A Phase 1/2 Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS)
Phase: PHASE1
Conditions: Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome
Sponsor: Astellas Pharma Global Development, Inc.

Sponsor: APGD 
ISN/Protocol 7517-CL-0101 
- CONFIDENTIAL - 
19 Sep 2022 
Astellas 
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Version 7.5 Incorporating Nonsubstantial Amendment 5 
A Phase 1/2 Open-label Study Investigating the Safety, Tolerability 
and Efficacy of ASP7517 in Subjects with Relapsed/Refractory Acute 
Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk 
Myelodysplastic Syndrome (MDS) 
 
ISN/Protocol 7517-CL-0101 
Version 7.5 
Incorporating Nonsubstantial Amendment 5 [See Section 13] 
19 Sep 2022 
 
IND 19575 
IND Grantor: CBER 
 
Sponsor: 
Astellas Pharma Global Development Inc. 
1 Astellas Way 
Northbrook, IL 60062, US 
Protocol History:  
Version 1.0 [19 Apr 2019] 
Version 2.0 [09 May 2019] Incorporating Substantial Amendment 1 
Version 3.0 [11 Jun 2019] Incorporating Substantial Amendment 2 
Version 4.0 [CN] [12 Sep 2019] Incorporating Country-specific Substantial Amendment 3 for China 
Version 5.0 [23 Apr 2020] Incorporating Substantial Amendment 4 
Version 6.0 [CN] [13 May 2020] Incorporating Country-specific Substantial Amendment 5 for China 
Version 7.0 [26 Apr 2021] Incorporating Substantial Amendment 6 
Version 7.1 [19 May 2021] Incorporating Nonsubstantial Amendment 1 
Version 7.2 [23 Jun 2021] Incorporating Nonsubstantial Amendment 2 
Version 7.3 [CN] [05 Aug 2021] Incorporating Country-specific Nonsubstantial Amendment 3 for 
China 
Version 7.4 [14 Oct 2021] Incorporating Nonsubstantial Amendment 4 
The information contained in this document is supplied as a background for clinical investigations. This document contains 
confidential information, which is the intellectual property of Astellas. By accepting or reviewing this document, you agree 
to hold this information in confidence and not copy or disclose it to others or use it for unauthorized purposes except (1) as 
otherwise agreed to in writing; (2) where required by applicable law; (3) where disclosure is directly related to the care and 
safety of the research subject; and (4) where disclosure of such information is made to a member of the investigator’s team 
who agrees to hold this information in confidence.  

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Version 7.5 Incorporating Nonsubstantial Amendment 5 
Table of Contents 
SIGNATURES ································
································
································
 9 
CONTACT DETAILS OF SPONSOR’S KEY PERSONNEL ································
·····  11 
1 
PROTOCOL SUMMARY ································
································
·······  13 
1.1 
Synopsis ································
································
························
 13 
1.2 
Study Schema ································
································
··················
 25 
1.3 
Schedules of Assessments ································
································
····  27 
2 
INTRODUCTION ································
································
·················
 39 
2.1 
Background ································
································
····················
 39 
2.1.1 
Nonclinical and Clinical Data ································
··························
 40 
2.1.1.1 
Pharmacology ································
································
······  40 
2.1.1.2 
Nonclinical Pharmacokinetics ································
····················
 41 
2.1.1.3 
Nonclinical Toxicology ································
···························
 41 
2.1.1.4 
Clinical Studies ································
································
····  41 
2.1.2 
Summary of Key Safety Information for Investigational Product ·················
 41 
2.1.2.1 
Potential Risk ································
································
······  41 
2.2 
Study Rationale ································
································
················
 44 
2.3 
Risk Benefit Assessment ································
································
·····  45 
3 
STUDY OBJECTIVE(S) AND ENDPOINT(S) ································
··············
 46 
4 
STUDY DESIGN AND DOSE RATIONALE ································
················
 47 
4.1 
Study Design ································
································
···················
 47 
4.1.1 
Study Periods ································
································
············
 47 
4.1.2 
Phase 1 Dose Escalation ································
································
 48 
4.1.3 
Dose Limiting Toxicity Criteria ································
·······················
 49 
4.1.4 
Dose Escalation and Safety Committee ································
···············
 50 
4.1.5 
Phase 2 (Dose Expansion) ································
······························
 51 
4.1.6 
Dose Rationale ································
································
···········
 52 
4.2 
End of Study Definition ································
································
······  53 
5 
STUDY POPULATION ································
································
··········
 53 
5.1 
Inclusion Criteria ································
································
··············
 53 
5.2 
Exclusion Criteria ································
································
·············
 55 
5.3 
Restrictions During The Study ································
······························
 56 
5.4 
Screen Failures ································
································
················
 56 

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5.4.1 
Rescreening ································
································
··············
 56 
6 
INVESTIGATIONAL PRODUCT ································
·····························
 57 
6.1 
Investigational Product Administered ································
······················
 57 
6.1.1 
Administration ································
································
···········
 57 
6.2 
Preparation/Handling/Storage/Accountability ································
·············
 57 
6.2.1 
Packaging and Labeling ································
································
 57 
6.2.2 
Handling, Storage and Accountability ································
················
 58 
6.3 
Randomization and Blinding ································
································
 58 
6.3.1 
Assignment and Allocation································
·····························
 58 
6.4 
Investigational Product Compliance ································
························
 58 
6.5 
Previous and Concomitant Treatment (Medication and Nonmedication Therapy) ····  59 
6.6 
Dose Modification ································
································
············
 59 
6.7 
Criteria for Continuation of Treatment ································
·····················
 59 
7 
STUDY PROCEDURES AND ASSESSMENTS ································
············
 59 
7.1 
Efficacy Assessments ································
································
·········  59 
7.1.1 
Response Criteria Definitions ································
··························
 59 
7.1.1.1 
Acute Myeloid Leukemia Response Criteria ································
···  59 
7.1.1.2 
Myelodysplastic Syndrome Response Criteria ································
· 61 
7.1.1.3 
Hematology Laboratory Assessments ································
···········
 62 
7.1.2 
Bone Marrow Aspirations and/or Biopsies ································
···········
 62 
7.2 
Safety Assessments ································
································
···········
 63 
7.2.1 
Adverse Events ································
································
··········
 63 
7.2.2 
Laboratory Assessments ································
································
 63 
7.2.3 
Vital Signs ································
································
················
 63 
7.2.4 
Physical Examination ································
································
···  64 
7.2.5 
Electrocardiogram ································
································
·······  64 
7.2.6 
Imaging ································
································
···················
 64 
7.2.7 
Eastern Cooperative Oncology Group ································
················
 64 
7.2.8 
Multigated Acquisition Scan or Echocardiogram ································
···  65 
7.2.9 
Disease Assessment ································
································
·····  65 
7.3 
Adverse Events and Other Safety Aspects ································
·················
 65 
7.3.1 
Time Period for Collecting Adverse Event and Serious Adverse Event 
Information ································
································
···············
 65 
7.3.2 
Method of Detecting Adverse Events and Serious Adverse Events ···············
 65 

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7.3.3 
Follow-up of Adverse Events ································
··························
 65 
7.3.4 
Reporting of Serious Adverse Events ································
·················
 66 
7.3.5 
Disease-related Events and/or Disease-related Outcomes Not Qualifying as 
Adverse Events or Serious Adverse Events ································
··········
 66 
7.3.6 
Special Situations ································
································
········  66 
7.3.7 
Defects of Investigational Product ································
····················
 67 
7.3.8 
Supply of New Information Affecting the Conduct of the Study ··················
 67 
7.3.9 
Urgent Safety Measures ································
································
 68 
7.3.10 
Reporting Urgent Safety Measures ································
····················
 68 
7.4 
Pharmacokinetics ································
································
··············
 68 
7.5 
Pharmacodynamics | Biomarkers ································
····························
 68 
7.5.1 
Blood Samples ································
································
···········
 69 
7.5.2 
Bone Marrow Aspirate Samples ································
·······················
 69 
7.6 
Other Assessments ································
································
············
 69 
7.6.1 
Sample for the Analysis of Genes Related to Pharmacogenomics ················
 69 
7.6.2 
Sample for Optional Banked Pharmacogenomic Sample Analysis················
 69 
7.6.3 
Sample for Anti-HLA Antibody ································
·······················
 70 
7.6.4 
Sample for Replication Competent Lentivirus ································
·······  70 
7.7 
Total Amount of Blood ································
································
·······  70 
8 
DISCONTINUATION ································
································
············
 70 
8.1 
Discontinuation of Individual Subject(s) ································
···················
 70 
8.1.1 
Discontinuation Criteria from Treatment for Individual Subject(s) ···············
 70 
8.1.2 
Discontinuation Criteria Post-Treatment for Individual Subject(s) ···············
 71 
8.2 
Discontinuation of Individual Subject(s) from Study ································
·····  71 
8.2.1 
Lost to Follow-up································
································
········  72 
8.3 
Discontinuation of the Study Site ································
···························
 72 
8.4 
Discontinuation of the Study································
································
· 72 
9 
STATISTICAL METHODOLOGY ································
···························
 72 
9.1 
Sample Size ································
································
····················
 72 
9.2 
Analysis Sets ································
································
···················
 73 
9.2.1 
Full Analysis Set ································
································
········  73 
9.2.2 
Response Analysis Set ································
································
··  73 
9.2.3 
Safety Analysis Set ································
································
······  73 
9.2.4 
Pharmacokinetic Analysis Set ································
·························
 73 

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9.2.5 
Pharmacodynamic Analysis Set ································
·······················
 73 
9.2.6 
DLT Evaluation Analysis Set ································
··························
 73 
9.3 
Demographics and Baseline Characteristics ································
···············
 74 
9.3.1 
Demographics ································
································
············
 74 
9.3.2 
Subject Disposition ································
································
······  74 
9.3.3 
Previous and Concomitant Treatment (Medication and Nonmedication 
Therapy) ································
································
··················
 74 
9.3.4 
Medical History ································
································
··········
 74 
9.3.5 
Investigational Product Exposure ································
·····················
 74 
9.4 
Analysis of Efficacy ································
································
··········
 74 
9.4.1 
Analysis of Primary Endpoint ································
·························
 74 
9.4.1.1 
Primary Analysis ································
································
···  74 
9.4.1.2 
Sensitivity Analysis ································
·······························
 75 
9.4.1.3 
Phase 2 Expansion ································
································
· 75 
9.4.2 
Analysis of Secondary Endpoints ································
·····················
 76 
9.4.3 
Analysis of Exploratory Endpoints ································
····················
 77 
9.4.3.1 
Analysis of Biomarkers ································
···························
 77 
9.4.3.2 
Analysis of Pharmacodynamic Activities ································
·······  77 
9.4.3.3 
Analysis of Pharmacokinetics ································
····················
 77 
9.5 
Analysis of Safety ································
································
·············
 77 
9.5.1 
Adverse Events ································
································
··········
 77 
9.5.2 
Laboratory Assessments ································
································
 78 
9.5.3 
Vital Signs ································
································
················
 78 
9.5.4 
Physical Examination ································
································
···  78 
9.5.5 
12-lead Electrocardiogram ································
·····························
 78 
9.5.6 
Eastern Cooperative Oncology Group Performance Status ························
 78 
9.5.7 
Dose Limiting Toxicities ································
·······························
 78 
9.5.8 
Liver Safety Assessment ································
·······························
 79 
9.6 
Major Protocol Deviations and Other Analyses ································
···········
 79 
9.7 
Interim Analysis (and Early Discontinuation of the Study) ······························
 79 
9.8 
Additional Conventions ································
································
······  80 
10 
OPERATIONAL CONSIDERATIONS ································
·······················
 80 
10.1 
Data Collection ································
································
················
 80 
10.2 
Demographics and Baseline Characteristics ································
···············
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10.2.1 
Demographics ································
································
············
 81 
10.2.2 
Medical History ································
································
··········
 81 
10.3 
Major Protocol Deviations ································
································
···  81 
10.4 
STUDY ORGANIZATION································
································
··  82 
10.4.1 
Dose Escalation and Safety Committee ································
···············
 82 
11 
REFERENCES ································
································
····················
 83 
12 
APPENDICES ································
································
·····················
 87 
12.1 
Ethical, Regulatory and Study Oversight Considerations ································
 87 
12.1.1 
Ethical Conduct of the Study ································
···························
 87 
12.1.2 
Institutional Review Board/Independent Ethics Committee/Competent 
Authorities ································
································
················
 87 
12.1.3 
Protocol Amendment and/or Revision ································
················
 87 
12.1.4 
Financial Disclosure ································
································
····  88 
12.1.5 
Informed Consent of Subjects ································
·························
 88 
12.1.5.1 
Subject Information and Consent ································
················
 88 
12.1.5.2 
Supply of New and Important Information Influencing the Subject’s 
Consent and Revision of the Written Information ·····························
 88 
12.1.6 
Source Documents ································
································
······  89 
12.1.7 
Record Retention ································
································
········  89 
12.1.8 
Subject Confidentiality and Privacy ································
···················
 90 
12.1.9 
Arrangement for Use of Information and Publication of the Study ···············
 91 
12.1.10 
Insurance of Subjects and Others (Specific to Japan) ·······························
 92 
12.1.11 
Signatory Investigator for Clinical Study Report ································
····  92 
12.2 
Procedure for Study Quality Control ································
·······················
 93 
12.2.1 
Study Monitoring ································
································
········  93 
12.2.2 
Direct Access to Source Data/Documents ································
············
 93 
12.2.3 
Data Management ································
································
·······  93 
12.2.4 
Quality Assurance ································
································
·······  93 
12.3 
Contraception Requirements ································
································
· 94 
12.4 
Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-
up and Reporting ································
································
··············
 97 
12.4.1 
Definition of Adverse Events ································
··························
 97 
12.4.1.1 
Abnormal Laboratory Findings ································
··················
 97 
12.4.1.2 
Potential Cases of Drug-induced Liver Injury ································
··  97 
12.4.2 
Definition of Serious Adverse Events································
·················
 97 

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12.4.3 
Criteria for Causal Relationship to Investigational Product ························
 98 
12.4.4 
Criteria for Defining the Severity of an Adverse Event ····························
 99 
12.4.5 
Reporting Procedures for Serious Adverse Events or Defect of 
Investigational Product ································
·······························
 100 
12.4.6 
Reporting Procedures for Special Situations ································
·······  101 
12.4.6.1 
Pregnancy ································
································
·········  101 
12.4.6.2 
Medication Error, Overdose and “Off-label Use” ···························
 102 
12.4.6.3 
Misuse/Abuse ································
································
····  102 
12.4.6.4 
Occupational Exposure ································
·························
 103 
12.4.6.5 
(Suspicion of)Transmission of Infectious Agent ·····························
 103 
12.4.6.6 
Suspected Drug-drug Interaction ································
··············
 103 
12.5 
Liver Safety Monitoring and Assessment ································
················
 104 
12.6 
List of Excluded Concomitant Medications································
··············
 107 
12.6.1 
Concomitant Medications ································
····························
 107 
12.6.2 
Other Investigational Agents ································
·························
 108 
12.6.3 
Other Treatments for Acute Myeloid Leukemia and/or Myelodysplastic 
Syndrome ································
································
···············
 108 
12.7 
Laboratory Assessments ································
································
····  109 
12.8 
Pharmacogenomic Analysis With Banked Sample ································
·····  111 
12.9 
Clinical Study Continuity ································
································
··  113 
12.10 
List of Abbreviations and Definition of Key Study Terms ·····························
 133 
13 
ATTACHMENT 1:  NONSUBSTANTIAL AMENDMENT 5 ··························
 137 
14 
SPONSOR SIGNATURES ································
································
····  138 
 
List of In-text Tables  
Table 1 
Schedule of Assessments – Phase 1 (Dose Escalation) ································
···  27 
Table 2 
Schedule of Assessments – Phase 2 (Dose Expansion) ································
···  31 
Table 3 
Schedule of Post-Treatment Period Assessments for Dose Escalation and Dose 
Expansion ································
································
······················
 35 
Table 4 
Schedule of Replication Competent Lentivirus for Dose Escalation and Dose 
Expansion ································
································
······················
 37 
Table 5 
Pharmacokinetics Sample Collection Schedule-Dose Escalation Cohort and 
Dose Expansion Cohort ································
································
······  38 
Table 6 
Potential Safety Concern of ASP7517 ································
······················
 42 
Table 7 
Study Objectives and Endpoints ································
·····························
 46 
Table 8 
Investigational Product ································
································
·······  57 

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Table 9 
ECOG Performance Status ································
································
···  64 
Table 10 
Grading Scale Defining the Severity of an Adverse Event ·······························
 99 
Table 11 
Moderate and Severe Liver Abnormalities ································
···············
 104 
Table 12 
Clinical Laboratory Tests ································
································
··  109 
Table 13 
Alternate Schedule of Assessments in Response to a Crisis – Phase 1 (Dose 
Escalation) ································
································
···················
 115 
Table 14 
Alternate Schedule of Assessments in Response to a Crisis – Phase 2 (Dose 
Expansion) ································
································
···················
 121 
Table 15 
Alternative Schedule of Post-Treatment Period Assessments in Response to a 
Crisis for Dose Escalation and Dose Expansion ································
·········  128 
Table 16 
Alternative Schedule of Assessments of Replication Competent Lentivirus for 
Dose Escalation and Dose Expansion in Response to a Crisis ·························
 131 
 
List of In-text Figures 
Figure 1 
Study Schema ································
································
··················
 25 
Figure 2 
Flow Chart ································
································
·····················
 26 
 

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SIGNATURES 
1.  AGREEMENT BETWEEN THE SPONSOR’S RESPONSIBLE PERSON AND 
THE INVESTIGATOR 
This study will be conducted in adherence to International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice 
(GCP) guidelines and applicable laws and regulatory requirements, as well as this protocol.  
This study will be conducted in compliance with Japanese regenerative medicine GCP (for 
Japan only). As the evidence of the agreement, the investigator (CHIKEN SEKININ ISHI) 
and responsible person of the sponsor (CHIKEN IRAI SEKININSHA) inscribe in the 
bipartite agreement by signature or “printed name and seal.” 
2.  SPONSOR’S SIGNATURES 
Required signatures (e.g., protocol authors and contributors, etc.) are located in [Section 14 
Sponsor Signatures].  
 

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3.  INVESTIGATOR’S SIGNATURE 
A Phase 1/2 Open-label Study Investigating the Safety, Tolerability and Efficacy 
of ASP7517 in Subjects with Relapsed/Refractory Acute Myeloid Leukemia 
(AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS) 
ISN/Protocol 7517-CL-0101  
Version 7.5 Incorporating Nonsubstantial Amendment 5 
19 Sep 2022 
I have read all pages of this protocol for which Astellas is the sponsor. I agree to conduct the study 
as outlined in the protocol and to comply with all the terms and conditions set out therein. I confirm 
that I will conduct the study in accordance with International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) 
guidelines and applicable local regulations. I will also ensure that subinvestigator(s) and other 
relevant members of my personnel have access to copies of this protocol and the ICH GCP 
guidelines to enable them to work in accordance with the provisions of these documents. 
Principal Investigator: 
Signature: 
 
 
 
 
Date (DD MMM YYYY) 
Printed 
Name: 
 
  
<Insert name and qualification of the investigator> 
Address: 
 
 
 
 
 
 
 
 
 
 

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CONTACT DETAILS OF SPONSOR’S KEY PERSONNEL 
24-hour Contact for 
Serious Adverse Events 
 
See [Appendix 12.4.5 
Reporting Procedures for 
Serious Adverse Events or 
Defect of Investigational 
Product] 
Please fax or email the serious adverse events/special 
situations worksheet to: 
Astellas Pharma Global Development Inc.  
Pharmacovigilance 
North America fax number: +1-888-396-3750 
North America alternate fax number: +1-847-317-1241 
International fax number: +44-800-471-5263 
Email: safety-us@astellas.com 
Specific to Japan: 
JUTOKUNA YUUGAIJISHOU OYOBIFUGUAI 
HOUKOKUSHO or JUTOKUNA YUUGAIJISHOU 
HOUKOKUSHO the special situations worksheet to: 
Astellas Pharma Inc. - Japan 
Pharmacovigilance 
Fax number: 03-3243-5747 
Email: rk-safety-jp@jp.astellas.com 
Medical Monitor/Study 
Physician 
 
 
Astellas Pharma Global Development Inc. 
 
 
Clinical Research Contact 
(Global) 
 
 
Astellas Pharma Global Development Inc. 
 
 
Clinical Research Contacts 
(Local Japan, as needed) 
Location: 2-5-1, Nihonbashi-Honcho, Chuo-ku, Tokyo 
103-8411, Japan 
Telephone number: +81-3-3244-0635 
Fax number: +81-3-3243-5737 
Sponsor’s personnel: 
 
Contact numbers during nonbusiness hours and for 
emergency:  
Telephone number:  
 
 
Table continued on next page 
PPD
PPD
PPD
PPD
PPD
PPD

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Contact Information for the 
Clinical Research 
Organization (CRO) Japan 
Corporate Name: Parexel International 
Location: Kayaba-cho Tower 13F, 1-21-2, Shinkawa, 
Chuo-ku, Tokyo 1040033, Japan 
Telephone number: +81-3-3537-5686 
Fax number: +81-3-6888-4978 
CRO’s personnel: 
 
Contact numbers during nonbusiness hours and for 
emergency:  
 
 
 
PPD
PPD

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1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Date and Version of Protocol Synopsis: 
19 Sep 2022, Version 7.5 
Sponsor:   
Astellas Pharma Global Development Inc. (APGD) 
Protocol Number: 
7517-CL-0101 
Compound Name:  
ASP7517 Injection 
Phase of Development: 
Phase 1/2 
Title of Study:  
A Phase 1/2 Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in 
Subjects with Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory 
Higher Risk Myelodysplastic Syndrome (MDS) 
Planned Study Period:  
From approximately 3Q2019 to 4Q2024 
Study Objective(s) and Endpoint(s):  
Objective(s) 
Endpoint(s) 
Primary 
● To evaluate the safety and tolerability of 
ASP7517 
● Safety and tolerability as noted by: DLTs, AEs, 
SAEs, laboratory test results (serum, chemistry, 
hematology, coagulation, and urinalysis, pregnancy 
test) ECGs, vital signs, physical exams and ECOG 
performance status scores 
● To determine the RP2D and/or the MTD of 
ASP7517 (phase 1) 
● To evaluate the clinical response of ASP7517  ● CRc rate for subjects with R/R AML and (CR + 
BM CR+ PR) rate for R/R higher risk MDS 
(phase 2) 
Secondary 
● To evaluate other measures of anticancer 
activity of ASP7517 
● Duration of remission 
● EFS 
● OS 
● CR, best response (CRc + PR) and CRh rates for 
subjects with R/R AML 
● CR, HI and objective response (CR + BM CR + PR 
+ HI) rates for subjects with R/R higher risk MDS 
Exploratory 
● To evaluate potential genomic, proteomic 
and/or other biomarkers that may correlate 
with treatment outcome 
● Exploratory biomarkers that may correlate with 
treatment outcome of ASP7517 
● To evaluate pharmacodynamic activities of 
ASP7517 
● Pharmacodynamic effects of ASP7517, such as 
changes in: 
o Cytokine expression and secretion (e.g., IFNg) 
o WT1-specific T lymphocytes (e.g., cytotoxic T 
lymphocytes) 
o Immune cell populations (NKT cells, NK cells, 
etc.) 
● To evaluate pharmacokinetics of ASP7517, 
which is determined by the kinetics of the 
cells 
● Cellular DNA load and kinetic parameter estimates 
for ASP7517 
AE: adverse event; AML: acute myeloid leukemia; BM: bone marrow; CR: complete remission; CRc: 
composite complete remission; CRh: complete remission with partial hematologic recovery;  
Footnotes continued on next page 

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DLT: dose limiting toxicity; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EFS: 
event-free survival; IFNg: interferon gamma; HI: hematologic improvement; MDS: myelodysplastic 
syndrome; MTD: maximum tolerated dose; NK: natural killer; NKT: natural killer T; OS: overall survival; 
PR: partial remission; R/R: relapsed/refractory; RP2D: recommended phase 2 dose; SAE: serious adverse 
event; WT1: Wilms’ tumor 1 protein. 
Planned Total Number of Study Centers and Location(s):   
Approximately 30 centers in Japan, US and China 
Phase 1 (Dose Escalation) will be conducted only in Japan 
Study Population:   
Phase 1 (Dose Escalation) and Phase 2 (Dose Expansion) 
The study will be conducted in adult subjects with relapsed/refractory (R/R) acute myeloid 
leukemia (AML) or R/R higher risk myelodysplastic syndrome (MDS). 
• A subject with R/R AML is defined as a subject who relapsed after or is refractory to induction 
and not a candidate for salvage therapy.  
• A subject with R/R higher risk MDS is defined as a subject with Revised International 
Prognostic Scoring System (IPSS-R) for myelodysplasia of > 3.5 who relapsed after, or is 
refractory to, induction. 
Number of Subjects to be Enrolled:   
A total of approximately 122 subjects are planned for enrollment in this study. 
Phase 1 (Dose Escalation) 
Approximately 18 subjects with either R/R AML or R/R higher risk MDS will be enrolled. 
Phase 2 (Dose Expansion) 
Approximately 104 subjects per dose level. Each dose level may enroll up to 52 R/R AML subjects 
and up to 52 R/R higher risk MDS subjects. Both groups of subjects will enroll in parallel and 
independently. 
Study Design Overview:   
This study is a phase 1/2, open-label study of ASP7517 (human embryonic kidney cell transfected 
with encoding target antigen Wilms’ tumor protein 1 [WT1]) in subjects with R/R AML and R/R 
higher risk MDS. Subjects will receive an intravenous infusion of ASP7517. Subjects will receive 
1 dose of ASP7517 per cycle for a total of up to 2 doses during the escalation phase and up to 
6 doses during the expansion phase.  
An End-of-Treatment (EoT) visit will be conducted for all subjects within 7 days of the principal 
investigator decision to discontinue the subject from treatment or prior to the initiation of new 
anticancer therapy, whichever occurs first. If a subject is completing all visits in the last treatment 
cycle, the EoT visit will be within 7 days from the last planned visit. 
After the EoT visit, Observation Period 1 will be 12 weeks or until 1 post-treatment 
discontinuation criterion is met. Subjects who achieve composite complete remission (CRc) or 
partial remission (PR) for AML and CR, bone marrow (BM) CR or PR or hematologic 
improvement (HI) for MDS or other clinical benefits, as determined by the investigator, will 
remain in the study in Observation Period 2 until 1 post-treatment discontinuation criterion is met. 
Safety and efficacy will be monitored during Observation Periods 1 and 2. 
Upon treatment or post-treatment discontinuation criterion is met and subjects discontinue from the 
Treatment Period, Observation Period 1, or Observation Period 2, all subjects will be followed for 
survival and subsequent anti-cancer treatments and outcomes by telephone calls every 3 months. 
In phase 1 (dose escalation), the starting dose level is 1 × 106 cells/dose and the decision to dose 
escalate to the next dose levels (1 × 107 and 1 × 108 cells/dose) will be made based on the 
assessment of safety variables, including the occurrence of dose limiting toxicities (DLTs). 

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In phase 2 (dose expansion), subjects who have not met any individual treatment discontinuation 
criteria and who are receiving clinical benefit (defined as achieving CRc or PR for AML and CR, 
BM CR, PR or HI for MDS, or other clinical benefits as determined by the investigator) will 
continue further treatment with ASP7517 after the first 2 cycles, as decided by the investigator. 
After completing 4 cycles of treatment, subjects who achieve CR will not continue with ASP7517; 
subjects who do not reach CR, but also do not experience disease progression, may receive an 
additional 2 doses for a total of 6 doses. 
Phase 1 Dose Escalation: 
The dose escalation portion will assess safety and tolerability of ASP7517. Subjects will receive 
2 single doses of ASP7517 via intravenous infusion. Dosing will occur on day 1 of each cycle, with 
a total of 2 cycles.  
Subjects must be managed under hospitalization for at least 7 days during the first cycle of the dose 
escalation phase. In addition, prior to hospital discharge, the investigator must ensure subject safety 
by performing medical tests and procedures listed on day 7 of cycle 1 and tests considered 
clinically necessary in the opinion of the investigator to evaluate the subject’s general condition 
and adverse event (AE) resolution. The subject should also be followed on an outpatient basis on 
planned visits during cycles 1 and 2 after hospital discharge during the DLT assessment period to 
closely monitor any AEs. Subjects may be hospitalized days 1 to 7 during cycle 2 based on 
investigator opinion.  
After dosing of ASP7517, subjects must be observed for safety for a minimum of 4 hours. The 
safety observation will consist of hourly vital signs and AE observations. If new AEs are observed 
that are ≥ grade 3 during this time, subjects should continue to be observed at the investigator’s 
discretion.  
Dose escalation will be guided according to the Bayesian optimal interval (BOIN) design [Liu et 
al, 2015] to determine the next dose level based on DLT occurrence. After the planned number of 
evaluable subjects have completed the DLT observation period for a given dose level, safety for 
that dose level will be assessed. Each dose level in the dose escalation will enroll a minimum of 3 
and may enroll a maximum of 8 subjects with up to 4 evaluable subjects for the initial assessment 
of each dose level. Refer to [Section 9.2.6 DLT Evaluation Analysis Set] for definition of evaluable 
subjects. Enrollment within each dose escalation cohort will be staggered such that there will be 28 
calendar days between the treatment initiation of the first subject and the second subject, as well as 
14 calendar days between the second subject and the third subject at the same dose level for all 
escalation cohorts. An interval of 28 calendar days will separate initiation of first dose of study 
treatment for the last subject in a dose cohort from the first dose of the first subject in the 
subsequent dose cohort. The 28-day separation is equivalent to the 28-DLT evaluation period. If 
the decision is made to stay at the current dose level, then an additional 3 or 4 evaluable subjects 
may be enrolled to the current dose level. Three to 18 subjects will be enrolled in the dose 
escalation phase. A minimum number of 6 and a maximum number of 8 subjects must be enrolled 
at the dose level used to determine the maximum tolerated dose (MTD) and the recommended 
phase 2 dose (RP2D). 
Study enrollment and study treatment will be temporarily interrupted during dose escalation 
pending review of the following: 
• 
Any death that is not related to disease progression occurring within 30 days of receiving 
investigational product. 
• 
Occurrence of two grade ≥ 4 DLTs in 2 study subjects. 
• 
Any grade 4 hypersensitivity reaction/anaphylaxis. 

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Dose Escalation and Safety Committee: 
A Dose Escalation and Safety Committee (DESC) consisting of sponsor representatives and 
investigators will convene once a dose level cohort completes the DLT observation period and data 
are available for review. Additional details regarding responsibilities, membership requirements 
and safety review time points are included in the DESC Charter. The DESC will also review the 
aggregate safety data from the phase 1 dose escalation and the phase 2 expansion cohorts. 
While safety data from the DLT observation period in the escalation cohorts are the minimum 
safety data needed for the DESC meeting, all available safety findings will be considered by the 
DESC. The DESC will assess whether a longer DLT observation period is warranted based on 
emerging data. Additionally, only when determining the RP2D, the DESC may choose a more 
conservative dosing decision than the MTD selected by BOIN design, based on evaluation of the 
safety data and other available data. 
The decision on the dose level for the next cohort will be based on the BOIN design. Also, MTD 
will be determined by BOIN from at least 6 subjects with the maximum of 8 subjects under the 
maximum of 2 cohorts. The dose for phase 2 expansion will not be higher than the MTD. 
Subject Replacement during Dose Escalation:  
Subjects may be replaced in the dose escalation cohort if: 
● Subject is discovered to have enrolled without fully satisfying eligibility criteria. 
● Subject received less than the planned dose in cycle 1 for reasons other than DLT. 
● Subject has no DLT and withdraws from the study before the end of the DLT evaluation period. 
The decision regarding replacement of individual subjects will be made by the sponsor with 
discussions with the treating investigator. 
Phase 2 (Dose Expansion): 
Phase 2 will assess the safety and efficacy of ASP7517. This phase of the study may open once the 
RP2D and/or MTD are determined from the dose escalation phase, OR all of the following 
conditions are met before the RP2D and/or MTD determination. 
⚫ At least 1 subject in the dose escalation cohort (phase 1) achieves CRc for AML subjects, or 
CR, BM CR or PR for MDS subjects. 
⚫ The dose level to be expanded is deemed tolerable by the DESC. 
⚫ The dose that will be opened for expansion is determined to be equal or lower than possible 
MTD. 
Phase 2 will include the following groups and may enroll in parallel and independently: 
⚫ Subjects with R/R AML. 
⚫ Subjects with R/R higher risk MDS. 
The CRc rate for subjects with R/R AML and CR + BM CR + PR rate for R/R higher risk MDS are 
continuously monitored using the Bayesian optimal phase 2 (BOP2) design [Zhou et al, 2017]. The 
number of dose levels investigated during phase 2 will be based upon the data from phase 1. 
Initially, 12 subjects will be enrolled at each dose level for each disease type during stage 1 of 
BOP2. If the response rate does not meet the optimal stopping boundaries (see table below), then 
stage 2 will open and an additional 20 subjects may be enrolled during this stage. Combining the 
data from stage 1 and stage 2, stage 3 may be opened for an additional 20 subjects for a total 
maximum sample size of 52 for each disease type, if the response rate does not meet the optimal 
stopping boundaries (see table below). Otherwise, the enrollment at that dose level will be closed.  
When the total number of subjects reaches the maximum sample size of 52, it may be concluded 
that ASP7517 is efficacious if the number of responses is greater than or equal to 12 and 10 for  

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AML and MDS, respectively. The number of subjects in stage 1, stage 2 and stage 3 may be 
changed according to the optimized stopping boundaries.  
Optimized Stopping Boundaries for AML 
Number of subjects treated 
Stop if number of responses ≤  
12 
1 
32 
5 
AML: acute myeloid leukemia 
Optimized Stopping Boundaries for MDS 
Number of subjects treated 
Stop if number of responses ≤  
12 
0 
32 
4 
MDS: myelodysplastic syndrome 
If more than 1 dose level is open for enrollment within a selected disease type, the newly enrolled 
subjects with that disease type will be randomly allocated to 1 of the open dose levels. 
Randomization will be weighted toward newly opened dose levels, with the allocation ratio based 
on the number of open slots still available at each dose level. For example, if dose level ‘x’ 
enrolled 3 subjects and dose level ‘y’ is newly opened for expansion, the next subject would be 
randomly allocated to dose level ‘x’ or ‘y’ with the ratio of 9:12.  
When escalation and expansion cohorts are both open for enrollment, enrollment into escalation 
cohorts takes priority such that subjects who are eligible for both will be preferentially enrolled in 
the escalation cohorts. 
Inclusion/Exclusion Criteria:  
Inclusion Criteria: 
Subject is eligible for participation in the study if all of the following apply: 
1. 
Institutional Review Board/Independent Ethics Committee-approved written informed consent 
and privacy language as per national regulations (e.g., Health Insurance Portability and 
Accountability Act authorization for US study sites) must be obtained from the subject or 
legally authorized representative prior to any study-related procedures (including withdrawal 
of prohibited medication, if applicable). 
2. 
Subject is considered an adult according to local regulation at the time of signing the informed 
consent form.  
3. 
Subject diagnosed with R/R AML or R/R higher risk MDS is defined as: 
⚫ R/R AML 
o Morphologically documented primary or secondary AML by the WHO criteria 
(2016), 
AND 
o Refractory to at least 2 cycles of induction chemotherapy/not a candidate for re-
induction OR relapsed after achieving remission with a prior therapy, 
AND 
o Received all standard therapies including targeted therapies (unless the therapy is 
contraindicated or intolerable) which are known to provide clinical benefit in the 
opinion of the treating investigator, 
AND 
o Received salvage therapy OR is not a candidate for salvage therapy 

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⚫ R/R Higher Risk MDS 
o Has MDS by the WHO criteria (2016),  
AND 
o Either relapsed after achieving remission or refractory to standard therapies, 
including ≥ 4 cycles of hypomethylating agents (unless the therapy is 
contraindicated or intolerable), 
AND 
o Is classified as higher risk MDS with a score of > 3.5 by Revised IPSS-R in MDS 
4. 
Subject has an Eastern Cooperative Oncology Group performance status of ≤ 2. 
5. 
Subject must meet the following criteria as indicated on the clinical laboratory tests during 
screening period: 
⚫ Serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × upper limit of 
normal (ULN) 
⚫ Serum total bilirubin ≤ 1.5 × ULN 
⚫ Serum creatinine ≤ 1.5 × ULN or an estimated glomerular filtration rate of > 50 mL/min 
as calculated by the Modification of Diet in Renal Disease equation. 
⚫ Platelets ≥ 50,000/μL at cycle 1 day 1 (C1D1) in the dose escalation cohorts only 
6. 
Subject has a life expectancy of ≥ 12 weeks at the time of screening in the opinion of the 
investigator. 
7. 
Subjects with AML must have peripheral blood absolute blast count of < 20,000/µL at C1D1. 
Note: Blast count can be controlled by hydroxyurea during screening period.  
8. 
Female subject is not pregnant [see Appendix 12.3 Contraception Requirements] and at least 1 
of the following conditions apply: 
⚫ Not a woman of childbearing potential (WOCBP) [see Appendix 12.3 Contraception 
Requirements] 
⚫ WOCBP who agrees to follow the contraceptive guidance [see Appendix 12.3 
Contraception Requirements] from the time of informed consent through at least 
180 days after final study treatment administration. 
9. 
Female subject must agree not to breastfeed starting at screening and throughout the study 
period and for 180 days after the final study treatment administration. 
10. Female subject must not donate ova starting at first dose of IP and throughout the study period 
and for 180 days after final study treatment administration. 
11. Male subject with female partner(s) of childbearing potential (including breastfeeding partner) 
must agree to use contraception [see Appendix 12.3 Contraception Requirements] throughout 
the treatment period and for 180 days after final study treatment administration. 
12. Male subject must not donate sperm during the treatment period and for 180 days after the 
final study treatment administration. 
13. Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the 
duration of the pregnancy throughout the study period and for 180 days after final study 
treatment administration. 
14. Subject agrees not to participate in another interventional study while receiving study 
treatment in the present study. 
Waivers to the inclusion criteria will NOT be allowed.  

