Clinical trial NCT04837196
Conditions: Advanced Malignancies Advanced Cancer
Keywords: Solid Tumors ASP7517 WT1 Antigen
Sponsor: Astellas Pharma Global Development, Inc.
Start date: 2021-11-11; Completion date: 2024-06-21
Enrollment: 24 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The purpose of this study was to evaluate the safety, tolerability, and clinical response of ASP7517, and determine the Recommended Phase 2 Dose (RP2D) and/or the Maximum Tolerated Dose (MTD) of ASP7517 when administered as a single agent and in combination with pembrolizumab.

This study also evaluated other measures of anticancer activity of ASP7517 when administered as a single agent and in combination with pembrolizumab based on central and local assessment.

Detailed description:
This study consisted of arms receiving ASP7517 monotherapy and arms receiving ASP7517 and pembrolizumab combination therapy in Phase 1 (dose escalation cohort) and Phase 2 (dose expansion cohort). Phase 2 monotherapy and combination dose expansion cohorts were opened after the phase 1 escalation cohort was completed.

Arms: arm 1: Participants received one dose of ASP7517 1x10\^7 cells/dose for up to 6 doses (168 days) by intravenous (IV) infusion (4 to 6 mL/minute) on Day 1 of each cycle (1 Cycle=28 days). Following first 2 cycles, participants not meeting treatment discontinuation criteria and receiving clinical benefit (defined:radiological response/SD/reduction of disease-related symptoms) continued treatment with ASP7517. After 4 cycles of treatment, participants achieving confirmed CR discontinued ASP7517, and participants who achieved PR or SD received an additional 2 doses. Participants entered an Observation Period except those with iCPD, iUPD and those not clinically stable or clinical progression was confirmed by investigator and followed up to 48 weeks until iCPD per independent central review, initiation of new anticancer therapy or meeting 1 of Observation Period discontinuation criteria, whichever occurred first. After EOT visit, participants completed Safety follow-up visits 30, 60 and 90 days. arm 2: Participants received one dose of ASP7517 1x10\^8 cells/dose by IV infusion (4 to 6 mL/minute) on Day 1 of each cycle (1 Cycle=28 days). Following first 2 cycles, participants not meeting treatment discontinuation criteria and receiving clinical benefit (defined as radiological response/ SD, or reduction of disease-related symptoms) continued treatment with ASP7517. After 4 cycles of treatment, participants achieving confirmed CR discontinued ASP7517, and any participants who achieved PR or SD received an additional 2 doses. Participants entered an Observation Period except those with iCPD, iUPD and those not clinically stable or clinical progression was confirmed by the investigator and followed for up to 48 weeks until iCPD per independent central review, initiation of a new anticancer therapy or meeting 1 of the Observation Period discontinuation criteria, whichever occurred first. After EOT visit, participants completed Safety follow-up visits 30, 60 and 90 days arm 3: Participants received ASP7517 1x10\^8 cells/dose by IV infusion (4 to 6 mL/minute) on Day 1 of each cycle (1 Cycle=28 days).Following the first 2 cycles, participants not meeting discontinuation criteria and were receiving clinical benefit (defined as radiological response/SD, or reduction of disease-related symptoms) continued treatment with ASP7517. After 4 cycles of treatment, participants achieving confirmed CR discontinued ASP7517, and any participants who achieved PR or SD received an additional 2 doses. Participants entered an Observation Period except those with iCPD, iUPD and who were not clinically stable or clinical progression was confirmed by the investigator and followed up to 48 weeks until iCPD per independent central review, initiation of a new anticancer therapy or meeting 1 of the Observation Period discontinuation criteria, whichever occurred first. After the EOT visit, participants completed the Safety follow-up visits 30, 60 and 90 days. arm 4: Participants received ASP7517 1x10\^7 cells/dose for up to 6 doses (168 days) on Day 1 of each cycle by IV infusion (4-6 mL/min) (1 Cycle = 28 days) with 400 mg pembrolizumab infusion (over 30 min) for up to 4 doses every 6 weeks. After 2 cycles, those not meeting discontinuation criteria and receiving clinical benefit continued ASP7517 and pembrolizumab. Participants with confirmed CR within 4 cycles did not receive ASP7517 at cycles 5-6; those with PR/SD after 4 doses received 2 more ASP7517 doses with pembrolizumab. After Treatment Period, all except those with iCPD, iUPD, or clinical progression entered Observation Period and continued pembrolizumab alone (up to 17 doses) to monitor response up to 96 weeks until iCPD, new therapy, or discontinuation criteria. After EOT visit, participants completed Safety follow-up at 30, 60, and 90 days. arm 5: Participants received ASP7517 1x10\^8 cells/dose for up to 6 doses (168 days) on Day 1 of each cycle by IV infusion (4-6 mL/min) (1 Cycle = 28 days) with 400 mg pembrolizumab infusion (over 30 min) for up to 4 doses every 6 weeks. After 2 cycles, those not meeting discontinuation criteria and receiving clinical benefit continued ASP7517 and pembrolizumab. Participants with confirmed CR within 4 cycles did not receive ASP7517 at cycles 5-6; those with PR/SD after 4 doses received 2 more ASP7517 doses with pembrolizumab. After Treatment Period, all except those with iCPD, iUPD, or clinical progression entered Observation Period and continued pembrolizumab alone (up to 17 doses) to monitor response up to 96 weeks until iCPD, new therapy, or discontinuation criteria. After EOT visit, participants completed Safety follow-up at 30, 60, and 90 days.
Interventions: intervention 1: ASP7517 intervention 2: Pembrolizumab
Intervention descriptions: intervention 1: Intravenous (IV) intervention 2: Intravenous (IV)

