRE and any safety information, the 
investigator, subinvestigator, and their staff will take measures to ensure adequate care in 
protecting subject privacy. To this end, a subject ID will be used to identify each subject. 
Financial aspects, subject insurance, and the publication policy for the trial will be 
documented in the agreement between the sponsor and the trial site. 
10.1.2 
Informed Consent 
Informed consent will be freely obtained from all subjects (or their guardian or legally 
acceptable representative, as applicable for local laws). The ICF will be approved by the 
same IRB that approves this protocol. 
Each ICF will comply with the ICH-GCP Guidelines (E6),25 and local regulatory 
requirements. In support of the site’s standard process for administering informed 
consent, this trial will also allow for eICF as a tool within applicable regions and trial 
sites. The eICF utilizes the IRB approved site-specific ICF to offer subjects an enhanced 
platform to review and understand their rights as a research subject as well as required 
trial procedures. When possible, trial sites will have subjects review and sign the eICF 
prior to starting any trial procedures; however, if local regulations do not allow for use of 
the electronic format, subjects may continue in the trial utilizing the standard paper and 
wet ink signature process. 
Investigators or subinvestigators may discuss trial availability and the possibility for 
entry with a potential subject without first obtaining consent. However, informed consent 
must be obtained and documented before initiation of any procedures that are performed 
solely for the purpose of determining eligibility for this trial, including withdrawal from 
current medication(s). 

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Potential subjects are free to refuse entry into the trial, or withdraw from the trial at any 
time, without justification, and there will be no consequences to their further care. 
Once appropriate essential information has been provided and fully explained in 
layman’s language to the subject by the investigator or subinvestigator (or a qualified 
designee), and it has been documented that the subject has had the opportunity to ask 
questions and have those questions answered, the IRB-approved ICF will be signed and 
dated by both the subject and the person obtaining consent (investigator/subinvestigator 
or designee), as well as by any other parties required by the IRB. The subject will receive 
a copy of the signed ICF; the original shall be kept on file by the investigator or 
subinvestigator. Subjects may be asked to sign additional ICFs if the protocol is amended 
and the changes to the protocol result in additional information that needs to be provided 
to the subjects, so that they can make a knowledgeable and voluntary decision on 
continued trial participation. Female partners of male subjects who become pregnant 
during the course of the trial may be asked to sign additional ICFs in order to collect 
additional information regarding the nonsubject partner and fetus. 
 
 
10.1.3 
Confidentiality 
All information generated in this trial will be considered confidential and will not be 
disclosed to anyone not directly concerned with the trial without the sponsor’s prior 
written permission. Subject confidentiality requirements of the region(s) where the trial is 
conducted will be met. However, authorized regulatory officials and sponsor personnel 
(or their representatives) may be allowed full access to inspect and copy the records, 
consistent with local requirements. All IMPs, subject bodily fluids, and/or other materials 
collected shall be used solely in accordance with this protocol, unless otherwise agreed to 
in writing by the sponsor. 
Subjects will be identified only by unique subject ID in the CRF. If further subject 
identification is required, subjects’ full names may be made known to a regulatory 
agency or other authorized officials if necessary, subject to local regulations. 
10.1.4 
Quality Control and Quality Assurance 
The sponsor will implement the quality management activities for this trial according to 
ICH-GCP guidance and standard operating procedures. 