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Exclusion Criteria: 
Subject will be excluded from participation in the study if any of the following apply: 
1. Subject was diagnosed with acute promyelocytic leukemia. 
2. Subject has breakpoint cluster region-Abelson-positive leukemia (BCR-ABL). 
3. Subject has persistent non-hematological toxicities of ≥ grade 2 (National Cancer Institute’s 
Common Terminology Criteria for Adverse Events [NCI-CTCAE], version 5.0), with 
symptoms and objective findings from prior AML or MDS treatment (including chemotherapy, 
kinase inhibitors, immunotherapy, experimental agents, radiation or surgery). 
4. Subject has received any of the following therapies:  
• 
Systemic immunomodulators or immunosuppressive drugs including steroids ≤ 28 days 
prior to C1D1 (steroids can be used if not intended for treatment of AML or MDS; 
steroids for AML/MDS related symptoms can be used at low doses [less than 10 mg/day 
dexamethasone]) 
• 
Cytotoxic agents (except hydroxyurea given for controlling blast cells) ≤ 28 days prior to 
C1D1 
• 
Investigational products for the treatment of AML or MDS within 5 half-lives prior to 
screening visit 
• 
Hematopoietic stem cell transplant (HSCT) 
• 
Radiation therapy ≤ 28 days prior to C1D1 
5. Subject has clinically active nervous system leukemia, per the investigator’s judgment. 
6. Subject has active or prior documented autoimmune or inflammatory disorders requiring 
systemic treatment. 
7. Subject has ongoing, untreated malignancy with the exception of the following: 
• 
Subjects with treated non-melanoma skin cancer, in situ carcinoma or cervical 
intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study 
if definitive treatment for the condition has been completed. 
• 
Subjects with organ-confined prostate cancer with no evidence of recurrent or progressive 
disease are eligible if hormonal therapy has been initiated or the malignancy has been 
surgically removed or treated with definitive radiotherapy. 
8. Subject with left ventricular ejection fraction of < 45% on echocardiogram or multigated 
acquisition scan (MUGA) performed within 28 days of screening. 
9. Subject has laboratory abnormalities or clinical evidence of disseminated intravascular 
coagulation, or ongoing history of coagulation disorder manifested by bleeding or clotting. 
10. Subject has an active uncontrolled infection. 
11. Subject is known to have human immunodeficiency virus infection. 
12. Subject has active hepatitis B or C or other active hepatic disorder. 
13. Subject has any condition, which in the investigator’s opinion, makes the subject unsuitable 
for study participation. 
14. Subject has a known or suspected hypersensitivity to bovine-derived protein or has suspected 
hypersensitivity to any ingredients of ASP7517. 
15. Subject is eligible for HSCT. 
Waivers to the exclusion criteria will NOT be allowed. 

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Investigational Product(s): 
ASP7517 injection 1 × 107 cells/mL, 2.5 mL/vial for intravenous infusion.  
Dose(s):   
Phase 1 (Dose Escalation) 
Starting dose of ASP7517 is 1 × 106 cells/dose, with escalation doses of 1 × 107 and  
1 × 108 cells/dose. 
Subjects will receive 2 single doses of ASP7517 on C1D1 and cycle 2 day 1 (C2D1). 
Phase 2 (Dose Expansion) 
Subjects will receive 1 dose of ASP7517 on day 1 of each 28-day cycle at RP2D or MTD as 
established by phase 1 for up to 6 doses total during the expansion phase. 
Mode(s) of Administration: 
ASP7517 will be diluted with normal saline to 50 mL and administered by intravenous infusion at 
4 to 6 mL/min infusion rate through a dedicated intravenous line, followed by flushing. 
Dose Limiting Toxicity Criteria: 
A DLT is defined as any of the following events that occur within 28 days starting with the first 
dose on C1D1 and that is considered to be related to IP. Confirmation of DLTs will be made by the 
DESC. The severity of AEs will be assessed according to NCI-CTCAE, version 5.0. 
DLT is defined as follows:  
⚫ Non-hematologic AEs that are ≥ grade 3. 
⚫ Confirmed Hy’s law case. 
⚫ New onset of grade 4 thrombocytopenia (with minimum of 2 grade worsening from baseline) 
within 24 hours of dosing. 
⚫ Prolonged myelosuppression, defined as absolute neutrophil count < 500/µL for more than 
28 days off therapy and in the absence of evidence of active leukemia or MDS in the marrow 
or blood, will be considered a DLT. 
The following AEs will not be considered as DLTs: 
● Electrolyte abnormalities that are not associated with clinical sequelae or deemed not clinically 
significant and corrected with appropriate management or supplementation within 72 hours of 
the onset. 
● Grade 3 infusion site reaction if successfully managed and resolved within 72 hours. 
● Grade 3 febrile neutropenia with or without infection. 
● Alopecia, anorexia or fatigue. 
● Grade 3 nausea and/or vomiting if not requiring tube feeding or total parenteral nutrition, or 
diarrhea and/or constipation if not requiring or prolonging hospitalization that can be managed 
to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at prescribed dose 
within 7 days of onset. 
● Grade 3 liver function test (LFT) elevations that resolve to ≤ grade 1 within 7 days; LFT 
elevations lasting > 7 days that are considered to be clinically significant and at least possibly 
related to ASP7517 will be considered to be a DLT. 
● Immune-related AEs grade 3 that resolve to ≤ grade 1 within 7 days. 
● Grade 3 or higher hyperuricemia due to tumor lysis that resolves to ≤ grade 1 with medical 
interventions, including hospitalization with intravenous hydration and/or rasburicase.      

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Dose evaluation and dose escalation stopping rules based on the BOIN design with target DLT 
rate of 0.30 and optimal interval of (0.236, 0.359) are as follows: 
Action 
Number of Subjects Treated at Current Dose Level 
3 
4 
5 
6 
7 
8 
Escalate dose if number of subjects with 
DLT ≤ 
0 
0 
1 
1 
1 
1 
Stay at current dose level if number of 
subjects with DLT = 
1 
1 
- 
2 
2 
2 
De-escalate if number of subjects with  
DLT = 
2 
2 
2 or 3 
3 
3 or 4 
3 or 4 
Stop if number of subjects with DLT ≥ 
3 
3 
4 
4 
5 
5 
DLT: dose limiting toxicity 
Dose escalation within individual subjects will not be allowed. 
Maximum Tolerated Dose 
The MTD determination will be based on at least 6 evaluable subjects at that dose level based on 
the BOIN design. Based on the observed DLT(s) during the DLT observation period, the MTD is 
the highest dose for which the isotonic estimate of the DLT rate is closest to, but not over, the 
target DLT rate of 0.30. 
The dose level determined to be the MTD must have data from at least 6 subjects. 
Recommended Phase 2 Dose 
The sponsor, in conjunction with the DESC, will determine the RP2D of ASP7517 taking into 
consideration the safety and efficacy data, as well as other available data, such as pharmacokinetics 
and pharmacodynamics of ASP7517. The RP2D will not exceed the MTD. 
The dose level determined to be the RP2D must have data from at least 6 subjects. 
Comparative Drug(s): 
None 
Concomitant Medication Restrictions or Requirements:  
The following treatments are prohibited during the study: 
⚫ Interferon/polyethylene-interferon 
⚫ High-dose systemic corticosteroids with the exception for immune-related AEs 
⚫ Immunosuppressive agents 
⚫ Investigational agents other than ASP7517 
⚫ Any other treatments of AML or MDS (including but not limited to chemotherapy, 
radiotherapy, surgery, immunotherapy or cellular therapy) are prohibited during the study with 
ASP7517 with the following exceptions: 
o Hydroxyurea up to 5 g daily for up to 2 weeks to keep the absolute blast count < 20,000/µL 
o Subject undergoing HSCT will be discontinued from the study  
o Intrathecal chemotherapy used as prophylaxis 

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Duration of Treatment:   
Treatment Period: 
Phase 1 (Dose Escalation) 
Subject will receive up to 2 single doses of ASP7517 via intravenous infusion on day 1 of each 
28-day cycle. 
Phase 2 (Dose Expansion): 
Subject will receive up to 6 doses of ASP7517 via intravenous infusion on day 1 of each 28-day 
cycle. 
Treatment Discontinuation Criteria 
Subjects who meet any of the following criteria will be withdrawn from the study treatment: 
⚫ 
Subject declines further study participation (i.e., withdrawal of consent). 
⚫ 
Any clinical or unacceptable AE/SAE, laboratory abnormality or intercurrent illness, in the 
opinion of the investigator, indicates continued treatment is not in the best interest of the 
subject. 
⚫ 
Subject is noncompliant with protocol based on the investigator or medical monitor 
assessment. 
⚫ 
Subject is found to have significantly deviated from any 1 of the inclusion or exclusion criteria 
after enrollment (subjects having clinical benefit and no DLT may be kept in the study after 
discussion with the medical monitor). 
⚫ 
Subject not achieving response (CRc or PR in AML or CR, BM CR or PR or HI in MDS) and 
the subject is no longer deriving clinical benefit, in the opinion of the investigator. 
⚫ 
Subject begins other anti-leukemic therapies or MDS therapies, including undergoing HSCT. 
⚫ 
Subject experiences disease relapse/progression. 
⚫ 
Investigator/subinvestigator determines that the continuation of the study treatment will be 
detrimental to the subject. 
⚫ 
Subject is lost to follow-up despite reasonable efforts by the investigator to locate the subject. 
⚫ 
Death. 
⚫ 
Female subject becomes pregnant. 
⚫ 
Subject develops a grade 4 DLT during cycle 1. 
⚫ 
Delay of > 2 weeks of a subsequent scheduled dose of ASP7517 due to ASP7517-related 
toxicities. 
Observation Period 1 and 2 Discontinuation Criteria 
⚫ Subject declines further study participation (i.e., withdrawal of consent). 
⚫ Subject is lost to follow-up despite reasonable efforts by the investigator to locate the subject. 
⚫ Subject begins other anti-leukemic therapies or MDS therapies, including undergoing HSCT. 
⚫ Subject experiences disease relapse/progression. 
⚫ Subject is no longer deriving clinical benefit, in the opinion of the investigator. 
⚫ Female subject becomes pregnant. 
⚫ Death. 

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Formal Stopping Rules: 
Stopping Rules based on Safety for Phase 2 
The stopping rules described below will be applied to both AML and MDS disease types. 
The safety in phase 2 will be monitored using Bayesian logistic model based on safety events 
including: 
⚫ All DLT data obtained at the time of the analysis from both escalation and expansion cohorts. 
⚫ Drug related treatment emergent AEs leading to death. 
Safety monitoring with the Bayesian model will start when phase 2 is opened. Enrollment in phase 
2 will be stopped based on the following 2 criteria: 
⚫ If the posterior mean of the safety event rate is higher than 30% as indicated by Bayesian 
logistic model across disease types at a given dose level, then enrollment will be stopped in 
phase 2 at that dose level and at higher dose levels for that therapy. 
⚫ Additionally, if the posterior mean of the safety event rate is higher than 30% as indicated by 
Bayesian logistic model in a specific disease type at a dose level, enrollment of that dose level 
and any higher dose-level will be stopped for that disease type. 
Statistical Methods 
Sample Size Justification:  
Phase 1 (Dose Escalation): The sample size for the dose escalation phase is not based on a 
statistical power calculation. The number of subjects enrolled will be dependent on the DLT 
incidence. The estimated number of subjects, a minimum of 6 evaluable and up to 18, should 
provide adequate information for the dose escalation and safety objectives of the study. 
Phase 2 (Dose Expansion): The sample size in phase 2 is up to 104 subjects per dose level. Each 
dose level may enroll up to 52 R/R AML subjects and up to 52 R/R higher risk MDS subjects. The 
response rate is monitored using the BOP2 design. For AML, with assumption of the efficacious 
CRc rate is 30% and the inefficacious CRc rate is 15%, the statistical power would be 
approximately 0.83 while controlling the type I error rate at 0.10. For MDS, with assumption of the 
efficacious CR + BM CR + PR rate is 25% and the inefficacious CR + BM CR + PR rate is 12%, 
the statistical power would be approximately 0.83, while controlling the type I error rate at 0.10. 
Efficacy:   
For R/R AML: Response to treatment will be defined per modified Cheson criteria [Cheson et al, 
2003]. 
For R/R higher risk MDS: Response to treatment will be defined per Cheson criteria [Cheson et al, 
2006]. 
Response rates will be summarized using exact 90% confidence interval by dose level for phase 1 
and by dose level and disease type for phase 2. Time to endpoints, including event free survival 
and overall survival, will be listed and summarized using Kaplan-Meier method. 
Pharmacokinetics:   
Summary statistics of pharmacokinetics may be tabulated. Exploratory analysis between 
pharmacokinetic parameter and clinical measures (e.g., efficacy or safety) may be performed. 

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Pharmacodynamics:   
Descriptive statistics will be provided for pharmacodynamics parameters whenever applicable. 
Exploratory analysis of the relationship between pharmacodynamic measurements and 
pharmacokinetics, efficacy and safety profile in subjects may be performed. 
Safety:  
Descriptive statistics will be used to summarize safety data. All safety data will be summarized by 
treatment received (safety analysis set).  
Safety analyses will consist of data summaries of AEs, DLTs and other safety parameters. The 
number and percentage of subjects experiencing 1 or more AE(s) will be summarized by cohort 
and dose level. The relationship to IP and severity of AE will also be summarized. All summaries 
of AEs will include only treatment-emergent events unless otherwise stated. AEs will be coded to 
system organ class and preferred term using MedDRA terminology and will be graded by the 
investigator using the NCI-CTCAE severity grade (version 5.0).  
Laboratory parameters will be summarized by cohort and dose level using descriptive statistics for 
shifts in change from baseline and will be presented in listings of clinically significant 
abnormalities. Vital signs and electrocardiogram parameters and their changes from baseline will 
be summarized by cohort and dose level using descriptive statistics. 
Interim Analysis:  
No interim analysis is planned. 
Safety, pharmacokinetic and other clinical data will be reviewed on an ongoing basis to determine 
if the study will proceed to the next dose level/phase. 
For phase 2, according to the BOP2 design, the futility analysis for efficacy will be performed at 
the end of stage 1 and stage 2. Twelve subjects will be enrolled at each dose level for each disease 
type during stage 1 of BOP2. If the response rate does not meet the optimal stopping boundaries, 
then stage 2 will open and an additional 20 subjects may be enrolled during this stage. Combining 
the data from stage 1 and stage 2, stage 3 may be opened for an additional 20 subjects for a total 
maximum sample size of 52 for each disease type, if the response rate does not meet the optimal 
stopping boundaries. 
 

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1.2 
Study Schema 
Figure 1 
Study Schema  
 
Doses:  1 × 106, 1 × 107, 1 × 108 cells/dose 
Dosing frequency:   
Phase 1 (Dose Escalation):  Subjects will receive 2 single doses of ASP7517 on day 1 of each 28 -day cycle. 
Phase 2 (Dose Expansion):  Subjects will receive 1 dose of ASP7517 on day 1 of each 28-day cycle at RP2D or MTD as established by phase 1 for up to 6 doses total during the 
expansion phase. 
AML: acute myeloid leukemia; BOP2: Bayesian optimal phase 2; DLT: dose limiting toxicity; MDS: myelodysplastic syndrome; MTD: maximum tolerated dose; subj.: subjects. 

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Figure 2 
Flow Chart 
 
IV: intravenous; mos: months; PI: principal investigator; Q3: every 3. 

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1.3 
Schedules of Assessments 
Table 1 
Schedule of Assessments – Phase 1 (Dose Escalation) 
Assessments 
Screen-
ing 
Period 
Treatment Period 
End of 
Treatmentp 
 
Post-Treatment 
Period 
Survival 
Follow-
up 
Periodt 
Cycle 1 
Cycle 2 
Obs 
Period 1 
Obs 
Period 2 
Visit Days 
-14 to  
-1 
Hospitalization Days 1 to 7 
during phase 1 
8 
11 
15 
 
18 
22 
25 
1 
2 
3 
4 
5 
6 
7 
8 
15 
22 
Every 2 
weeks for 
up to 12 
weeks or  
until 1 
post-
treatment 
discontin-
uation 
criterion  
is met 
Every 4 
weeks or 
until 1 
post-
treatment 
discontin-
uation 
criterion is 
met 
Every 3 
months 
 
 
 
1 
 
 
 
2 
 
 
 
3 
 
 
 
4 
 
 
 
5 
 
 
 
6 
 
 
 
7 
Window(days) 
 
 
0 
0 
0 
0 
0 
0 
± 1 
± 1 
± 1 
± 1 
+ 3 
0 
0 
0 
0 
0 
0 
± 1 
± 1 
± 1 
+ 7 
 
± 3 
Signed ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference Table 3: 
Schedule of 
Post-Treatment Period 
Assessments 
 
Medical and Disease 
History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disease Assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
Physical Examinationc 
X 
Xa 
X 
X 
X X X 
X 
X 
X 
X 
X 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xq 
 
Vital Signs 
X 
Xb 
X 
 
X 
 
 
 
X 
X 
X 
X 
Xb 
X 
 
X 
 
 
 
X 
X 
X 
Xq 
 
ECOG Performance 
X 
Xa 
X 
 
X 
 
 
 
X 
X 
X 
X 
Xa 
X 
 
X 
 
 
 
X 
X 
X 
Xq 
 
Prior and Concomitant 
Medications 
Xd 
X 
X 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
 
X 
 
 
 
X 
X 
X 
X 
 
Pregnancy Test for 
WOCBP 
Xe 
Xa 
 
 
 
 
 
 
 
 
 
 
Xa 
 
 
 
 
 
 
 
 
 
X 
 
12-Lead ECGf 
Xg 
Xb 
 
 
 
 
 
 
 
 
 
 
Xb 
 
 
 
 
 
 
 
 
 
X 
 
Clinical Laboratory 
Tests (chemistry, 
hematology, 
urinalysis)h 
Xg 
Xa 
X 
X 
X X X 
X 
X 
X 
X 
X 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xq 
 
Coagulation Profile 
(PT/INR, D-dimer, 
fibrinogen)h 
Xg 
Xa 
X 
X 
X X X 
X 
X 
X 
X 
X 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xq 
 
Table continued on next page 

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Assessments 
Screen-
ing 
Period 
Treatment Period 
End of 
Treatmentp 
 
Post-Treatment 
Period 
Survival 
Follow-
up 
Periodt 
Cycle 1 
Cycle 2 
Obs 
Period 1 
Obs 
Period 2 
Visit Days 
-14 to  
-1 
Hospitalization Days 1 to 7 
during phase 1 
8 
11 
15 
 
18 
22 
25 
1 
2 
3 
4 
5 
6 
7 
8 
15 
22 
Every 2 
weeks for 
up to 12 
weeks or  
until 1 
post-
treatment 
discontin-
uation 
criterion  
is met 
Every 4 
weeks or 
until 1 
post-
treatment 
discontin-
uation 
criterion is 
met 
Every 3 
months 
 
 
 
1 
 
 
 
2 
 
 
 
3 
 
 
 
4 
 
 
 
5 
 
 
 
6 
 
 
 
7 
Window(days) 
 
 
0 
0 
0 
0 
0 
0 
± 1 
± 1 
± 1 
± 1 
+ 3 
0 
0 
0 
0 
0 
0 
± 1 
± 1 
± 1 
+ 7 
 
± 3 
Chest X-ray (or CT of 
chest) 
Xi 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference Table 3: 
Schedule of 
Post-Treatment Period 
Assessments 
 
MUGA or ECHO 
Xj 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bone Marrow 
Aspiration and/or 
Biopsyk 
Xk 
 
 
 
 
 
 
 
 
 
 
 
Xa,k 
 
 
 
 
 
 
 
 
 
Xk 
 
Blood Sample for 
Disease Assessmentl 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
AE/SAE Assessment 
X 
X 
X 
X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Pharmacokinetic: 
Blood Sample for Cell 
Kinetics 
 
See Table 5 for detailed sample time points 
PGx 
 
Xm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference Table 3: 
Schedule of 
Post-Treatment Period 
Assessments 
 
Blood Sample for 
WT1 Expression 
 
Xa 
 
 
 
 
 
 
 
 
 
 
Xa 
 
 
 
 
 
 
 
 
 
Xq 
 
Blood Sample for 
Mutational Profiling 
 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xq 
 
Blood Sample for 
Immune Response 
Biomarker (ELISpot) 
 
Xa 
 
 
 
 
 
 
X 
 
X 
 
Xa 
 
 
 
 
 
 
X 
X 
 
Xq 
 
Buccal Swab for HLA 
Typing 
 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table continued on next page 

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Assessments 
Screen-
ing 
Period 
Treatment Period 
End of 
Treatmentp 
 
Post-Treatment 
Period 
Survival 
Follow-
up 
Periodt 
Cycle 1 
Cycle 2 
Obs 
Period 1 
Obs 
Period 2 
Visit Days 
-14 to  
-1 
Hospitalization Days 1 to 7 
during phase 1 
8 
11 
15 
 
18 
22 
25 
1 
2 
3 
4 
5 
6 
7 
8 
15 
22 
Every 2 
weeks for 
up to 12 
weeks or  
until 1 
post-
treatment 
discontin-
uation 
criterion  
is met 
Every 4 
weeks or 
until 1 
post-
treatment 
discontin-
uation 
criterion is 
met 
Every 3 
months 
 
 
 
1 
 
 
 
2 
 
 
 
3 
 
 
 
4 
 
 
 
5 
 
 
 
6 
 
 
 
7 
Window(days) 
 
 
0 
0 
0 
0 
0 
0 
± 1 
± 1 
± 1 
± 1 
+ 3 
0 
0 
0 
0 
0 
0 
± 1 
± 1 
± 1 
+ 7 
 
± 3 
Blood Sample for 
Immune Response 
Biomarker (Tetramer)  
 
Xa 
 
 
 
 
 
 
 
 
X 
 
Xa 
 
 
 
 
 
 
 
X 
 
Xq 
Reference Table 3: 
Schedule of 
Post-Treatment Period 
Assessments 
 
Blood Sample for 
Immune Cell 
Phenotyping 
 
Xa 
 
 
 
 
 
 
X 
 
X 
 
Xa 
 
 
 
 
 
 
X 
X 
 
Xq 
 
Blood Sample for 
Cytokines 
 
Xa 
X 
 
X 
 
 
 
X 
 
X 
 
Xa 
X 
 
X 
 
 
 
X 
X 
 
Xq 
 
Blood Sample for 
Anti-HLA Antibody 
 
Xa 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
X 
 
X 
 
IRT Transaction 
Required 
X 
Xn 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
ASP7517 Dosing at 
the Clinic 
 
Xo 
 
 
 
 
 
 
 
 
 
 
Xo 
 
 
 
 
 
 
 
 
 
 
 
Survival Follow-upr 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
AE: adverse event; CT: computed tomography; C: cycle; D: day; C1D1: cycle 1 day 1; ECG: electrocardiogram; ECHO: echocardiogram; ECOG: Eastern Cooperative Oncology 
Group; ELISpot: enzyme-linked immunospot; EoT: end-of-treatment; HLA: human leukocyte antigen; ICF: informed consent form; INR: international normalization ratio; 
IRT: interactive response technology; MUGA: multigated acquisition scan; Obs: observation; PGx: pharmacogenomics; PT: prothrombin time; SAE: serious adverse event; WOCBP: 
women of childbearing potential; WT1: Wilms’ tumor 1 protein. 
a. Obtained predose. 
b. Obtained predose and postdose (including flushing) (vital signs: hourly [± 10 minute window] for up to 4 hours postdose; ECG: 1 to 2 hours postdose) on C1D1 and C2D1. 
c. Height measurement performed only at screening. Weight measurement should be performed at screening and day 1 of each cycle. 
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d. Includes medications taken within 28 days prior to C1D1. 
e. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 72 hours prior to the 
start of study treatment. 
f. The 12-lead ECGs will be recorded in triplicate (at least 2 minutes apart per time point) and transmitted electronically for central reading.  
g. Laboratory samples will be analyzed by the institution’s local laboratory. However, sample results must also be submitted for centralized data entry. Laboratory tests and/or 
ECG can be repeated during screening period. 
h. Laboratory samples will be analyzed by the institution’s local laboratory and results will be submitted for centralized data entry. 
i. Chest X-ray (or CT of chest) does not need to be repeated if performed within 2 weeks prior to start of screening. 
j. MUGA scans or ECHO (per standard of care) performed at screening or within 28 days prior to screening will be accepted. 
k. Screening samples may be collected up to 28 days prior to C1D1. End of treatment bone marrow sample does not need to be repeated if collected within 2 weeks of the last  
disease assessment. Samples must be submitted to a central laboratory for analysis. If bone marrow aspirate is unobtainable (e.g., dry tap), an additional ethylenediaminetetraacetic 
acid tube of whole blood should be collected instead. Bone marrow aspirate is required, and bone marrow biopsy is preferred. In case of inadequate aspirate, bone marrow biopsy is 
required. 
l. Samples must be submitted to a central laboratory for analysis. 
m. Whole blood and buccal swab for optional PGx study may be collected at C1D1 prior to first investigational product administration. 
n. Subject enrollment in the study will be conducted via IRT transaction. 
o. After dosing of ASP7517, subjects must be observed for safety for a minimum 4 hours. The safety observation will consist of hourly vital signs and AE observations. If new 
AEs are observed that are ≥ grade 3 during this time, subjects should continue to be observed at the investigator’s discretion.  
p. The EoT visit will occur within 7 days of the principal investigator decision to discontinue the subject for treatment or prior to the initiation of new anticancer treatment, 
whichever occurs first. If a subject is completing all visits in the last treatment cycle, the EoT visit will be within 7 days from the last planned visit. 
q. Assessment does not need to be repeated if collected at a regularly scheduled visit within 3 days of EoT visit. 
r. Telephone contact for survival status and subsequent anti-cancer treatments and outcomes. 
 