Protocol documents:
Prot_000.pdf: 
Sponsor: APGD 
ISN/Protocol 7517-CL-1101 
CONFIDENTIAL - 
Clinical Study Protocol 
10 Feb 2022 
Astellas 
Page 1 of 155 
Version 7.0 Incorporating Substantial Amendment 6 
A Phase 1/2, Open-label Study Investigating the Safety, 
Tolerability and Efficacy of ASP7517 as a Single Agent and in 
Combination with Pembrolizumab in Patients with Advanced 
Solid Tumors Known to Express WT1 Antigen 
 
ISN/Protocol 7517-CL-1101 
Version 7.0 
Incorporating Substantial Amendment 6 
10 Feb 2022 
 
 
IND 025239 
IND Grantor:  CBER 
 
Sponsor: 
Astellas Pharma Global Development Inc. 
1 Astellas Way 
Northbrook, IL 60062, US 
 
 
Protocol History: 
Version 1.0 [01 Sep 2020] 
Version 2.0 [04 Dec 2020] Incorporating Substantial Amendment 1 
Version 3.0 [02 Mar 2021] Incorporating Substantial Amendment 2  
Version 4.0 [11 May 2021] Incorporating Nonsubstantial Amendment 3 
Version 5.0 [23 Jun 2021] Incorporating Substantial Amendment 4 
Version 6.0 [28 Oct 2021] Incorporating Nonsubstantial Amendment 5 
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 participant; 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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Table of Contents 
SIGNATURES ································································································ 9 
CONTACT DETAILS OF SPONSOR’S KEY PERSONNEL ····································· 11 
1 
PROTOCOL SUMMARY ······································································· 12 
1.1 
Synopsis ························································································ 12 
1.2 
Study Schema ·················································································· 21 
1.3 
Schedules of Assessments ···································································· 25 
2 
INTRODUCTION ················································································· 40 
2.1 
Study Rationale ················································································ 40 
2.2 
Background ···················································································· 40 
2.2.1 
Melanoma ················································································ 41 
2.2.2 
Colorectal Cancer ······································································· 41 
2.2.3 
Ovarian Cancer ·········································································· 41 
2.3 
Risk/Benefit Assessment ····································································· 42 
2.3.1 
ASP7517 Risk Assessment ····························································· 42 
2.3.1.1 
Liver ················································································· 43 
2.3.1.2 
Hematology ········································································· 43 
2.3.1.3 
Pancreas ············································································· 44 
2.3.1.4 
Kidney ·············································································· 44 
2.3.1.5 
Spleen ··············································································· 44 
2.3.1.6 
Infusion-related Reactions ························································ 44 
2.3.1.7 
Allergic Reactions and Anaphylaxis ············································ 45 
2.3.1.8 
Other ················································································ 45 
2.3.1.9 
Pembrolizumab Risk Assessment ················································ 45 
2.3.2 
Risk Mitigation ·········································································· 46 
2.3.3 
Benefit Assessment ····································································· 47 
2.3.4 
Overall Risk-Benefit Conclusion ······················································ 47 
3 
OBJECTIVES, ENDPOINTS ··································································· 48 
4 
STUDY DESIGN AND DOSE RATIONALE ················································ 49 
4.1 
Overall Study Design ········································································· 49 
4.1.1 
Study Periods ············································································ 49 
4.1.2 
ASP7517 Monotherapy Arm in Dose Escalation Phase 1 Cohort ················· 50 
4.1.3 
ASP7517 and Pembrolizumab Combination Therapy Arm in Dose 
Escalation Phase 1 Cohort ······························································ 51 


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4.1.4 
Dose Limiting Toxicity Criteria ······················································· 52 
4.1.4.1 
ASP7517 Monotherapy Arm DLTs ············································· 52 
4.1.4.2 
ASP7517 and Pembrolizumab Combination Therapy Arm DLTs ··········· 52 
4.1.5 
Phase 1 Dose Escalation ································································ 54 
4.1.5.1 
Safety Requirement for Monotherapy and Combination Therapy Dose 
Escalation ··········································································· 54 
4.1.5.2 
Phase 1 Dose Escalation Cohort for Monotherapy and Combination 
Therapy Arms ······································································ 54 
4.1.6 
Phase 2 Dose Expansion Cohort ······················································· 56 
4.1.6.1 
Monotherapy Arm Dose Expansion Cohort ···································· 56 
4.1.6.2 
Combination Therapy Arm Dose Expansion Cohort ·························· 57 
4.2 
Scientific Rationale for Study Design ······················································ 58 
4.3 
Dose Rationale ················································································ 59 
4.3.1 
ASP7517·················································································· 59 
4.3.2 
Pembrolizumab ·········································································· 60 
4.4 
End of Study Definition ······································································ 60 
5 
STUDY POPULATION ·········································································· 61 
5.1 
Inclusion Criteria ·············································································· 61 
5.2 
Exclusion Criteria ············································································· 63 
5.3 
Lifestyle Considerations ······································································ 65 
5.4 
Screen Failures ················································································ 65 
5.4.1 
Rescreening ·············································································· 65 
6 
INVESTIGATIONAL PRODUCT(S) AND OTHER STUDY TREATMENT(S) ···· 66 
6.1 
Investigational Product(s) and Other Study Treatments Administered ················· 66 
6.1.1 
Investigational Product Administration ··············································· 66 
6.2 
Preparation/Handling/Storage/Accountability ············································· 66 
6.2.1 
Packaging and Labeling ································································ 66 
6.2.2 
Handling, Storage and Accountability ················································ 67 
6.3 
Randomization ················································································· 67 
6.3.1 
Assignment and Allocation····························································· 67 
6.4 
Investigational Product and Other Study Treatment Compliance ······················· 68 
6.5 
Dose Modification ············································································ 68 
6.6 
Continued Access to Investigational Product After the End of the Study ·············· 68 
6.7 
Treatment of Overdose ······································································· 69 