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Details of the quality management activities will be separately provided in the quality 
management plan. 
10.1.4.1 
Monitoring 
The sponsor has ethical, legal, and scientific obligations to follow this trial in accordance 
with established research principles, ICH-GCP Guideline (E6)25, and applicable 
regulatory requirements and local laws. As part of a concerted effort to fulfill these 
obligations (maintain current personal knowledge of the progress of the trial), the 
sponsor’s monitors will visit the site during the trial, as well as communicate frequently 
via telephone, e-mail, and written communications. In addition, all investigators or 
subinvestigators and trial site personnel will undergo initial and ongoing training for this 
particular trial, and this training will be clearly documented. 
10.1.4.2 
Auditing 
The sponsor’s Quality Assurance Unit (or representative) may conduct trial site audits. 
Audits will include, but are not limited to, IMP supply, presence of required documents, 
the informed consent process, and a review of the CRF with source documents, as 
applicable. The investigator will cooperate with audits. 
Regulatory authorities may inspect the trial site during or after the trial. The investigator 
will cooperate with such inspections and will contact the sponsor immediately if such an 
inspection occurs. 
10.1.5 
Protocol Deviations 
In the event of a significant deviation from the protocol due to an emergency, accident, or 
mistake (eg, violation of informed consent process, IMP dispensing or subject dosing 
error, treatment assignment error, subject enrolled in violation of eligibility criteria or 
concomitant medication criteria), the investigator/subinvestigator or designee will contact 
the sponsor or designee at the earliest possible time by telephone or via e-mail. The 
investigator/subinvestigator and sponsor (or designee) will come as quickly as possible to 
a joint decision regarding the subject’s continuation in the trial. This decision will be 
documented by the investigator/subinvestigator and the sponsor (or designee) and 
reviewed by the site monitor. 
Any major protocol deviation will be recorded in the CRF along with the start date and 
details of the deviation. 

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10.1.6 
Records Management 
10.1.6.1 
Source Documents 
Source documents are defined as the results of original observations and activities of a 
clinical investigation. Source documents will include but are not limited to medical 
records, electronic data, screening logs, and recorded data from automated instruments. 
All source documents pertaining to this trial will be maintained by the trial site and made 
available for direct inspection by authorized persons. 
Investigator(s)/trial site(s) will permit trial-related monitoring, audits, IRB review, and 
regulatory inspection(s) by providing direct access to source data/documents by 
authorized persons as defined in the ICF. Documents (eg, original copies of reports and 
measurement data) for drug concentration measurement, 
 will be stored by the bioanalytical laboratory, 
respectively. In all cases, subject confidentiality must be maintained in 
accordance with local regulatory requirements. 
10.1.6.2 
Data Collection 
During each subject’s visit to the site, an investigator/subinvestigator or their designee 
participating in the trial will record information to document all significant observations. 
At a minimum, these notes will contain: 
• Documentation of the informed consent process, including any revised consents; 
• Documentation of the investigator/subinvestigator’s decision to enroll the subject into 
the trial, the review of all inclusion/exclusion criteria prior to IMP administration, and 
confirmation of the subject’s actual participation in the trial; 
• The date of the visit and the corresponding Visit or Day in the trial schedule; 
• General subject status remarks, including any significant medical findings. The 
severity, frequency, duration, action taken, and outcome of any AEs and the 
investigator/subinvestigator’s assessment of relationship to IMP must also be 
recorded; 
• Any changes in concomitant medications or dosages; 
• Date and time of taking IMP; 
• A general reference to the procedures completed  
• The signature (or initials) and date of the investigator or subinvestigator (or designee) 
who made an entry in the medical record. 
 
In addition, any contact with the subject via telephone or other means that provides 
significant clinical information will also be documented in the progress notes as 
described above. 

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Any changes to information in medical records and other source documents will be 
initialed and dated on the day the change is made by a trial site staff member authorized 
to make the change. Changes will be made by striking a single line through erroneous 
data (so as not to obliterate the original data), and clearly entering the correct data (eg, 
wrong data right data). If the reason for the change is not apparent, a brief explanation for 
the change will be written in the source documentation by the 
investigator/subinvestigator or their designee. 
Information from medical records and other source documents will be entered by trial site 
personnel onto eCRFs in the sponsor’s electronic data capture (EDC) system that is 21 
CRF Part 11 compliant. Changes to the data will be captured by an automatic audit trail 
in the EDC system. 
. 
 