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Table 2 
Schedule of Assessments – Phase 2 (Dose Expansion) 
Assessments 
Screen-
ing 
Period 
Treatment Period 
End of 
Treatmento 
Post-Treatment Period 
Survival 
Follow-up 
Period 
Screen-
ing 
Cycle 1 
Cycle 2 
Cycles 3 - 4r 
Cycles 5 - 6s 
Observation 
Period 1 
Observation 
Period 2 
Survival 
Follow-up 
Visit Days Days -14 
to -1 
D1 
D2 
D8 
D15 
D22 
D1 
D2 
D8 
D15 
D22 
D1 
D15 
D1 
D15 
Every 2 weeks 
for up to 12 
weeks or  
until 1 post-
treatment 
discontinuation 
criterion  
is met 
Every 4 
weeks or until
1 post-
treatment 
discontin-
uation 
criterion is 
met 
Every 3 
months 
Window(days) 
 
 
0 
± 1 
± 1 
± 1 
+ 3 
0 
± 1 
± 1 
± 1 
+ 3 
± 1 
+ 3 
± 1 
+ 7 
 
± 3 
Signed ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference Table 3: Schedule of 
Post-Treatment Period 
Assessments 
 
Medical and Disease 
History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disease Assessmentt 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
Physical Examinationc 
X 
Xa 
X 
X 
X 
X 
Xa 
X 
X 
X 
X 
Xa 
X 
Xa 
X 
Xp 
 
Vital Signs 
X 
Xb 
X 
X 
X 
X 
Xb 
X 
X 
X 
X 
Xb 
X 
Xb 
X 
Xp 
 
ECOG Performance 
X 
Xa 
X 
X 
X 
X 
Xa 
X 
X 
X 
X 
Xa 
X 
Xa 
X 
Xp 
 
Prior and Concomitant 
Medications 
Xd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Pregnancy Test for 
WOCBP 
Xe 
Xa 
 
 
 
 
Xa 
 
 
 
 
Xa 
 
Xa 
 
X 
 
12-Lead ECGf 
Xg 
Xb 
 
 
 
 
Xb 
 
 
 
 
Xb 
 
Xb 
 
X 
 
Clinical Laboratory Tests 
(chemistry, hematology, 
urinalysis) 
Xg 
Xa 
X 
X 
X 
X 
Xa 
X 
X 
X 
X 
Xa 
X 
Xa 
X 
Xp 
 
Coagulation Profile 
(PT/INR, D-dimer, 
fibrinogen) 
Xg 
Xa 
X 
X 
X 
X 
Xa 
X 
X 
X 
X 
Xa  
X 
Xa 
X 
Xp 
 
Table continued on next page 

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Assessments 
Screen-
ing 
Period 
Treatment Period 
End of 
Treatmento 
Post-Treatment Period 
Survival 
Follow-up 
Period 
Screen-
ing 
Cycle 1 
Cycle 2 
Cycles 3 - 4r 
Cycles 5 - 6s 
Observation 
Period 1 
Observation 
Period 2 
Survival 
Follow-up 
Visit Days Days -14 
to -1 
D1 
D2 
D8 
D15 
D22 
D1 
D2 
D8 
D15 
D22 
D1 
D15 
D1 
D15 
Every 2 weeks 
for up to 12 
weeks or  
until 1 post-
treatment 
discontinuation 
criterion  
is met 
Every 4 
weeks or until
1 post-
treatment 
discontin-
uation 
criterion is 
met 
Every 3 
months 
Window(days) 
 
 
0 
± 1 
± 1 
± 1 
+ 3 
0 
± 1 
± 1 
± 1 
+ 3 
± 1 
+ 3 
± 1 
+ 7 
 
± 3 
Chest X-ray (or CT of 
chest) 
Xh 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference Table 3: Schedule of 
Post-Treatment Period 
Assessments 
 
MUGA or ECHO 
Xi 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bone Marrow Aspiration 
and/or Biopsyj 
Xj 
 
 
 
 
 
Xa,j 
 
 
 
 
Xa,j  
 
Xa,j  
 
Xj 
 
Blood Sample for Disease 
Assessmentk 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
AE/SAE Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Pharmacokinetic: Blood 
Sample for Cell Kinetics 
 
See Table 5 for detailed sample time points 
PGx 
 
Xl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference Table 3: Schedule of 
Post-Treatment Period 
Assessments 
 
Blood Sample for WT1 
Expression 
 
Xa 
 
 
 
 
Xa 
 
 
 
 
Xa  
 
Xa 
 
Xp 
 
Blood Sample for 
Mutational Profiling 
 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xp 
 
Blood Sample for 
Immune Response 
Biomarker (ELISpot) 
 
Xa 
 
X 
X 
 
Xa 
 
X 
X 
 
Xa  
X 
Xa 
X 
Xp 
 
Buccal Swab for HLA 
Typing 
 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table continued on next page 

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Assessments 
Screen-
ing 
Period 
Treatment Period 
End of 
Treatmento 
Post-Treatment Period 
Survival 
Follow-up 
Period 
Screen-
ing 
Cycle 1 
Cycle 2 
Cycles 3 - 4r 
Cycles 5 - 6s 
Observation 
Period 1 
Observation 
Period 2 
Survival 
Follow-up 
Visit Days Days -14 
to -1 
D1 
D2 
D8 
D15 
D22 
D1 
D2 
D8 
D15 
D22 
D1 
D15 
D1 
D15 
Every 2 weeks 
for up to 12 
weeks or  
until 1 post-
treatment 
discontinuation 
criterion  
is met 
Every 4 
weeks or until
1 post-
treatment 
discontin-
uation 
criterion is 
met 
Every 3 
months 
Window(days) 
 
 
0 
± 1 
± 1 
± 1 
+ 3 
0 
± 1 
± 1 
± 1 
+ 3 
± 1 
+ 3 
± 1 
+ 7 
 
± 3 
Blood Sample for 
Immune Response 
Biomarker (Tetramer)  
 
Xa 
 
 
X 
 
Xa 
 
 
X 
 
Xa 
X 
Xa 
X 
Xp 
Reference Table 3: Schedule of 
Post-Treatment Period 
Assessments 
 
Blood Sample for 
Immune Cell Phenotyping 
 
Xa 
 
X 
X 
 
Xa 
 
X 
X 
 
Xa 
X 
Xa 
X 
Xp 
 
Blood Sample for 
Cytokines 
 
Xa 
X 
X 
X 
 
Xa 
X 
X 
X 
 
Xa 
X 
Xa 
X 
Xp 
 
Blood Sample for Anti-
HLA Antibody 
 
Xa 
 
 
 
 
Xa 
 
 
 
 
Xa 
 
Xa 
 
X 
 
IRT Transaction Required 
X 
Xm 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
ASP7517 Dosing at the 
Clinic 
 
Xn 
 
 
 
 
Xn 
 
 
 
 
Xn 
 
Xn 
 
 
 
Survival Follow-upq 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
AE: adverse event; CT: computed tomography; C: cycle; C1D1: cycle 1 day 1; CR: complete remission; D: day; ECG: electrocardiogram; ECHO: echocardiogram; ECOG: Eastern 
Cooperative Oncology Group; ELISpot: enzyme-linked immunospot; EoT: end-of-treatment; HLA: human leukocyte antigen; ICF: informed consent form; INR: international 
normalization ratio; IP: investigational product; IRT: interactive response technology; MUGA: multigated acquisition scan; PGx: pharmacogenomics; PT: prothrombin time; SAE: 
serious adverse event; WOCBP: women of childbearing potential; WT1: Wilms’ tumor 1 protein. 
a. Obtained predose. 
b. Obtained predose and postdose (vital signs: hourly [± 10 minute window] for up to 4 hours postdose; ECG: 1 to 2 hours postdose) on day 1 of each cycle. 
c. Height measurement performed only at screening. Weight measurement should be performed at screening and day 1 of each cycle. 
d. Includes medications taken within 28 days prior to C1D1. 
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e. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 72 hours prior to the start 
of study treatment. 
f. The 12-lead ECGs will be recorded in triplicate (at least 2 minutes apart per time point) and transmitted electronically for central reading.  
g. Laboratory samples will be analyzed by the institution’s local laboratory. However, sample results must also be submitted for centralized data entry. Laboratory tests and/or ECG 
can be repeated during screening period. Laboratory samples will be analyzed by the institution’s local laboratory and results will be submitted for centralized data entry. 
h. Chest X-ray (or CT of chest) does not need to be repeated if performed within 2 weeks prior to start of screening. 
i. MUGA scans or ECHO (per standard of care) performed at screening or within 28 days prior to screening will be accepted. 
j. Screening samples may be collected up to 28 days prior to C1D1. End of treatment bone marrow sample does not need to be repeated if collected within 2 weeks of the last  
disease assessment. Samples must be submitted to a central laboratory for analysis. If bone marrow aspirate is unobtainable (e.g., dry tap), an additional ethylenediaminetetraacetic 
acid tube of whole blood should be collected instead. Bone marrow aspirate is required, and bone marrow biopsy is preferred. In case of inadequate aspirate, bone marrow biopsy is 
required. 
k. Samples must be submitted to a central laboratory for analysis. If a participant achieves CR at any point during the treatment period and ASP7517 is not continued, an EoT visit 
should be performed and the participant should proceed to observation period 1. 
l. Whole blood and buccal swab for optional PGx study may be collected at C1D1 prior to first investigational product administration. 
m. Subject enrollment in the study will be conducted via IRT transaction. 
n. After dosing of ASP7517, subjects must be observed for safety for a minimum 4 hours. The safety observation will consist of vital signs and AE observations. If new AEs are 
observed that are ≥ grade 3 during this time, subjects should continue to be observed at the investigator’s discretion.  
o. The EoT visit will occur within 7 days of the principal investigator decision to discontinue the subject for treatment or prior to the initiation of a new anticancer treatment, 
whichever occurs first. If a subject is completing all visits in the last treatment cycle, the EoT visit will be within 7 days from the last planned visit. 
p. Assessment does not need to be repeated if collected at a regularly scheduled visit within 3 days of EoT visit. 
q. Telephone contact for survival status and subsequent anti-cancer treatments and outcomes. 
r. After the first 2 cycles of treatment, subjects who have not met any individual treatment discontinuation criteria and are receiving clinical benefit (defined as achieve CRc or 
PR for AML and CR, BM CR or PR or HI for MDS or other clinical benefits, as determined by the investigator) will continue further treatment of ASP7517 as decided by the 
investigator. 
s. After the first 4 cycles of treatment, subjects who achieve CR will not continue with ASP7517; subjects who do not reach CR, but also do not experience disease progression, 
may receive an additional 2 doses for a total of 6 doses. If a participant experiences CR during cycle 5 or 6 (except if confirmed on day 1 of these cycles), the participant can 
complete the cycle and EoT will be performed as defined in footnote “o”. 
t. Extramedullary disease assessment is required at screening, day 1 of every cycle starting with cycle 2, EoT, and observation visits. 

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Table 3 
Schedule of Post-Treatment Period Assessments for Dose Escalation and Dose Expansion 
Assessments 
Post-Treatment Period 
Observation Period 1 
Observation Period 2 
12 weeks or until 1 post-treatment discontinuation criterion is met 
Until 1 post-treatment discontinuation 
criterion is met 
Visit Week 
2 
4 
6 
8 
10 
12 
Monthly Safety 
Assessment Visit 
Assessment Visit 
Every 3 months 
Window (days) 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Physical Examinationa 
X 
X 
X 
X 
X 
X 
X 
X 
Disease Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG Performance 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medicationsi 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECGb 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Laboratory Tests (chemistry, 
hematology, coagulation, urinalysis)g 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy Test for WOCBP 
X 
X 
X 
X 
X 
X 
X 
X 
Bone Marrow Aspiration and/or Biopsyc 
 
 
 
 
 
Xh 
 
X 
Blood Sample for Disease Assessmentd 
 
X 
 
X 
 
 
 
X 
AE/SAE Assessmenti 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetic: Blood Sample for Cell 
Kinetics 
See Table 5 for detailed sample time points  
Blood Sample for WT1 Expression 
 
X 
 
X 
 
Xj 
 
Xf 
Blood Sample for Immune Response 
Biomarker (ELISpot) 
 
X 
 
X 
 
Xj 
 
Xe 
Blood Sample for Immune Response 
Biomarker (Tetramer)  
 
X 
 
X 
 
Xj 
 
Xf 
Blood Sample for Immune Cell 
Phenotyping 
 
X 
 
X 
 
Xj 
 
Xe 
Blood Sample for Cytokines 
 
X 
 
X 
 
Xj 
 
Xe 
Blood Sample for Anti-HLA Antibody 
 
 
 
 
 
Xj 
 
Xf 
AE: adverse event; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; ELISpot: enzyme-linked immunospot; HLA: human leukocyte antigen; IP: investigational 
product; SAE: serious adverse event; WOCBP: women of childbearing potential; WT1: Wilms’ tumor 1 protein. 
Footnotes continued on next page 

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a. Height measurement performed only at screening. 
b. The 12-lead ECGs will be recorded as a single assessment (in triplicate if deemed necessary, at least 2 minutes apart per time point) and read locally.  
c. After the completion of Observation Period 1 (12 weeks), subjects remaining in the study will have bone marrow samples collected in Observation Period 2 every 3 months or if 
there is suspicion of relapse in the whole blood. Samples must be submitted to a central laboratory for analysis. If bone marrow aspirate is unobtainable (e.g., dry tap), an additional 
ethylenediaminetetraacetic acid tube of whole blood should be collected instead. Bone marrow aspirate is required, and bone marrow biopsy is preferred. In case of inadequate 
aspirate, bone marrow biopsy is required. 
d. Samples must be submitted to a central laboratory for analysis. 
e. Maximum of 1 sample collected during Observation Period 2. 
f. Maximum of 5 samples collected during Observation Period 2. 
g. Laboratory samples will be analyzed by the institution’s local laboratory and results will be submitted for centralized data entry. Subjects who are transfusion dependent should be 
subjected to more frequent laboratory assessments to determine transfusion need based on the judgment of the investigator. 
h. Subjects not proceeding to observation period 2 are required to provide a bone marrow sample at the last visit of observation period 1. 
i. Concomitant medications and AEs are collected until post-treatment period and at least 30 days after last IP dose and prior to the start of new anticancer treatment. In addition, the 
following will be collected regardless of the start of new anticancer therapy: Any IP-related SAE that is ongoing will be followed until resolved, and any SAE that is deemed to be 
related to IP by the investigator. 
j. Applicable only for subjects in dose expansion phase. 

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Table 4 
Schedule of Replication Competent Lentivirus for Dose Escalation and Dose Expansion 
Assessment 
C1D1 
3 Months After 
Treatment Initiation or 
End of Treatment, 
Whichever is First 
6 Months After Treatment 
Initiation 
12 Months After Treatment 
Initiation 
18 Months After Treatment 
Initiationc 
Window 
0 
± 1 day 
± 1 month 
± 1 month 
± 1 month 
Blood Sample for RCLa 
Xb 
X 
X 
X 
X 
C1D1: cycle 1 day 1; RCL: replication competent lentivirus 
a. If there are positive results, additional follow-up assessments may be required. Refer to Section 7.6.4 Sample for Replication Competent Lentivirus. 
b. Obtained predose. 
c. Only applicable to subjects in the expansion cohort. 
 

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Table 5 
Pharmacokinetics Sample Collection Schedule-Dose Escalation Cohort and Dose Expansion Cohort 
Cycle 
Day 
Time Point 
Window 
Dose Escalation 
Dose Expansion 
Cycle 1 
1 
Predose 
- 60 mina 
X 
X 
End of ASP7517 Infusion 
+ 10 minb 
X 
X 
30 minutes post ASP7517 Infusion 
± 10 min 
 
X 
1 hour post ASP7517 Infusion 
± 10 min 
X 
X 
2 hours post ASP7517 Infusion 
± 15 min 
 
X 
5 hours post ASP7517 Infusion 
± 15 min 
X 
X 
2 
24 hours post ASP7517 Infusion 
± 60 min 
X 
4 
NA 
- 
X  
 
8 
NA 
- 
X 
 
15 
NA 
- 
X 
 
Cycle 2 
1 
Predose 
- 60 mina 
X 
X 
End of ASP7517 Infusion 
+ 10 minb 
X 
X 
30 minutes post ASP7517 Infusion 
± 10 min 
 
X 
1 hour post ASP7517 Infusion 
± 10 min 
X 
X 
2 hours post ASP7517 Infusion 
± 15 min 
 
X 
5 hours post ASP7517 Infusion 
± 15 min 
X 
X 
2 
24 hours post ASP7517 Infusion 
± 60 min 
X 
 
4 
NA 
- 
X 
 
8 
NA 
- 
X 
 
15 
NA 
- 
X 
 
Cycle 4 
1 
Predose 
- 60 mina 
 
X 
End of ASP7517 Infusion 
+ 10 minb 
X 
Cycle 6 
1 
Predose 
- 60 mina 
X 
End of ASP7517 Infusion 
+ 10 minb 
X 
EoT 
EoT 
NA 
± 1 day 
X 
X 
Observation Period 1 
4 weeks 
NA 
± 3 days 
X 
X 
C: cycle; D: day; EoT: end of treatment; NA: not applicable. 
a. 
Within 60 min prior to ASP7517 infusion. 
b. Within 10 min after the end of ASP7517 infusion (including flushing). 

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2 
INTRODUCTION 
2.1 
Background 
Acute Myeloid Leukemia (AML) is the most common type of leukemia in adults. AML 
accounts for approximately 32% of acute leukemia diagnosed in adults [American Cancer 
Society, 2014]. The median age at diagnosis is 67 years of age, with 54% of patients 
diagnosed at 65 years or older [O’Donnell et al, 2012]. In Japan, it was estimated that 
5600 patients were diagnosed with AML in 2017 [Kantar Health, 2017]. It is estimated that 
19940 people will be diagnosed with AML, and 11180 will die from the disease in 2020 in 
the US [American Cancer Society, 2020]. While 60% to 80% of younger patients achieve a 
complete remission (CR) with standard therapy, only about 20% to 30% of the overall patient 
population has long-term disease-free survival. Outcomes are worse for patients aged 
60 years or over, with CR rates in the range of 40% to 55% and poor long-term survival rates. 
Along with age, remission rates and overall survival (OS) depend on a number of other 
factors, including cytogenetics, previous bone marrow disorders (such as myelodysplastic 
syndromes [MDS]) and co-morbidities [Rowe & Tallman, 2010; Rowe et al, 2010; Breems 
et al, 2005; Karanes et al, 1999]. Although FDA approved targeted therapies for AML (both 
newly diagnosed and relapsed/refractory [R/R] patients) have become available, currently 
there is no effective cure for the disease. 
Approximately 30% of adult AML patients are refractory to induction therapy. Furthermore, 
of those who achieve CR, approximately 75% will relapse. Several chemotherapy regimens 
have been used for patients with resistant or relapsed disease; however, the chemotherapy 
combinations are universally dose-intensive, with high risk of unacceptable toxicity in older 
patients. While these regimens may generate second remission rates of up to 50% in patients 
with a first remission of more than 1 year, toxicity is prohibitively high in most patients over 
50 to 60 years [Rowe & Tallman, 2010; Rowe et al, 2010; Breems et al, 2005; Karanes et al, 
1999]. Additionally, if the patient (including younger patients) relapses within 6 months of 
their initial CR, the chance of attaining a second remission is less than 20% with 
chemotherapy alone. Furthermore, survival after first relapse is approximately 10%, 
demonstrating the lack of an effective cure for patients in relapsed AML [Rowe & Tallman, 
2010]. Patients who are in second relapse or refractory to first salvage have an extremely 
poor prognosis, with survival measured in weeks [Giles et al, 2005].  
MDSs are a heterogeneous group of clonal stem cell disorders with an inherent tendency for 
leukemic transformation. In Japan, it was estimated that 8500 patients were diagnosed with 
MDS in 2017 [Kantar Health, 2018]. In the US, the incidence of MDS has been estimated 
between 5.3 and 13.1 cases per 100,000 population per year, rising with age to an estimated 
75 to 162 cases per 100,000 population per year among patients ≥ 65 years of age [Cogle, 
2015]. MDS is clinically characterized by peripheral blood cytopenias; as a result, the clinical 
course of MDS patients is often fraught with complications related to peripheral blood 
cytopenias along with an inherent risk for leukemic transformation, which is encountered in 
30% of de novo MDS patients [Dotson & Lebowicz, 2018]. The outcome of MDS patients is 
extremely variable with median survival ranging from over 5 years to less than 9 months. 

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Therefore, over the years, several prognostic scoring systems have been developed to enable 
accurate risk-stratification of these patients [Greenberg et al, 2012; Greenberg et al, 1997; 
Malcovati et al, 2007; Kantarjian et al, 2008]. In addition, recent discovery of genes is being 
used to refine the current diagnostic and prognostic approach [Bejar et al, 2011; Bejar et al, 
2012] and additionally serve as novel therapeutic targets for ongoing clinical trials in MDS. 
Currently approved drugs for the treatment of MDS are not curative and no standard of care 
is available for patients after failure to respond to hypomethylating agents [Uy et al, 2017]. 
Allogeneic stem cell transplant is the only curative therapy, but the morbidity and mortality 
associated with the latter precludes it from being a feasible option in the vast majority of 
MDS patients with a median age at diagnosis of 70 to 75 years [Sekeres & Culter, 2014].  
The majority of patients with MDS and AML are not cured with available therapies, 
underscoring the urgent need for new therapeutic alternatives that will improve the clinical 
outcomes of these patients.  
The Wilms’ Tumor 1 (WT1) gene is located on the short arm of chromosome 11. WT1 
suppresses transcription of hemopoietic related proteins including macrophage 
colony-stimulating factor, transforming growth factor-beta, and retinoic acid receptor-alpha 
[Rosenfeld et al, 2003]. This gene, originally defined as a tumor suppressor gene, is also a 
gene transcription factor overexpressed in leukemic cells, where it induces inhibition of 
apoptosis and differentiation [Polák et al, 2012]. The gene is essential in mesenchymal tissue 
maintenance through the Wnt4 pathway [Chau & Hastie, 2012] and it is expressed in a small 
percentage of bone marrow CD34+ cells [Fraizer et al, 1995]. It is upregulated in early 
myeloid progenitors and is down regulated at later stages of differentiation. Studies in mice 
have shown that WT1 overexpression is required for leukemogenesis [Hosen et al, 2007; 
Hohenstein & Hastie, 2006]. Most patients with AML (86% to 91%) [NCCN Guidelines, 
2018] and MDS show overexpressed WT1 [Rautenberg et al, 2018; Miyagi et al, 1993; Miwa 
et al, 1992]. 
2.1.1 
Nonclinical and Clinical Data 
2.1.1.1 Pharmacology 
ASP7517 is an artificial adjuvant vector cell (aAVC) vaccine that induces both natural killer 
(NK) cell dependent antitumor effects (innate immunity) and WT1-specific T cell dependent 
antitumor effects (adaptive immunity). In a B16-F10 mouse metastatic melanoma model, a 
single intravenous dose of the murine ASP7517-surrogate suppressed an increase of lung 
weights caused by lung metastasis. Under the condition of NK cell depletion in mice, the 
antitumor effect was canceled. These results provide a proof of mechanism that the 
ASP7517-surrogate exerts an antitumor effect through NK-cell derived innate immunity 
(Study 7517-PH-9007). 
To assess adaptive immunity, a murine AML survival model was used, where mice were 
inoculated with murine C1498 AML cells. ASP7517-surrogate significantly prolonged 
survival time in mice inoculated with WT1 expressing C1498 cells, when compared with 
mice inoculated with C1498 cells not expressing WT1 (Study 7517-PH-9003). 

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In this same AML model, mice administered ASP7517-surrogate (5 × 102, 5 × 103 or 5 × 104 
cells/mouse) showed a dose-related response to this therapeutic (Study 7517-PH-9012). 
2.1.1.2 Nonclinical Pharmacokinetics 
A biodistribution study for ASP7517 was performed by determining tissue distribution of the 
human genomic Alu sequence. After a single intravenous administration of ASP7517 to 
C57BL/6J mice at 1 × 108 cells/kg, ASP7517-derived human DNA in tissues was detected in 
the blood and in all tissues examined 1 hour after administration, and the levels of the 
ASP7517 DNA in the blood and lung were higher than in other tissues. ASP7517 DNA 
decreased rapidly and was below the limit of quantification in almost all tissues at 24 hours 
after administration. ASP7517 DNA was not detected in urine or feces. No remarkable sex 
differences were observed (Study 7517-ME-0001). 
2.1.1.3 Nonclinical Toxicology 
General toxicity of ASP7517 was evaluated in 2 Good Laboratory Practice toxicity studies in 
C57BL/6J mice (Studies 7517-TX-0002 and 7517-TX-0005). 
The target organs of toxicity identified included the liver, spleen, kidney, pancreas, urinary 
bladder and epididymis. In addition, emboli were observed in the liver and spleen, and 
decreases in platelet counts were transiently noted on day 1 after the first or second dose. All 
of the observed toxicities listed above were reversible. No observed adverse effect level 
(NOAEL) was not determined. 
These preclinical studies have identified the liver as the dose limiting target organ of toxicity 
for ASP7517. Liver-related findings included increased aspartate aminotransferase (AST) 
and alanine aminotransferase (ALT), increased liver weight, white foci, emboli, mixed 
inflammatory cell infiltration and focal necrosis of hepatocytes at doses ≥ 1 × 105 cells/kg at 
1 day after a single dose of ASP7517. These findings completely resolved by 28 days 
postdose. Administration of a second dose of ASP7517, 4 weeks after the first dose, resulted 
in liver findings similar to those seen after the first dose. Dose-related decreases in platelet 
counts were observed 1 day after administering ASP7517 at doses ≥ 1 × 105 cells/kg. Platelet 
counts showed signs of recovery by 7 days and fully recovered by day 28. 
2.1.1.4 Clinical Studies 
Aside from the ongoing trial, no clinical studies of ASP7517 have been conducted. 
2.1.2 
Summary of Key Safety Information for Investigational Product 
2.1.2.1 Potential Risk 
No studies with ASP7517 in humans have been conducted yet. The potential risks described 
below are based on ASP7517 nonclinical studies and clinical data from compounds with 
similar mechanism of action or composition. The management of toxicities should be based 
on institutional standard of care, published guidelines, as well as on investigator judgment, 
the protocol instructions regarding risk monitoring, and interruption or discontinuation of 
investigational product (IP) treatment. 

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Table 6 
Potential Safety Concern of ASP7517 
Key Safety Targets 
Key Observations 
Relevance to 
Human Usage 
Liver 
Increased liver weight, increased AST and ALT, emboli, 
hepatocyte focal necrosis, mixed inflammatory cell 
infiltration, microgranuloma, granulomatous 
inflammation  
(at ≥ 1 × 105 cells/kg); mononuclear cell aggregation, 
pigment laden macrophage infiltration (at ≥ 1 × 107 
cells/kg) 
Possible risk 
Spleen 
Increased spleen weight (at ≥ 1 × 105 cells/kg); 
extramedullary hematopoiesis  
(at ≥ 1 × 106 cells/kg) 
Possible risk 
Circulatory system 
Emboli in the spleen and liver  
(at ≥ 1 × 105 cells/kg) 
Possible risk 
Kidney 
Increased creatinine, tubular basophilia, mononuclear cell 
infiltration (at ≥ 1 × 106 cells/kg) 
Possible risk 
Hematology 
Decreased platelet count 1 day after dose, increased 
platelet count 7 days after dose  
(at ≥ 1 × 105 cells/kg) 
Possible risk 
Pancreas 
Focal necrosis (at 1 × 108 cells/kg) 
Low potential risk 
Urinary bladder 
Mononuclear cell infiltration (at 1 × 108 cells/kg) 
Low potential risk 
Epididymis 
Interstitial fibrosis and granuloma  
(at 1 × 108 cells/kg) 
Low potential risk 
Tumorigenicity 
No colony formation in soft agar test 
No human cells (ASP7517) detected within 2-weeks in 
NOG mice after a dose of  
1 × 108 cells/kg 
Low potential risk 
Embryo-fetal 
development 
No embryo-fetal development studies have been 
performed to date 
Unknown 
ALT: alanine aminotransferase; AST: aspartate aminotransferase; NOG: NOD.Cg-Prkdcscid Il2rgtm1Sug/Jic. 
2.1.2.1.1 
Liver 
Preclinical studies demonstrated that the liver could be the target organ of toxicity for 
ASP7517, which is related to the activation of an innate immune response by presenting 
α-GalCer linked to CD1d on the surface of ASP7517 to natural killer T (NKT) cells. The 
activation of NKT cells is thought to be responsible for the hepatic injury induced with 
ASP7517. The hepatic findings could be monitored (increased AST and ALT 1 day after 
administration) and were completely reversed by 28 days after ASP7517 administration. The 
adverse events (AEs) in mice included increased liver weight, AST and ALT elevation, 
emboli, hepatocyte focal necrosis, mixed inflammatory cell infiltration, microgranuloma, 
granulomatous inflammation, mononuclear cell aggregation and pigment laden macrophage 
infiltration. Close monitoring of liver function and toxicities is required during clinical 
studies. 

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2.1.2.1.2 
Hematology 
A dose-related decrease in platelet count was noted 1 day after the first dose. There was also 
a dose related decrease in platelet count following the second dose. Platelet counts were 
increased above baseline 7 days after the first and second dose and recovered to normal 
physiological ranges by day 28. The standard assessment of hematology is recommended in 
clinical studies. 
2.1.2.1.3 
Kidney 
Increased serum creatinine was seen 1 day after the first dose. This finding was completely 
resolved 7 days after the first dose. In addition, histological assessment showed basophilic 
tubules and infiltration of mononuclear cells 7 days after the second dose. These histological 
findings were completely resolved 28 days after the second dose. The presence of basophilic 
tubules is interpreted as regeneration of renal tubules. The standard monitoring of kidney 
function parameters (creatinine, blood urea nitrogen) is recommended in clinical studies. 
2.1.2.1.4 
Spleen 
Spleen weights were increased 1 day after the first and second dose and showed a trend 
toward recovery in 28 days. In addition, histological assessments showed apoptosis in 
lymphoid follicle of the spleen 1 day after the first or second dose. This finding was 
completely resolved by 7 days after ASP7517 administration. Also, emboli were observed in 
the spleen 1 day after administering the first and second dose of ASP7517 and resolved 
completely by 7 days after dosing.  
In addition, lymphoid follicular hyperplasia was noted 7 days after the first or second dose 
that increased in incidence and severity with dose increase, whereas it had not been observed 
1 day after the first and second doses. This finding was partially or completely resolved by 
28 days post dosing. Standard hematology testing is recommended in clinical studies. 
2.1.2.1.5 
Other 
AEs reported from solid tumor, early phase clinical trials using α-GalCer based 
immunotherapies include: fever, headache, fatigue, dizziness, chest pain, lymphopenia, hot 
flash, hyperkalemia, lactate dehydrogenase increase, creatinine increase, anemia, increased 
cancer pain and hyperbilirubinemia. In general, these therapies were shown to be safe and no 
severe adverse events (SAEs) are related to the treatment [Kunii et al, 2009; Motohashi et al, 
2009; Uchida et al, 2008; Ishikawa et al, 2005]. 
The AEs reported in early phase WT1- peptide vaccine clinical studies in AML and MDS 
patients were mainly grade 1 or 2 events including fatigue, headache, pruritus, muscular 
weakness, bone pain, pain in extremity, flushing, dry skin, transient local erythema and 
induration, fever, transient erythema nodosum-like lesions and persistent cough. Also, grade 
3 and 4 AEs reported as lymphocyte count decrease, neutrophil count decrease, white blood 
cell count decrease and platelet count decrease. Overall, the protocol treatments were well 
tolerated and associated only with transient local grade 1 or 2 toxicities [Maslak, 2018; 
Keilholz et al, 2009]. 

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In addition, based on the above and the mechanism of action of ASP7517, immune-related 
adverse reactions (e.g., fever, headache, fatigue, hot flashes, diarrhea and muscular and joint 
pain) should be considered and managed as required per standard of care. 
2.1.2.1.6 
Infusion-related Reactions 
In nonclinical studies with ASP7517, infusion-related reactions (IRRs)/cytokine-release 
syndrome (CRS) were not seen. However, there are potential toxicities with intravenous 
infusion immunotherapy and the exact mechanism causing standard infusion reactions is 
unclear, but most reactions appear to arise from cytokine release from immune-mediated 
mechanisms [Lee et al, 2014]. 
The symptoms and signs associated with a standard infusion reaction include fever, shaking 
chills, flushing and/or itching, changes in heart rate and blood pressure, shortness of breath or 
chest discomfort, pain in back or abdomen, nausea, vomiting and/or diarrhea and skin rash. 
In addition to the signs and symptoms associated with a standard infusion reaction, CRS may 
result in neurologic signs and symptoms such as mental status changes, confusion and 
delirium. Renal and hepatic manifestations may include azotemia, elevated transaminases and 
hyperbilirubinemia, respectively. Coagulation parameters maybe also be affected and 
manifested by elevated D-dimer and hypofibrinogenemia, with or without bleeding. In 
addition, tumor lysis syndrome may also be associated with CRS [Lee et al, 2014]. Patients 
should be closely monitored for IRRs and CRS and appropriately managed per standard of 
care. 
2.1.2.1.7 
Allergic Reactions and Anaphylaxis 
Based on the nonclinical data, no signs or symptoms of allergic reaction or anaphylaxis were 
seen following ASP7517 administration. The signs and symptoms of anaphylaxis overlap 
with those of standard infusion reactions. However, certain features are highly suggestive of 
anaphylaxis, such as urticaria, repetitive cough, wheeze, throat tightness and change in voice, 
angioedema (usually of face, eyelids or lip), hypotension, loss of consciousness, nausea, 
vomiting, abdominal cramping and diarrhea. Patients should be monitored closely for any 
signs or symptoms of allergic reaction or anaphylaxis and managed appropriately per 
standard of care. 
2.1.2.1.8 
Potential for Anti-HLA Antibodies 
Anti-human leukocyte antigen (HLA) antibodies are formed following exposure to foreign 
HLA antigens, which may occur following the exposure to ASP7517. The presence of anti-
HLA antibodies can result in engraftment failure in hematopoietic stem cell transplantation 
(HSCT). Patients will be monitored for the presence of Anti-HLA antibodies in clinical trials. 
2.2 
Study Rationale 
Correlations between WT1 expression level and AML and MDS disease condition/ 
progression have been reported [Miyawaki et al, 2005; Tamaki et al, 1999]. In patients with 
MDS, expression of WT1 is associated with higher blast counts and an increased risk of 
progression to AML [Tamaki et al, 1999]. ASP7517 has effects against WT1 expressing 

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tumors by inducing both NK cell activity (innate immunity) and WT1-specific T cell 
dependent antitumor effects (adaptive immunity). Nonclinical studies were performed to 
demonstrate that both the innate and adaptive immune systems were activated by aAVC. In 
addition, nonclinical data suggest that ASP7517 is active in AML as described in 
[Section 2.1.1 Nonclinical and Clinical Data] and the Investigator’s Brochure; therefore, 
ASP7517 is targeting WT1 for the treatment of AML/MDS and may result in clinical benefit. 
2.3 
Risk Benefit Assessment 
Among AML patients, approximately 30% are refractory to induction therapy and of those 
who achieve CR, approximately 75% will relapse. Generally, there is no established standard 
of care for these patients and less than 20% will achieve CR with subsequent treatment. The 
response duration for patients who achieve CR with subsequent treatment is limited and most 
patients relapse. Patients who are in second relapse or refractory to first salvage have an 
extremely poor prognosis, with survival measured in weeks.  
For MDS, the currently available treatments are not curative and no standard of care is 
available for patients after failure to respond to hypomethylating agents [Uy et al, 2017]. 
Patients with higher-risk disease have an expected median overall survival of less than 
2 years. Patients who experience standard treatment failure have median survival of less than 
6 months and limited treatment options with consideration given to clinical trials [Sekeres & 
Culter, 2014]. 
ASP7517 has effects against WT1 expressing tumors and showed no significant safety 
findings in the pre-clinical pharmacology studies. In the repeated dose toxicity studies with 
mice, all major findings were reversible and monitorable and will not interfere with human 
clinical studies recruiting AML and MDS patients, considering its potential benefit against 
the risk. 

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3 
STUDY OBJECTIVE(S) AND ENDPOINT(S) 
The study objectives and endpoints for this study are provided in Table 7. 
Table 7 
Study Objectives and Endpoints 
Objective(s) 
Endpoint(s) 
Primary 
● To evaluate the safety and tolerability of 
ASP7517 
● Safety and tolerability as noted by: DLTs, AEs, 
SAEs, laboratory test results (serum, chemistry, 
hematology, coagulation, and urinalysis, 
pregnancy test) ECGs, vital signs, physical exams 
and ECOG performance status scores 
● To determine the RP2D and/or the MTD of 
ASP7517 (phase 1) 
● To evaluate the clinical response of ASP7517 
● CRc rate for subjects with R/R AML and 
(CR + BM CR + PR) rate for R/R higher risk 
MDS (phase 2) 
Secondary 
● To evaluate other measures of anticancer activity 
of ASP7517 
● Duration of remission 
● EFS 
● OS 
● CR, best response (CRc + PR) and CRh rates for 
subjects with R/R AML 
● CR, HI and objective response (CR + BM CR + 
PR + HI) rates for subjects with R/R higher risk 
MDS 
Exploratory 
● To evaluate potential genomic, proteomic and/or 
other biomarkers that may correlate with 
treatment outcome 
● Exploratory biomarkers that may correlate with 
treatment outcome of ASP7517 
● To evaluate pharmacodynamic activities of 
ASP7517 
● Pharmacodynamic effects of ASP7517, such as 
changes in: 
o Cytokine expression and secretion 
(e.g., IFNg) 
o WT1-specific T lymphocytes 
(e.g., cytotoxic T lymphocytes) 
o Immune cell populations (NKT cells, NK 
cells, etc.) 
● To evaluate pharmacokinetics of ASP7517, 
which is determined by the kinetics of the cells 
● Cellular DNA load and kinetic parameter 
estimates for ASP7517 
AE: adverse event; AML: acute myeloid leukemia; BM: bone marrow; CR: complete remission; CRc: composite 
complete remission; CRh: complete remission with partial hematologic recovery; DLT: dose limiting toxicity; 
ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EFS: event-free survival; IFNg: interferon 
gamma; HI: hematologic improvement; MDS: myelodysplastic syndrome; MTD: maximum tolerated dose; NK: 
natural killer; NKT: natural killer T; OS: overall survival; PR: partial remission; R/R: relapsed/refractory; RP2D: 
recommended phase 2 dose; SAE: serious adverse event; WT1: Wilms’ tumor 1 protein. 
 