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6.8 
Concomitant Therapy ········································································· 69 
7 
STUDY PROCEDURES AND ASSESSMENTS ············································ 70 
7.1 
Efficacy Assessments ········································································· 70 
7.2 
Safety Assessments ··········································································· 71 
7.2.1 
Laboratory Assessments ································································ 71 
7.2.2 
Vital Signs ················································································ 71 
7.2.3 
Physical Examination ··································································· 72 
7.2.4 
Electrocardiogram ······································································· 72 
7.2.5 
Imaging ··················································································· 73 
7.2.6 
ECOG Performance Status ····························································· 73 
7.2.7 
Order of Assessments ··································································· 73 
7.3 
Adverse Events and Other Safety Aspects ················································· 73 
7.3.1 
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information····························································· 74 
7.3.2 
Method of Detecting Adverse Events and Serious Adverse Events ··············· 74 
7.3.3 
Follow-up of Adverse Events and Serious Adverse Events ························ 74 
7.3.4 
Regulatory Reporting Requirements for Serious Adverse Events ················· 75 
7.3.5 
Disease-related Events and/or Disease-related Outcomes Not Qualifying as 
Adverse Events or Serious Adverse Events ·········································· 75 
7.3.6 
Adverse Events of Special Interest ···················································· 76 
7.3.7 
Special Situations ········································································ 76 
7.4 
Pharmacokinetics ·············································································· 76 
7.5 
Pharmacodynamics ··········································································· 77 
7.5.1 
Blood Samples ··········································································· 77 
7.5.2 
Tumor Tissue Samples ·································································· 77 
7.5.3 
Buccal Swab Samples ··································································· 78 
7.6 
Pharmacogenomics ··········································································· 78 
7.7 
Other Assessments ············································································ 78 
7.7.1 
Replication Competent Lentivirus ····················································· 78 
7.8 
Total Amount of Blood ······································································· 78 
8 
PARTICIPANT DISCONTINUATION ······················································ 80 
8.1 
Discontinuation of Individual Participant(s) from Study Treatment ···················· 80 
8.2 
Discontinuation of Individual Participant(s) from Study ································· 81 
8.3 
Lost to Follow-up ············································································· 81 


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9 
STATISTICAL CONSIDERATIONS ························································· 81 
9.1 
Statistical Hypotheses ········································································ 81 
9.2 
Sample Size Determination ·································································· 82 
9.3 
Populations for Analyses ····································································· 83 
9.4 
Statistical Analyses ··········································································· 83 
9.4.1 
General Considerations ································································· 83 
9.4.2 
Analysis of Efficacy ····································································· 84 
9.4.2.1 
Analysis of Primary Endpoint ···················································· 84 
9.4.2.2 
Sensitivity Analysis ······························································· 84 
9.4.2.3 
Analysis of Secondary Endpoints ················································ 84 
9.4.3 
Analysis of Safety ······································································· 85 
9.4.3.1 
Adverse Events····································································· 86 
9.4.3.2 
Laboratory Assessments ·························································· 86 
9.4.3.3 
Vital Signs ·········································································· 86 
9.4.3.4 
Electrocardiogram ································································· 86 
9.4.3.5 
Eastern Cooperative Oncology Group Performance Status ··················· 86 
9.4.3.6 
Concentration-response Relationship Analysis ································ 87 
9.4.4 
Analysis of Pharmacokinetics ·························································· 87 
9.4.5 
Analysis of Pharmacodynamics Activities ··········································· 87 
9.4.5.1 
Analysis of Exploratory Biomarker(s) ·········································· 87 
9.5 
Interim Analysis ··············································································· 87 
9.6 
Additional Conventions ······································································ 88 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ············································································· 89 
10.1 
Appendix 1: Ethical, Regulatory and Study Oversight Considerations ················· 89 
10.1.1 
Regulatory and Ethical Considerations ··············································· 89 
10.1.2 
Financial Disclosure ···································································· 89 
10.1.3 
Informed Consent of Participants······················································ 89 
10.1.3.1 
Informed Consent Process ························································ 89 
10.1.3.2 
Supply of New and Important Information Influencing the 
Participant’s Consent and Revision of the Written Information ············· 90 
10.1.4 
Data Protection ·········································································· 90 
10.1.5 
Committee(s) Structure ································································· 91 
10.1.5.1 
Dose Escalation and Safety Committee ········································· 91 
10.1.6 
Dissemination of Clinical Study Data················································· 91 