 
10.1.6.3 
File Management at the Trial Site 
The head of the trial site will ensure that the trial site file is maintained in accordance 
with the ICH-GCP Guideline (E6) Chapter 8 and as required by applicable local 
regulations. The trial site will take measures to prevent accidental or premature 
destruction of these documents. 
10.1.6.4 
Records Retention at the Trial Site 
The trial site will maintain all materials and records relevant to this trial for the longest of 
the following 3 periods. If the sponsor needs a longer retention, however, the trial site 
will discuss the period and method of retention with the sponsor. 
• A period of at least 2 years after the date on which approval to market the drug is 
obtained; however, if the sponsor notifies the trial site that the drug development is 
terminated or the results of the trial are not included in the new drug application form, 
a period of at least 3 years after the notification. 
• A period of at least 3 years after the trial is discontinued or completed. 
• 
  
 
The trial site must not dispose of any records relevant to this trial without either (1) 
written permission from the sponsor or (2) provision of an opportunity for the sponsor to 

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collect such records. The trial site will be responsible to maintain adequate and accurate 
electronic or hard copy source documents of all observations and data generated during 
this trial including any data clarification forms received from the sponsor. Such 
documentation is subject to inspection by the sponsor and relevant regulatory authorities. 
10.1.6.5 
Publication Authorship Requirements 
Authorship for any Otsuka-sponsored publications resulting from the conduct of this trial 
will be based on International Committee of Medical Journal Editors (ICMJE) authorship 
criteria (http://www.icmje.org/recommendations). According to ICMJE guidelines, one 
may be considered an author only if the following criteria are met: 
1) Substantial contributions to the conception or design of the work; or the 
acquisition, analysis, or interpretation of data for the work; AND 
2) Drafting the work or revising it critically for important intellectual content; AND 
3) Final approval of the version to be published; AND 
4) Agreement to be accountable for all aspects of the work in ensuring that questions 
related to the accuracy or integrity of any part of the work are appropriately 
investigated and resolved. 
 
All authors must meet the above criteria, and all who qualify for authorship based on the 
above criteria should be listed as authors. 
Investigators or other trial subjects who do not qualify for authorship may be 
acknowledged in publications resulting from the trial. By agreeing to participate in the 
trial, investigators or other trial subjects consent to such acknowledgement in any 
publications resulting from its conduct. 

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10.2 
Appendix 2: Clinical Laboratory Tests 
The tests detailed in Table 10.2-1 will be performed. 
Table 10.2-1 
Clinical Laboratory Assessments 
Hematology 
Serum Chemistry 
Urinalysis 
• Complete blood count (CBC) 
- Hemoglobin 
- Hematocrit 
- Red blood cell count 
- White blood cell (WBC) 
count 
- Platelet count 
• WBC differential 
- Neutrophils 
- Eosinophils 
- Basophils 
- Lymphocytes 
- Monocytes 
- Abnormal lymphocytes 
• Albumin 
• Alkaline phosphatase (ALP) 
• Alanine aminotransferase 
(ALT)  
• Aspartate aminotransferase 
(AST)  
• Blood urea nitrogen (BUN) 
• Total bilirubin 
• Direct bilirubin 
• Creatinine 
• γ-Glutamyl transpeptidase (γ-
GTP) 
• Glucose (fasting)  
• Lactate dehydrogenase (LDH) 
• Calcium 
• Chloride 
• Inorganic phosphorus 
• Potassium 
• Sodium 
• Total protein 
• Uric acid 
• Amylase 
• Amylase isozymes 
• Lipase 
• Hemoglobin A1c 
• C-reactive protein (CRP) 
• KL-6 
• 
 