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4 
STUDY DESIGN AND DOSE RATIONALE 
4.1 
Study Design 
This study is a phase 1/2, open-label study of ASP7517 (human embryonic kidney cell 
transfected with encoding target antigen WT1) in subjects with R/R AML and R/R higher 
risk MDS. 
A total of approximately 122 subjects are planned for enrollment in this study. 
In phase 1 (Dose Escalation), approximately 18 subjects with either AML or MDS will be enrolled. 
In phase 2 (Dose Expansion), approximately 104 subjects will be enrolled per dose level. Each 
dose level may enroll up to 52 subjects with R/R AML and up to 52 subjects with R/R higher 
risk MDS. Both groups of subjects will enroll in parallel and independently. 
4.1.1 
Study Periods 
The study consists of the following periods:  
● 
Screening (up to 14 days) 
● 
Treatment (two 28-day cycles during escalation phase; up to six 28-day cycles during 
expansion phase) 
● 
EoT visit 
● 
Post-Treatment 
○ Observation Period 1 (12 weeks or until 1 post-treatment discontinuation criterion 
is met, whichever occurs first) 
○ Observation Period 2 (assessment visit every month until 1 post-treatment 
discontinuation criterion is met) 
● 
Survival and subsequent treatment follow-up every 3 months 
During the treatment period, subjects will receive an intravenous infusion of ASP7517 
(human embryonic kidney cell transfected with encoding target antigen WT1).  
In phase 1 (dose escalation), subjects will receive 1 dose of ASP7517 per cycle for a total of 
2 doses.  
In phase 2 (dose expansion), subjects who have not met any individual treatment 
discontinuation criteria and who are receiving clinical benefit (defined as achieving CRc or 
PR for AML and CR, BM CR, PR or HI for MDS, or other clinical benefits as determined by 
the investigator) will continue further treatment with ASP7517 after the first 2 cycles, as 
decided by the investigator.   
After completing 4 cycles of treatment, subjects who achieve CR will not continue with 
ASP7517; subjects who do not reach CR, but also do not experience disease progression, 
may receive an additional 2 doses for a total of 6 doses. 
Each cycle is defined as 28 days with a total of up to 6 treatment cycles.  
An End-of-Treatment (EoT) visit will be conducted for all subjects within 7 days of the 
principal investigator decision to discontinue the subject from treatment or prior to the 

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initiation of new anticancer therapy, whichever occurs first. If a subject is completing all visits 
in the last treatment cycle, the EoT visit will be within 7 days from the last planned visit. 
After the EoT visit, Observation Period 1 will be 12 weeks or until 1 post-treatment 
discontinuation criterion is met, whichever comes first. Subjects who achieve composite 
complete remission (CRc) or PR for AML and CR, bone marrow (BM) CR or PR or HI for 
MDS or other clinical benefits, as determined by the investigator, will remain in the study in 
Observation Period 2 until 1 post-treatment discontinuation criterion is met. Safety and 
efficacy will be monitored during Observation Periods 1 and 2. 
Upon treatment or post-treatment discontinuation criterion is met and subjects discontinue 
from the Treatment Period, Observation Period 1, or Observation Period 2, all subjects will 
be followed for survival and subsequent anti-cancer treatments and outcomes by telephone 
calls every 3 months. 
This study consists of 2 parts: phase 1 dose escalation and phase 2 dose expansion. 
4.1.2 
Phase 1 Dose Escalation 
The dose escalation portion will assess safety and tolerability of ASP7517. In the dose 
escalation phase, subjects must be managed under hospitalization for at least 7 days during 
the first cycle of the dose escalation phase. In addition, prior to hospital discharge, the 
investigator must ensure subject safety by performing medical tests and procedures listed on 
day 7 of cycle 1 and tests considered clinically necessary in the opinion of the investigator to 
evaluate the subject’s general condition and AE resolution. The subject should also be 
followed on an outpatient basis on planned visits during cycle 1 and 2 after hospital discharge 
during the DLT assessment period to closely monitor any AEs. Subjects may be hospitalized 
days 1 to 7 during cycle 2 based on investigator opinion.  
After dosing of ASP7517, subjects must be observed for safety for a minimum of 4 hours. 
The safety observation will consist of hourly vital signs and AE observations. If new AEs are 
observed that are ≥ grade 3 during this time, subjects should continue to be observed at the 
investigator’s discretion.  
In phase 1 (dose escalation), the starting dose level is 1 × 106 cells/dose and the decision to 
dose escalate to the next dose levels (1 × 107 and 1 × 108 cells/dose) will be made based on 
the assessment of safety variables, including the occurrence of dose limiting toxicities 
(DLTs). Dose escalation will be guided according to the Bayesian optimal interval (BOIN) 
design [Liu et al, 2015] to determine the next dose level based on DLT occurrence. After the 
planned number of evaluable subjects have completed the DLT observation period for a 
given dose level, safety for that dose level will be assessed. Each dose level in the dose 
escalation phase will enroll a minimum of 3 and may enroll a maximum of 8 subjects with up 
to 4 evaluable subjects for the initial assessment of each dose level. Enrollment within each 
dose escalation cohort will be staggered such that there will be 28 calendar days between the 
treatment initiation of the first subject and the second subject, as well as 14 calendar days 
between the second subject and the third subject at the same dose level for all escalation 
cohorts. An interval of 28 calendar days will separate initiation of first dose of study 

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treatment for the last subject in a dose cohort from the first subject in the subsequent dose 
cohort. The 28-day separation is equivalent to the 28-DLT evaluation period. If the decision 
is made to stay at the current dose level, then an additional 3 or 4 evaluable subjects may be 
enrolled to the current dose level. Three to 18 subjects will be enrolled in the dose escalation 
phase. A minimum number of 6 subjects and a maximum number of 8 subjects must be 
enrolled at the dose level used to determine the maximum tolerated dose (MTD) and the 
recommended phase 2 dose (RP2D). 
Safety data and other available clinical data will be reviewed on an ongoing basis to 
determine if the study will proceed to the next dose level/phase.  
Subject Replacement during Dose Escalation:  
Subjects may be replaced in the dose escalation cohort if: 
● 
Subject is discovered to have enrolled without fully satisfying eligibility criteria. 
● 
Subject received less than the planned dose in cycle 1 for reasons other than DLT. 
● 
Subject has no DLT and withdraws from the study before the end of the DLT evaluation 
period. 
The decision regarding replacement of individual subjects will be made by the sponsor with 
discussions with the treating investigator. 
4.1.3 
Dose Limiting Toxicity Criteria 
A DLT is defined as any of the following events that occur within 28 days starting with the 
first dose on C1D1 and that is considered to be related to IP. Confirmation of DLTs will be 
made by the Dose Escalation and Safety Committee (DESC). The severity of AEs will be 
assessed according to NCI-CTCAE, version 5.0. 
DLT is defined as follows:  
⚫ 
Non-hematologic AEs that are ≥ grade 3. 
⚫ 
Confirmed Hy’s law case. 
⚫ 
New onset of grade 4 thrombocytopenia (with minimum of 2 grade worsening from 
baseline) within 24 hours of dosing. 
⚫ 
Prolonged myelosuppression, defined as ANC < 500/µL for more than 28 days off 
therapy and in the absence of evidence of active leukemia or MDS in the marrow or 
blood, will be considered a DLT. 
The following AEs will not be considered as DLTs: 
● 
Electrolyte abnormalities that are not associated with clinical sequelae or deemed not 
clinically significant and corrected with appropriate management or supplementation 
within 72 hours of onset. 
● 
Grade 3 infusion site reaction if successfully managed and resolved within 72 hours. 
● 
Grade 3 febrile neutropenia with or without infection.  
● 
Alopecia, anorexia or fatigue. 
● 
Grade 3 nausea and/or vomiting if not requiring tube feeding or total parenteral nutrition, 
or diarrhea and/or constipation if not requiring or prolonging hospitalization that can be 

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managed to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at 
prescribed doses within 7 days of onset. 
● 
Grade 3 liver function test (LFT) elevations that resolve to ≤ grade 1 within 7 days; LFT 
elevations lasting > 7 days that are considered to be clinically significant and at least 
possibly related to ASP7517 will be considered to be a DLT. 
● 
Immune-related AEs grade 3 that resolve to ≤ grade 1 within 7 days. 
● 
Grade 3 or higher hyperuricemia due to tumor lysis that resolves to ≤ grade 1 with 
medical interventions, including hospitalization with intravenous hydration and/or 
rasburicase. 
Dose evaluation and dose escalation stopping rules based on the BOIN design with target 
DLT rate of 0.30 and optimal interval of (0.236, 0.359) are as follows: 
Action 
Number of Subjects Treated at 
Current Dose Level 
3 
4 
5 
6 
7 
8 
Escalate dose if number of subjects with DLT ≤ 
0 
0 
1 
1 
1 
1 
Stay at current dose level if number of subjects 
with DLT = 
1 
1 
- 
2 
2 
2 
De-escalate if number of subjects with  
DLT = 
2 
2 
2 or 3 
3 
3 or 4 
3 or 4 
Stop if number of subjects with DLT ≥ 
3 
3 
4 
4 
5 
5 
DLT: dose limiting toxicity 
Dose escalation within individual subjects will not be allowed. 
4.1.4 
Dose Escalation and Safety Committee 
A DESC consisting of sponsor representatives and investigators will convene once a dose 
level cohort completes the DLT observation period and data are available for review. Refer to 
[Section 10.4.1 Dose Escalation and Safety Committee] and DESC charter for additional 
details. 
The DESC will also review the aggregate safety data from the phase 1 dose escalation and 
the phase 2 expansion cohorts.  
Study enrollment and study treatment will be temporarily interrupted during dose escalation 
pending review of the following: 
● 
Any death that is not related to disease progression occurring within 30 days of receiving 
investigational product. 
● 
Occurrence of two grade ≥ 4 DLTs in 2 study subjects. 
● 
Any grade 4 hypersensitivity reaction/anaphylaxis. 
Additional information regarding DESC responsibilities, membership requirements and 
safety review time points are described in [Section 10.4 Dose Escalation and Safety 
Committee] and further detailed in the DESC Charter.  

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4.1.5 
Phase 2 (Dose Expansion) 
Phase 2 will assess the safety and efficacy of ASP7517. This phase of the study may open 
once the RP2D and/or MTD are determined from the dose escalation phase, OR all of the 
following conditions are met before the RP2D and/or MTD determination. 
● 
At least 1 subject in the dose escalation cohort (phase 1) achieves CRc for AML 
subjects, or CR, BM CR or PR for MDS subjects. 
● 
The dose level to be expanded is deemed tolerable by the DESC. 
● 
The dose that will be opened for expansion is determined to be equal or lower than the 
possible MTD. 
Phase 2 will include the following groups and may enroll in parallel and independently: 
● 
Subjects with R/R AML. 
● 
Subjects with R/R higher risk MDS. 
The CRc rate for subjects with R/R AML and CR + BM CR + PR rate for R/R higher risk 
MDS are continuously monitored using the Bayesian optimal phase 2 (BOP2) design [Zhou 
et al, 2017]. The number of dose levels investigated during phase 2 will be based upon the 
data from phase 1. Initially, 12 subjects will be enrolled at each dose level for each disease 
type during stage 1 of BOP2. If the response rate does not meet the optimal stopping 
boundaries (see table below), then stage 2 will open and an additional 20 subjects may be 
enrolled during this stage. Combining the data from stage 1 and stage 2, stage 3 may be 
opened for an additional 20 subjects for a total maximum sample size of 52 for each disease 
type, if the response rate does not meet the optimal stopping boundaries (see table below). 
Otherwise, the enrollment at that dose level will be closed.  
When the total number of subjects reaches the maximum sample size of 52, it may be 
concluded that ASP7517 is efficacious if the number of responses is greater than or equal to 
12 and 10 for AML and MDS, respectively. The number of subjects in stage 1, stage 2 and 
stage 3 may be changed according to the optimized stopping boundaries.  
Optimized Stopping Boundaries for AML 
Number of subjects treated 
Stop if number of responses ≤  
12 
1 
32 
5 
AML: acute myeloid leukemia 
 
Optimized Stopping Boundaries for MDS 
Number of subjects treated 
Stop if number of responses ≤  
12 
0 
32 
4 
MDS: myelodysplastic syndrome 

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Stopping Rules based on Safety for Phase 2 
The stopping rules described below will be applied to both AML and MDS disease types. 
The safety in phase 2 will be monitored using a Bayesian logistic model based on safety 
events including: 
⚫ All DLT data obtained at the time of the analysis from both escalation and expansion 
cohorts.  
⚫ Drug related treatment emergent AEs leading to death. 
Safety monitoring with these models will start when phase 2 is opened. Enrollment in phase 2 
will be stopped based on the following 2 criteria: 
⚫ If the posterior mean of the safety event rate is higher than 30% as indicated by Bayesian 
logistic model across disease types at a given dose level, then enrollment will be stopped 
in phase 2 at that dose level and at higher dose levels for that therapy. 
⚫ Additionally, if the posterior mean of the safety event rate is higher than 30% as indicated 
by Bayesian logistic model in a specific disease type at a dose level, enrollment of that 
dose level and any higher dose level will be stopped for that disease type. 
4.1.6 
Dose Rationale 
The starting dose for the first in human (FiH) study is anticipated to be safe with minimal 
pharmacological activity, as supported by the nonclinical studies. The starting dose of 
ASP7517 is set to 1 × 106 cells/dose by intravenous infusion. 
Nonclinical pharmacology data suggest ASP7517-surrogate shows prolonged survival when 
administered intravenously to a C1498-WT1 inoculated mouse AML model (per 30 g mouse), 
and prolonged survival was confirmed at the lowest dose level (5 × 102 cells/mouse) in the 
study. The dose of 5 × 102 cells/mouse is calculated as 1.7 × 104 cells/kg (5 × 102 cells/30 g); 
therefore, the starting dose is estimated to be 1 × 106 cells/dose (1.7 × 104 cells/kg × 60 kg). 
The starting dose was also assessed according to the results of the nonclinical toxicology 
studies. Toxicities (e.g., liver findings, changes in platelet count) were observed after 
ASP7517 intravenous administration at the lowest dose used in nonclinical studies 
(1 × 105 cells/kg: equivalent to 6 × 106 cells/dose, administered per 60 kg human), and the 
NOAEL was not established in the studies. However, these adverse effects are considered to 
be immune-related reactions based on the mechanism of action of ASP7517, and it is expected 
that the toxicities are reversible and monitorable in the nonclinical studies. Consequently, it is 
considered possible to set the starting dose for the FiH study as 1 × 106 cells/dose, 6-fold 
lower than the lowest dose of nonclinical toxicology studies, with careful clinical monitoring. 
The dosing regimen for the FiH study is a total of up to 2 doses in the escalation phase and up 
to 6 doses in the expansion phase, one dose in each 28-day cycle, which is supported by 
nonclinical pharmacology data. In mice immunized with specific antigen expressing aAVC at 
day 0 and day 28, NKT cells and T cells were stimulated after first and second 
administration. Also, long term antigen-specific antitumor immune memory was 
demonstrated in an EG7 inoculated mouse model after single administration. 

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4.2 
End of Study Definition  
The study start is defined as the date the first subject signs the informed consent form (ICF). 
End of the study is defined as the last visit or scheduled procedure shown in the Schedule of 
Assessments for the last subject in the study. 
Study completion is defined as the conclusion of data collection for the defined study endpoints. 
The study may be closed within a participating country per local regulations once the study has 
been completed and if all subjects enrolled in the country are no longer receiving IP. 
5 
STUDY POPULATION 
Subjects with R/R AML or R/R higher risk MDS will be included. 
All screening assessments must be completed and reviewed to confirm the potential subject 
meets all eligibility criteria. Prospective approval of protocol deviations to eligibility criteria 
(also known as protocol waivers or exemptions) is not permitted. 
5.1 
Inclusion Criteria 
Subject is eligible for participation in the study if all of the following apply: 
1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
informed consent and privacy language as per national regulations (e.g., Health 
Insurance Portability and Accountability Act authorization [HIPAA] for US study sites) 
must be obtained from the subject or legally authorized representative prior to any study-
related procedures (including withdrawal of prohibited medication, if applicable). 
2. Subject is considered an adult according to local regulation at the time of signing the ICF.  
3. Subject diagnosed with R/R AML or R/R higher risk MDS is defined as: 
⚫ R/R AML 
o Morphologically documented primary or secondary AML by the WHO criteria 
(2016),  
AND 
o Refractory to at least 2 cycles of induction chemotherapy/not a candidate for 
re-induction OR relapsed after achieving remission with a prior therapy, 
AND 
o Received all standard therapies including targeted therapies (unless the therapy 
is contraindicated or intolerable) which are known to provide clinical benefit in 
the opinion of the investigator, 
AND 
o Received salvage therapy OR is not a candidate for salvage therapy 
⚫ R/R Higher Risk MDS 
o Has MDS by the WHO criteria (2016), 
AND 

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o Either relapsed after achieving remission or refractory to standard therapies, 
including ≥ 4 cycles of hypomethylating agents (unless the therapy is 
contraindicated or intolerable), 
AND 
o Is classified as higher risk MDS with a score of > 3.5 by Revised International 
Prognostic Scoring System (IPSS-R) in MDS 
4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. 
5. Subject must meet the following criteria as indicated on the clinical laboratory tests 
during screening period: 
⚫ Serum AST and ALT ≤ 2.5 × upper limit of normal (ULN) 
⚫ Serum total bilirubin (TBL) ≤ 1.5 × ULN 
⚫ Serum creatinine ≤ 1.5 × ULN or an estimated glomerular filtration rate of 
> 50 mL/min as calculated by the Modification of Diet in Renal Disease equation 
⚫ Platelets ≥ 50,000/μL at cycle 1 day 1 (C1D1) in the dose escalation cohort only 
6. Subject has a life expectancy of ≥ 12 weeks at the time of screening in the opinion of the 
investigator. 
7. Subjects with AML must have peripheral blood absolute blast count of < 20,000/µL at 
C1D1. 
Note: Blast count can be controlled by hydroxyurea during screening period.  
8. Female subject is not pregnant [see Appendix 12.3 Contraception Requirements] and at 
least 1 of the following conditions apply: 
⚫ Not a woman of childbearing potential (WOCBP) [see Appendix 12.3 
Contraception Requirements] 
⚫ WOCBP who agrees to follow the contraceptive guidance [see Appendix 12.3 
Contraception Requirements] from the time of informed consent through at least 
180 days after final study treatment administration 
9. Female subject must agree not to breastfeed starting at screening and throughout the 
study period and for 180 days after the final study treatment administration. 
10. Female subject must not donate ova starting at first dose of IP and throughout the study 
period and for 180 days after final study treatment administration. 
11. Male subject with female partner(s) of childbearing potential (including breastfeeding 
partner) must agree to use contraception [see Appendix 12.3 Contraception 
Requirements] throughout the treatment period and for 180 days after final study 
treatment administration. 
12. Male subject must not donate sperm during the treatment period and for 180 days after 
the final study treatment administration. 

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13. Male subject with pregnant partner(s) must agree to remain abstinent or use a condom 
for the duration of the pregnancy throughout the study period and for 180 days after final 
study treatment administration. 
14. Subject agrees not to participate in another interventional study while receiving study 
treatment in the present study.  
Waivers to the inclusion criteria will NOT be allowed. 
5.2 
Exclusion Criteria 
Subject will be excluded from participation in the study if any of the following apply: 
1. Subject was diagnosed with acute promyelocytic leukemia. 
2. Subject has breakpoint cluster region-Abelson-positive leukemia (BCR-ABL). 
3. Subject has persistent non-hematological toxicities of ≥ grade 2 (National Cancer 
Institute’s Common Terminology Criteria for Adverse Events [NCI-CTCAE], version 
5.0), with symptoms and objective findings from prior AML or MDS treatment 
(including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, 
radiation or surgery). 
4. Subject has received any of the following therapies:  
● 
Systemic immunomodulators or immunosuppressive drugs including steroids  
≤ 28 days prior to C1D1 (steroids can be used if not intended for treatment of AML 
or MDS; steroids for AML/MDS related symptoms can be used at low doses [less 
than 10 mg/day dexamethasone]) 
● 
Cytotoxic agents (except hydroxyurea given for controlling blast cells) ≤ 28 days 
prior to C1D1 
● 
IPs for the treatment of AML or MDS within 5 half-lives prior to screening visit 
● 
HSCT 
● 
Radiation therapy ≤ 28 days prior to C1D1 
5. Subject has clinically active nervous system leukemia, per the investigator’s judgment. 
6. Subject has active or prior documented autoimmune or inflammatory disorders requiring 
systemic treatment. 
7. Subject has ongoing, untreated malignancy with the exception of the following: 
● 
Subjects with treated non-melanoma skin cancer, in situ carcinoma or cervical 
intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this 
study if definitive treatment for the condition has been completed. 
● 
Subjects with organ-confined prostate cancer with no evidence of recurrent or 
progressive disease are eligible if hormonal therapy has been initiated or the 
malignancy has been surgically removed or treated with definitive radiotherapy. 
8. Subject with left ventricular ejection fraction of < 45% on echocardiogram (ECHO) or 
multigated acquisition scan (MUGA) performed within 28 days of screening. 

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9. Subject has laboratory abnormalities or clinical evidence of disseminated intravascular 
coagulation, or ongoing history of coagulation disorder manifested by bleeding or 
clotting. 
10. Subject has an active uncontrolled infection. 
11. Subject is known to have human immunodeficiency virus infection. 
12. Subject has active hepatitis B or C or other active hepatic disorder. 
13. Subject has any condition, which in the investigator’s opinion, makes the subject 
unsuitable for study participation. 
14. Subject has a known or suspected hypersensitivity to bovine-derived protein or has 
suspected hypersensitivity to any ingredients of ASP7517. 
15. Subject is eligible for HSCT. 
Waivers to the exclusion criteria will NOT be allowed. 
5.3 
Restrictions During The Study 
Not applicable. 
5.4 
Screen Failures 
A screen failure is defined as a potential subject who signed the ICF but did not meet 1 or 
more criteria required for participation in the study and was not enrolled. 
For screen failures, the demographic data, date of signing the ICF, inclusion and exclusion 
criteria, AEs up to the time of screen failure and reason for screen failure will be collected in 
the electronic case report form (eCRF). 
5.4.1 
Rescreening 
Results of screening assessments that do not meet the parameters required by eligibility 
criteria (e.g., clinical laboratory tests, vital signs, physical examination, electrocardiogram 
[ECG], etc.) may be repeated once within the 14-day screening period without the need to 
register the subject as a screen failure. If more than 14 days elapse from the date of signing 
the ICF, the subject must be documented as a screen failure. In order to rescreen, a new ICF 
must be signed and the subject must be entered into screening with a new subject 
identification number. Rescreening is only allowed once for an individual subject. The bone 
marrow sample and ECHO/MUGA screening assessments completed within 28 days prior to 
first dose do not need to be repeated.  

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6 
INVESTIGATIONAL PRODUCT 
6.1 
Investigational Product Administered 
Table 8 
Investigational Product 
Name 
ASP7517 
Dosage Formulation 
Suspension for injection 
Physical Description 
Opalescent and white to slightly yellowish-white suspension 
Unit Dose Strength 
1 × 107 cells/mL 
Packaging and Labeling 
Clear single use vial 
Route of Administration 
Intravenous infusion 
Administration 
Instruction 
Fifty (50) mL of diluted IP will be administered by intravenous infusion at 4 
to 6 mL/min infusion rate through a dedicated intravenous line, followed by 
flushing  
IMP or Non-IMP 
IMP 
Storage 
-150°C or below 
Sourcing 
Provided centrally by sponsor 
IMP: Investigational Medicinal Product. 
Refer to the pharmacy manual for detailed information regarding preparation, handling and 
storage of the IP. 
6.1.1 
Administration 
ASP7517 will be infused in 50 mL of normal saline solution at 1 × 106, 1 × 107, or 1 × 108 
total cells/dose. It will be administered by intravenous infusion with an infusion rate between 
4 to 6 mL/min through a dedicated intravenous line, followed by flushing. 
Refer to the pharmacy manual for detailed information regarding administration of the IP. 
6.2 
Preparation/Handling/Storage/Accountability 
6.2.1 
Packaging and Labeling 
All IP used in this study will be prepared, packaged and labeled under the responsibility of 
qualified personnel at Astellas Pharma Global Development Inc. (APGD) or sponsor’s 
designee in accordance with APGD or sponsor’s designee standard operating procedures 
(SOPs), Good Manufacturing Practice (GMP) guidelines, International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good 
Clinical Practice (GCP) guidelines and applicable local laws/regulations. The intravenous 
infusion will be prepared onsite by a pharmacist or qualified person using aseptic technique 
as specified in the pharmacy manual. 
Each vial will bear a label conforming to regulatory guidelines, GMP and local laws and 
regulations that identifies the contents as investigational drug. 
Refer to the pharmacy manual for detailed information regarding packaging and labeling of 
the IP. 

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6.2.2 
Handling, Storage and Accountability 
● 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all IP received and any discrepancies are reported and 
resolved before use of the IP. 
● 
Only subjects enrolled in the study may receive IP and only authorized study site 
personnel may supply or administer IP. Only IP with appropriate expiry/retest dating 
may be dispensed. 
● 
All IP must be stored in a secure, environmentally controlled and monitored (manual or 
automated) area in accordance with the labeled storage conditions and access must be 
limited to the investigator and authorized study site personnel. 
● 
The investigator, institution or the head of the medical institution (where applicable) is 
responsible for accountability, reconciliation and record maintenance (i.e., receipt, 
reconciliation and final disposition records).  
● 
Further guidance and instruction on final disposition of used and unused IP is provided 
in the pharmacy manual. 
Refer to the pharmacy manual for detailed information regarding IP handling, storage and 
accountability of the IP. 
6.3 
Randomization and Blinding 
This is an open-label study. Subject enrollment and dispensation of IP will be performed via 
the interactive response technology (IRT) system. Specific IRT procedures will be described 
in the respective study manual. 
6.3.1 
Assignment and Allocation 
Priority for enrollment will be given to the phase 1 dose escalation portion before phase 2 
dose expansion. 
For phase 2 enrollment, if more than 1 dose level is open for enrollment within a selected 
disease type, the newly enrolled subjects with that disease type will be randomly allocated to 
1 of the open dose levels. Randomization will be weighted towards newly opened dose 
levels, with the allocation ratio based on the number of open slots still available at each dose 
level. For example, if dose level ‘x’ enrolled 3 subjects and dose level ‘y’ is newly opened for 
expansion, the next subject would be randomly allocated to dose level ‘x’ or ‘y’ with the ratio 
of 9:12. 
When escalation and expansion cohorts are both open for enrollment, enrollment into 
escalation cohorts takes priority such that subjects who are eligible for both will be 
preferentially enrolled in the escalation cohorts. 
6.4 
Investigational Product Compliance 
Dosing will take place in the clinical unit. The administration of IP will be supervised to 
ensure treatment compliance. The exact day and time of IP administration will be 
documented. 

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6.5 
Previous and Concomitant Treatment (Medication and Nonmedication 
Therapy) 
The following treatments are prohibited during the study: 
● 
Interferon/polyethylene-interferon 
● 
High-dose systemic corticosteroids with the exception for immune-related AEs 
● 
Immunosuppressive agents 
● 
Investigational agents other than ASP7517 
● 
Any other treatments of AML or MDS (including but not limited to chemotherapy, 
radiotherapy, surgery, immunotherapy or cellular therapy) are prohibited during the 
study with ASP7517 with the following exceptions: 
o Hydroxyurea up to 5 g daily for up to 2 weeks to keep the absolute blast count 
< 20,000/µL 
o Subject undergoing HSCT will be discontinued from the study  
o Intrathecal chemotherapy used as prophylaxis 
Refer to [Appendix 12.6 List of Excluded Concomitant Medications] for a detailed list of 
drug classes and/or specific medications that are prohibited during participation in the study. 
6.6 
Dose Modification 
Dose modifications are not allowed. Any subjects who do not receive a subsequent dose 
within the scheduled time window in the Schedule of Assessments [Table 1 and Table 2] can 
only resume treatment after discussion with the medical monitor. Any subject experiencing a 
grade 3 AE related to IP after receiving a dose of ASP7517 may receive the subsequent 
scheduled dose of ASP7517 only after the observed grade 3 AE has resolved to grade 1; the 
subsequent dose of ASP7517 may be reduced to a dose level deemed safe by the DESC. 
Further treatment reduction/withdrawal can be implemented after discussion with the medical 
monitor, including for any clinically significant AEs affecting vital organs (e.g., cardiac 
events).  
6.7 
Criteria for Continuation of Treatment 
ASP7517 will not be made available after conclusion of the study to subjects who are still 
receiving and benefitting from study treatment in countries where the product does not have 
marketing approval and is not commercially available. ASP7517 is given as a maximum of 
6 doses (up to 2 doses in the escalation phase; up to 6 doses in the expansion phase).  
7 
STUDY PROCEDURES AND ASSESSMENTS 
7.1 
Efficacy Assessments 
7.1.1 
Response Criteria Definitions 
7.1.1.1 Acute Myeloid Leukemia Response Criteria 
Response to treatment will be defined per modified criteria [Cheson et al, 2003] as outlined 
below. 

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● 
Complete Remission (CR) 
For subjects to be classified as being in CR at a post-baseline visit, they must have bone 
marrow regenerating normal hematopoietic cells and achieve a morphologic leukemia-
free state and must have an absolute neutrophil count (ANC) ≥ 1 × 109/L and platelet 
count ≥ 100 × 109/L, and normal marrow differential with < 5% blasts, and they will be 
red blood cell (RBC) and platelet transfusion independent (defined as 1 week without 
RBC transfusion and 1 week without platelet transfusion). There must be no presence of 
Auer rods. There should be no evidence of extramedullary leukemia. The blast counts in 
peripheral blood must be ≤ 2%.  
● 
Complete Remission with Incomplete Platelet Recovery (CRp) 
For subjects to be classified as being in CRp at a post-baseline visit, they must achieve 
CR except for incomplete platelet recovery (< 100  109/L). 
● 
Complete Remission with Incomplete Hematological Recovery (CRi) 
For subjects to be classified as being in CRi at a post-baseline visit, they must fulfill all 
the criteria for CR except for incomplete hematological recovery with residual 
neutropenia (ANC < 1  109/L) with or without complete platelet recovery. RBC and 
platelet transfusion independence is not required. 
● 
Composite Complete Remission (CRc) 
For subjects to be classified as being in CRc at a post-baseline visit, they must either 
achieve CR, CRp or CRi at the visit. 
● 
Complete Remission with Partial Hematologic Recovery (CRh) 
For subjects to be classified as CRh at a post-baseline visit, if they have marrow blasts 
< 5%, partial hematologic recovery ANC ≥ 0.5 × 109/L and platelets ≥ 50 × 109/L, no 
evidence of extramedullary leukemia and cannot be classified as CR. The blast counts in 
peripheral blood must be ≤ 2%. 
● 
Partial Remission (PR) 
For subjects to be classified as being in PR at a post-baseline visit, they must have bone 
marrow regenerating normal hematopoietic cells with evidence of peripheral recovery 
with no (or only a few regenerating) circulating blasts and with a decrease of at least 
50% in the percentage of blasts in the bone marrow aspirate with the total marrow blasts 
between 5% and 25%. A value of less or equal than 5% blasts is also considered a PR if 
Auer rods are present. There should be no evidence of extramedullary leukemia. 
● 
Not Evaluable (NE)/No Response (NR) 
In the situation where no bone marrow assessments are performed or myeloblast value is 
missing, blast value from peripheral blood is missing or ≤ 2%, and extramedullary 
leukemia is missing or not present, the response will be classified as NE. In any case 
response cannot be categorized as CR, CRp, CRi, PR or NE, it will be categorized as 
NR. 

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● 
Relapse 
Relapse after CR, CRh, CRp or CRi is defined as a reappearance of leukemic blasts in 
the peripheral blood (> 2%) or ≥ 5% blasts in the bone marrow aspirate not attributable 
to any other cause or reappearance or new appearance of extramedullary leukemia. 
Relapse after PR is similarly defined with reappearance of significant numbers of 
peripheral blasts and an increase in the percentage of blasts in the bone marrow aspirate 
to > 25% not attributable to any other cause or reappearance or new appearance of 
extramedullary leukemia. 
7.1.1.2 Myelodysplastic Syndrome Response Criteria 
Response to treatment will be defined according to the modified International Working 
Group response criteria [Cheson et al, 2006] as outlined below. 
● 
Complete Remission (CR) 
For subjects to be classified as being in CR at a post-baseline visit, they must have all of 
the following maintained for a minimum of 4 weeks: 
o Bone marrow evaluation: ≤ 5% myeloblasts with normal maturation of all cell 
lines 
o Peripheral blood evaluation: 
▪ Hemoglobin ≥ 11 g/dL  
▪ Platelets ≥ 100 × 109/L 
▪ Neutrophils ≥ 1.0 × 109/L 
▪ 0% blasts in blood 
● 
Partial Remission (PR) 
For subjects to be classified as being in PR at a post-baseline visit, they must have all 
CR criteria if abnormal before treatment except the following for a minimum of 
4 weeks: 
o Bone marrow blasts decreased by ≥ 50% over pretreatment but still > 5% 
o Cellularity and morphology not relevant 
● 
Marrow CR  
For subjects to be classified as being in marrow CR at a post-baseline visit, they must 
have all of the following for a minimum of 4 weeks: 
o Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment 
▪ Peripheral blood: if HI responses, they will be noted in addition to marrow 
CR 
● 
Hematologic Improvement (HI) 
Requires 1 measurement of the following maintained for at least 8 weeks without 
ongoing cytotoxic therapy: 
o HI – erythroid: 

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▪ Hemoglobin increase of ≥ 1.5 g/dL 
or 
▪ For RBC transfusions performed for hemoglobin ≤ 9.0 g/dL: reduction in 
RBC units transfused in 8 weeks by ≥ 4 units compared to the number of 
units transfused in the 8 weeks prior to treatment 
o HI – platelets: 
▪ For pre-treatment platelet count of >20 ×109/L platelet, absolute increase of 
≥ 30 ×109/L 
▪ For pre-treatment platelet count of < 20 ×109/L, platelet absolute increase 
of > 20 ×109/L and ≥ 100% increase from pre-treatment level 
o HI – neutrophils: 
▪ Neutrophil count increase of ≥ 100% from pre-treatment level and an 
absolute increase of > 0.5 ×109/L 
● 
Relapse after CR or PR  
Requires at least 1 of the following: 
o Return to pre-treatment bone marrow blast percentage 
o Decrement of ≥ 50% from maximum response levels in granulocytes or platelets 
o Transfusion dependence or hemoglobin level ≥ 1.5 g/dL lower than prior to 
therapy 
7.1.1.3 Hematology Laboratory Assessments 
Primary endpoints of hematology clinical laboratory tests will be performed at every visit. 
Refer to [Section 9.4.1 Analysis of Primary Endpoint] for definitions of CRc for subjects 
with R/R AML and CR + BM CR + PR for R/R higher risk MDS. 
Secondary endpoints of hematology clinical laboratory tests will be performed at every visit. 
Refer to [Section 9.4.1 Analysis of Primary Endpoint] for definitions of duration of 
remission, event-free survival (EFS), OS, CR, BM CR, best response, CRh, HI, and objective 
response. 
7.1.2 
Bone Marrow Aspirations and/or Biopsies 
Study procedures and their timing are summarized in the Schedules of Assessments [Table 1 
and Table 2]. After the completion of Observation Period 1 (8 weeks), subjects remaining in 
the study, because they achieved remission (CRc or PR for AML subjects and CR, BM CR, 
PR, or HI for MDS subjects) or have clinical benefit as determined by investigator, will have 
bone marrow samples collected in Observation Period 2 every 3 months or if there is 
suspicion of relapse in the whole blood. If bone marrow aspirate is unobtainable (e.g., dry 
tap), an additional ethylenediaminetetraacetic acid tube of whole blood should be collected 
instead. Bone marrow aspirate is required, and bone marrow biopsy is preferred. In case of 
inadequate aspirate, bone marrow biopsy is required. Samples must be submitted to a central 
laboratory for analysis. Please refer to the laboratory manual for additional information. 