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10.1.7 
Data Quality Assurance ································································· 91 
10.1.8 
Source Documents ······································································ 92 
10.1.9 
Study and Site Start and Closure ······················································ 93 
10.1.10 
Arrangement for Use of Information and Publication of the Study ··············· 94 
10.1.11 
Insurance of Participants and Others (UNIQUE to Japan) ························· 94 
10.1.12 
Quality Assurance ······································································· 95 
10.2 
Appendix 2: Contraception Requirements ················································· 97 
10.3 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up and Reporting ······················································ 99 
10.3.1 
Definition of Adverse Events ·························································· 99 
10.3.1.1 
Abnormal Laboratory Findings ················································ 100 
10.3.1.2 
Potential Cases of Drug-induced Liver Injury ································ 100 
10.3.2 
Definition of Serious Adverse Events··············································· 100 
10.3.3 
Assessment of Causality ······························································ 101 
10.3.4 
Assessment of Severity ······························································· 103 
10.3.5 
Recording and Follow-up of AEs and/or SAEs ···································· 103 
10.3.6 
Reporting Procedures for Serious Adverse Events ································ 104 
10.3.7 
Reporting Procedures for Special Situations ······································· 106 
10.3.7.1 
Contraceptive Guidance and Collection of Pregnancy Information ······· 106 
10.3.7.2 
Medication Error, Overdose and “Off-label Use” ··························· 106 
10.3.7.3 
Misuse/Abuse ···································································· 107 
10.3.7.4 
Occupational Exposure ························································· 107 
10.3.7.5 
(Suspicion of) Transmission of Infectious Agent ···························· 107 
10.3.7.6 
Suspected Drug-drug Interaction ·············································· 107 
10.3.7.7 
Reporting Procedures for Product Defect ····································· 107 
10.3.8 
Supply of New Information Affecting the Conduct of the Study ················ 108 
10.3.8.1 
Collection of Defect Information in Stage of Manufacture, Delivery 
and Storage ······································································· 108 
10.3.9 
Urgent Safety Measures ······························································ 109 
10.3.10 
Reporting Urgent Safety Measures ·················································· 109 
10.4 
Appendix 4: Liver Safety Monitoring and Assessment ································· 110 
10.5 
Appendix 5: List of Excluded Concomitant Medications ······························ 113 
10.5.1 
Concomitant Medications ···························································· 113 
10.5.2 
Other Investigational Agents ························································· 113 
10.6 
Appendix 6: Clinical Laboratory Assessments ·········································· 114 


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10.7 
Appendix 7: Pharmacogenomic Analysis With Banked Sample ······················ 116 
10.8 
Appendix 8:  Infusion Reaction Dose Modification and Treatment (Guidelines 
for ASP7517 and Pembrolizumab) ························································ 118 
10.9 
Appendix 9:  Monitoring of Pembrolizumab Potential Immune-related Adverse 
Events························································································· 120 
10.10 
Appendix 10: Dose Modification and Toxicity Management for Immune-related 
AEs ··························································································· 121 
10.11 
Appendix 11: Dose Modification and Toxicity Management of Infusion 
Reactions Related to Pembrolizumab ····················································· 125 
10.12 
Appendix 12: Clinical Study Continuity ················································· 127 
10.13 
List of Abbreviations and Definition of Key Study Terms ····························· 146 
11 
REFERENCES ·················································································· 150 
12 
ATTACHMENT 1: PROTOCOL AMENDMENT SUMMARY OF CHANGES ·· 153 
Summary of Changes ·················································································· 153 
13 
SPONSOR SIGNATURE ······································································ 155 
 
List of In-text Tables  
Table 1 
Schedule of Assessments – Dose Escalation Cohort ······································ 25 
Table 2 
Schedule of Assessments for Dose Expansion Cohort ···································· 29 
Table 3 
Schedule of Assessments for Safety Follow-up, Observation Period and 
Survival Follow-up Period for Participants who End the Treatment Early or 
Completed the Treatment Period ···························································· 33 
Table 4 
Schedule of Assessments for Observation Period, Safety Follow-up and 
Survival Follow-up for Participants who Receive Pembrolizumab Monotherapy 
in the Observation Period ···································································· 35 
Table 5 
Schedule of Replication Competent Lentivirus for Dose Escalation Cohort and 
Dose Expansion Cohort ······································································ 37 
Table 6 
Sample Collection Schedule-Dose Escalation Cohort and Dose Expansion 
Cohort ·························································································· 38 
Table 7 
Potential Safety Concerns of ASP7517 based on Preclinical Studies ··················· 43 
Table 8 
Study Objectives and Endpoints ····························································· 48 
Table 9 
Investigational Product(s) ···································································· 66 
Table 10 
ECOG Performance Status ··································································· 73 
Table 11 
Quality Tolerance Limits ····································································· 95 
Table 12 
Grading Scale Defining the Severity of an Adverse Event ····························· 103 
Table 13 
Moderate and Severe Liver Abnormalities ··············································· 110 
Table 14 
Clinical Laboratory Tests ·································································· 114 


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Table 15 
Infusion Reaction Dose Modification and Treatment (Guidelines for ASP7517 
and Pembrolizumab) ········································································ 118 
Table 16 
Monitoring of Pembrolizumab Potential Immune-related Adverse Events ·········· 120 
Table 17 
Dose Modification and Toxicity Management Guidelines for Immune-related 
Adverse Events Associated with Pembrolizumab ······································· 121 
Table 18 
Pembrolizumab Infusion Reaction Dose Modification and Treatment Guidelines ·· 125 
Table 19 
Study Interruption: Schedule of Assessments – Dose Escalation Cohort ············ 129 
Table 20 
Study Interruption: Schedule of Assessments for Dose Expansion Cohort ·········· 134 
Table 21 
Study Interruption: Schedule of Assessments for Safety Follow-up, Observation 
Period and Survival Follow-up Period for Participants who End the Treatment 
Early or Completed the Treatment Period ················································ 139 
Table 22 
Study Interruption: Schedule of Assessments for Observation Period, Safety 
Follow-up and Survival Follow-up for Participants who Receive 
Pembrolizumab Monotherapy in the Observation Period ······························ 141 
Table 23 
Study Interruption: Schedule of Replication Competent Lentivirus for Dose 
Escalation Cohort and Dose Expansion Cohort ········································· 144 
 
List of In-text Figures 
Figure 1 
Monotherapy: ASP7517 ······································································ 21 
Figure 2 
Combination Therapy:  ASP7517 + Pembrolizumab ····································· 22 
Figure 3 
ASP7517 Monotherapy Arm ································································ 23 
Figure 4 
Combination Therapy ASP7517 + Pembrolizumab Arm ································ 24 
 


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SIGNATURES 
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.” 
1.  SPONSOR’S SIGNATURES 
Required signatures (e.g., protocol authors and contributors, etc.) are located in [Section 13 
Sponsor’s Signatures].  
 