• 
 
• Occult blood 
• Glucose 
• Ketones 
• pH 
• Protein 
Coagulation 
Virus tests 
Pregnancy test 
• Prothrombin time/international 
normalized ratio (PT-INR)  
• Activated partial 
thromboplastin time (APTT) 
• HIV antibody 
• HBc antibody 
• HBs antibody 
• HBV-DNA 
• HCV antibody 
• Urine [or serum] pregnancy for 
FOCBP 
 

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10.3 
Appendix 3: Contraceptive Guidance and Collection of Pregnancy 
Information 
Females of childbearing potential are females whose menstruation has started and who 
are not documented as sterile (eg, have had a bilateral oophorectomy, or hysterectomy, or 
who have been postmenopausal for at least 12 months, except for cases where menopause 
could be due to the effect of antineoplastic treatment). 
For males and FOCBP who are sexually active, there must be a documented agreement 
that the subject and their partner will take effective measures (ie, 2 different approved 
methods of birth control) to prevent pregnancy during the course of the trial and for 
3 months after the last dose of IMP. Unless the subject or their partner is sterile (ie, 
females who have had a bilateral oophorectomy, have had a hysterectomy, or have been 
postmenopausal for at least 12 consecutive months except for cases where menopause 
could be due to the effect of antineoplastic treatment; or males who have had a bilateral 
orchiectomy), 2 of the following approved methods of birth control must be used: 
vasectomy, tubal ligation, intrauterine device, birth control pill, or condom (all of these 
methods are approved or certified in Japan). Abstinence is not an acceptable method of 
birth control. Any single method of birth control, including vasectomy and tubal ligation, 
may fail, leading to pregnancy. Male subjects must also agree not to donate sperm from 
trial screening through 3 months after the last dose of IMP. 
 
Before enrolling males and females in this clinical trial, investigators or subinvestigators 
must review the below information about trial participation as part of the ICF process. 
The topics should generally include: 
• General information 
• Informed consent form 
• Pregnancy prevention information 
• Drug interactions with hormonal contraceptives 
• Contraceptives in current use 
• Follow-up of a reported pregnancy 
 
Before trial enrollment, males and FOCBP must be advised of the importance of avoiding 
pregnancy during trial participation and the potential risk factors for an unintentional 
pregnancy. Subjects must sign the ICF confirming that the above-mentioned risk factors 
and the consequences were discussed. 

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A urine or serum pregnancy test for hCG will be performed at screening on all FOCBP. If 
a urine test is performed and is positive, the investigator or subinvestigator will follow-up 
with a confirmatory serum test. 
During the trial, all FOCBP should be instructed to contact the investigator or 
subinvestigator immediately if they suspect they might be pregnant (eg, missed or late 
menstrual cycle). Male subjects must be instructed to contact the investigator 
immediately, during the trial, if their partner suspects that they might be pregnant (eg, 
missed or late menstrual cycle). 
If a subject is suspected to be pregnant before she receives IMP, the IMP administration 
must be withheld until the results of serum pregnancy tests are available. If the pregnancy 
is confirmed, the subject must not receive the IMP and must not be enrolled in the trial. If 
pregnancy is suspected while the subject is taking IMP, the IMP must be withheld 
immediately (if reasonable, taking into consideration any potential withdrawal risks) until 
the result of the pregnancy test is known. If pregnancy is confirmed, the IMP will be 
permanently discontinued in an appropriate manner (eg, dose tapering if necessary for 
subject safety) and the subject will be withdrawn from the trial. Exceptions to trial 
discontinuation may be considered for life-threatening conditions only after consultations 
with the IRE contact (see the title page of this protocol for contact information). 
The investigator or subinvestigator must immediately notify the sponsor (within 24 
hours) of any pregnancy associated with IMP exposure during the trial and for at least 30 
days after the last dose of IMP, and record the event on the IRE form, etc, and forward it 
to the sponsor. The sponsor will forward the Pregnancy Surveillance Form(s) to the 
investigator or subinvestigator for monitoring the outcome of the pregnancy. 
Protocol required procedures for trial discontinuation and follow-up must be performed 
on the subject unless contraindicated by pregnancy (eg, x-ray studies). Other appropriate 
pregnancy follow-up procedures should be considered if indicated. In addition, the 
investigator or subinvestigator must report to the sponsor, on the Pregnancy Surveillance 
Form(s), follow-up information regarding the course of the pregnancy, including 
perinatal and neonatal outcome. Infants will be followed for a minimum of 6 months 
from the date of birth. 