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7.2 
Safety Assessments 
Study procedures and their timing are summarized in the Schedules of Assessments [Table 1 
and Table 2]. Protocol waivers or exemptions are not allowed. 
Procedures conducted as part of a subject’s routine clinical management (i.e., standard of 
care) obtained before signing the ICF may be utilized for screening or baseline purposes, 
provided the procedures met the protocol-specified criteria and were performed within the 
timeframe, as defined in the Schedules of Assessments [Table 1 and Table 2].  
7.2.1 
Adverse Events 
See [Section 7.3 Adverse Events and Other Safety Aspects] and [Section 12.4 Adverse 
Events: Definitions and Procedures for Recording, Evaluating, Follow-up and Reporting] for 
information regarding AE collection and data handling. 
7.2.2 
Laboratory Assessments 
● 
See [Appendix 12.7 Laboratory Assessments] for the list of clinical laboratory tests to be 
performed and refer to the Schedules of Assessments [Table 1 and Table 2] for timing 
and frequency. 
● 
Laboratory samples will be analyzed by the institution’s local laboratory. However, 
ONLY local sample results must be submitted for centralized data entry. Refer to the 
laboratory manual for additional information. 
● 
Additional laboratory tests should be performed according to institutional standard of 
care.  
● 
Local testing of bone marrow aspirate and/or biopsy will be reported in the eCRF; 
however, samples must also be submitted to a central laboratory for analysis. Refer to the 
laboratory manual for additional information. 
● 
The investigator or subinvestigator must review the laboratory report and document this 
review. 
● 
Clinical significance of out-of-range laboratory findings is to be determined and 
documented by the investigator or subinvestigator who is a qualified physician. 
7.2.3 
Vital Signs 
Blood pressure, radial pulse rate and body temperature will be measured as specified in the 
Schedules of Assessments [Table 1 to Table 2]. Blood pressure should be measured prior to 
other clinical assessments. Whenever possible, the blood pressure determinations should be 
undertaken at approximately the same time of day for each study visit. 
A calibrated blood pressure measuring device should be used for all blood pressure 
measurements. 
Prior to measuring blood pressure, the study subject should be seated in a quiet room for at 
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7.2.4 
Physical Examination  
The investigator or designee (a physician or licensed practitioner) will perform standard, full 
physical examinations as specified in the Schedules of Assessments [Table 1 and Table 2]. 
Height and body weight will be measured at the screening visit, and the body weight 
measurement will be repeated on day 1 of each cycle. 
7.2.5 
Electrocardiogram  
A standard 12-lead ECG will be performed at the screening visit for purposes of assessing 
subject eligibility. ECG can be repeated during the screening period. ECG assessments will 
be performed and assessed locally at predose and postdose (1 to 2 hours) day 1 of each cycle, 
at EoT visit, and during observation periods 1 and 2. The 12-lead ECGs will be recorded in 
triplicate (at least 2 minutes apart per time point) and transmitted electronically for central 
read during the Screening and Treatment Periods, and as a single assessment (in triplicate, if 
deemed necessary, at least 2 minutes apart per time point) and read locally during the 
Observation Periods 1 and 2. 
ECGs will be recorded after the subject has been in a resting, supine position for at least 
5 minutes. Further details of the procedure will be separately specified in the procedural 
manual. 
7.2.6 
Imaging  
Chest X-ray or computed tomography (CT) scan is to be performed at screening. A chest 
X-ray (or CT of chest) does not need to be repeated if performed within 2 weeks prior to start 
of screening. 
7.2.7 
Eastern Cooperative Oncology Group 
The ECOG Scale [Oken et al, 1982] will be used to assess performance status [Table 9] at 
time points outlined in the Schedules of Assessments [Table 1 and Table 2]. 
Table 9 
ECOG Performance Status 
Grade 
Description 
0 
Fully active, able to carry on all predisease performance without restriction. 
1 
Restricted in physically strenuous activity, but ambulatory and able to carry out work of 
a light or sedentary nature, e.g., light house work, 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. 
ECOG: Eastern Cooperative Oncology Group 
 

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7.2.8 
Multigated Acquisition Scan or Echocardiogram 
A MUGA or ECHO (as per standard of care) is to be performed at screening or within 28 days 
prior to screening. 
7.2.9 
Disease Assessment 
Disease assessments as per standard of care and including extramedullary leukemia assessment 
will be performed as specified in the Schedule of Assessments [Table 1 and Table 2]. The 
extramedullary leukemia assessment results must be entered into the eCRF. Blood samples must 
be submitted to a central laboratory for analysis. Please refer to the laboratory manual for 
additional information.  
7.3 
Adverse Events and Other Safety Aspects 
The definitions of an AE or SAE can be found in [Appendix 12.4 AEs: Definitions and 
Procedures for Recording, Evaluating, Follow-up and Reporting].  
The investigator and medically qualified designee(s) are responsible for detecting, documenting 
and recording events that met the definition of an AE or SAE. Collection, reporting and follow-
up of Special Situations and defect in IP follow the procedures for AE and SAE. 
7.3.1 
Time Period for Collecting Adverse Event and Serious Adverse Event 
Information 
In order to identify any events that may be associated with study procedures and could lead to 
a change in the conduct of the study, the sponsor collects AEs even if the subject has not 
received IP. AE collection will begin from time of informed consent and continue through 
post-treatment period and at least 30 days after last IP dose and prior to the start of new 
anticancer treatment. In addition, the following will be collected regardless of the start of new 
anticancer therapy:  
● 
Any IP-related SAE that is ongoing will be followed until resolved 
● 
Any SAE that is deemed to be related to IP by the investigator 
7.3.2 
Method of Detecting Adverse Events and Serious Adverse Events 
The methods of recording, evaluating and assessing seriousness, causality and severity of 
AEs and SAEs are described in [Appendix 12.4 AEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up or Reporting]. Care will be taken not to introduce bias 
when detecting AEs and/or SAEs. Open-ended and nonleading verbal questioning of the 
subject is the preferred method to inquire about AE occurrences. 
An AE with a change in severity is recorded as a new AE. 
7.3.3 
Follow-up of Adverse Events 
If after the protocol-defined AE collection period [see Section 7.3.1 Time Period for 
Collecting AE and SAE Information], an AE progresses to an SAE, or the investigator learns 
of any (S)AE (SAE or AE) including death, where he/she considers there is reasonable 
possibility it is related to the IP or study participation, the investigator must promptly notify 

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the sponsor. Such events should be collected and followed up until resolved or judged to be 
no longer clinically significant, or until they become chronic to the extent that they can be 
fully characterized by the investigator. 
7.3.4 
Reporting of Serious Adverse Events 
Prompt notification by the investigator to the sponsor of an SAE is essential, so that legal 
obligations and ethical responsibilities towards the safety of subjects and the safety of a study 
intervention under clinical investigation are met. 
In the case of an SAE, the investigator must contact the sponsor by fax or email immediately 
(within 24 hours of awareness). 
Procedures for reporting SAEs to the sponsor are described in [Section 12.4.5 Reporting 
Procedures for SAEs or Defect of Investigational Product]. 
7.3.5 
Disease-related Events and/or Disease-related Outcomes Not Qualifying as 
Adverse Events or Serious Adverse Events 
Under this protocol, the following event(s) will not be considered as an (S)AE: 
● 
Disease progression: events including defined study endpoints that are clearly consistent 
with the expected pattern of progression of the underlying disease are not to be recorded 
as AEs. These data will be captured as efficacy assessment data as outlined in 
[Section 7.1 Efficacy Assessments]. If there is any uncertainty as to whether an event is 
due to anticipated disease progression and/or if there is evidence suggesting a causal 
relationship between the IP and the event, it should be reported as an (S)AE. All deaths 
up to 30 days after the final administration of IP must be reported as an SAE, even if 
attributed to disease progression. 
● 
Pre-planned and elective hospital/clinical procedures/interventions or procedures for 
diagnostic, therapeutic, or surgical procedures for a pre-existing condition that did not 
worsen during the course of the study. For example, admission for treatment of a 
pre-existing condition not associated with the development of a new AE or with a 
worsening of the preexisting condition such as transfusion for preexisting anemia, 
leukopenia or thrombocytopenia will not be reported as an SAE. These procedures are 
collected per the eCRF’s completion guidelines. 
7.3.6 
Special Situations  
Certain special situations observed in association with the IP, such as incorrect administration 
(e.g., wrong dose of IP or background therapy) are collected in the eCRF, as protocol 
deviation per [Section 10.3 Major Protocol Deviations] or may require special reporting, as 
described below. These special situations are not considered AEs, but do require to be 
communicated to Astellas as per the timelines defined below. 
If a special situation is associated with, or results in, an AE, the AE is to be assessed 
separately from the special situation and captured as an AE in the eCRF. If the AE meets the 
definition of an SAE, the SAE is to be reported as described in [Section 12.4.5 Reporting 

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Procedures for SAEs or Defect of Investigational Product] and the details of the associated 
special situation are to be included in the clinical description on the SAE worksheet. 
The special situations are: 
● 
Pregnancy  
● 
Medication error, overdose and use outside protocol 
● 
Misuse/abuse 
● 
Occupational exposure 
● 
(Suspicion of) Transmission of infectious agent related to microbiological contamination 
at the site 
● 
Suspected drug-drug interaction 
Instructions and procedures for reporting special situations are provided in [Appendix 12.4.6 
Reporting Procedures for Special Situations].  
7.3.7 
Defects of Investigational Product 
Defect is defined as the product defect, which may cause generally poor conditions where the 
cells cause adverse reactions that affect the human body. When a defect in IP occurs, the 
investigator must contact the sponsor by fax or email immediately (within 24 hours of 
awareness). Instructions and procedures for the expedited reporting of defects are provided in 
[Appendix 12.4.5 Reporting Procedures for SAEs or Defect of Investigational Product]. 
7.3.8 
Supply of New Information Affecting the Conduct of the Study 
When new information becomes available that is necessary for conducting the study properly, 
the sponsor will inform all investigators involved in the study as well as the appropriate 
regulatory authorities. Investigators should inform the IRB/IEC of such information when 
needed.  
The investigator will also inform the subjects, who will be required to sign an updated ICF in 
order to continue in the study. 
Specific to Japan: 
1. When information is obtained regarding serious and unexpected adverse drug reactions 
(or other) that are specified in Article 273 of the Act on Securing Quality, Efficacy and 
Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy 
Products, Gene Therapy Products, and Cosmetics, in compliance with Article 80-2 
Paragraph 6 of the Pharmaceutical Affairs Law, the sponsor should inform all 
investigators involved in the study, head of the study site and appropriate regulatory 
authorities of such information. The head of the study site who receives such information 
will decide whether the study should be continued after hearing the opinions of the IRB. 
The investigator will supply the new information to the subjects, in compliance with 
[Appendix 12.1.5.2 Supply of New and Important Information Influencing the Subject’s 
Consent and Revision of the Written Information].  

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2. In addition, when the head of the study site receives the revisions of the investigator’s 
brochure, protocol, written information, information on the matters covering the quality 
of the test product, efficacy and safety, information necessary for conducting the study 
properly or documents to be examined by the IRB, these documents should be sent to the 
IRB. 
3. When the sponsor receives a safety issue from any source either Japan or worldwide that 
requires an urgent safety measure (USM) to be implemented, then the sponsor will report 
that safety information to all study sites in Japan and rest of world (within 24 hours of 
awareness). 
7.3.9 
Urgent Safety Measures  
An USM is an intervention that is not defined by the protocol and can be put in place with 
immediate effect without needing to gain prior approval by the sponsor, relevant competent 
authorities (CA), IRB/IEC, where applicable, in order to protect subjects from any immediate 
hazard to their health and/or safety. Either the investigator or the sponsor can initiate a USM. 
The cause of a USM can be safety-, product- or procedure-related.  
7.3.10 Reporting Urgent Safety Measures 
In the event of a potential USM, the investigator must contact the study physician and/or 
Astellas team member (within 24 hours of awareness). Full details of the potential USM are 
to be recorded in the subject’s medical records. The sponsor may request additional 
information related to the event to support their evaluation.  
If the event is confirmed to be a USM, the sponsor will take appropriate action to ensure the 
safety and welfare of the subjects. These actions may include but are not limited to a change 
in study procedures or study treatment, halting further enrollment in the study, or stopping 
the study in its entirety. The sponsor or sponsor's designee will notify the relevant CA and 
concerned ethics committee within the timelines required per current local regulations, and 
will inform the investigators, as required. When required, investigators must notify their 
IRB/IEC within timelines set by regional regulations. 
7.4 
Pharmacokinetics 
Whole blood will be collected to monitor pharmacokinetics of ASP7517 cells via 
determination of genomic DNA in the cell by a quantitative polymerase chain reaction 
method. Sampling time points are as shown in the Pharmacokinetics Sample Collection 
Schedule-Dose Escalation Cohort and Dose Expansion Cohort [Table 5].  
Refer to the laboratory manual for detailed information regarding sampling, processing, 
shipping and storage instructions. 
7.5 
Pharmacodynamics | Biomarkers 
Samples for exploratory pharmacodynamics and biomarker analyses will be collected 
according to the Schedules of Assessments [Table 1 and Table 2]. 

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The samples described in [Sections 7.5.1 Blood Samples and 7.5.2 Bone Marrow Aspirate 
Samples for Biomarker Analysis] may be analyzed for other biomarkers including DNA, 
RNA and protein, to investigate possible associations with mechanisms of resistance or 
sensitivity to study treatment, dynamic changes associated with study treatment (in terms of 
dose, safety, tolerability and efficacy, etc.) and method development or validation of 
diagnostic assays related to ASP7517.  
The samples may be stored at the study sponsor’s facility or a contract laboratory facility for 
up to 15 years after study database closure, at which time the samples will be destroyed. 
The procedures for the collection, handling and shipping of laboratory samples will be 
specified in a laboratory manual. 
7.5.1 
Blood Samples 
Blood samples will be collected from all subjects and used for the analysis of 
pharmacodynamics changes related to treatment effect and potential biomarkers of response 
or resistance related to treatment effect as described in [Section 9.4.3.1 Analysis of 
Biomarkers]. Examples of these biomarkers include, but are not limited to, cytokine 
expression and secretion (e.g., IFNγ), WT1-specific T lymphocytes (e.g., cytotoxic T 
lymphocytes), immune cell populations (e.g., NKT cells, NK cells, etc.), expression levels of 
WT1 and mutations in AML/MDS related genes that may modify treatment effect.  
7.5.2 
Bone Marrow Aspirate Samples 
Bone marrow aspirate samples will be collected at the time points indicated in the Schedule 
of Assessments [Table 1 and Table 2] (as clinically indicated). Bone marrow aspirate samples 
will be used for biomarker analyses as described in [Section 9.4.3.1 Analysis of Biomarkers]. 
Examples of biomarkers include, but are not limited to, expression of WT1 and other genes 
and proteins that may be related to treatment response or treatment effect. 
7.6 
Other Assessments 
7.6.1 
Sample for the Analysis of Genes Related to Pharmacogenomics  
Buccal swabs for biomarker analysis will be used to genotype the human leukocyte antigen 
(HLA) gene complex. Knowledge of the specific HLA gene complex in each subject may 
help understand/explain observed differences in efficacy or treatment effect. For detailed 
sample collection, sample labeling and sample shipment procedures refer to the laboratory 
manual. All samples will be transferred to the analytical laboratory; pharmacogenomic (PGx) 
samples will be kept for up to 15 years, or as specified in the ICF.  
7.6.2 
Sample for Optional Banked Pharmacogenomic Sample Analysis 
PGx research may be conducted in the future to analyze or determine genes of relevance to 
clinical response, pharmacokinetics and toxicity/safety. An optional 4 to 6 mL whole blood 
and buccal swab sample for possible banked PGx analysis will be collected as indicated in 
the Schedule of Assessments [Table 1 and Table 2]. Samples will be shipped to a sponsor-
designated banking clinical research organization (CRO).  

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Details on sample collection, labeling, storage and shipment procedures will be provided in a 
separate laboratory manual. 
See [Appendix 12.8 Pharmacogenomic Analysis with Banked Sample] for further details on 
the banking procedures. 
7.6.3 
Sample for Anti-HLA Antibody 
Blood samples will be collected from all subjects and used for the analysis of anti-HLA 
antibody production. Sampling time points are as shown in the Schedule of Assessments 
[Table 1 and Table 2]. Sample processing, storage and shipment instructions will be provided 
in the laboratory manual. 
7.6.4 
Sample for Replication Competent Lentivirus 
Blood samples will be collected from all subjects and used to monitor the absence of 
replication competent lentivirus (RCL). Sampling time points are as shown in the Schedule of 
Assessments [Table 4]. If there is a positive result during the first year of assessments, 
additional follow-up assessments may be required on an annual basis. Sample processing, 
storage and shipment instructions will be provided in the laboratory manual. 
7.7 
Total Amount of Blood 
The total amount of blood for each subject will vary depending on the course of their disease, 
duration on treatment and local laboratory requirements. At any time during the study, if any 
laboratory abnormality is found for a subject, additional blood may be drawn for safety 
monitoring or local standard of care. 
The maximum amount of blood planned to be collected within 24 hours is approximately 
71 mL on C1D1. 
8 
DISCONTINUATION 
8.1 
Discontinuation of Individual Subject(s) 
A discontinuation from treatment is defined as a subject who enrolled in the study and for 
whom study treatment is permanently discontinued for any reason. 
The subject is free to withdraw from the study treatment and/or study for any reason and at 
any time without giving reason for doing so and without penalty or prejudice. The 
investigator is also free to discontinue the subject from study treatment or to terminate a 
subject’s involvement in the study at any time if the subject’s clinical condition warrants it. 
8.1.1 
Discontinuation Criteria from Treatment for Individual Subject(s) 
The reason for discontinuation from study treatment must be documented in the subject’s 
medical records. 
A subject must discontinue study treatment for any of the following reasons: 
● 
Subject declines further study participation (i.e., withdrawal of consent).  

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● 
Any clinical or unacceptable AE/SAE, laboratory abnormality or intercurrent illness, in 
the opinion of the investigator, indicates continued treatment is not in the best interest of 
the subject. 
● 
Subject is noncompliant with protocol based on the investigator or medical monitor 
assessment. 
● 
Subject is found to have significantly deviated from any 1 of the inclusion or exclusion 
criteria after enrollment (subjects having clinical benefit and no DLT may be kept in the 
study after discussion with the medical monitor). 
● 
Subject not achieving remission (CRc or PR in AML or CR, BM CR or PR or HI in MDS) 
and the subject is no longer deriving clinical benefit, in the opinion of the investigator. 
● 
Subject begins other anti-leukemic therapies or MDS therapies, including undergoing HSCT. 
● 
Subject experiences disease relapse/progression. 
● 
Investigator/subinvestigator determines that the continuation of the study treatment will 
be detrimental to the subject. 
● 
Subject is lost to follow-up despite reasonable efforts by the investigator to locate the 
subject. 
● 
Female subject becomes pregnant.  
● 
Death. 
● 
Subject develops a grade 4 DLT during cycle 1. 
● 
Delay of > 2 weeks of a subsequent scheduled dose of ASP7517 due to ASP7517-related 
toxicities. 
8.1.2 
Discontinuation Criteria Post-Treatment for Individual Subject(s) 
The reason for discontinuation from study post-treatment must be documented in the 
subject’s medical records. 
A subject must discontinue post-treatment for any of the following reasons: 
● 
Subject declines further study participation (i.e., withdrawal of consent). 
● 
Subject is lost to follow-up despite reasonable efforts by the investigator to locate the 
subject. 
● 
Subject begins other anti-leukemic therapies or MDS therapies, including undergoing 
HSCT. 
● 
Subject experiences disease relapse/progression. 
● 
Subject is no longer deriving clinical benefit, in the opinion of the investigator. 
● 
Female subject becomes pregnant. 
● 
Death. 
8.2 
Discontinuation of Individual Subject(s) from Study 
All subjects who discontinue study treatment will remain in the study and must continue to 
be followed for protocol-specific follow-up procedures as outlined in [Section 4.1 Study 
Design] and the Schedule of Assessments [Table 1, Table 2, Table 3 and Table 4]. The only 
exception to this is when the subject specifically withdraws consent for any further contact 
with him/her or persons previously authorized by the subject to provide this information. 

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All subjects who discontinue study treatment are to be followed for survival every 3 months 
after their final visit until death or the final analysis, whichever occurs first per [Section 4.1 
Study Design] and the Schedule of Assessments [Table 1, Table 2, Table 3 and Table 4].  
8.2.1 
Lost to Follow-up 
Every reasonable effort is to be made to contact any subject lost to follow-up during the 
course of the study to complete study-related assessments, record outstanding data and 
retrieve IP.  
8.3 
Discontinuation of the Study Site 
If an investigator intends to discontinue participation in the study, the investigator must 
immediately inform the sponsor and the head of the study site. 
8.4 
Discontinuation of the Study 
The sponsor may terminate this study prematurely, either in its entirety or at any study site, 
for reasonable cause provided that written notice is submitted in advance of the intended 
termination. Advance notice is not required if the study is stopped due to safety concerns. If 
the sponsor terminates the study for safety reasons, the sponsor will immediately notify the 
investigator and subsequently provide written instructions for study termination.  
9 
STATISTICAL METHODOLOGY 
A statistical analysis plan (SAP) will be written to provide details of the analysis, along with 
specifications for tables, listings and figures to be produced. The SAP will be finalized before 
the database soft-lock at the latest. Changes from the planned analyses in the final SAP that 
impact the statistical analyses will be justified in the clinical study report (CSR). 
In general, all data will be summarized by dose level and overall with descriptive statistics 
for continuous endpoints, and frequency and percentage for categorical endpoints, unless 
otherwise specified. Percentages by categories will be based on the number of subjects with 
no missing data (i.e., will add up to 100%). Kaplan-Meier estimates will be provided for 
time-to-event endpoints. Separate data displays will be produced for each phase of the study. 
For phase 1 dose escalation, all data will be summarized by dose level and overall, unless 
otherwise specified. For phase 2 dose expansion, all data will be summarized by disease 
group, dose level and overall, unless otherwise specified. 
Baseline will be defined as the last nonmissing observation on or prior to first administration 
of IP, unless otherwise specified. 
9.1 
Sample Size 
Phase 1 (Dose Escalation) 
The sample size for the dose escalation phase is not based on a statistical power calculation. 
The number of subjects enrolled will be dependent on the DLT incidence. The estimated 
number of subjects, a minimum of 6 evaluable and up to 18, should provide adequate 
information for the dose escalation and safety objectives of the study. 

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Phase 2 (Dose Expansion) 
The sample size in phase 2 is up to 104 subjects per dose level. Each dose level may enroll up 
to 52 R/R AML subjects and up to 52 R/R higher risk MDS subjects. The response rate is 
monitored using the BOP2 design. For AML, with assumption of the efficacious CRc rate is 
30% and the inefficacious CRc rate is 15%, the statistical power would be approximately 
0.83 while controlling the type I error rate at 0.10. For MDS, with assumption of the 
efficacious CR + BM CR + PR rate is 25% and the inefficacious CR + BM CR + PR rate is 
12%, the statistical power would be approximately 0.83, while controlling the type I error 
rate at 0.10. 
9.2 
Analysis Sets 
Detailed criteria for analysis sets will be laid out in classification specifications and the 
allocation of subjects to analysis sets will be determined prior to database hard-lock.  
For each dose level group, the number and percentage of subjects will be characterized for all 
treated subjects and by each analysis set. 
9.2.1 
Full Analysis Set 
The full analysis set (FAS) will consist of all subjects who are enrolled and receive at least 
1 dose of study treatment. This will be the primary analysis set for efficacy analyses. 
9.2.2 
Response Analysis Set 
The response analysis set will consist of all subjects who are enrolled and receive at least 
1 dose of study treatment and have at least 1 post baseline primary efficacy measurement. 
This will be used as a sensitivity analysis set for response related endpoints. 
9.2.3 
Safety Analysis Set 
The safety analysis set (SAF) consists of all subjects who receive at least 1 dose of IP. 
The SAF will be used for all summaries of the safety data. 
9.2.4 
Pharmacokinetic Analysis Set 
The pharmacokinetic analysis set (PKAS) consists of the administered population for which 
pharmacokinetics data are available at least for 1 time point. Additional subjects may be 
excluded from the PKAS at the discretion of the pharmacokineticist.  
9.2.5 
Pharmacodynamic Analysis Set 
The pharmacodynamic analysis set (PDAS) will include the subjects from the administered 
population for whom sufficient pharmacodynamic measurements were collected. The PDAS 
will be used for all analyses of pharmacodynamic data. 
9.2.6 
DLT Evaluation Analysis Set 
The DLT Evaluation Analysis Set (DEAS) is defined as all subjects in SAF by excluding 
subjects who meet any of the following criteria: 

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● 
Subject is discovered to have enrolled without fully satisfying eligibility criteria. 
● 
Subject received less than the planned dose in cycle 1 for reasons other than DLT. 
● 
Subject has no DLT and withdraws from the study before the end of the DLT evaluation 
period 
The DEAS will be used for the analysis of DLT data. 
9.3 
Demographics and Baseline Characteristics  
9.3.1 
Demographics 
Demographics and baseline characteristics will be summarized by dose level and overall for 
all treated subjects. 
9.3.2 
Subject Disposition  
The number and percentage of subjects who completed and discontinued treatment and 
reasons for treatment discontinuation will be presented for all enrolled subjects by dose level 
group and overall. Similar tables for screening disposition, observation period disposition and 
follow-up disposition will also be presented for all treated subjects by dose level and overall. 
All disposition details and dates of first and last evaluations for each subject will be listed. 
9.3.3 
Previous and Concomitant Treatment (Medication and Nonmedication 
Therapy)  
All previous and concomitant treatment will be listed. The frequency of previous and 
concomitant medications (prescription, over-the-counter, and nutritional supplements) will be 
summarized by dose level and overall. 
9.3.4 
Medical History  
Medical history for each subject will be listed. 
9.3.5 
Investigational Product Exposure 
The number and percentage of subjects exposed to IP will be summarized by dose level and 
cycle.  
All IP exposure data will be listed. 
9.4 
Analysis of Efficacy  
Efficacy analysis will be conducted on the FAS. The interpretation of results from statistical 
tests will be based on the FAS. 
9.4.1 
Analysis of Primary Endpoint  
9.4.1.1 Primary Analysis 
CRc rate is defined for AML subjects as the number of subjects who achieve the best response 
of CRc (CR, CRp or CRi) divided by the number of subjects in the analysis population. 
Response to treatment will be defined per modified Cheson criteria [Cheson et al, 2003]. 

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CR + BM CR + PR rate is defined for MDS subjects as the number of subjects who achieve 
the best response of CR + BM CR + PR divided by the number of subjects in the analysis 
population. Response to treatment will be defined per Cheson criteria [Cheson et al, 2006]. 
Response rates will be calculated and its 90% confidence interval will be constructed by 
Clopper-Pearson method by dose level for phase 1 and by dose level and disease type for 
phase 2. 
9.4.1.2 Sensitivity Analysis 
Sensitivity analysis will be defined in the SAP. 
9.4.1.3 Phase 2 Expansion 
The CRc rate for subjects with R/R AML and CR + BM CR + PR rate for R/R higher risk 
MDS are continuously monitored using the BOP2 design [Zhou et al, 2017]. The number of 
dose levels investigated during phase 2 will be based upon the data from phase 1. Initially, 
12 subjects will be enrolled at each dose level for each disease type during stage 1 of BOP2. 
If the response rate does not meet the optimal stopping boundaries (see table below), then 
stage 2 will open and an additional 20 subjects may be enrolled during this stage. Combining 
the data from stage 1 and stage 2, stage 3 may be opened for an additional 20 subjects for a 
total maximum sample size of 52 for each disease type, if the response rate does not meet the 
optimal stopping boundaries (see table below). Otherwise, the enrollment at that dose level 
will be closed.  
When the total number of subjects reaches the maximum sample size of 52, it may be 
concluded that ASP7517 is efficacious if the number of responses is greater than or equal to 
12 and 10 for AML and MDS, respectively. The number of subjects in stage 1, stage 2 and 
stage 3 may be changed according to the optimized stopping boundaries.  
Optimized Stopping Boundaries for AML 
Number of subjects treated 
Stop if number of responses ≤  
12 
1 
32 
5 
AML: acute myeloid leukemia 
 
Optimized Stopping Boundaries for MDS 
Number of subjects treated 
Stop if number of responses ≤  
12 
0 
32 
4 
MDS: myelodysplastic syndrome 
 

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9.4.2 
Analysis of Secondary Endpoints  
● 
CR rate is defined as the number of subjects who achieve CR at any of the postbaseline 
visits divided by the number of subjects in the analysis population. 
● 
CRh rate is defined as the number of subjects who achieve CRh at any of the 
postbaseline visits divided by the number of subjects in the analysis population. CRh is 
applicable for AML subjects only. 
● 
CR/CRh rate is defined as the number of subjects who achieve CR or CRh at any of the 
postbaseline visits divided by the number of subjects in the analysis population. CR/CRh 
is applicable for AML subjects only. 
● 
Best Response Rate is defined as the number of subjects who achieve CRc or PR at any 
of the postbaseline visits divided by the number of subjects in the analysis population. 
Best response rate is applicable for AML subjects only. 
○ Best response for AML subjects is defined as the best measured response to 
treatment for all visits (in the order of CR, CRp, CRi, PR, NR and NE) post-
baseline. Subjects who achieve the best responses of CR, CRp, CRi, or PR will be 
classified as responders. Subjects who do not achieve at least a best response of PR 
will be classified as non-responders. 
○ Best response for MDS subjects is defined as the best measured response to 
treatment for all visits (in the order of CR, PR, HI, SD and PD) post-baseline. 
Subjects who achieve the best responses of CR or PR will be classified as 
responders. Subjects who do not achieve at least a best response of PR will be 
classified as non-responders. 
● 
Objective Response Rate (ORR) is defined as the number of subjects who achieve CR, 
BM CR or PR or HI at any of the postbaseline visits divided by the number of subjects in 
the analysis population. ORR is applicable for MDS subjects only. 
CR, CRh, CR/CRh, best response and ORRs will be calculated and its 90% confidence 
interval will be constructed by Clopper-Pearson method by dose level for phase 1 and by 
dose level and disease type for phase 2. 
● 
OS is defined as the time from the date of first dose until the date of death from any 
cause (death date – first dose date + 1). For a subject who is not known to have died by 
the end of study follow-up, OS is censored at the date of last contact (date of last 
contact – first dose date + 1).  
● 
EFS is defined as the time from the date of first dose until the date of documented 
relapse, treatment failure or death from any cause within 30 days after the last dose of IP 
(whichever occurs first earliest of [relapse date, treatment failure date, death date] – first 
dose date + 1). 
● 
Duration of remission for AML includes duration of CRc, duration of CR/CRh, duration 
of CRh, duration of CR, and duration of response (i.e., CRc + PR). 
● 
Duration of remission for MDS includes duration of CR and duration of response (i.e., 
CR + BM CR + PR). 

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The distribution of OS, EFS and duration of remission will be estimated for each dose level 
using Kaplan-Meier methodology. 
9.4.3 
Analysis of Exploratory Endpoints  
9.4.3.1 Analysis of Biomarkers 
Associations between biomarkers [Section 7.5 Pharmacodynamics | Biomarkers] and clinical 
results (efficacy, safety or pharmacodynamics) may be performed on subjects who have the 
necessary baseline and on-study measurements to provide interpretable results for specific 
parameters of interest.  
Biomarkers may be summarized graphically or descriptively as they relate to clinical 
measures, as applicable. Summary statistics may be tabulated.  
Additional post hoc statistical analyses not specified in the protocol, such as alternative 
modeling approaches, may be conducted. All analyses described in this section are based on 
the availability of the data. 
9.4.3.2 Analysis of Pharmacodynamic Activities 
Descriptive statistics will be provided for pharmacodynamics parameters whenever 
applicable. Exploratory analysis of the relationship between pharmacodynamic measurements 
and pharmacokinetics, efficacy and safety profile in subjects may be performed. 
9.4.3.3 Analysis of Pharmacokinetics 
Cellular DNA load and kinetic parameters will be summarized by using descriptive statistics 
including n, mean, standard deviation, minimum, median, maximum, coefficient of variation 
(CV), geometric mean, and geometric CV. Time-course of cellular DNA load will be plotted 
as appropriate.  
Subjects with sufficient cellular DNA samples will have kinetic parameter estimates for 
ASP7517 including calculation of AUC, Cmax, Ctrough and tmax using standard 
noncompartmental analysis. Exploratory analysis between pharmacokinetic parameter and 
clinical measures (e.g., efficacy or safety) may be performed. 
9.5 
Analysis of Safety 
Descriptive statistics will be used to summarize safety data. All safety data will be 
summarized by treatment received (SAF). 
9.5.1 
Adverse Events  
AEs will be coded using MedDRA v21.1 and graded using NCI CTCAE 5.0.  
A treatment-emergent adverse event (TEAE) is defined as an AE observed after starting 
administration of the IP and 30 days after the final administration of IP. An IP-related TEAE 
is defined as any TEAE with a causal relationship assessed as “yes” by the investigator. 
The number and percentage of subjects with TEAEs, drug-related TEAEs, serious TEAEs, 
drug-related serious TEASs, TEAEs leading to withdrawal of treatment and drug related 

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TEAEs leading to withdrawal of treatment will be summarized by SOC, preferred term and 
treatment group. The number and percentage of TEAEs by severity will also be summarized. 
The worst severity will be summarized if the same AE is recorded more than once for a 
subject.  
AE data will be listed. 
9.5.2 
Laboratory Assessments  
For quantitative clinical laboratory measurements (hematology and biochemistry), descriptive 
statistics will be used to summarize results and change from baseline by dose level and time 
point.  
Shifts from baseline to the worst grade based on NCI CTCAE 5.0 during the treatment period 
in clinical laboratory tests will be tabulated.  
Laboratory data will be listed. 
9.5.3 
Vital Signs  
Descriptive statistics will be used to summarize vital sign results and changes from baseline 
for subjects in the SAF by dose level and time point.  
Vital signs data will be listed. 
9.5.4 
Physical Examination  
Physical examination will be listed. 
9.5.5 
12-lead Electrocardiogram 
For all analyses, replicates at each time point will be averaged for each 12-lead ECG 
parameter. Baseline will be defined as the average of the triplicate readings at screening.  
Descriptive statistics will be used to summarize the 12-lead ECG parameter results and 
changes from baseline by dose level and time point.  
A shift analysis table showing shifts from baseline in overall ECG (normal and abnormal) 
will be provided.  
The 12-lead ECG data (individual replicates and the averages) will be listed. 
9.5.6 
Eastern Cooperative Oncology Group Performance Status 
Summary statistics (number and percent of subjects) for each category of the ECOG 
performance status at each assessment will be provided. The change from baseline to final 
visit or early termination will also be summarized. Negative change scores indicate an 
improvement. Positive scores indicate a decline in performance.  
9.5.7 
Dose Limiting Toxicities 
A DLT event, as defined in [Section 4.1.3 Dose Limiting Toxicity Criteria], will be 
summarized by dose level using DEAS. Details of DLTs will be presented in listings and 
subject narratives. 