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2.  INVESTIGATOR’S SIGNATURE 
A Phase 1/2, Open-label Study Investigating the Safety, Tolerability and Efficacy 
of ASP7517 as a Single Agent and in Combination with Pembrolizumab in 
Patients with Advanced Solid Tumors Known to Express WT1 Antigen 
ISN/Protocol 7517-CL-1101 
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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 of 
trial site: 
 
 
 
 
 
 
 
 
 




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1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Title of Study:   
A Phase 1/2, Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP7517 as a 
Single Agent and in Combination with Pembrolizumab in Patients with Advanced Solid Tumors 
Known to Express WT1 Antigen 
Planned Study Period/Duration:  
From approximately 2Q2021 to 4Q2024 
Planned Total Number of Study Sites and Location(s):   
Approximately 30 sites in Japan and US 
Study Objectives and Endpoints:  
Objectives 
Endpoints 
Primary 
● 
To evaluate the safety and tolerability of 
ASP7517 when administered as a single agent 
and in combination with pembrolizumab 
● 
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 when administered as a single agent 
and in combination with pembrolizumab 
(phase 1) 
● 
DLTs 
● 
To evaluate the clinical response of ASP7517 
when administered as a single agent and in 
combination with pembrolizumab (phase 2) 
● 
Objective response rate per iRECIST (iORR) 
by independent central review 
Secondary 
● 
To evaluate other measures of anticancer 
activity of ASP7517 when administered as a 
single agent and in combination with 
pembrolizumab based on central and local 
assessment 
● 
Objective response rate per RECIST v1.1 
(ORR) 
● 
Disease control rate per iRECIST (iDCR) and 
RECIST v1.1 (DCR) 
● 
Progression-free survival per iRECIST (iPFS) 
and RECIST v1.1 (PFS) 
● 
Overall survival (OS) 
● 
Duration of response per iRECIST (iDOR) 
and RECIST v1.1 (DOR) 
Table continued on next page 
 


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Exploratory 
● 
To evaluate potential genomic, proteomic 
and/or other biomarkers that may correlate 
with treatment outcome when ASP7517 
administered as a single agent and in 
combination with pembrolizumab 
● 
Exploratory tumor and peripheral biomarkers 
that may correlate with treatment outcome of 
ASP7517 monotherapy or in combination 
with pembrolizumab 
● 
To evaluate pharmacodynamic activities of 
ASP7517 as a single agent and in combination 
with pembrolizumab 
● 
Pharmacodynamic effects of ASP7517 as a 
monotherapy or in combination with 
pembrolizumab, such as changes in: 
o Cytokine expression and secretion 
(e.g., IFNγ) 
o WT1-specific T lymphocytes 
(e.g., cytotoxic T lymphocytes) 
o Immune cell populations (NKT cells, 
NK cells, etc.)  
o Anti-WT1 antibodies 
o Tumor microenvironment 
● 
To characterize the pharmacokinetic profile of 
ASP7517 when administered as a 
monotherapy and in combination with 
pembrolizumab 
● 
Cellular DNA load and kinetic parameter 
estimates (including AUC, Cmax, Ctrough and 
tmax) for ASP7517 as a monotherapy or in 
combination with pembrolizumab 
AE: adverse event; DLT: dose limiting toxicity; ECG: electrocardiogram; ECOG: Eastern Cooperative 
Oncology Group; IFNγ: interferon gamma; iRECIST: immune response evaluation criteria in solid tumors; 
MTD: maximum tolerated dose; NK: natural killer; NKT: natural killer T; RECIST: response evaluation 
criteria in solid tumors; RP2D: recommended phase 2 dose; SAE: serious adverse event; WT1: Wilms’ tumor 
protein 1. 
Study Population:   
Participants with locally progressive (unresectable) or metastatic solid tumor malignancies known 
to express Wilms’ tumor protein 1 (WT1) antigen (including but not limited to melanoma, ovarian 
cancer and colorectal cancer [CRC] who have received all standard therapies except checkpoint 
inhibitor [CPI]-naïve melanoma in phase 2). 
Number of Participants:  
Approximately 385 participants may be enrolled. 
Phase 1 (Dose Escalation Cohort):  Approximately 24 participants may be enrolled in the escalation 
cohorts (approximately 12 participants for monotherapy and 12 participants for combination 
therapy).  
Phase 2 (Dose Expansion Cohort):  The total number of participants in the expansion cohorts will 
depend on the observed antitumor activity. It is estimated that approximately 361 participants may 
be enrolled in the monotherapy and combination therapy arms (approximately 129 participants for 
monotherapy and 232 participants for combination therapy). 
Study Design Overview:   
This study is a phase 1/2, open-label study of ASP7517 as monotherapy and in combination with 
pembrolizumab in selected participants with advanced solid tumors known to express WT1 
antigen.  