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10.4 
Appendix 4: Abbreviations 
Abbreviation 
Definition 
%TBSA 
Percentage total body surface area 
ALK 
Anaplastic lymphoma kinase 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ATLL 
Adult T-cell leukemia /lymphoma  
AUC 
Area under the concentration time curve 
AUC_%Extrap 
Percentage of AUC due to extrapolation from tlast to infinity 
[(AUC∞ - AUCt) / AUC∞ × 100] 
AUC∞ 
Area under the concentration time curve from time zero to infinity 
AUC24h 
Area under the concentration-time curve from time zero to 24 hours 
AUC∞/D 
AUC∞ normalized by dose 
AUC 
Area under the concentration time curve during a dosing interval () 
at steady state 
AUCt 
Area under the concentration time curve calculated to the last 
observable concentration at time t 
AUCt/D 
AUCt normalized by dose 
BUN 
Blood urea nitrogen  
CAR-T 
Chimeric antigen receptor T cell 
CFR 
Code of Federal Regulations 
cIAP 
Cellular inhibitor of apoptosis protein 
CIOMS 
Council for International Organizations of Medical Science 
CL/F 
Apparent clearance of drug from plasma after extravascular 
administration 
CL/F/BW 
CL/F normalized in body weight 
Cmax 
Maximum (peak) plasma concentration of the drug 
Cmax/D 
Cmax normalized by dose 
CR 
Complete response 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTCL 
Cutaneous T-cell lymphoma 
 
 
 
 
 
 
DLBCL 
Diffuse large B-cell lymphoma 
DLT 
Dose-limiting toxicity 
DNA 
Deoxyribonucleic acid 
DOR 
Duration of response 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
Electronic data capture 
EDTA 
Ethylenediaminetetraacetic acid 

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Abbreviation 
Definition 
 
 
 
 
 
 
FDG 
Fluorodeoxyglucose 
GCP 
Good Clinical Practice 
G-CSF 
Granulocyte colony-stimulating factor 
GFR 
Glomerular filtration rate 
γ-GTP 
γ-Glutamyl transpeptidase 
HBc 
Hepatitis B core 
HBs 
Hepatitis B surface 
HBV 
Hepatitis B virus 
hCG 
Human chorionic gonadotropin 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
HTLV-1 
Human T-cell leukemia virus type 1 
IAP 
Inhibitor of apoptosis protein 
IB 
Investigator’s brochure 
ICH 
The International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use  
ICMJE 
International Committee of Medical Journal Editors 
INR 
International normalized ratio 
IPI 
International prognostic index 
IRE 
Immediately reportable event 
IWG 
International working group 
JCOG 
Japan Clinical Oncology Group 
λz 
Apparent terminal-phase disposition rate constant (first-order) 
LDH 
Lactate (lactic acid) dehydrogenase 
LDi 
Longest transverse diameter of a lesion 
LVEF 
Left ventricular ejection fraction 
MedDRA 
Medical Dictionary for Regulatory Activities 
mSWAT 
Modified severity weighted assessment tool 
MTD 
Maximum tolerated dose 
MUGA 
Multiple gated acquisition 
NK 
Natural killer 
NYHA 
New York Heart Association 
ORR 
Overall response rate 
OS 
Overall survival 
 
 
PD 
Pharmacodynamic 
PET-CT 
Positron emission tomography-computed tomography 
PFS 
Progression free survival 
PQC 
Product quality complaint 
PR 
Partial response 
PS 
Performance status 
PTCL 
Peripheral T-cell lymphoma 