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DLT review for dose escalation decisions and declaration of DLT and MTD will be 
performed for each dose level throughout the trial. Dose escalation decisions will be guided 
by BOIN as described in [Section 4.1.3 Dose Limiting Toxicity Criteria]. 
9.5.8 
Liver Safety Assessment 
The liver safety assessments will be summarized by the categories below based on the 
measurements from alkaline phosphatase (ALP), ALT, TBL, AST and their combination. The 
subject’s highest post-baseline value will be used. 
● 
ALT > 3 × ULN, > 5 × ULN, > 10 × ULN, > 20 × ULN 
● 
AST > 3 × ULN, > 5 × ULN, > 10 × ULN, > 20 × ULN 
● 
ALT or AST > 3 × ULN, > 5 × ULN, > 10 × ULN, > 20 × ULN 
● 
ALP > 1.5 × ULN 
● 
TBL > 2 × ULN 
● 
(ALT or AST > 3 × ULN) and TBL > 2 × ULN 
● 
(ALT or AST > 3 × ULN) and ALP < 2 × ULN and TBL > 2 × ULN 
The last 2 criteria where 2 or more parameters are evaluated will be with the measurements 
on the same day. 
9.6 
Major Protocol Deviations and Other Analyses 
Major protocol deviations as defined in [Section 10.3 Major Protocol Deviations] will be 
summarized for all treated subjects by dose level and overall, as well as by study site. 
Major protocol deviation data will be listed by study site and subject. 
The major protocol deviation criteria will be uniquely identified in the summary table and 
listing. 
9.7 
Interim Analysis (and Early Discontinuation of the Study) 
No interim analysis is planned. 
Safety, pharmacokinetic and other clinical data will be reviewed on an ongoing basis to 
determine if the study will proceed to the next dose level/phase. 
For phase 2, according to the BOP2 design, the futility analysis for efficacy will be 
performed at the end of stage 1 and stage 2. Twelve subjects will be enrolled at each dose 
level for each disease type during stage 1 of BOP2. If the response rate does not meet the 
optimal stopping boundaries, then stage 2 will open and an additional 20 subjects may be 
enrolled during this stage. Combining the data from stage 1 and stage 2, stage 3 may be 
opened for an additional 20 subjects for a total maximum sample size of 52 for each disease 
type, if the response rate does not meet the optimal stopping boundaries. 
The safety in phase 2 will be monitored using Bayesian logistic model based on all DLT data 
obtained at the time of the analysis for both escalation and expansion cohorts and drug-
related TEAEs leading to death. Safety monitoring with these models will start when phase 2 
is opened. Enrollment in phase 2 may be held based on the following 2 criteria: 

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1. If the posterior mean of the DLT rate is higher than 30% as indicated by Bayesian 
logistic model across disease types at a given dose level, then enrollment will be stopped 
in phase 2 at that dose level and at higher dose levels for that therapy. 
2. Additionally, if the posterior mean of the DLT rate is higher than 30% as indicated by 
Bayesian logistic model in a specific disease type at a dose level, enrollment of that dose 
level and any higher dose-level will be stopped for that disease type. 
9.8 
Additional Conventions 
If the start and stop dates of AEs and concomitant medications are incomplete, imputed dates 
will be used to determine whether an AE is/is not treatment emergent or to allocate a 
concomitant medication to the study period it was taken. 
See the SAP for details of the definition for analysis windows to be used for analyses by visit. 
Study sites that do not enroll at least 1 subject will be pooled for analyses by study site. The 
pooling decisions will be made and documented prior to study hardlock. 
As a general principle, no imputation of missing data will be done. Exceptions are the start 
and stop dates of AEs and concomitant medications if they are missing on day of first IP 
administration. The imputed dates will be used to assess if the AEs or concomitant 
medications are treatment emergent or concomitant, respectively. Listings of the AEs and 
concomitant medications will present the actual partial dates; imputed dates will not be 
shown. 
10 
OPERATIONAL CONSIDERATIONS 
10.1 
Data Collection 
The investigator or site designee will enter data collected using an electronic data capture 
system. In the interest of collecting data in the most efficient manner, the investigator or 
designee should record data (including clinical laboratory values, if applicable) in the eCRF 
within 5 days after the subject’s visit.  
The investigator or site designee is responsible to ensure that all data in the eCRFs and 
queries are accurate and complete and that all entries are verifiable with the source. These 
documents should be appropriately maintained by the study site. 
The monitor should verify the data in the eCRFs with the source and confirm that there are no 
inconsistencies among them. 
Clinical laboratory tests are performed and analyzed by the institution’s local laboratory. The 
local laboratory results must be submitted for centralized data entry (centralized laboratory 
data will be transferred electronically to the sponsor or designee at predefined intervals 
during the study). The centralized laboratory data vendor will provide the sponsor or 
designee with a complete and clean copy of the data.  

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10.2 
Demographics and Baseline Characteristics 
10.2.1 Demographics 
Demographics and other baseline characteristics will be summarized by treatment group. 
Descriptive statistics will include number of subjects, mean, standard deviation, minimum, 
median and maximum for continuous endpoints and frequency and percentage for categorical 
endpoints.  
10.2.2 Medical History 
A detailed medical history for each subject will be obtained during screening period and will 
be summarized by treatment group. 
10.3 
Major Protocol Deviations 
A protocol deviation is generally an unplanned excursion from the protocol that is not 
implemented or intended as a systematic change. All deviations from the protocol are to be 
recorded. A protocol waiver is a documented prospective approval of a request from an 
investigator to deviate from the protocol. Protocol waivers are strictly prohibited. 
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol and must protect the rights, safety and 
well-being of subjects. The investigator should not implement any deviation from, or changes 
of, the protocol, unless it is necessary to eliminate an immediate hazard to subjects.  
A major protocol deviation is one that may potentially impact the completeness, accuracy or 
reliability of data contributing to the primary endpoint or affect the rights, safety or 
well-being of a subject. Major protocol deviations will have additional reporting 
requirements. 
When a major deviation from the protocol is identified for an individual subject, the 
investigator or designee must ensure the sponsor is notified. The sponsor will follow up with 
the investigator, as applicable, to assess the deviation and the possible impact to the safety 
and/or efficacy of the subject to determine subject continuation in the study.  
The major protocol deviation criteria that will be summarized at the end of the study are as 
follows: 
PD1 - Entered into the study even though the subject did not satisfy entry criteria  
PD2 - Developed withdrawal criteria during the study and was not withdrawn 
PD3 - Received wrong treatment or incorrect dose 
PD4 - Received excluded concomitant treatment 
The investigator will also assure that deviations meeting IRB/IEC and appropriate regulatory 
authorities’ criteria are documented and communicated appropriately. All documentation and 
communications to the IRB/IEC and appropriate regulatory authorities will be provided to the 
sponsor and maintained within the Trial Master File.  

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10.4 
STUDY ORGANIZATION 
10.4.1 Dose Escalation and Safety Committee 
A DESC consisting of sponsor representatives and investigators will convene once a dose 
level cohort completes the DLT observation period and data are available for review. 
Additional details regarding responsibilities, membership requirements and safety review 
time points are included in the DESC Charter. The DESC will also review the aggregate 
safety data from the phase 1 dose escalation and the phase 2 expansion cohorts. 
While safety data from the DLT observation period in the escalation cohorts are the 
minimum safety data needed for the DESC meeting, all available safety findings will be 
considered by the DESC. The DESC will assess whether a longer DLT observation period is 
warranted, based on emerging data. Additionally, only when determining RP2D, the DESC 
may choose a more conservative dosing decision than the MTD selected by BOIN design, 
based on evaluation of the safety data and other available data. 
The decision on the dose level for the next cohort will be based on the BOIN design. Also, 
MTD will be determined by BOIN from at least 6 subjects with the maximum of 8 subjects 
under the maximum of 2 cohorts. The dose for phase 2 expansion will not be higher than the 
MTD.  

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11 
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12 
APPENDICES 
12.1 
Ethical, Regulatory and Study Oversight Considerations 
12.1.1 Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, ICH guidelines, applicable 
regulations and guidelines governing study conduct and the ethical principles that have their 
origin in the Declaration of Helsinki.  
12.1.2 Institutional Review Board/Independent Ethics Committee/Competent 
Authorities 
There will be a subsequent conclusion of contracts with the study sites after the approval. 
GCP requires that the protocol, any protocol amendments, investigator’s brochure, ICF and 
all other forms of subject information related to the study (e.g., advertisements used to recruit 
subjects) and any other necessary documents be reviewed by an IRB/IEC. The IRB/IEC will 
review the ethical, scientific and medical appropriateness of the study before it is conducted. 
IRB/IEC approval of the protocol, ICF and subject information and/or advertising, as 
relevant, will be obtained prior to initiation of any study-specific procedures. 
Any substantial amendments to the protocol will require CA and IRB/IEC approval before 
implementation, except for changes necessary to eliminate an immediate hazard to subjects. 
The investigator will be responsible for the following: 
● 
Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies and procedures established by 
the IRB/IEC. 
● 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
● 
Providing oversight of the conduct of the study at the study site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, EU Regulation No. 536/2014 for 
studies (if applicable), and all other applicable local regulations. 
12.1.3 Protocol Amendment and/or Revision 
Any changes to the study that arise after approval of the protocol must be documented as 
protocol amendments and/or revisions: substantial amendments/revisions and/or 
nonsubstantial amendments/revisions. Depending on the nature of the amendment and/or 
revisions, either IRB/IEC or CA approval or notification may be required. The changes will 
become effective only after the approval of the sponsor, investigator, IRB/IEC and 
appropriate regulatory authorities.  
Amendments to this protocol and/or revisions must be signed by the sponsor and investigator. 
Written verification of IRB/IEC approval will be obtained before any amendment and/or 
revision is implemented. Modifications to the protocol that are administrative in nature do not 

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require IRB/IEC approval, but will be submitted to the IRB/IEC for their information, if 
required by local regulations. 
If there are changes to the ICF, written verification of IRB/IEC approval must be forwarded 
to the sponsor. An approved copy of the new ICF must also be forwarded to the sponsor. 
12.1.4 Financial Disclosure  
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study. 
12.1.5 Informed Consent of Subjects 
12.1.5.1 Subject Information and Consent 
The investigator or his/her representative will explain the nature of the study to the subject 
and answer all questions regarding this study. Prior to any study-related screening procedures 
being performed on the subject, the ICF will be reviewed, signed or place a personal seal, and 
dated by the subject, the person who administered the ICF and any other signatories 
according to local requirements. A voluntary ICF for PGx samples will be reviewed, signed 
or place a personal seal, and dated by the subject, the person who administered the ICF and 
any other signatories according to local requirements. A copy of the signed or sealed ICF(s) 
will be given to the subject and the original will be placed in the subject’s medical record. An 
entry must also be made in the subject’s dated source documents to confirm that the ICF was 
signed prior to any study-related procedures and that the subject received a signed copy of the 
ICF. 
The signed ICFs will be retained by the investigator and made available (for review only) to 
the study monitor, auditor and appropriate regulatory authorities and other applicable 
individuals upon request. 
12.1.5.2 Supply of New and Important Information Influencing the Subject’s Consent 
and Revision of the Written Information 
1. The investigator or his/her representative will immediately inform the subject verbally 
whenever new information becomes available that may be relevant to the subject’s 
consent or may influence the subject’s willingness to continue participating in the study 
(e.g., report of serious adverse drug reaction). The communication must be documented 
in the subject’s medical records and whether the subject is willing to remain in the study 
or not must be confirmed and documented.  
2. The investigator must update the subject’s ICF and submit it for approval to the 
IRB/IEC. The investigator or his/her representative must obtain written informed consent 
from the subject on all updated ICFs throughout their participation in the study. The 
investigator or his/her designee must reconsent subjects with the updated ICF even if 
relevant information was provided verbally. The investigator or his/her representative 

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who obtained the written informed consent and the subject should sign and date the ICF 
or place a personal seal. A copy of the signed or sealed ICF will be given to the subject 
and the original will be placed in the subject’s medical record. An entry must be made in 
the subject’s records documenting the reconsent process. 
12.1.6 Source Documents 
Source data must be available at the study site to document the existence of the subjects and 
to substantiate the integrity of study data collected. Source data must include the original 
documents relating to the study, as well as the medical treatment and medical history of the 
subject.  
The investigator is responsible for ensuring the source data are attributable, legible, 
contemporaneous, original, accurate and complete whether the data are handwritten on paper 
or entered electronically. If source data are created (first entered), modified, maintained, 
achieved, retrieved or transmitted electronically via computerized systems (and/or other kind 
of electronic devices) as part of regulated study activities, such systems must be compliant 
with all applicable laws and regulations governing use of electronic records and/or electronic 
signatures. Such systems may include, but are not limited to, electronic medical/health 
records, protocol-related assessments, AE tracking, electronic certificate of analysis (eCOA) 
and/or drug accountability.  
Paper records from electronic systems used in place of electronic format must be certified 
copies. A certified copy must be an exact copy and must have all the same attributes and 
information as the original. Certified copies must include signature and date of the individual 
completing the certification. Certified copies must be a complete and chronological set of 
study records (including notes, attachments, and audit trail information, if applicable). All 
printed records must be kept in the subject file and be available for archiving.  
12.1.7 Record Retention 
The investigator will archive all study data (e.g., subject identification code list, source data 
case report forms and investigator's file) and relevant correspondence. These documents are 
to be kept on file for the appropriate term determined by local regulation (for US study sites, 
2 years after approval of the NDA or discontinuation of the IND). The sponsor will notify the 
study site/investigator if the NDA/MAA/J-NDA is approved or if the IND/investigational 
medicinal product dossier/CHIKEN TODOKE is discontinued. The investigator agrees to 
obtain the sponsor's agreement prior to disposal, moving or transferring of any study-related 
records. The sponsor will archive and retain all documents pertaining to the study according 
to local regulations. 
Data generated by the methods described in the protocol will be recorded in the subject’s 
medical records and/or study progress notes. 

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The following are the major documents to be retained at the study site. 
1. Source documents (clinical data, documents and records for preparing the eCRF) hospital 
records, medical records, test records, memoranda, checklists for evaluation, 
administration records, data recorded by automatic measuring instruments, reproductions 
or transcripts verified as precise copies, microfiche, negative films, microfilms/magnetic 
media, X-ray films, subject files and study-related records kept at either a pharmacy, a 
laboratory, or medical technical office, as well as subject registration forms, laboratory 
test slips including central measurement, worksheets specified by the sponsor, records of 
clinical coordinators, and records related to the study selected from those verified in other 
departments or hospitals.  
2. Study contracts, written ICFs, written information and other documents or their copies 
prepared by the study personnel. A letter of request for study (including a request for 
continuation/amendment), letter of request for review, notice of study contract, study 
contract, notification of discontinuation or completion of clinical study, written 
information for informed consent (including revisions), signed and dated written 
informed consent (including revisions), curriculum vitae of investigators, list of 
subinvestigators, list of signatures and print of seals (copy) and eCRF (copy), etc.  
3. The protocol, documents obtained from the IRB related to the adequacy of conducting the 
study by the head of the study sites (Article 32-1, MHW Ordinance No. 28), documents 
obtained from the IRB related to the adequacy of conducting a study whose period 
exceeds 1 year or the adequacy of continuously conducting the study from which 
information on adverse drug reactions is obtained, and other documents obtained. A 
finalized protocol (including revisions), finalized investigator’s brochure (including 
revisions), operational procedures for the investigator, materials and information supplied 
by the sponsor (e.g., AE report), matters reported by the investigator (revisions of the 
protocol, AE reports, etc.), operational procedures for the IRB, the list of names of the 
IRB members, materials for IRB review (including continuous deliberation), IRB review 
records (including continuous deliberation) and the review result report of the IRB 
(including continuous deliberation), etc.  
4. Records of control for IP and other duties related to the study. Procedure for controlling 
the IP, drug inventory and accountability record, vouchers for the receipt and return of the 
IP, and the prescriptions for concomitant medications 
The documents of the efficacy and safety evaluation committee (minutes and SOPs and 
others) and the judgment committee outside the study sites (minutes and SOPs and others) 
shall be retained by the sponsor. 
12.1.8 Subject Confidentiality and Privacy 
For clinical research performed at a facility that is not a covered entity under HIPAA, 
language consistent with the principles of HIPAA should be included in the ICF to describe 
the provisions in place to protect subject privacy and to seek consent for use of private 
information obtained during the study. 

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Individual subject medical information obtained as a result of this study is considered 
confidential and disclosure to third parties is prohibited unless the subject provides written 
consent or approval. Additional medical information may be given only after approval of the 
subject to the investigator or to other appropriate medical personnel responsible for the 
subject's well-being. 
The sponsor shall not disclose any confidential information on subjects obtained during the 
performance of their duties in the study without justifiable reasons. 
Even though any individuals involved in the study, including the study monitors and auditors, 
may get to know matters related to a subject’s privacy due to direct access to source 
documents, or from other sources, they may not disclose the content to third parties.  
The sponsor affirms the subject's right to protection against invasion of privacy. Only a 
subject identification number will identify subject data retrieved by the sponsor. However, 
the sponsor requires the investigator to permit the sponsor, sponsor's representative(s), the 
IRB/IEC and when necessary, representatives of the regulatory health authorities to review 
and/or to copy any medical records relevant to the study. 
The sponsor agrees to comply and process personal data in accordance with all applicable 
privacy laws and regulations, including, without limitation, the Personal Information 
Protection Law in Japan and privacy laws in the US. If the services will involve the collection 
or processing of personal data (as defined by applicable data protection legislation) within the 
European Economic Area (EEA), then the sponsor shall serve as the controller of such data, 
as defined by the EU Data Protection Directive (DPD), and investigator and/or third party 
shall act only under the instructions of the sponsor in regard to personal data. If the sponsor is 
not based in the EEA, the sponsor must appoint a third party to act as its local data protection 
representative or arrange for a co-controller established in the EU for data protection 
purposes in order to comply with the DPD. 
12.1.9 Arrangement for Use of Information and Publication of the Study 
Information concerning the test product, patent applications, processes, unpublished scientific 
data, the investigator’s brochure and other pertinent information is confidential and remains 
the property of the sponsor. Details should be disclosed only to the persons involved in the 
approval or conduct of the study. The investigator may use this information for the purpose 
of the study only. It is understood by the investigator that the sponsor will use the 
information obtained during the study in connection with the development of the drug and 
therefore may disclose it as required to other clinical investigators or to regulatory agencies. 
In order to allow for the use of the information derived from this study, the investigator 
understands that he/she has an obligation to provide the sponsor with all data obtained during 
the study. 
Publication of the study results is discussed in the study agreement. 

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12.1.10 Insurance of Subjects and Others (Specific to Japan) 
If a subject suffers any study-related injury, the sponsor will compensate the subject 
appropriately according to the severity and duration of the damage. However, if the injury 
was caused intentionally or was due to gross negligence by the study site, the sponsor will 
consult with the study site about handling the injury, based on the agreed study contract. 
Compensation for the study-related injury is provided by the following procedures: 
1. If a subject incurs an injury as a result of participation in the study, the study site should 
provide medical treatment and other necessary measures. The sponsor should be notified 
of the injury.  
2. When the subject claims compensation from the study site for the above study-related 
injury, or such compensation may be claimed, the study site should immediately 
communicate the fact to the sponsor. Both parties should work together towards a 
compensation settlement. 
3. The sponsor shall pay compensation or indemnification and bear expenses necessary for 
the settlement as provided in the study contract. 
4. The sponsor shall make an arrangement for insurance and take measures necessary to 
ensure the compensation or indemnification mentioned above. 
12.1.11 Signatory Investigator for Clinical Study Report 
ICH E3 guidelines recommend and EU Directive 2001/83/EC requires that a final CSR that 
forms part of a marketing authorization application, be signed by the representative for the 
coordinating investigator(s) or the principal investigator(s). The representative for the 
coordinating investigator(s) or the principal investigator(s) will have the responsibility to 
review the final study results to confirm to the best of his/her knowledge it accurately 
describes the conduct and results of the study. The representative for the coordinating 
investigator(s) or the principal investigator(s) will be selected from the participating 
investigators by the sponsor prior to database hard-lock. 

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12.2 
Procedure for Study Quality Control 
12.2.1 Study Monitoring 
The sponsor or delegated CRO is responsible for monitoring the study to ensure that the 
rights, safety and well-being of subjects are protected, the study is properly conducted in 
adherence to the current protocol and GCP and the study data reported by the 
investigator/subinvestigator are accurate, complete and verifiable with the source. The 
sponsor is responsible for assigning the study monitor(s) to this study for proper monitoring. 
They will monitor the study in accordance with planned monitoring procedures. 
12.2.2 Direct Access to Source Data/Documents 
The investigator and the study site must accept monitoring and auditing by the sponsor or 
delegated CRO, as well as inspections from the IRB/IEC and appropriate regulatory 
authorities. In these instances, they must provide all study-related records including source 
documents when they are requested by the sponsor monitors and auditors, the CRO, the 
IRB/IEC or appropriate regulatory authorities. The confidentiality of the subject’s identity 
shall be well protected consistent with local and national regulations when the source 
documents are subject to direct access. 
12.2.3 Data Management 
Data management will be coordinated by the designee of the sponsor in accordance with the 
SOPs for data management. All study-specific processes and definitions will be documented 
by data management. eCRF completion will be described in the eCRF instructions. Coding of 
medical terms and medications will be performed using MedDRA and the WHO Drug 
Dictionary, respectively. Data management is accountable for eCOA. 
12.2.4 Quality Assurance 
The sponsor is implementing and maintaining quality assurance (QA) and quality control 
(QC) systems with written SOPs to ensure that studies are conducted and data are generated, 
documented, recorded, and reported in compliance with the protocol, GCP and applicable 
regulatory requirement(s). Where applicable, the QA and QC systems and written SOPs of 
the CRO will be applied. 
The sponsor or sponsor’s designee may arrange to audit the study at any or all study sites and 
facilities. The audit may include on-site review of regulatory documents, CRFs and source 
documents. Direct access to these documents will be required by the auditors.  
• 
QTLs will be predefined in the applicable plan(s) to identify systematic issues that 
can impact participant safety and/or reliability of study results. These predefined 
parameters will be monitored during the study, and important deviations from the 
QTLs and remedial actions taken will be summarized in the CSR. 

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12.3 
Contraception Requirements 
WOCBP who are eligible for participation in the study, including those who choose complete 
abstinence, must have pregnancy tests as specified in the Schedules of Assessments [Table 1 
and Table 2]. Pregnancy test results must confirm that the subject is not pregnant. 
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND METHODS OF 
CONTRACEPTION DEFINITIONS 
A female is considered fertile (i.e., WOCBP) following menarche and until becoming 
postmenopausal unless permanently sterile.  
Females in the following categories are not considered WOCBP: 
● 
Premenarchal 
● 
Premenopausal with 1 of the following (i.e., permanently sterile): 
○ Documented hysterectomy 
○ Documented bilateral salpingectomy 
○ Documented bilateral oophorectomy 
● 
Postmenopausal 
A postmenopausal state is defined as at least 12 months after last menstrual bleeding without 
an alternative medical cause.  
In case the last menstrual bleeding cannot be clearly determined, confirmation with more 
than 1 follicle-stimulating hormone (FSH) measurement of at least > 40 IU/L (or higher per 
local institutional guidelines) is required.  
Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt 
will be required to use 1 of the nonestrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT 
to allow confirmation of postmenopausal status by repeated FSH measurements before study 
enrollment. 
Documentation of any of these categories can come from the study site personnel’s review of 
the female subject’s medical records, medical examination or medical history interview. 
CONTRACEPTION GUIDANCE FOR FEMALE SUBJECTS OF CHILDBEARING 
POTENTIAL 
Female subjects of childbearing potential are eligible for participation in the study if they 
agree to use 1 of the highly effective methods of contraception listed below from the time of 
signing the ICF and until the end of relevant systemic exposure, defined as 6 months after the 
final IP administration.a 
a Local laws and regulations may require use of alternative and/or additional contraception methods. 
 

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Highly effective methods of contraception (failure rate of < 1% per year when used 
consistently and correctly)b: 
● 
Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation 
○ Oral 
○ Intravaginal 
○ Transdermal 
● 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
○ Oral 
○ Injectable 
○ Implantable 
● 
Other combined (estrogen- and progesterone-containing) methods 
○ Vaginal ring 
○ Injectable 
○ Implantable 
○ Intrauterine hormone-releasing system or intrauterine device 
● 
Bilateral tubal occlusion 
● 
Vasectomized partner 
A vasectomized partner is a highly effective contraception method provided that the 
partner is the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used. 
● 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining 
from heterosexual intercourse during the entire period of risk associated with the test 
product. The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the study and the preferred and usual lifestyle of the subject. It is not 
necessary to use any other method of contraception when complete abstinence is elected. 
b Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies. 

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(Specific to Japan) 
Highly effective methods of contraception (failure rate of < 1% per year when used 
consistently and correctly)b: 
● 
Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation 
○ Oral 
● 
Other Hormonal methods of contraception containing progesterone 
○ Intrauterine hormone-releasing system(IUS) 
● 
Other methods of contraception 
○ Intrauterine device(IUD) 
○ Bilateral tubal occlusion 
● 
Vasectomized partner 
A vasectomized partner is a highly effective contraception method provided that the 
partner is the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used. 
● 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining 
from heterosexual intercourse during the entire period of risk associated with the test 
product. The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the study and the preferred and usual lifestyle of the subject. It is not 
necessary to use any other method of contraception when complete abstinence is elected. 
a Local laws and regulations may require use of alternative and/or additional contraception methods. 
b Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies. 
CONTRACEPTION GUIDANCE FOR MALE SUBJECTS WITH PARTNER(S) OF 
CHILDBEARING POTENTIAL. 
Male subjects with female partners of childbearing potential are eligible for participation in 
the study if they agree to the following during treatment and until the end of relevant 
systemic exposure defined as 6 months after final drug administration.a 
● 
Inform any and all partner(s) of their participation in a clinical drug study and the need to 
comply with contraception instructions as directed by the investigator 
● 
Use a condom 
● 
Female partners of male subjects who have not undergone a vasectomy with the absence 
of sperm confirmed or a bilateral orchiectomy should consider use of effective methods 
of contraception 
a 
Local laws and regulations may require use of alternative and/or additional contraception methods. 

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12.4 
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up and Reporting 
12.4.1 Definition of Adverse Events 
An AE is any untoward medical occurrence in a subject administered an IP, and which does 
not necessarily have to have a causal relationship with this treatment. An AE can therefore be 
any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease (new or exacerbated) temporally associated with the use of IP whether or not 
considered related to the IP. 
12.4.1.1 Abnormal Laboratory Findings 
Any abnormal laboratory test result (e.g., hematology, biochemistry or urinalysis) or other 
safety assessment (e.g., vital signs, physical examination, ECGs or radiographic scans), 
including those that worsen from baseline, that is considered to be clinically significant in the 
medical and scientific judgment of the investigator and not related to underlying disease, is to 
be reported as an (S)AE. 
Any clinically significant abnormal laboratory finding or other abnormal safety assessment, 
which is associated with the underlying disease, does not require reporting as an (S)AE, 
unless judged by the investigator to be more severe than expected for the subject’s condition. 
Repeating an abnormal laboratory test or other safety assessment, in the absence of any of the 
above criteria, does not constitute an AE. Any abnormal test result that is determined to be an 
error does not require reporting as an AE. 
12.4.1.2 Potential Cases of Drug-induced Liver Injury 
Refer to [Appendix 12.5 Liver Safety Monitoring and Assessment] for detailed instructions 
on drug induced liver injury. Abnormal values in AST and/or ALT concurrent or with 
abnormal elevations in TBL that meet the criteria outlined in [Appendix 12.5 Liver Safety 
Monitoring and Assessment], in the absence of other causes of liver injury, are considered 
potential cases of drug-induced liver injury (potential Hy’s Law cases) and are always to be 
considered important medical events and reported per [Appendix 12.4.5 Reporting 
Procedures for SAEs or Defect of Investigational Product].  
12.4.2 Definition of Serious Adverse Events 
An AE is considered “serious” if, in the view of either the investigator or sponsor, the event:  
● 
Results in death 
● 
Is life-threatening (An AE is considered “life-threatening” if, in the view of either the 
investigator or sponsor, its occurrence places the subject at immediate risk of death; it 
does not include an AE that, had it occurred in a more severe form, might have caused 
death.) 
● 
Results in persistent or significant disability/incapacity or substantial disruption of the 
ability to conduct normal life functions  
● 
Results in congenital anomaly, or birth defect 

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● 
Requires inpatient hospitalization (except for planned procedures as allowed per study) 
or leads to prolongation of hospitalization (except if prolongation of planned 
hospitalization is not caused by an AE)  
● 
Other medically important events (defined in paragraph below) 
Medical and scientific judgment should be exercised in deciding whether expedited reporting 
is appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization, but may jeopardize the 
subject or may require intervention to prevent 1 of the other outcomes listed in the definition 
above. These events, including those that may result in disability/incapacity, usually are 
considered serious. Examples of such events are intensive treatment in an emergency room or 
at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in 
hospitalization, or development of drug dependency or drug abuse.  
12.4.3 Criteria for Causal Relationship to Investigational Product 
A medically qualified investigator is obligated to assess the relationship between IP and each 
occurrence of each (S)AE. This investigator will use medical judgment as well as the 
reference safety information [Section 2.1.2 Summary of Key Safety Information for 
Investigational Product] to determine the relationship. The causality assessment is 1 of the 
criteria used when determining regulatory reporting requirements. 
The investigator is requested to provide an explanation for the causality assessment for each 
(S)AE and must document in the medical notes that he/she has reviewed the (S)AE and has 
provided an assessment of causality.  
Following a review of the relevant data, the causal relationship between the IP and each 
(S)AE will be assessed by answering “yes” or “no” to the question “Do you consider that 
there is a reasonable possibility that the event may have been caused by the IP?” 
When making an assessment of causality, the following factors are to be considered when 
deciding if there is evidence and/or arguments to suggest there is a “reasonable possibility” 
that an (S)AE may have been caused by the IP (rather than a relationship cannot be ruled out) 
or if there is evidence to reasonably deny a causal relationship: 
● 
Has the subject been administered IP?  
● 
Plausibility (i.e., could the event been caused by the suspect drug? Consider biologic 
and/or pharmacologic mechanism, half-life, literature evidence, drug class, preclinical 
and study data, etc.) 
● 
De-challenge/dose reduction/rechallenge:  
○ De-challenge: Did the (S)AE resolve or improve after only stopping the dose of 
the suspect drug without any treatment? 
○ Dose reduction: Did the (S)AE resolve or improve after reducing the dose of the 
suspect drug? 
○ Rechallenge: Did the (S)AE reoccur if the suspected drug was reintroduced after 
having been stopped?  

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● 
Laboratory or other test results: a specific lab investigation supports the assessment of 
the relationship between the (S)AE and the IP (e.g., based on values pre-, during and 
post-treatment) 
● 
Available alternative explanations independent of IP exposure; such as other 
concomitant drugs, past medical history, concurrent or underlying disease, risk factors 
including medical and family history, season, location, etc., and strength of the 
alternative explanation  
● 
Finally, judging which are more likely based on all the above contents, factors of 
reasonable possibility or confounding factors, comprehensive judgment of plausible 
temporal relationship between exposure to the IP and (S)AE onset and/or resolution will 
be provided. Did the (S)AE occur in a reasonable temporal relationship to the 
administration of the IP? 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the sponsor. However, it is very important that 
the investigator always assesses causality for every event before the initial transmission of the 
SAE data to the sponsor. With limited or insufficient information about the event to make an 
informed medical judgment and in absence of any indication or evidence to establish a causal 
relationship, a causality assessment of “no” is to be considered. In such instance, the 
investigator is expected to obtain additional information regarding the event as soon as 
possible and to re-evaluate the causality upon receipt of additional information. The 
medically qualified investigator may revise his/her assessment of causality in light of new 
information regarding the SAE and shall send an SAE follow-up report and update the eCRF 
with the new information and updated causality assessment.  
12.4.4 Criteria for Defining the Severity of an Adverse Event 
AEs, including abnormal clinical laboratory values, will be graded using the NCI-CTCAE 
guidelines (version 5.0). The items that are not stipulated in the NCI-CTCAE guidelines 
(version 5.0) will be assessed according to the criteria below and entered into the eCRF: 
Table 10 
Grading Scale Defining the Severity of an Adverse Event 
Grade 
Assessment Standard 
1 - Mild 
Asymptomatic or mild symptoms, clinical or diagnostic observations only; 
intervention not indicated 
2 - Moderate 
Minimal local or noninvasive intervention indicated; limiting age-appropriate 
instrumental ADL† 
3 - Severe 
Medically significant but not immediately life threatening, hospitalization or 
prolonged hospitalization indicated; disabling; limiting self-care ADL‡ 
4 - Life-threatening 
Life threatening consequences, urgent intervention indicated 
5 - Death 
Death related to AE 
ADL: activities of daily living; AE: adverse event. 
†Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc. 
‡Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications and not 
bedridden. 