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This study consists of arms receiving ASP7517 monotherapy and arms receiving ASP7517 and 
pembrolizumab combination therapy in phase 1 (dose escalation cohort) and phase 2 (dose 
expansion cohort). Phase 2 monotherapy and combination dose expansion cohorts will be opened 
after the phase 1 dose escalation has been completed for the monotherapy and the combination 
therapy, independently. 
In this study, 28 days will define each cycle during Cycles 1 to 6. 
Additional cohort may be added by a protocol amendment to further evaluate ASP7517 as a single 
agent and/or in combination with another anti-cancer agent. 
ASP7517 Monotherapy Arm  
This arm will consist of Screening (up to 28 days); Treatment (up to 6 doses); End of Treatment 
(EOT) visit; Safety follow-up (30, 60 and 90 days); Observation Period (up to 48 weeks); and 
Survival follow-up (up to 12 months). 
Participants will receive 1 dose of ASP7517 on Day 1 of each 28-day cycle for up to 6 doses. 
Following the first 2 cycles, participants who have not met any individual treatment discontinuation 
criteria and are receiving clinical benefit (defined as radiological response or stable disease [SD], 
or reduction of disease-related symptoms) will continue further treatment with ASP7517, as 
decided by the investigator. 
After completing 4 cycles of treatment, participants who achieve confirmed complete response 
(CR) will not continue with ASP7517, and participants who achieve partial response (PR) or SD 
may receive an additional 2 doses. An EOT visit will be conducted for all participants within 
7 days of EOT determination or prior to the initiation of new anticancer therapy, whichever occurs 
first. After the EOT visit, participants will complete 30-day, 60-day and 90-day safety follow-up 
visits.  
All participants will enter an observation period except those with confirmed disease progression 
by immune response evaluation criteria in solid tumors (iRECIST) (iCPD), unconfirmed disease 
progression disease based on iRECIST (iUPD) (per independent central review or local review) 
and who are not clinically stable or clinical progression is confirmed by the investigator. 
Participants in the Observation Period will be followed for up to 48 weeks until iCPD per 
independent central review, initiation of a new anticancer therapy or meeting one of the 
Observation Period discontinuation criteria, whichever occurs first. 
All participants will be followed for the survival period. Survival follow-up will be assessed by 
telephone calls every 3 months for up to 12 months. 
ASP7517 and Pembrolizumab Combination Therapy Arm  
This arm will consist of Screening (up to 28 days); Treatment period (up to 6 doses of ASP7517 in 
combination with up to 4 doses of pembrolizumab); Observation Period (up to 96 weeks); EOT 
visit; 30-day, 60-day and 90-day Safety follow-up; and Survival follow-up (up to 12 months). 
Pembrolizumab monotherapy may be extended up to a total of 17 doses for qualifying participants. 
In the combination treatment arm, ASP7517 will be given on Day 1 of each 28-day cycle for up to 
6 doses in combination with pembrolizumab for up to 4 doses administered every 6 weeks, starting 
from Day 1 of Cycle 1. Following the first 2 cycles, participants who have not met any individual 
treatment discontinuation criteria and are receiving clinical benefit (defined as radiological 
response or SD, or reduction of disease-related symptoms) will continue further treatment with 
ASP7517 and pembrolizumab as decided by the investigator. 
Participants who achieve confirmed CR within the first 4 cycles will not receive further treatment 
with ASP7517 at Cycle 5 and Cycle 6 (end of Treatment period) and participants who achieve PR 
or SD after 4 doses may receive additional 2 doses of ASP7517 in combination with 
pembrolizumab.  


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Participants completing the Treatment period who enter the Observation Period with CR, PR or SD 
are allowed to continue on pembrolizumab alone up to a total of 17 doses for those participants 
who, in the opinion of the investigator, are continuing to derive clinical benefit. 
Subsequent to the Treatment period, all participants, except those with iCPD, iUPD who are not 
clinically stable or have clinical disease progression per independent central review or local review, 
will enter the Observation Period to monitor treatment response. Participants in the Observation 
Period will be followed for up to 96 weeks until iCPD (confirmed by independent central review or 
local review), initiation of a new anticancer therapy or meeting 1 of the Observation Period 
discontinuation criteria, whichever occurs first. After discontinuation of investigational product 
(IP), all participants will complete an EOT visit, along with 30-, 60- and 90-day safety follow-up 
visits from the last dose of IP or prior to the initiation of new anticancer treatment.  
All participants will be followed for survival, subsequent anticancer treatments and treatment 
outcomes following the conclusion of the Observation Period. Survival follow-up will be assessed 
by telephone calls every 3 months for up to 12 months. 
Phase 1 Dose Escalation   
Both the monotherapy and combination arms will evaluate escalating doses of ASP7517 in 
approximately 9 to 12 participants evaluable for dose limiting toxicities (DLTs). In the combination 
therapy arm, a fixed dose of 400 mg pembrolizumab will be evaluated in combination with 
ASP7517. The starting dose level of ASP7517 is 1 x 107 cells/dose. The dose of ASP7517 may be 
escalated to 1 x 108 cells/dose or de-escalated to 1 x 106 cells/dose based on the assessment of 
safety variables, including the occurrence of DLTs. 
Dose escalation will be guided according the Bayesian optimal interval (BOIN) design [Liu & 
Yuan, 2015] to determine the next dose level based on DLT occurrence.  
Study enrollment and study treatment will be temporarily interrupted during dose escalation of 
monotherapy or combination therapy arms pending review of the following: 
● 
Any death that is not related to disease progression occurring within 30 days of receiving IP 
● 
Occurrence of 2 grade ≥ 4 DLTs in 2 study participants 
● 
Any grade 4 hypersensitivity reaction/anaphylaxis 
In the Monotherapy Arm Dose Escalation Cohort, the starting dose level is 1 × 107 cells/dose and 
the decision to escalate to the next dose levels (1 × 108 cells/dose) will be made based on the 
assessment of safety variables, including the occurrence of DLTs. Dose level may be de-escalated 
to a lower dose level (1 × 106 cells/dose) based on the occurrence of DLTs.   
The initial dose escalation cohort of ASP7517 in combination with pembrolizumab will use a dose 
of ASP7517 1 × 107 cells/dose. In the combination treatment arm, a 400 mg pembrolizumab 
infusion will be administered first, followed by an ASP7517 infusion at least 1 hour after the 
completion of the pembrolizumab infusion.  
The decision to escalate to the next dose level (1 × 108 cells/dose) will be made based on the 
assessment of safety variables, including the occurrence of DLTs. A dose level of ASP7517 may be 
de-escalated to a lower dose level (1 × 106 cells/dose) based on the occurrence of DLTs. 