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Abbreviation 
Definition 
QTc 
QT corrected for heart rate 
QTcF 
QT corrected for heart rate by Fridericia’s formula 
r/r 
Relapsed/refractory 
Rac(AUC24h) 
Accumulation ratio of multiple dose to first dose at regular 
administration for AUC24h 
Rac(Cmax) 
Accumulation ratio of multiple dose to first dose at regular 
administration for Cmax 
Rac(Ctrough) 
Accumulation ratio of multiple dose to first dose at regular 
administration for Ctrough 
RD 
Recommended dose 
RNA 
Ribonucleic acid 
RP2D 
Recommended phase 2 dose 
SD 
Stable disease 
SPD 
Sum of the product of the perpendicular diameters for multiple 
lesions 
SpO2 
Percutaneous oxygen saturation 
ST 
Trimethoprim-sulfamethoxazole 
t1/2,z 
Terminal phase elimination half life 
TEAE 
Treatment-emergent adverse event 
tlast 
Time of last measurable (positive) concentration 
tmax 
Time to maximum (peak) plasma concentration 
TRAF2 
TNF receptor associated factor 2 
TTP 
Time to progression 
TTR 
Time to response 
ULN 
Upper limit of normal 
WHO 
World Health Organization 
XIAP 
X-linked inhibitor of apoptosis protein 
 

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10.5 
Appendix 5: Protocol Amendments 
The investigator or subinvestigator will not make any changes to this protocol without the 
sponsor’s prior written consent and subsequent approval/favorable opinion by the IRB. 
Any permanent change to the protocol, whether an overall change or a change for 
specific trial site(s), must be handled as a protocol amendment. Any amendment will be 
written by the sponsor. Each amendment will be submitted to the IRB, as required by 
local regulations. Except for “administrative” or “nonsubstantial” amendments, 
investigators or subinvestigators will wait for IRB approval/favorable opinion of the 
amended protocol before implementing the change(s). Administrative amendments are 
defined as having no effect on the safety of subjects, conduct or management of the trial, 
trial design, or the quality or safety of IMP(s) used in the trial. A protocol change 
intended to eliminate an apparent immediate hazard to subjects should be implemented 
immediately, followed by IRB notification within local applicable timelines. If necessary, 
the sponsor will submit protocol amendments to the applicable regulatory agencies within 
local applicable timelines. 
When the IRB, investigators, and/or the sponsor conclude that the protocol amendment 
substantially alters the trial design and/or increases the potential risk to the subject, the 
currently approved written ICF will require similar modification. In such cases, after 
approval/favorable opinion of the new ICF by the IRB, repeat written informed consent 
will be obtained from subjects enrolled in the trial before expecting continued 
participation and before the amendment-specified changes in the trial are implemented. 