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12.4.5 Reporting Procedures for Serious Adverse Events or Defect of Investigational 
Product  
The investigator must complete and submit an SAE worksheet containing all information that 
is required by local and/or regional regulations to the sponsor by fax or email immediately 
(within 24 hours of awareness).  
The SAE worksheet must be signed by a medically qualified investigator (as identified on 
delegation of authority log). Signature confirms accuracy and completeness of the SAE data 
as well as the investigator causality assessment including the explanation for the causality 
assessment.  
For contact details, see Contact Details of Sponsor's Key Personnel. Fax or email the 
SAE/special situations worksheet to: 
Astellas Pharma Global Development Inc. 
Pharmacovigilance  
North America fax number: +1-888-396-3750 
North America alternate fax number: +1-847-317-1241 
Email: safety-us@astellas.com 
Specific to Japan: 
In the case of a SAE or defect, the investigator or subinvestigator must report to the head of 
the study site and must contact the sponsor by fax or email immediately (within 24 hours of 
awareness).  
The investigator should complete and submit JUTOKUNA YUUGAIJISHOU 
OYOBIFUGUAI HOUKOKUSHO or JUTOKUNA YUUGAIJISHOU HOUKOKUSHO 
containing all information that is required by the appropriate regulatory authorities to the 
sponsor by fax or email immediately (within 24 hours of awareness) and to the head of the 
hospital. 
Fax or email JUTOKUNA YUUGAIJISHOU OYOBIFUGUAI HOUKOKUSHO or 
JUTOKUNA YUUGAIJISHOU HOUKOKUSHO and special situations worksheet to: 
Astellas Pharma Inc. – Japan 
Pharmacovigilance 
Fax number: 03-3243-5747 
Email: rk-safety-jp@jp.astellas.com 
If there are any questions, or if clarification is needed regarding the SAE, please contact the 
sponsor’s medical monitor/study physician or their designee [see Contact Details of 
Sponsor’s Key Personnel].  
Follow-up information for the event should be sent promptly (as soon as available, but no 
longer than within 7 days of the initial notification or for Japan sites, within 2 days for the 
initial notification). 

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Full details of the SAE should be recorded on the medical records, SAE/special situation 
worksheet and on the eCRF. 
The following minimum information is required: 
● 
International study number/study number  
● 
Subject number, sex and age 
● 
Date of report 
● 
Description of the SAE (event and seriousness criteria) and defect (if applicable) 
● 
Causal relationship to the IP (including reason) 
● 
Drug provided (if any)  
The sponsor or sponsor’s designee will medically evaluate the SAE and determine if the report 
meets the requirements for expedited reporting based on seriousness, causality, and expectedness 
of the events (e.g., suspected unexpected serious adverse reactions [SUSAR] reporting) 
according to current local/regional regulatory requirements. The sponsor or sponsor's designee 
will submit expedited safety reports to CAs and concerned ethics committee per current local 
regulations, and will inform the investigators of such regulatory reports as required. Investigators 
must submit safety reports as required by their IRB/IEC within timelines set by regional 
regulations (e.g., EMA, FDA) where required. Documentation of the submission to and receipt 
by the IRB/ IEC of expedited safety reports should be retained by the study site. In the US, FDA 
expedited IND reporting guidelines will be followed. 
The sponsor will notify all investigators responsible for ongoing clinical studies with the test 
product of all SUSARs, which require submission per local requirements IRB/IEC/head of 
the study site. 
The heads of the study sites/investigators should provide written documentation of IRB/IEC 
notification for each report to the sponsor. 
The investigator may contact the sponsor’s medical monitor/study physician for any other 
problem related to the rights, safety or well-being of the subject. 
12.4.6 Reporting Procedures for Special Situations 
12.4.6.1 Pregnancy 
If a female subject becomes pregnant during the study dosing period or within 180 days from 
the discontinuation of dosing, the investigator is to report the information to the sponsor 
according to the timelines in [Appendix 12.4.5 Reporting Procedures for SAEs or Defect of 
Investigational Product] using the SAE worksheet as a special situation and in the eCRF.  
The investigator will attempt to collect pregnancy information on any female partner of a 
male subject who becomes pregnant during the study dosing period or within 180 days from 
the discontinuation of dosing and report the information to sponsor according to the timelines 
in [Appendix 12.4.5 Reporting Procedures for SAEs or Defect of Investigational Product] 
using the SAE worksheet as a special situation.  

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The expected date of delivery or expected date of the end of the pregnancy, last menstruation, 
estimated conception date, pregnancy result and neonatal data, etc., should be included in this 
information. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
termination (including elective termination) of a pregnancy is to be reported for a female 
subject as an AE in the eCRF or SAE per [Appendix 12.4.5 Reporting Procedures for SAEs 
or Defect of Investigational Product]. For (S)AEs experienced by a female partner of a male 
subject, (S)AEs are to be reported via the SAE worksheet.  
Additional information regarding the outcome of a pregnancy when also categorized as an 
SAE is mentioned below: 
● 
“Spontaneous abortion” includes miscarriage, abortion and missed abortion. 
● 
Death of a newborn or infant within 1 month after birth is to be reported as an SAE 
regardless of its relationship with the IP. 
● 
If an infant dies more than 1 month after the birth, it is to be reported if a relationship 
between the death and intrauterine exposure to the IP is judged as “possible” by the 
investigator. 
● 
Congenital anomaly (including anomaly in miscarried fetus) 
Unless a congenital anomaly is identified prior to spontaneous abortion or miscarriage, the 
embryo or fetus should be assessed for congenital defects by visual examination or other 
means as appropriate. (S)AEs experienced by the newborn/infant should be reported via the 
pregnancy reporting form. Generally, follow up will be no longer than 6 to 8 weeks following 
the estimated delivery date.  
12.4.6.2 Medication Error, Overdose and “Off-label Use” 
If a medication error (defined as an unintended failure in the treatment process that leads to, 
or has the potential to lead to, harm to the subject), overdose or “off-label use” (i.e., use 
outside of what is stated in the protocol) is suspected, refer to [Section 10.3 Major Protocol 
Deviations]. Any associated (S)AEs are to be reported in the eCRF. If the AE meets the 
definition of an SAE, the SAE is also to be reported as described in [Appendix 12.4.5 
Reporting Procedures for SAEs or Defect of Investigational Product] together with the details 
of the medication error, overdose and/or “off-label use.” 
No information on overdose of ASP7517 is available. As ASP7517 is administered 
intravenously, the pharmacy manual will provide detailed instructions for preparation to 
ensure that the correct dose is dispensed. In the event of an overdose, subjects should be 
managed by symptomatic and supportive care and observed in a controlled medical setting. 
In the event of suspected ASP7517 medication error, the subject should receive supportive 
care and monitoring. The medical monitor/expert should be contacted as applicable.  
12.4.6.3 Misuse/Abuse 
Definition of misuse: Situations where the IP is/are intentionally and inappropriately used not 
in accordance with the intended use as defined in the protocol. 

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Definition of abuse: Persistent or sporadic, intentional excessive use of medicinal products 
which is accompanied by harmful physical or psychological effects. 
If misuse or abuse of the IP is suspected, the investigator must forward the special situation 
worksheet to the sponsor by fax or email immediately (within 24 hours of awareness). Any 
associated (S)AEs are to be reported in the eCRF. If the AE meets the definition of an SAE, 
the SAE is also to be reported as described in [Appendix 12.4.5 Reporting Procedures for 
SAEs or Defect of Investigational Product] together with details of the misuse or abuse of the 
IP. 
12.4.6.4 Occupational Exposure 
If occupational exposure (e.g., inadvertent exposure to the IP of study site personnel while 
preparing it for administration to the subject) to the IP occurs, the investigator must forward 
the special situation worksheet to the sponsor by fax or email immediately (within 24 hours 
of awareness). Any associated (S)AEs occurring to the individual associated with or resulting 
from the special situation are to be reported on the special situations worksheet. 
12.4.6.5 (Suspicion of)Transmission of Infectious Agent 
If transmission of an infectious agent related to the microbiological contamination at the site 
is suspected, the investigator must forward the special situation worksheet to the sponsor by 
fax or email immediately (within 24 hours of awareness) and any associated (S)AEs are to be 
reported in the eCRF. If the AE meets the definition of an SAE, the SAE is also to be 
reported as described in [Section 12.4.5 Reporting Procedures for SAEs or Defect of 
Investigational Product] together with the details of the suspected transmission of infectious 
agent. 
12.4.6.6 Suspected Drug-drug Interaction 
If a drug-drug interaction associated with the IP is suspected, the investigator must forward 
the special situation worksheet to the sponsor by fax or email immediately (within 24 hours 
of awareness). Any associated (S)AEs are to be reported in the eCRF. If the AE meets the 
definition of an SAE, the SAE is also to be reported as described in [Appendix 12.4.5 
Reporting Procedures for SAEs or Defect of Investigational Product] together with details of 
the suspected drug-drug interaction. 

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12.5 
Liver Safety Monitoring and Assessment 
The purpose of this appendix is to provide guidance for the monitoring of drug-induced liver 
injury during the course of the study. It should be noted that this section does not specify the 
End of Study analyses of liver enzymes. The end of study liver enzymes analyses will be 
described in the SAP. Any subject enrolled in a study with active drug therapy and reveals an 
increase of serum aminotransferases (AT) to > 3 × ULN or bilirubin > 2 × ULN should 
undergo detailed testing for liver enzymes (including at least ALP, ALT, AST and TBL). 
Testing should be repeated within 72 hours of notification of the test results. Subjects should 
be asked if they have any symptoms suggestive of hepatobiliary dysfunction. 
Definition of Liver Abnormalities 
Confirmed abnormalities will be characterized as moderate and severe where ULN is as 
shown below. 
Table 11 
Moderate and Severe Liver Abnormalities 
 
ALT or AST 
 
TBL 
Moderate 
> 3 × ULN 
or 
> 2 × ULN 
Severe 
> 3 × ULN 
and† 
> 2 × ULN 
ALT: alanine aminotransferase; AST: aspartate aminotransferase; TBL: total bilirubin; ULN: upper limit of normal 
†Samples taken simultaneously or within maximum 24 hours. 
In addition, the subject should be considered to have severe hepatic abnormalities for any of 
the following: 
● 
ALT or AST > 8 × ULN 
● 
ALT or AST > 5 × ULN for more than 2 weeks. 
● 
ALT or AST > 3 × ULN and† TBL > 2 × ULN or international normalized ratio (INR) 
> 1.5 (if INR testing is applicable/evaluated) 
● 
ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash and/or eosinophilia (> 5%)  
† Samples taken simultaneously or within a maximum of 24 hours. 
The investigator may determine that abnormal liver function results, other than as described 
above, may qualify as moderate or severe abnormalities and require additional monitoring 
and follow-up. 
Follow-up Procedures 
Confirmed moderate and severe abnormalities in hepatic functions should be thoroughly 
characterized by obtaining appropriate expert consultations, detailed pertinent history, 
physical examination and clinical laboratory tests. The study site personnel are to complete 
the liver abnormality case report form (LA-CRF). Subjects with confirmed abnormal LFTs 
should be followed as described below. 
Confirmed moderately abnormal LFTs should be repeated 2 to 3 times weekly, and then weekly 
or less if abnormalities stabilize or the IP has been discontinued and the subject is asymptomatic.  

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Severe hepatic liver function abnormalities as defined above, in the absence of another 
etiology, may be considered an important medical event and may be reported as a SAE. The 
sponsor should be contacted and informed of all subjects for whom severe hepatic liver 
function abnormalities possibly attributable to IP are observed. 
To further assess abnormal hepatic laboratory findings, the investigator is expected to: 
● 
Obtain a more detailed history of symptoms and prior or concurrent diseases. Symptoms 
and new-onset diseases are to be recorded as “AEs” within the eCRF. Illnesses and 
conditions such as hypotensive events, and decompensated cardiac disease that may lead 
to secondary liver abnormalities should be noted. Nonalcoholic steatohepatitis is seen in 
obese hyperlipoproteinemic and/or diabetic subjects, and may be associated with 
fluctuating AT levels. The investigator should ensure that the medical history form 
captures any illness that predates study enrollment that may be relevant in assessing 
hepatic function.  
● 
Obtain a history of concomitant drug use (including nonprescription medication, 
complementary and alternative medications), alcohol use, recreational drug use and 
special diets. Medications are to be entered in the eCRF. Information on alcohol, other 
substance use and diet should be entered on the LA-CRF or an appropriate document. 
● 
Obtain a history of exposure to environmental chemical agents. 
● 
Based on the subject’s history, other testing may be appropriate including:  
○ Acute viral hepatitis (A, B, C, D, E or other infectious agents) 
○ Ultrasound or other imaging to assess biliary tract disease 
○ Other clinical laboratory tests, including INR and direct bilirubin 
● 
Consider gastroenterology or hepatology consultations. 
● 
Submit results for any additional testing and possible etiology on the LA-CRF or an 
appropriate document. 
Study Treatment Discontinuation 
In the absence of an explanation for increased LFTs, such as viral hepatitis, preexisting or 
acute liver disease, or exposure to other agents associated with liver injury, the subject may 
be discontinued from study treatment. The investigator may determine that it is not in the 
subject’s best interest to continue study treatment. Discontinuation of study treatment should 
be considered if: 
● 
ALT or AST > 8 × ULN 
● 
ALT or AST > 5 × ULN for more than 2 weeks 
● 
ALT or AST > 3 × ULN and† TBL > 2 × ULN or INR > 1.5) (if INR testing is 
applicable/evaluated) 
● 
ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash and/or eosinophilia (> 5%)  
† Samples taken simultaneously or within a maximum of 24 hours. 
In addition, if close monitoring for a subject with moderate or severe hepatic laboratory tests 
is not possible, study treatment should be discontinued. 

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Hy’s Law definition: Drug-induced jaundice caused by hepatocellular injury, without a 
significant obstructive component, has a high rate of bad outcomes, from 10% to 50% 
mortality (or transplant).  
The 2 “requirements” for Hy’s Law are:  
1. Evidence that a drug can cause hepatocellular-type injury, generally shown by an increase 
in AT elevations > 3 × ULN (“2 × ULN elevations are too common in treated and 
untreated subjects to be discriminating”).  
2. Cases of increased TBL (at least 2 × ULN) with concurrent AT elevations at least 
3 × ULN and no evidence of intra- or extra-hepatic bilirubin obstruction (elevated ALP) 
or Gilbert’s syndrome [Temple, 2006]. 
FDA Guidance for Industry titled, “Drug-induced Liver Injury: Premarketing Clinical 
Evaluation” issued by the FDA on July 2009: 
1. The drug causes hepatocellular injury, generally shown by a higher incidence of 3-fold or 
greater elevations above the ULN of ALT or AST than the (nonhepatotoxic) control drug 
or placebo. 
2. Among subjects showing such AT elevations, often with ATs much greater than 
3 × ULN, 1 or more also show elevation of serum TBL to > 2 × ULN, without initial 
findings of cholestasis (elevated serum ALP). 
3. No other reason can be found to explain the combination of increased AT and TBL, such 
as viral hepatitis A, B, or C; preexisting or acute liver disease; or another drug capable of 
causing the observed injury. 
References 
Temple R. Hy’s Law: Predicting Serious Hepatotoxicity. Pharmacoepidemiol Drug Saf. 
2006;15(4):241-3. 

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12.6 
List of Excluded Concomitant Medications 
12.6.1 Concomitant Medications 
The following list describes concomitant medications that are prohibited. This list should not 
be considered all inclusive. If there are concerns or questions about concomitant use of any 
drugs listed below, discussion with the medical monitor is strongly encouraged. 
Drug Type 
Generic Drug Name 
Corticosteroids* 
Dexamethasone 
Prednisone (Deltasone, Orasone, Predone, 
RAYOS, Sterapred, etc.) 
Interferon/polyethylene-interferon 
 
Immunosuppressive Agents 
Abatacept (Orencia, etc.) 
Adalimumab (Humira, etc.) 
Anajunra (Kineret, etc.) 
Azathioprine (Azasan, Imuran, etc.) 
Budesonide (Entocort EC, etc.) 
Certolizumab (Cimzia, etc.) 
Cyclosporine (Neoral, Sandimmune, SangCya, 
etc.) 
Etanercept (Enbrel, etc) 
Everolimus (Afinitor, Zortress, etc.) 
Golimumab (Simponi, etc.) 
Infliximab (Remicade, etc.) 
Ixekizumab (Taltz, etc.) 
Leflunomide (Arava, etc.) 
Mycophenolate (CellCept, Myfortic, etc.) 
Natalizumab (Tysabri, etc.) 
Prednisolone (Millipred, etc.) 
Rituximab (Rituxan, etc.) 
Secukinumab (Cosentyx, etc.) 
Sirolimus (Rapamune, etc.) 
Tocilizumab (Actemra, etc.) 
Tofacitinib (Xeljanz, etc.) 
Ustekinumab (Stelara, etc.) 
Vedolizumab (Entyvio, etc.) 
*The use of high dose system corticosteroids are prohibited, with the exception of immune-related AEs (steroids 
can be used if not intended for treatment of AML or MDS; steroids for AML/MDS related symptoms can be 
used at low doses [less than 10 mg/day dexamethasone]). 
 

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12.6.2 Other Investigational Agents 
Treatment with investigational agents other than ASP7517 is prohibited. If there are concerns 
or questions about concomitant use of these drugs, discussion with the co-chairs and protocol 
officer is strongly encouraged. 
12.6.3 Other Treatments for Acute Myeloid Leukemia and/or Myelodysplastic 
Syndrome 
Any other treatments of AML or MDS (including, but not limited to, chemotherapy, 
radiotherapy, surgery, immunotherapy and cellular therapy) are prohibited, with the 
following exceptions: 
● 
Hydroxyurea up to 5 g daily for up to 2 weeks to keep the absolute blast count  
< 20,000/µL. 
● 
Subject undergoing HSCT will be discontinued from the study.  
● 
Intrathecal chemotherapy used as prophylaxis. 
If there are concerns or questions about concomitant use of these drugs, discussion with the 
medical monitor is strongly encouraged. 

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12.7 
Laboratory Assessments 
Laboratory tests will be performed and analyzed by the institution’s local laboratory 
according to the Schedules of Assessments [Table 1 and Table 2] and results submitted for 
centralized data entry. 
Additional laboratory tests should be performed according to the institutional standard of care. 
Clinical significance of out-of-range laboratory findings is to be determined and documented 
by the investigator/or delegated subinvestigator who is a qualified physician. 
Table 12 
Clinical Laboratory Tests 
Panel/Assessments 
Parameters to be Analyzed 
Hematology 
Blast count and cell count 
Hematocrit (Hct)  
Hemoglobin (Hgb)  
Mean corpuscular volume (MCV) 
Mean corpuscular hemoglobin (MCH) 
Mean corpuscular hemoglobin concentration (MCHC) 
Platelet count  
Red blood cell count (RBC) 
White blood cell count (WBC)  
White blood cell count differential  
Chemistry 
Sodium (Na) 
Potassium (K) 
Chloride (Cl) 
Bicarbonate (HCO3) 
Blood urea nitrogen (BUN) 
Creatinine (Cr) 
Glucose (Gl) 
Calcium (Ca) 
Phosphate (Pi) 
Magnesium (Mg) 
Albumin (Alb) 
Total protein (T Prot) 
Alkaline phosphatase (ALP) 
Lactate dehydrogenase (LDH) 
Creatine phosphokinase (CK) 
Liver function tests including: 
Bilirubin total (TBL) 
Alanine aminotransferase (ALT) 
Aspartate aminotransferase (AST) 
Table continued on next page 

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Panel/Assessments 
Parameters to be Analyzed 
Urinalysis 
Color 
Appearance 
Specific gravity 
pH 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocyte esterase 
Nitrite 
Protein 
Urobilinogen 
Urine/Serum Pregnancy 
Test ** 
hCG 
Coagulation Profile 
(PT/INR, D-Dimer, 
Fibrinogen) 
Activated partial thromboplastin time (aPTT) 
International normalized ratio (INR) 
Prothrombin time (sec) (PT) 
Fibrinogen  
D-Dimer  
Bone Marrow*** 
Blast count and cell counts * 
Flow cytometry for blasts 
Blood Sample for Disease 
Assessment*** 
Blast count and cell counts 
eCRF: electronic case report form; hCG: human chorionic gonadotrophin. 
* In addition to the central read of these values, local results will also be collected and entered into the eCRF. 
** Local results will be collected and entered into the eCRF. 
*** Samples must be submitted to a central laboratory for analysis. Refer to the laboratory manual for 
additional information. 
 

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12.8 
Pharmacogenomic Analysis With Banked Sample 
INTRODUCTION 
PGx research aims to provide information regarding how naturally occurring differences in a 
subject’s gene and/or expression of genes based on genetic variation may impact what 
treatment options are best suited for the subject. Through investigation of PGx by 
technologies such as genotyping, gene sequencing, statistical genetics and Genome-Wide 
Association studies, the relationship between gene profiles and a drug’s kinetics, efficacy or 
toxicity may be better understood. As many diseases may be influenced by 1 or more genetic 
variations, PGx research may identify which genes are involved in determining the way a 
subject may or may not respond to a drug. 
OBJECTIVES 
The PGx research that may be conducted in the future with acquired blood samples is 
exploratory. The objective of this research will be to analyze or determine genes of relevance 
to clinical response, pharmacokinetics and/or toxicity/safety. 
By analyzing genetic variations, it may be possible to predict an individual subject’s response 
to treatment in terms of efficacy and/or toxicity. 
SUBJECT PARTICIPATION 
Subjects who have consented to participate in this study may participate in the PGx substudy. 
Subjects must provide written consent prior to providing any blood samples that may be used 
at a later time for PGx analysis. 
SAMPLE COLLECTION AND STORAGE 
Subjects who consent to participate in this substudy will provide 4 to 6 mL sample of whole 
blood and buccal swab per Astellas’ instructions. Each sample will be identified by the 
unique subject number. Samples will be shipped to a designated banking CRO as directed by 
Astellas. 
PGx ANALYSIS 
Details on the potential PGx analysis cannot be established yet. Astellas may initiate the PGx 
analysis if evidence suggests that genetic variants may be influencing the drug’s 
pharmacokinetics, efficacy and/or safety.  
DISPOSAL OF PGx SAMPLES/DATA 
All PGx samples collected will be stored for a period of up to 15 years following study 
database hard-lock. If there is no requirement for analysis, the whole blood sample will be 
destroyed after the planned storage period. The subject has the right to withdraw consent at 
any time. When a subject’s withdraw notification is received, the PGx sample will be 
destroyed. The results of any PGx analysis conducted on a sample prior to its withdrawal will 
be retained at Astellas indefinitely unless otherwise specified by local regulation. 

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INFORMATION DISCLOSURE TO THE SUBJECTS 
Exploratory PGx analysis may be conducted following the conclusion of the study, if 
applicable. The results of the PGx analysis will not be provided to any investigators or 
subjects, nor can the results be requested at a later date. Any information that is obtained 
from the PGx analysis will be the property of Astellas.  
 

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12.9 
Clinical Study Continuity 
INTRODUCTION 
The purpose of this appendix is to provide acceptable alternate methods to assess safety and 
efficacy parameters, as appropriate, in the event the clinical study is interrupted at the 
country, state, site or subject level during any crisis (e.g., natural disaster, pandemic).  
BENEFIT-RISK RATIONALE 
Maintaining the safety of clinical study subjects and delivering continuity of care in the 
clinical study setting is paramount during any crisis. The site is expected to follow the 
protocol and associated Schedules of Assessments [Table 1, Table 2, Table 3 and Table 4] 
unless the site principal investigator discusses the need with the Astellas medical monitor to 
implement the alternate measures.  
The approach outlined within this appendix defines which assessments are required to 
maintain a favorable benefit/risk to the subject, to maintain overall study integrity and to 
provide acceptable alternate methods to complete the study required assessments and 
procedures if study activities are unable to be performed as described in [Section 7 Study 
Procedures and Assessments] due to a crisis. 
INFORMED CONSENT 
Subjects who need to follow any or all of the alternate measures outlined in this Appendix 
will be required to provide informed consent which explicitly informs them of the nature of, 
and rationale for these changes, and gain their agreement to continue participation in the 
study prior to the implementation of any of these changes. In the event the urgency of 
implementing the alternate measures does not allow for the subject to provide written consent 
prior to implementation, the principal investigator or designee will obtain oral agreement 
from the subject followed by written documentation as soon as is feasible. A separate 
addendum to the study informed consent will be provided to document the subject’s consent 
of the changes. 
SUBJECT PROCEDURES ASSESSMENT 
Sites with subjects who are currently enrolled into this clinical study may consider 
implementing the alternate methods outlined below if one or more of the following 
conditions are met due to the crisis: 
● 
Regional or local travel has been restricted, inclusive of mandatory shelter in place 
measures, which makes subject travel to/from the study site nearly impossible 
● 
Site facilities have been closed for clinical study conduct  
● 
Site has been restricted to treating subjects with conditions outside of the scope of the 
study 
● 
Site personnel have temporarily relocated the conduct of the study to a location that 
place a burden on the subject with respect to time and travel 
● 
Subject(s) have temporarily relocated from the current study site to an alternate study site 
avoid placing a burden on the subject with respect to travel 

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● 
Subject(s) have temporarily relocated from their home location and the new distances 
from the site would cause undue burden with respect to time and travel 
● 
Subject has risk factors for which traveling to the site poses an additional risk to the 
subject’s health and safety 
Adherence to the original protocol as reflected in the Schedules of Assessments [Table 1, 
Table 2, Table 3 and Table 4] is expected, where plausible, in the case of a crisis. The 
alternate measures as noted in Table 13, Table 14, Table 15 and Table 16 below are only 
permissible in the event of a crisis, and after discussing the need with the Astellas medical 
monitor to implement the alternate measures. This is to allow for continuity of receiving 
Investigational Medicinal Product (IMP) and maintaining critical safety and efficacy 
assessments for subjects participating in the study at a time of crisis. 
If one or more of the alternate measures noted below is implemented for a subject, the site 
should document in the subject’s source document the justification for implementing the 
alternate measure and the actual alternate measures that were implemented, along with the 
corresponding time point(s).  
 

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Astellas 
Page 115 of 138 
Version 7.5 Incorporating Nonsubstantial Amendment 5 
Table 13 
Alternate Schedule of Assessments in Response to a Crisis – Phase 1 (Dose Escalation) 
Assessments 
Alternate 
Approach(es) 
Treatment Period 
End of 
Treatmentk 
 
Post-Treatment 
Period 
Survival 
Follow-up 
Periods 
Cycle 1 
Cycle 2 
Obs 
Period 1 
Obs 
Period 2 
Visit Days 
 
Hospitalization Days 1 to 7 
during phase 1 
8 
11 
15 
 
18 
22 
25 
1 
2 
3 
4 
5 
6 
7 
8 
15 
22 
Every 2 
weeks for 
up to 12 
weeks or  
until 1 
post-treat-
ment 
discontin-
uation 
criterion  
is met 
Every 4 
weeks or 
until 1 
post-treat-
ment 
discontin-
uation 
criterion 
is met 
Every 3 
months 
 
 
 
1 
 
 
 
2 
 
 
 
3 
 
 
 
4 
 
 
 
5 
 
 
 
6 
 
 
 
7 
Window(days) 
 
 
0 
0 
0 
0 
0 
0 
±1 
±1 
± 1 
± 1 + 3 0 
0 
0 
0 
0 
0 ± 1 
± 1 
± 1 
+ 7 
 
± 3 
Physical Examinationc 
For Cycle 1, there are 7 days of hospitalization and each cycle day 1 are IP administration days. 
Other visits can be obtained at local facility and results submitted to PI. 
Disease Assessment 
Except for IP 
administration days, 
assessment can be 
performed locally and 
results submitted to PI 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
Vital Signs 
Except for IP 
administration days and 
hospitalization on C1D1 
to C1D7, exams can be 
performed at a local 
facility and results 
submitted to PI. 
Xb X 
 
X 
 
 
 
X 
X 
X 
X 
Xb X 
 
X 
 
 
 
X 
X 
X 
Xl 
Reference Table 15: 
Alternative Schedule 
of Post-Treatment 
Period Assessments in 
Response to a Crisis 
 
ECOG Performance 
Except for IP 
administration days and 
hospitalization on C1D1 
to C1D7, can be 
completed by remote/ 
telemedicine visit. 
Xa X 
 
X 
 
 
 
X 
X 
X 
X 
Xa X 
 
X 
 
 
 
X 
X 
X 
Xl 
 
Table continued on next page 

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Version 7.5 Incorporating Nonsubstantial Amendment 5 
Assessments 
Alternate 
Approach(es) 
Treatment Period 
End of 
Treatmentk 
 
Post-Treatment 
Period 
Survival 
Follow-up 
Periods 
Cycle 1 
Cycle 2 
Obs 
Period 1 
Obs 
Period 2 
Visit Days 
 
Hospitalization Days 1 to 7 
during phase 1 
8 
11 
15 
 
18 
22 
25 
1 
2 
3 
4 
5 
6 
7 
8 
15 
22 
Every 2 
weeks for 
up to 12 
weeks or  
until 1 
post-treat-
ment 
discontin-
uation 
criterion  
is met 
Every 4 
weeks or 
until 1 
post-treat-
ment 
discontin-
uation 
criterion 
is met 
Every 3 
months 
 
 
 
1 
 
 
 
2 
 
 
 
3 
 
 
 
4 
 
 
 
5 
 
 
 
6 
 
 
 
7 
Window(days) 
 
 
0 
0 
0 
0 
0 
0 
±1 
±1 
± 1 
± 1 + 3 0 
0 
0 
0 
0 
0 ± 1 
± 1 
± 1 
+ 7 
 
± 3 
Prior and Concomitant 
Medications 
Remote/Virtual/Telemedicine Visits allowed for nondosing visits. Please refer to protocol schedule of assessments. 
Every Visit. 
Pregnancy Test for 
WOCBP 
Test must be completed 
prior to dosing, however 
EoT test may be 
performed at local clinic 
and result submitted to 
PI. 
Xa 
 
 
 
 
 
 
 
 
 
 
Xa 
 
 
 
 
 
 
 
 
 
X 
Reference Table 15: 
Alternative Schedule 
of Post-Treatment 
Period Assessments in 
Response to a Crisis 
 
12-Lead ECGd 
Except for IP 
administration days 
triplicate may be 
performed as possible at 
a local clinic and results 
submitted to PI. If 
cannot be performed, 
Astellas medical 
monitor to assess for 
study continuation. 
Xb 
 
 
 
 
 
 
 
 
 
 
Xb 
 
 
 
 
 
 
 
 
 
X 
 
Clinical Laboratory 
Tests (chemistry, 
hematology, 
urinalysis)e 
Except for IP administration days and hospitalization on C1D1 to C1D7, collection of samples at local facility acceptable if results can be made available to investigative site. 
Table continued on next page 

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Astellas 
Page 117 of 138 
Version 7.5 Incorporating Nonsubstantial Amendment 5 
Assessments 
Alternate 
Approach(es) 
Treatment Period 
End of 
Treatmentk 
 
Post-Treatment 
Period 
Survival 
Follow-up 
Periods 
Cycle 1 
Cycle 2 
Obs 
Period 1 
Obs 
Period 2 
Visit Days 
 
Hospitalization Days 1 to 7 
during phase 1 
8 
11 
15 
 
18 
22 
25 
1 
2 
3 
4 
5 
6 
7 
8 
15 
22 
Every 2 
weeks for 
up to 12 
weeks or  
until 1 
post-treat-
ment 
discontin-
uation 
criterion  
is met 
Every 4 
weeks or 
until 1 
post-treat-
ment 
discontin-
uation 
criterion 
is met 
Every 3 
months 
 
 
 
1 
 
 
 
2 
 
 
 
3 
 
 
 
4 
 
 
 
5 
 
 
 
6 
 
 
 
7 
Window(days) 
 
 
0 
0 
0 
0 
0 
0 
±1 
±1 
± 1 
± 1 + 3 0 
0 
0 
0 
0 
0 ± 1 
± 1 
± 1 
+ 7 
 
± 3 
Coagulation Profile 
(PT/INR, D-dimer, 
fibrinogen)e 
Except for IP 
administration days and 
hospitalization on C1D1 
to C1D7, collection of 
samples at local facility 
acceptable if results can 
be made available to 
investigative site. 
Xa X X X X X X 
X 
X 
X 
X 
Xa X X 
X 
X X X X 
X 
X 
Xl 
Reference Table 15: 
Alternative Schedule 
of Post-Treatment 
Period Assessments in 
Response to a Crisis 
 
Bone Marrow 
Aspiration and/or 
Biopsyf 
May be obtained at a 
delayed time point when 
subject can visit the site 
and local BM collection 
is option to collect this 
data. 
 