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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 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 maximum tolerated dose (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. In addition, 
MTD will be determined by BOIN from at least 6 participants. The dose for phase 2 expansion will 
not be higher than the MTD. 
Participant Replacement during Dose Escalation Cohort 
Participants may be replaced in the dose escalation cohort if: 
● Participant is discovered to have enrolled without fully satisfying eligibility criteria 
● Participant received less than the planned dose in Cycle 1 for reasons other than DLT 
● Participant has no DLT and withdraws from the study before the end of DLT evaluation 
period 
The decision regarding replacement of individual participants will be made by the sponsor with 
discussions with the treating investigator. Participants who experience DLTs in the dose escalation 
cohort will not be replaced. 
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 Participants Treated at 
Current Dose Level 
3 
4 
5 
6 
7 
8 
Escalate dose if number of participants with DLT ≤ 
0 
0 
1 
1 
1 
1 
Stay at current dose level if number of participants with DLT = 
1 
1 
- 
2 
2 
2 
De-escalate if number of participants with  
DLT = 
2 
2 
2 or 3 
3 
3 or 4 
3 or 4 
Stop if number of participants with DLT ≥ 
3 
3 
4 
4 
5 
5 
DLT: dose limiting toxicity 
Dose escalation within individual participants will not be allowed. 
Maximum Tolerated Dose 
The MTD determination will be based on at least 6 evaluable participants 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 for monotherapy and combination therapy. 
The dose level determined to be the MTD must have data from at least 6 participants. 
Determination of MTD will be done for monotherapy and combination therapy separately. 


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Recommended Phase 2 Dose 
The sponsor, in conjunction with the DESC, will determine the RP2D of ASP7517 as a single 
agent and in combination with pembrolizumab 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 participants. 
Determination of RP2D will be done for monotherapy and combination therapy separately. 
Phase 2 Monotherapy Arm Dose Expansion Cohort  
Monotherapy dose expansion will be opened after the phase 1 monotherapy arm dose escalation 
has been completed and RP2D is established. If confirmed response (PR based on iRECIST [iPR] 
or a CR based on iRECIST [iCR] per independent central review) is observed in a monotherapy 
arm dose escalation cohort, a tumor-specific dose expansion cohort may be opened in that tumor 
type after the phase 1 dose escalation has been completed. Additionally, once RP2D is determined, 
melanoma expansion cohort may be opened (even if no response is observed in the dose escalation 
cohort). Participants with CPI refractory metastatic melanoma will be enrolled in the monotherapy 
dose escalation or expansion cohorts to allow for enrollment of this patient population in the 
combination arm dose expansion cohort. If antitumor activity was observed in dose escalation or 
melanoma dose expansion Stage 1, expansion cohorts for CRC and ovarian cancer may be opened. 
Objective response rate per iRECIST (iORR), as confirmed per independent central review, is 
monitored using the Bayesian optimal phase 2 (BOP2) design [Zhou et al, 2017]. In case the 
enrollment for both the monotherapy arm escalation cohort and combination arm escalation cohort 
therapies opens together, participants will be randomized to either monotherapy or combination 
cohort in 1:1 ratio. 
When escalation and expansion cohorts are both open for enrollment, enrollment into escalation 
cohorts takes priority such that participants who are eligible for both will be preferentially enrolled 
in the escalation cohorts. Additionally, enrollment in the expansion cohorts may be prematurely 
closed at the discretion of the sponsor. 
UNIQUE to Japan Sites 
Japanese participants will be enrolled in the monotherapy arm of the dose expansion cohort. 
Phase 2 Combination Therapy Arm Dose Expansion Cohort  
The combination therapy arm dose expansion cohort will be opened after the phase 1 dose 
escalation cohort has been completed and MTD/RP2D of ASP7517 combination therapy has been 
determined. Metastatic melanoma CPI naïve cohort will be opened. If 5 confirmed responses (iPR 
or iCR, per independent central review) were observed in metastatic melanoma CPI naïve 
participants, expansion cohorts for CRC, ovarian cancer and metastatic melanoma CPI refractory 
may be opened. In addition, if a confirmed response (iPR or iCR, per independent central review) 
was observed in metastatic melanoma CPI refractory participants in the monotherapy arm, an 
expansion cohort for melanoma refractory participants may be opened for combination arm 
therapy, if not yet opened. 
Replacement of Participants in Phase 2 Dose Expansion Cohort 
If a participant in a phase 2 dose expansion cohort is not response evaluable (defined as the 
response analysis set [RAS]), an additional participant may be enrolled in that cohort based on 
sponsor discretion. 
UNIQUE to Japan Sites 
Japanese participants will be enrolled in the monotherapy arm of the dose expansion cohort. 