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11 
References 
1 
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. 
Recommendations for initial evaluation, staging and response assessment of Hodgkin 
and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059-
68. 
2 
Olsen EA, Whittaker S, Kim YH, Duvic M, Prince HM, Lessin SR, et al. Clinical End 
Points and Response Criteria in Mycosis Fungoides and Sézary Syndrome: A 
Consensus Statement of the International Society for Cutaneous Lymphomas, the 
United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma 
Task Force of the European Organisation for Research and Treatment of Cancer. J 
Clin Oncol. 2011;29(18):2598–607.  
3 
International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive 
model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993;329(14):987-
94. 
4 
Fulda S, Vucic D. Targeting IAP proteins for therapeutic intervention in cancer. Nat 
Rev Drug Disc. 2012;11(2):109–24. 
5 
Holcik M, Yeh C, Korneluk RG, Chow T. Translational upregulation of X-linked 
inhibitor of apoptosis (XIAP) increases resistance to radiation-induced cell death. 
Oncogene. 2000;19(36):4174-7. 
6 
Astex Pharmaceuticals, Inc. ASTX660 Investigator Brochure, edition 4.1 issued 8 
Feb 2019. 
7 
Chihara D, Ito H, Matsuda T, Shibata A, Katsumi A, Nakamura S, et al. Differences 
in incidence and trends of haematological malignancies in Japan and the United 
States. Br J Haematol. 2014;164(4):536-45. 
8 
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO 
Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised Fourth 
Edition 2017. 
9 
Aoki R, Karube K, Sugita Y, Nomura Y, Shimizu K, Kimura Y, et al. Distribution of 
malignant lymphoma in Japan: analysis of 2260 cases, 2001-2006. Pathol Int. 
2008;58(3):174-82. 
10 Vose JM, Armitage J, Weisenburger D. International TCLP. International peripheral 
T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical 
outcomes. J Clin Oncol. 2008;26(25):4124–30. 
11 The Japanese Society of Hematology, ed. Chapter 7 Peripheral T-cell lymphoma 
(PTCL). In: Practical Guidelines for Hematological Malignancies 2018. Kanehara & 
Co., Ltd, Tokyo. 2018. p. 266-72. 
12 The Non-Hodgkin's Lymphoma Classification Project. A clinical evaluation of the 
International Lymphoma Study Group classification of non-Hodgkin's lymphoma. 
Blood. 1997;89(11):3909-18. 
13 The Japanese Society of Hematology, ed. Practical Guidelines for Hematological 
Malignancies 2018. Kanehara & Co., Ltd., Tokyo. 2018. p. 273-85. 
14 Laribi K, Alani M, Truong C, Baugier de Materre A. Recent Advances in the 
Treatment of Peripheral T-Cell Lymphoma. Oncologist. 2018 (9):1039-53. 

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15 Japanese Dermatological Association and Japanese Skin Cancer Society. Part 2 
Clinical Guidelines for Cutaneous lymphoma. In: Evidence-based Clinical Guidelines 
for Skin Malignancies Version 2. Kanehara & Co., Ltd. 2015/07/09 Available from: 
https://minds.jcqhc.or.jp/n/med/4/med0136/G0000836/0011/0063 
16 Ministry of Health, Labour and Welfare. Revision to the “Guidelines for Clinical 
Evaluation of Antimalignant Tumor Drugs.” PFSB/ELD Notification No. 1101001. 
01 Nov 2005. 
17 Ogura M, Ishida T, Hatake K, Taniwaki M, Ando K, Tobinai K, et al. Multicenter 
phase II study of mogamulizumab (KW-0761), a defucosylated anti-cc chemokine 
receptor 4 antibody, in patients with relapsed peripheral T-cell lymphoma and 
cutaneous T-cell lymphoma. J Clin Oncol. 2014;32(11):1157-64. 
18 Maruyama D, Tsukasaki K, Uchida T, Maeda Y, Shibayama H, Nagai H, et al. 
Multicenter phase 1/2 study of forodesine in patients with relapsed peripheral T cell 
lymphoma. Ann Hematol. 2019;98(1):131-42. 
19 Maruyama D, Nagai H, Maeda Y, Nakane T, Shimoyama T, Nakazato T, et al. Phase 
I/II study of pralatrexate in Japanese patients with relapsed or refractory peripheral T-
cell lymphoma. Cancer Sci. 2017; 108(10):2061-8. 
20 Maruyama D, Tobinai K, Ogura M, Uchida T, Hatake K, Taniwaki M, et al. 
Romidepsin in Japanese patients with relapsed or refractory peripheral T-cell 
lymphoma: a phase I/II and pharmacokinetics study. Int J Hematol. 2017;106(5):655-
65. 
21 Tsukasaki K, et al. Definition, prognostic factors, treatment, and response criteria of 
adult T-cell leukemia-lymphoma : a proposal from an international consensus 
meeting. J Clin Oncol. 2009; 27(3):453-9. 
22 Ministry of Health, Labour and Welfare. Clinical Trials That Use Pharmacogenomics. 
PMSB/ELD Notification No. 0930007, 30 Sep 2008. 
23 International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use. Guideline on Genomic Sampling and Management 
of Genomic Data: E18. [finalized September 2017]. Available from: 
https://database.ich.org/sites/default/files/E18_Guideline.pdf. 
24 Drafting Committee for Hepatitis Management Guidelines of the Japan Society of 
Hepatology, ed. Guidelines for the prevention of hepatitis B virus reactivation in 
patients receiving immunosuppressive therapy or chemotherapy. In: JSH Guidelines 
for the Management of Hepatitis B Virus Infection, Version 3.1. March 2019. p. 129-
130. Available from: https://www.jsh.or.jp/files/uploads/HBV_GL_ver3.1_v1.2-
1__2.pdf 
25 International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use [homepage on the Internet]. E6(R2): Good Clinical 
Practice: Integrated Addendum to ICH E6(R1) [finalized 2016 November; cited 2018 
Dec 3]. Available from: 
https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf. 
 