 
 
 
 
 
 
 
 
 
 
Xa,f  
 
 
 
 
 
 
 
 
Xf 
 
Blood Sample for 
Disease Assessmentg 
May be obtained at a 
local clinical and results 
submitted to Investigator 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
AE/SAE Assessment 
Completion by phone contact allowed for non-dosing visits with further assessment at local clinic if needed. 
Every Visit. 
Pharmacokinetic: 
Blood Sample for Cell 
Kinetics 
None 
See Table 5 for detailed sample time points 
Table continued on next page 

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Version 7.5 Incorporating Nonsubstantial Amendment 5 
Assessments 
Alternate 
Approach(es) 
Treatment Period 
End of 
Treatmentk 
 
Post-Treatment 
Period 
Survival 
Follow-up 
Periods 
Cycle 1 
Cycle 2 
Obs 
Period 1 
Obs 
Period 2 
Visit Days 
 
Hospitalization Days 1 to 7 
during phase 1 
8 
11 
15 
 
18 
22 
25 
1 
2 
3 
4 
5 
6 
7 
8 
15 
22 
Every 2 
weeks for 
up to 12 
weeks or  
until 1 
post-treat-
ment 
discontin-
uation 
criterion  
is met 
Every 4 
weeks or 
until 1 
post-treat-
ment 
discontin-
uation 
criterion 
is met 
Every 3 
months 
 
 
 
1 
 
 
 
2 
 
 
 
3 
 
 
 
4 
 
 
 
5 
 
 
 
6 
 
 
 
7 
Window(days) 
 
 
0 
0 
0 
0 
0 
0 
±1 
±1 
± 1 
± 1 + 3 0 
0 
0 
0 
0 
0 ± 1 
± 1 
± 1 
+ 7 
 
± 3 
PGx 
None 
Xh 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference Table 15: 
Alternative Schedule 
of Post-Treatment 
Period Assessments in 
Response to a Crisis 
 
Blood Sample for 
WT1 Expression 
None 
Xa 
 
 
 
 
 
 
 
 
 
 
Xa 
 
 
 
 
 
 
 
 
 
Xl 
 
Blood Sample for 
Mutational Profiling 
None 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xl 
 
Blood Sample for 
Immune Response 
Biomarker (ELISpot) 
None 
Xa 
 
 
 
 
 
 
X 
 
X 
 
Xa 
 
 
 
 
 
 
X 
X 
 
Xl 
 
Buccal Swab for HLA 
Typing 
None 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood Sample for 
Immune Response 
Biomarker (Tetramer)  
None 
Xa 
 
 
 
 
 
 
 
 
X 
 
Xa 
 
 
 
 
 
 
 
X 
 
Xl 
Reference Table 15: 
Alternative Schedule 
of Post-Treatment 
Period Assessments in 
Response to a Crisis 
 
Blood Sample for 
Immune Cell 
Phenotyping 
None 
Xa 
 
 
 
 
 
 
X 
 
X 
 
Xa 
 
 
 
 
 
 
X 
X 
 
Xl 
 
Blood Sample for 
Cytokines 
None 
Xa X 
 
X 
 
 
 
X 
 
X 
 
Xa X 
 
X 
 
 
 
X 
X 
 
Xl 
 
Blood Sample for 
Anti-HLA Antibody 
None 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
IRT Transaction 
Required 
None 
Xi 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
Table continued on next page 

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19 Sep 2022 
Astellas 
Page 119 of 138 
Version 7.5 Incorporating Nonsubstantial Amendment 5 
Assessments 
Alternate 
Approach(es) 
Treatment Period 
End of 
Treatmentk 
 
Post-Treatment 
Period 
Survival 
Follow-up 
Periods 
Cycle 1 
Cycle 2 
Obs 
Period 1 
Obs 
Period 2 
Visit Days 
 
Hospitalization Days 1 to 7 
during phase 1 
8 
11 
15 
 
18 
22 
25 
1 
2 
3 
4 
5 
6 
7 
8 
15 
22 
Every 2 
weeks for 
up to 12 
weeks or  
until 1 
post-treat-
ment 
discontin-
uation 
criterion  
is met 
Every 4 
weeks or 
until 1 
post-treat-
ment 
discontin-
uation 
criterion 
is met 
Every 3 
months 
 
 
 
1 
 
 
 
2 
 
 
 
3 
 
 
 
4 
 
 
 
5 
 
 
 
6 
 
 
 
7 
Window(days) 
 
 
0 
0 
0 
0 
0 
0 
±1 
±1 
± 1 
± 1 + 3 0 
0 
0 
0 
0 
0 ± 1 
± 1 
± 1 
+ 7 
 
± 3 
ASP7517 Dosing at 
the Clinic 
None 
Xj 
 
 
 
 
 
 
 
 
 
 
Xj 
 
 
 
 
 
 
 
 
 
 
Reference Table 15: 
Alternative Schedule 
of Post-Treatment 
Period Assessments in 
Response to a Crisis 
 
Survival Follow-upm 
Can be completed by 
phone contact per 
protocol design 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
AE: adverse event; CT: computed tomography; C: cycle; D: day; C1D1: cycle 1 day 1; ECG: electrocardiogram; ECHO: echocardiogram; ECOG: Eastern Cooperative Oncology 
Group; ELISpot: enzyme-linked immunospot; EoT: end-of-treatment; HLA: human leukocyte antigen; ICF: informed consent form; INR: international normalization ratio; 
IP: investigational product; IRT: interactive response technology; MUGA: multigated acquisition scan; Obs: observation; PGx: pharmacogenomics; PI: principal investigator; 
PT: prothrombin time; SAE: serious adverse event; WOCBP: women of childbearing potential; WT1: Wilms’ tumor 1 protein. 
a. Obtained predose. 
b. Obtained predose and postdose (including flushing) (vital signs: hourly [± 10 minute window] for up to 4 hours postdose; ECG: 1 to 2 hours postdose) on C1D1 and C2D1. 
c. Height measurement performed only at screening. Weight measurement should be performed at screening and day 1 of each cycle. 
d. The 12-lead ECGs will be recorded in triplicate (at least 2 minutes apart per time point) and transmitted electronically for central reading.  
e. Laboratory samples will be analyzed by the institution’s local laboratory and results will be submitted for centralized data entry. 
f. Screening samples may be collected up to 28 days prior to C1D1. End of treatment bone marrow sample does not need to be repeated if collected within 2 weeks of the last  
disease assessment. Samples must be submitted to a central laboratory for analysis. If bone marrow aspirate is unobtainable (e.g., dry tap), an additional ethylenediaminetetraacetic 
acid tube of whole blood should be collected instead. Bone marrow aspirate is required, and bone marrow biopsy is preferred. In case of inadequate aspirate, bone marrow biopsy is 
required. 
g. Samples must be submitted to a central laboratory for analysis. 
h. Whole blood and buccal swab for optional PGx study may be collected at C1D1 prior to first investigational product administration. 
Footnotes continued on next page 

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Version 7.5 Incorporating Nonsubstantial Amendment 5 
i. Subject enrollment in the study will be conducted via IRT transaction. 
j. After dosing of ASP7517, subjects must be observed for safety for a minimum 4 hours. The safety observation will consist of hourly vital signs and AE observations. If new 
AEs are observed that are ≥ grade 3 during this time, subjects should continue to be observed at the investigator’s discretion.  
k. The EoT visit will occur within 7 days of the principal investigator decision to discontinue the subject for treatment or prior to the initiation of new anticancer treatment, 
whichever occurs first. If a subject is completing all visits in the last treatment cycle, the EoT visit will be within 7 days from the last planned visit. 
l. Assessment does not need to be repeated if collected at a regularly scheduled visit within 3 days of EoT visit. 
m. Telephone contact for survival status and subsequent anti-cancer treatments and outcomes. 
 

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Page 121 of 138 
Version 7.5 Incorporating Nonsubstantial Amendment 5 
Table 14 
Alternate Schedule of Assessments in Response to a Crisis – Phase 2 (Dose Expansion) 
Assessments 
Alternative 
Approach(es) 
Treatment Period 
EoTj 
Post-Treatment Period 
Survival 
Follow-up
Period 
 
Cycle 1 
Cycle 2 
Cycles 3 – 
4m 
Cycles 5 – 
6n 
Obs Period 1 
Obs Period 2 
Survival 
Follow-up
Visit Days
 
D1 
D2 
D8 
D15 
D22 
D1 
D2 
D8 
D15 
D22 
D1 D15 D1 D15 
Every 2 weeks 
for up to 12 
weeks or  
until 1 post-
treatment 
discontinuation 
criterion  
is met 
Every 4 weeks or 
until 1 post-
treatment 
discontinuation 
criterion is met 
Every 3 
months 
Window(days)
 
 
0 
± 1 
± 1 
± 1 
+ 3 
0 
± 1 
± 1 
± 1 
+ 3 
± 1 + 3 ± 1 
+7 
 
± 3 
Physical Examinationc 
Cycle day 1 are IP administration days and must be performed in office. 
Other visits can be obtained at local facility and results submitted to PI. 
Disease Assessmento 
Except for IP 
administration days, 
assessment can be 
performed locally 
and results submitted 
to PI 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
Reference Table 15: Alternative 
Schedule of Post-Treatment Period 
Assessments in Response to a Crisis 
 
Vital Signs 
Except for IP 
administration days, 
exams can be 
performed at a local 
facility and results 
submitted to PI 
Xb 
X 
X 
X 
X 
Xb 
X 
X 
X 
X 
Xb 
X 
Xb 
X 
Xk 
 
Table continued on next page 

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Page 122 of 138 
Version 7.5 Incorporating Nonsubstantial Amendment 5 
Assessments 
Alternative 
Approach(es) 
Treatment Period 
EoTj 
Post-Treatment Period 
Survival 
Follow-up
Period 
 
Cycle 1 
Cycle 2 
Cycles 3 – 
4m 
Cycles 5 – 
6n 
Obs Period 1 
Obs Period 2 
Survival 
Follow-up
Visit Days
 
D1 
D2 
D8 
D15 
D22 
D1 
D2 
D8 
D15 
D22 
D1 D15 D1 D15 
Every 2 weeks 
for up to 12 
weeks or  
until 1 post-
treatment 
discontinuation 
criterion  
is met 
Every 4 weeks or 
until 1 post-
treatment 
discontinuation 
criterion is met 
Every 3 
months 
Window(days)
 
 
0 
± 1 
± 1 
± 1 
+ 3 
0 
± 1 
± 1 
± 1 
+ 3 
± 1 + 3 ± 1 
+7 
 
± 3 
ECOG Performance 
Except for IP 
administration days, 
can be completed by 
remote/ telemedicine 
visit 
Xa 
X 
X 
X 
X 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
Xk 
Reference Table 15: Alternative 
Schedule of Post-Treatment Period 
Assessments in Response to a Crisis 
 
Pregnancy Test for 
WOCBP 
Test must be 
completed prior to 
dosing, however 
EoT test may be 
performed at local 
clinic and result 
submitted to PI 
Xa 
 
 
 
 
Xa 
 
 
 
 
Xa 
 
Xa 
 
X 
 
Prior and Concomitant 
Medications 
Remote/Virtual/Telemedicine Visits allowed for non-dosing visits. Please refer to protocol schedule of assessments. 
Table continued on next page 

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Version 7.5 Incorporating Nonsubstantial Amendment 5 
Assessments 
Alternative 
Approach(es) 
Treatment Period 
EoTj 
Post-Treatment Period 
Survival 
Follow-up
Period 
 
Cycle 1 
Cycle 2 
Cycles 3 – 
4m 
Cycles 5 – 
6n 
Obs Period 1 
Obs Period 2 
Survival 
Follow-up
Visit Days
 
D1 
D2 
D8 
D15 
D22 
D1 
D2 
D8 
D15 
D22 
D1 D15 D1 D15 
Every 2 weeks 
for up to 12 
weeks or  
until 1 post-
treatment 
discontinuation 
criterion  
is met 
Every 4 weeks or 
until 1 post-
treatment 
discontinuation 
criterion is met 
Every 3 
months 
Window(days)
 
 
0 
± 1 
± 1 
± 1 
+ 3 
0 
± 1 
± 1 
± 1 
+ 3 
± 1 + 3 ± 1 
+7 
 
± 3 
12-Lead ECGd 
Except for IP 
administration days 
triplicate may be 
performed as 
possible at a local 
clinic and results 
submitted to PI. If 
cannot be 
performed, Astellas 
Medical Monitor to 
assess for study 
continuation. 
Xb 
 
 
 
 
Xb 
 
 
 
 
Xb 
 
Xb 
 
X 
Reference Table 15: Alternative 
Schedule of Post-Treatment Period 
Assessments in Response to a Crisis 
 
Clinical Laboratory Tests 
(chemistry, hematology, 
urinalysis) 
Except for IP administration days, collection of samples at local facility acceptable if results can be made available to investigative site. 
Table continued on next page 

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Version 7.5 Incorporating Nonsubstantial Amendment 5 
Assessments 
Alternative 
Approach(es) 
Treatment Period 
EoTj 
Post-Treatment Period 
Survival 
Follow-up
Period 
 
Cycle 1 
Cycle 2 
Cycles 3 – 
4m 
Cycles 5 – 
6n 
Obs Period 1 
Obs Period 2 
Survival 
Follow-up
Visit Days
 
D1 
D2 
D8 
D15 
D22 
D1 
D2 
D8 
D15 
D22 
D1 D15 D1 D15 
Every 2 weeks 
for up to 12 
weeks or  
until 1 post-
treatment 
discontinuation 
criterion  
is met 
Every 4 weeks or 
until 1 post-
treatment 
discontinuation 
criterion is met 
Every 3 
months 
Window(days)
 
 
0 
± 1 
± 1 
± 1 
+ 3 
0 
± 1 
± 1 
± 1 
+ 3 
± 1 + 3 ± 1 
+7 
 
± 3 
Coagulation Profile 
(PT/INR, D-dimer, 
fibrinogen) 
Except for IP 
administration 
days, collection of 
samples at local 
facility acceptable 
if results can be 
made available to 
investigative site 
Xa 
X 
X 
X 
X 
Xa 
X 
X 
X 
X 
Xa 
X 
Xa 
X 
Xk 
Reference Table 15: Alternative 
Schedule of Post-Treatment Period 
Assessments in Response to a Crisis 
 
Bone Marrow Aspiration 
and/or Biopsye 
May be obtained at a 
delayed time point 
when subject can 
visit the site and 
local BM collection 
is option to collect 
this data 
 
 
 
 
 
Xa,e 
 
 
 
 
Xa,e 
 
Xa,e 
 
Xe 
 
Blood Sample for Disease 
Assessmentf 
Except for IP 
administration days, 
may be obtained 
locally and results 
submitted to PI 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
Table continued on next page 

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Version 7.5 Incorporating Nonsubstantial Amendment 5 
Assessments 
Alternative 
Approach(es) 
Treatment Period 
EoTj 
Post-Treatment Period 
Survival 
Follow-up
Period 
 
Cycle 1 
Cycle 2 
Cycles 3 – 
4m 
Cycles 5 – 
6n 
Obs Period 1 
Obs Period 2 
Survival 
Follow-up
Visit Days
 
D1 
D2 
D8 
D15 
D22 
D1 
D2 
D8 
D15 
D22 
D1 D15 D1 D15 
Every 2 weeks 
for up to 12 
weeks or  
until 1 post-
treatment 
discontinuation 
criterion  
is met 
Every 4 weeks or 
until 1 post-
treatment 
discontinuation 
criterion is met 
Every 3 
months 
Window(days)
 
 
0 
± 1 
± 1 
± 1 
+ 3 
0 
± 1 
± 1 
± 1 
+ 3 
± 1 + 3 ± 1 
+7 
 
± 3 
AE/SAE Assessment 
Completion by phone contact allowed for non-dosing visits with further assessment at local clinic if needed. 
Pharmacokinetic: Blood 
Sample for Cell Kinetics 
None 
See Table 5 for detailed sample time points 
PGx 
None 
Xg 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reference Table 15: Alternative 
Schedule of Post-Treatment Period 
Assessments in Response to a Crisis 
 
Blood Sample for WT1 
Expression 
None 
Xa 
 
 
 
 
Xa 
 
 
 
 
Xa 
 
Xa 
 
Xk 
 
Blood Sample for 
Mutational Profiling 
None 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xk 
 
Blood Sample for Immune 
Response Biomarker 
(ELISpot) 
None 
Xa 
 
X 
X 
 
Xa 
 
X 
X 
 
Xa 
X 
Xa 
X 
Xk 
 
Buccal Swab for HLA 
Typing 
None 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood Sample for Immune 
Response Biomarker 
(Tetramer)  
None 
Xa 
 
 
X 
 
Xa 
 
 
X 
 
Xa 
X 
Xa 
X 
Xk 
 
Table continued on next page 

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Page 126 of 138 
Version 7.5 Incorporating Nonsubstantial Amendment 5 
Assessments 
Alternative 
Approach(es) 
Treatment Period 
EoTj 
Post-Treatment Period 
Survival 
Follow-up
Period 
 
Cycle 1 
Cycle 2 
Cycles 3 – 
4m 
Cycles 5 – 
6n 
Obs Period 1 
Obs Period 2 
Survival 
Follow-up
Visit Days
 
D1 
D2 
D8 
D15 
D22 
D1 
D2 
D8 
D15 
D22 
D1 D15 D1 D15 
Every 2 weeks 
for up to 12 
weeks or  
until 1 post-
treatment 
discontinuation 
criterion  
is met 
Every 4 weeks or 
until 1 post-
treatment 
discontinuation 
criterion is met 
Every 3 
months 
Window(days)
 
 
0 
± 1 
± 1 
± 1 
+ 3 
0 
± 1 
± 1 
± 1 
+ 3 
± 1 + 3 ± 1 
+7 
 
± 3 
Blood Sample for Immune 
Cell Phenotyping 
None 
Xa 
 
X 
X 
 
Xa 
 
X 
X 
 
Xa 
X 
Xa 
X 
Xk 
Reference Table 15: Alternative 
Schedule of Post-Treatment Period 
Assessments in Response to a Crisis 
 
Blood Sample for 
Cytokines 
None 
Xa 
X 
X 
X 
 
Xa 
X 
X 
X 
 
Xa 
X 
Xa 
X 
Xk 
 
Blood Sample for Anti-
HLA Antibody 
None 
Xa 
 
 
 
 
Xa 
 
 
 
 
Xa 
 
Xa 
 
X 
 
IRT Transaction Required 
None 
Xh 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
ASP7517 Dosing at the 
Clinic 
None 
Xi 
 
 
 
 
Xi 
 
 
 
 
Xi 
 
Xi 
 
 
 
Survival Follow-upl 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
AE: adverse event; CT: computed tomography; C: cycle; C1D1: cycle 1 day 1; CR: complete remission; D: day; ECG: electrocardiogram; ECHO: echocardiogram; ECOG: Eastern 
Cooperative Oncology Group; ELISpot: enzyme-linked immunospot; EoT: end-of-treatment; HLA: human leukocyte antigen; ICF: informed consent form; INR: international 
normalization ratio; IP: investigational product; IRT: interactive response technology; MUGA: multigated acquisition scan; PGx: pharmacogenomics; PI: principal investigator; PT: 
prothrombin time; SAE: serious adverse event; WOCBP: women of childbearing potential; WT1: Wilms’ tumor 1 protein. 
a. Obtained predose. 
b. Obtained predose and postdose (vital signs: hourly [± 10 minute window] for up to 4 hours postdose; ECG: 1 to 2 hours postdose) on day 1 of each cycle. 
c. Height measurement performed only at screening. Weight measurement should be performed at screening and day 1 of each cycle. 
d. The 12-lead ECGs will be recorded in triplicate (at least 2 minutes apart per time point) and transmitted electronically for central reading.  
e. Screening samples may be collected up to 28 days prior to C1D1. End of treatment bone marrow sample does not need to be repeated if collected within 2 weeks of the last  
disease assessment. Samples must be submitted to a central laboratory for analysis. If bone marrow aspirate is unobtainable (e.g., dry tap), an additional ethylenediaminetetraacetic 
acid tube of whole blood should be collected instead. Bone marrow aspirate is required, and bone marrow biopsy is preferred. In case of inadequate aspirate, bone marrow biopsy is 
required.  
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f. Samples must be submitted to a central laboratory for analysis. If a participant achieves CR at any point during the treatment period and ASP7517 is not continued, an EoT 
visit should be performed and the participant should proceed to observation period 1. 
g. Whole blood and buccal swab for optional PGx study may be collected at C1D1 prior to first investigational product administration. 
h. Subject enrollment in the study will be conducted via IRT transaction. 
i. After dosing of ASP7517, subjects must be observed for safety for a minimum 4 hours. The safety observation will consist of vital signs and AE observations. If new AEs are 
observed that are ≥ grade 3 during this time, subjects should continue to be observed at the investigator’s discretion.  
j. The EoT visit will occur within 7 days of the principal investigator decision to discontinue the subject for treatment or prior to the initiation of new anticancer treatment, 
whichever occurs first. If a subject is completing all visits in the last treatment cycle, the EoT visit will be within 7 days from the last planned visit. 
k. Assessment does not need to be repeated if collected at a regularly scheduled visit within 3 days of EoT visit. 
l. Telephone contact for survival status and subsequent anti-cancer treatments and outcomes. 
m. After the first 2 cycles of treatment, subjects who have not met any individual treatment discontinuation criteria and are receiving clinical benefit (defined as achieve CRc or PR for 
AML and CR, BM CR or PR or HI for MDS or other clinical benefits, as determined by the investigator) will continue further treatment of ASP7517 as decided by the investigator. 
n. After the first 4 cycles of treatment, subjects who achieve CR will not continue with ASP7517; subjects who do not reach CR, but also do not experience disease progression, may 
receive an additional 2 doses for a total of 6 doses. If a participant experiences CR during cycle 5 or 6 (except if confirmed on day 1 of these cycles), the participant can complete 
the cycle and EoT will be performed as defined in footnote “j”. 
o. Extramedullary disease assessment is required at screening, day 1 of every cycle starting with cycle 2, EoT, and observation visits. 
 

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Table 15 
Alternative Schedule of Post-Treatment Period Assessments in Response to a Crisis for Dose Escalation and Dose Expansion 
Assessments 
Alternate 
Approach(es) 
Post-Treatment Period 
Observation Period 1 
Observation Period 2 
12 weeks or until 1 post-treatment discontinuation criterion is 
met 
Until 1 post-treatment discontinuation criterion 
is met 
Visit Week 
 
2 
4 
6 
8 
10 
12 
Monthly Safety 
Assessment Visit 
Assessment Visit 
Every 3 months 
Window (days) 
 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Physical Examinationa 
Can be obtained at local 
facility and results 
submitted to PI 
X 
X 
X 
X 
X 
X 
X 
X 
Disease Assessment 
Except for IP 
administration days, 
assessment can be 
performed locally and 
results submitted to PI 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
Exams can be performed 
at a local clinic per SOC 
and results submitted to PI 
for evaluation 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG Performance 
Can be completed by 
phone contact 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medicationsi 
Can be completed by 
phone contact 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECGb 
Except for IP 
administration days, 
assessment may be 
performed, as possible, at 
a local clinic and results 
submitted to PI. If cannot 
be performed, Astellas 
medical monitor to assess 
for study continuation. 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Laboratory Tests 
(chemistry, hematology, 
coagulation, urinalysis)g 
Collection of samples at 
local facility acceptable if 
results can be made 
available to investigative 
site 
X 
X 
X 
X 
X 
X 
X 
X 
Table continued on next page 

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Assessments 
Alternate 
Approach(es) 
Post-Treatment Period 
Observation Period 1 
Observation Period 2 
12 weeks or until 1 post-treatment discontinuation criterion is 
met 
Until 1 post-treatment discontinuation criterion 
is met 
Visit Week 
 
2 
4 
6 
8 
10 
12 
Monthly Safety 
Assessment Visit 
Assessment Visit 
Every 3 months 
Window (days) 
 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Pregnancy Test for WOCBP 
Test may be performed at 
local clinical and result 
submitted to PI 
X 
X 
X 
X 
X 
X 
X 
X 
Bone Marrow Aspiration and/or 
Biopsyc 
Except for IP 
administration days, may 
be obtained locally and 
results submitted to PI 
 
 
 
 
 
Xh 
 
X 
Blood Sample for Disease 
Assessmentd 
Except for IP 
administration days, may 
be obtained locally and 
results submitted to PI 
 
X 
 
X 
 
 
 
X 
AE/SAE Assessment 
Completed by phone 
contact allowed with 
further assessment at local 
clinic if needed 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetic: Blood Sample 
for Cell Kinetics 
None 
See Table 5 for detailed sample time points  
Blood Sample for WT1 
Expression 
None 
 
X 
 
X 
 
Xj 
 
Xf 
Blood Sample for Immune 
Response Biomarker (ELISpot) 
None 
 
X 
 
X 
 
Xj 
 
Xe 
Blood Sample for Immune 
Response Biomarker (Tetramer)  
None 
 
X 
 
X 
 
Xj 
 
Xf 
Blood Sample for Immune Cell 
Phenotyping 
None 
 
X 
 
X 
 
Xj 
 
Xe 
Blood Sample for Cytokines 
None 
 
X 
 
X 
 
Xj 
 
Xe 
AE: adverse event; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; ELISpot: enzyme-linked immunospot; HLA: human leukocyte antigen; PI: principal 
investigator; SAE: serious adverse event; WOCBP: women of childbearing potential; WT1: Wilms’ tumor 1 protein. 
a. Height measurement performed only at screening. 
b. The 12-lead ECGs will be recorded as a single assessment (in triplicate if deemed necessary, at least 2 minutes apart per time point) and read locally.  
Footnotes continued on next page 

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c. After the completion of Observation Period 1 (12 weeks), subjects remaining in the study will have bone marrow samples collected in Observation Period 2 every 3 months or if 
there is suspicion of relapse in the whole blood. Samples must be submitted to a central laboratory for analysis. If bone marrow aspirate is unobtainable (e.g., dry tap), an additional 
ethylenediaminetetraacetic acid tube of whole blood should be collected instead. Bone marrow aspirate is required, and bone marrow biopsy is preferred. In case of inadequate 
aspirate, bone marrow biopsy is required. 
d. Samples must be submitted to a central laboratory for analysis. 
e. Maximum of 1 sample collected during Observation Period 2. 
f. Maximum of 5 samples collected during Observation Period 2. 
g. Laboratory samples will be analyzed by the institution’s local laboratory and results will be submitted for centralized data entry. Subjects who are transfusion dependent should be 
subjected to more frequent laboratory assessments to determine transfusion need based on the judgment of the investigator. 
h. Subjects not proceeding to observation period 2 are required to provide a bone marrow sample at the last visit of observation period 1. 
i. Concomitant medications and AEs are collected until post-treatment period and at least 30 days after last IP dose and prior to the start of new anticancer treatment. In addition, the 
following will be collected regardless of the start of new anticancer therapy: Any IP-related SAE that is ongoing will be followed until resolved, and any SAE that is deemed to be 
related to IP by the investigator. 
j. Applicable only for subjects in dose expansion phase. 
 

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Table 16 
Alternative Schedule of Assessments of Replication Competent Lentivirus for Dose Escalation and Dose Expansion in Response to 
a Crisis 
Assessment 
Alternate 
Approach(es) 
C1D1 
3 Months After 
Treatment Initiation or 
End of Treatment, 
Whichever is First 
6 Months After 
Treatment 
Initiation 
12 Months After Treatment 
Initiation 
18 Months After Treatment 
Initiationc 
Window 
0 
± 1 day 
± 1 month 
+1 month 
±1 month 
Blood Sample for RCLa 
None: to 
collect at the 
first time 
subject is able 
to come to the 
clinic 
Xb 
X 
X 
X 
X 
C1D1: cycle 1 day 1; RCL: replication competent lentivirus 
a. If there are positive results, additional follow-up assessments may be required. Refer to [Section 7.6.4 Sample for Replication Competent Lentivirus]. 
b. Obtained predose. 
c. Only applicable to subjects in the expansion cohort. 
 
 

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INVESTIGATIONAL PRODUCT SUPPLY 
If any of the conditions outlined above in the Subjects Procedures Assessment are met, one or 
all of the following mitigating strategies will be employed, as needed, to ensure continuity of 
IP supply to the subjects:  
● 
Increase stock of IP on site to reduce number of shipments required, if site space will 
allow. 
DATA COLLECTION REQUIREMENTS 
Additional data may be collected in order to indicate how participation in the study may have 
been affected by a crisis and to accommodate data collection resulting from alternate 
measures implemented to manage the conduct of the study and subject safety.  
● 
Critical assessments for safety and efficacy based on study endpoints to be identified as 
missing or altered (performed virtually, at alternative locations, out of window or other 
modifications) due to the crisis.  
 

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12.10 List of Abbreviations and Definition of Key Study Terms 
List of Abbreviations 
Abbreviations 
Description of Abbreviations 
aAVC 
artificial adjuvant vector cell 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
APGD 
Astellas Pharma Global Development Inc. 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
BCR-ABL 
breakpoint cluster region-Abelson-positive leukemia 
BM 
bone marrow 
BOIN 
Bayesian optimal interval 
BOP2 
Bayesian optimal phase 2 
C1D1 
cycle 1 day 1 
C2D1 
cycle 2 day 1 
CA 
competent authorities 
Cmax 
maximum concentration 
CR 
complete remission 
CRc 
composite complete remission 
CRh 
complete remission with partial hematologic recovery 
CRi 
complete remission with incomplete hematological recovery 
CRp 
complete remission with incomplete platelet recovery 
CRO 
contract research organization 
CRS 
cytokine-release syndrome 
CSR 
clinical study report 
CT 
computed tomography 
CTCAE 
common terminology criteria for adverse events 
Ctrough 
trough concentration; the lowest concentration reached by a drug before the 
next dose is administered 
CV 
coefficient of variation 
DESC 
dose escalation and safety committee 
DLT 
dose limiting toxicity 
DPD 
Data Protection Directive 
ECG 
electrocardiogram 

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Abbreviations 
Description of Abbreviations 
ECHO 
echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EEA 
European Economic Area 
EFS 
event-free survival 
EoT 
end-of-treatment 
FAS 
full analysis set 
FiH 
first in human 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practices 
HI 
hematologic improvement 
HIPAA 
Health Insurance Portability and Accountability Act 
HLA 
human leukocyte antigen 
HRT 
hormone replacement therapy 
HSCT 
hematopoietic stem cell transplant 
ICF 
informed consent form 
ICH  
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
INR 
international normalized ratio 
IP 
investigational product 
IPSS-R 
Revised International Prognostic Scoring System 
IRB 
Institutional Review Board 
IRR 
Infusion-related reactions 
IRT 
interactive response technology 
ISN 
international study number 
iv 
intravenous 
LA-CRF 
liver abnormality case report form 
LFT 
liver function test 
MDS 
myelodysplastic syndrome 
mRNA 
messenger RNA 
MTD 
maximum tolerated dose 
MUGA 
multigated acquisition scan 
NCI-CTCAE 
National Cancer Institute’s common terminology criteria for adverse events 
NE 
not evaluable 
NK 
natural killer 

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Abbreviations 
Description of Abbreviations 
NKT 
natural killer T 
NR 
no response 
ORR 
objective response rate 
OS 
overall survival 
PGx 
pharmacogenomics 
PKAS 
pharmacokinetic analysis set 
PR 
partial remission 
QA 
quality assurance 
QC 
quality control 
QTcF 
QT corrected by Fridericia's Correction formula 
R/R 
relapsed/refractory 
RBC 
red blood cell 
RCL 
replication competent lentivirus 
RP2D 
recommended phase 2 dose 
(S)AE 
serious adverse event or adverse event 
SAE 
serious adverse event 
SAF 
safety analysis set 
SAP 
statistical analysis plan 
SD 
stable disease 
SOP 
standard operating procedure 
SUSAR 
suspected unexpected serious adverse reactions 
TEAE 
treatment-emergent adverse event 
TBL 
total bilirubin 
tmax 
time of maximum concentration  
ULN 
upper limit of normal 
USM 
urgent safety measure 
WOCBP 
woman of childbearing potential 
WT1 
Wilms’ tumor 1protein 

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Definition of Key Study Terms 
Terms 
Definition of Terms 
Baseline  
Assessments of subjects as they enter a study before they receive any 
treatment.  
Endpoint  
Variable that pertains to the efficacy or safety evaluations of a study. 
Note: Not all endpoints are themselves assessments since certain endpoints 
might apply to populations or emerge from analysis of results. That is, 
endpoints might be facts about assessments (e.g., prolongation of survival). 
Enroll 
To register or enter a subject into a study. Note: Once a subject has received 
the investigational product or placebo, the protocol applies to the subject.  
Intervention 
The drug, device, therapy or process under investigation in a study that is 
believed to have an effect on outcomes of interest in a study (e.g., health-
related quality of life, efficacy, safety and pharmacoeconomics).  
Investigational 
period 
Period of time where major interests of protocol objectives are observed, and 
where the test product or comparative drug (sometimes without 
randomization) is given to a subject, and continues until the last assessment 
after completing administration of the test product or comparative drug. 
Post investigational 
period 
Period of time after the last assessment of the protocol. Follow-up 
observations for sustained adverse events and/or survival are done in this 
period. 
Randomization 
The process of assigning subjects to treatment or control groups using an 
element of chance to determine assignments in order to reduce bias. 
Note: Unequal randomization is used to allocate subjects into groups at a 
differential rate; for example, 3 subjects may be assigned to a treatment 
group for every one assigned to the control group. 
Screening 
A process of active consideration of potential subjects for enrollment in a 
study. 
Screen failure 
Potential subject who signed the informed consent form, but did not meet 1 
or more criteria required for participation in the study and was not enrolled. 
Screening period 
Period of time before entering the investigational period, usually from the 
time when a subject signs the consent form until just before the test product 
or comparative drug (sometimes without randomization) is given to a 
subject.  
Study period 
Period of time from the first study site initiation date to the last study site 
completing the study. 
Variable 
Any quantity that varies; any attribute, phenomenon or event that can have 
different qualitative or quantitative values. 
 

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13 
ATTACHMENT 1:  NONSUBSTANTIAL AMENDMENT 5 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Protocol 7517-CL-0101 A Phase 1/2 Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects with 
Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS)  
Amendment 5 Nonsubstantial 19 Sep 2022 
This amendment is considered to be nonsubstantial based on the criteria set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament 
and the Council of the European Union because it neither significantly impacts the safety or physical/mental integrity of participants nor the scientific 
value of the study. 
Overall Rationale for the Amendment: 
The overall rationale for this amendment is to update the protocol to adjust study timelines, provide clarification and correct errors. 
Summary of Changes 
Table 1 
Nonsubstantial Changes 
Section Number 
Description of Change 
Brief Rationale 
Clinical Research 
Contacts, 14 
Contact details for the clinical research contacts are 
updated. 
Contact details of sponsor personnel are updated based on 
changes to study personnel. 
1.1 
The approximate study end date is adjusted from 
4Q2022 to 4Q2024. 
To update timelines for this study. 
1.3 (Table 1) 
Cycle 2 blood sample for Anti-HLA Antibody moved 
from day 1 to day 15. 
Updated to correct an error. 
1.3 (Table 5) 
Several PK time point sampling windows changed 
from 15 to 10 minutes. 
To obtain accurate PK samples as defined in Table 5. 
12.2.2.4 
Replace QTL text in Quality Assurance section with 
bullet point from current template. 
To reflect the current protocol template version. QTL definitions 
and details will be managed in a separate plan. 

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14 
SPONSOR SIGNATURES 
Astellas Signatories 
(Electronic signatures are attached at the end of the document.) 
 
 
Medical Science 
 
 
Data Science 
 
PPD
PPD