 
 

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Agreement 
I, the undersigned principal investigator, have read and understand the protocol (including the 
Investigator’s Brochure) and agree that it contains all the ethical, legal, and scientific information 
necessary to conduct this trial in accordance with the principles of Good Clinical Practices and as 
described herein and in the sponsor’s (or designee’s) Clinical Trial Agreement. 
 
I will provide copies of the protocol to all physicians, nurses, and other professional personnel to 
whom I delegate trial responsibilities. I will discuss the protocol with them to ensure that they are 
sufficiently informed regarding the investigational new drug, ASTX660, the concurrent medications, 
the efficacy and safety parameters and the conduct of the trial in general. I am aware that this protocol 
must be approved by the Institutional Review Board (IRB) responsible for such matters in the clinical 
trial facility where ASTX660 will be tested prior to commencement of this trial. I agree to adhere 
strictly to the attached protocol (unless amended in the manner set forth in the sponsor’s Clinical Trial 
Agreement, at which time I agree to adhere strictly to the protocol as amended). 
 
I understand that this IRB-approved protocol will be submitted to the appropriate regulatory 
authority/ies by the sponsor. I agree that clinical data entered on eCRF by me and my staff will be 
utilized by the sponsor in various ways, such as for submission to governmental regulatory authorities 
and/or in combination with clinical data gathered from other research sites, whenever applicable. I 
agree to allow sponsor and designee monitors and auditors full access to all medical records at the 
research facility for subjects screened or enrolled in the trial. 
 
I agree to await IRB approval before implementation of any substantial amendments to this protocol. 
If, however, there is an immediate hazard to subjects, I will implement the amendment immediately, 
and provide the information to the IRB within the required local applicable timelines. Administrative 
changes to the protocol will be transmitted to the IRB for informational purposes only, if required by 
local regulations. 
 
I agree to provide all subjects with informed consent forms, as required by the applicable regulations 
and by ICH guidelines. I agree to report to the sponsor any adverse experiences in accordance with the 
terms of the sponsor’s Clinical Trial Agreement and the relevant regional regulation(s) and 
guideline(s). I further agree to provide all required information regarding financial certification or 
disclosure to the sponsor for all investigators and subinvestigators in accordance with the terms of the 
relevant regional regulation(s). I understand that participation in the protocol involves a commitment 
to publish the data from this trial in a cooperative publication before publication of efficacy and safety 
results on an individual basis may occur, and I consent to be acknowledged in any such cooperative 
publications that result. 
 
____________________________ 
_____________________________ 
Principal Investigator Print Name  
Trial Site Name  
 
 
 
__________________________ 
__________________________ 
Signature 
 
 
 
Date 
 
This agreement is electronically signed by the sponsor. The sponsor signature page is 
attached to this document.