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DLT Criteria 
A DLT is defined as any of the following events that occur within 28 days starting with the first 
dose on Cycle 1 Day 1 (C1D1) and that is considered to be related to IP. Confirmation of DLTs 
will be made by the DESC. The severity of adverse events (AEs) will be assessed according to the 
National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE), 
version 5.0. 
DLTs Requiring Discontinuation of Treatment 
● 
If a study participant develops a grade 4 DLT after receiving Cycle 1, then the study 
participant should not receive Cycle 2 of the study product. 
● 
If a study participant develops a grade ≥ 3 non-hematological AE that does not resolve to 
≤ grade 2 within 72 hours of onset, it should be considered a DLT and the study participant 
should not receive Cycle 2 of the study product. 
● 
If there is a delay in administration of Cycle 2 by > 4 weeks, it may result in discontinuation of 
treatment after discussion with the sponsor.  
ASP7517 Monotherapy Arm DLTs: 
● 
Non-hematologic AEs that are ≥ grade 3 and that do not resolve to ≤ grade 2 within 72 hours 
of onset 
● 
Confirmed Hy’s law case 
● 
Infusion-related reaction (IRR) that requires the infusion to be discontinued 
● 
Prolonged delay (> 2 weeks) in initiating Cycle 2 due to treatment-related toxicity 
● 
Any treatment-related toxicity that causes the participant to discontinue treatment during 
Cycle 1 
● 
Grade ≥ 3 thrombocytopenia accompanied by bleeding that requires transfusion or 
hospitalization 
● 
Grade ≥ 3 anemia requiring transfusion 
● 
Grade 3 febrile neutropenia with or without infection 
● 
Grade 5 treatment-related toxicity 
The following AEs will not be considered as DLTs in the ASP7517 monotherapy arm: 
● 
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 
● 
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 72 hours 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 
● 
Grade 3 immune-related AEs (irAEs) that resolve to ≤ grade 1 within 72 hours of onset 


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ASP7517 and Pembrolizumab Combination Therapy Arm DLT: 
● 
Grade ≥ 3 non-hematological AE that does not resolve to ≤ grade 2 within 72 hours of onset  
● 
Grade ≥ 3 febrile neutropenia  
o Grade 3 febrile neutropenia is defined as absolute neutrophil count (ANC) < 1000/mm3 
with a single temperature of > 38.3°C (101°F) or a sustained temperature of ≥ 38°C 
(100.4°F) for more than 1 hour. 
o Grade 4 febrile neutropenia is defined as ANC < 1000/mm3 with a single temperature 
of > 38.3°C (101°F) or a sustained temperature of ≥ 38°C (100.4°F) for more than 1 hour, 
with life-threatening consequences and urgent intervention indicated. 
● 
Grade ≥ 3 thrombocytopenia accompanied by bleeding that requires transfusion or 
hospitalization 
● 
Grade ≥ 3 anemia requiring transfusion 
● 
Grade ≥ 2 pneumonitis 
● 
Grade ≥ 2 encephalopathy, meningitis, or motor or sensory neuropathy 
● 
Confirmed Hy’s law cases 
● 
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 × upper limit of 
normal (ULN) in participants without liver metastases 
● 
AST or ALT > 8 × ULN in participants with liver metastases 
● 
Total bilirubin > 3 × ULN (grade ≥ 3) 
● 
Guillain-Barré syndrome or myasthenic syndrome/myasthenia gravis 
● 
IRR that requires the infusion to be discontinued 
● 
Prolonged delay (> 2 weeks) in initiating Cycle 2 due to treatment-related toxicity 
● 
Any treatment-related toxicity that causes the participant to discontinue treatment during 
Cycle 1 
● 
Grade 5 treatment-related toxicity 
Participants experiencing a DLT will be discontinued from the study unless the participants are 
deriving clinical benefit from the study treatment in the opinion of the investigator; in those cases, 
after discussion with the sponsor, participants may be allowed to continue study treatment with 
ASP7517 upon resolution of the DLT event to ≤ grade 1 or baseline. Participants who are tolerating 
IP at a dose level that is being reviewed due to the occurrence of DLTs in another participant will 
not be automatically precluded from continued dosing during the safety review, and will be 
allowed to continue dosing for as long as tolerated unless directed otherwise as a result of the 
safety review by the DESC. 
DLTs Requiring Discontinuation of Treatment 
● 
If a study participant develops a grade 4 DLT after receiving Cycle 1, then the study 
participant should not receive Cycle 2 of the study product. 
● 
If a study participant develops a grade ≥ 3 non-hematological AE that does not resolve to 
≤ grade 2 within 72 hours of onset, it should be considered a DLT and the study participant 
should not receive Cycle 2 of the study product. 
● 
If there is a delay in administration of Cycle 2 by > 4 weeks, it may result in discontinuation of 
treatment after discussion with the sponsor. 
 


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Treatment Groups and Duration:  
Monotherapy: 
Arm/IP Name 
ASP7517 
Use 
Test product 
Dose 
1 × 107 cells/dose, 1 × 108 cells/dose 
Frequency 
Single dose on Day1 every 4 weeks 
Route 
Intravenous 
Duration 
up to 6 doses 
 
Combination Therapy: 
Arm/IP Name 
ASP7517 and pembrolizumab 
Use 
Test product 
Dose 
1 × 107 cells/dose, 1 × 108 cells/dose (ASP7517); 400 mg 
(pembrolizumab) 
Frequency 
ASP7517, Single dose on Day 1 every 4 weeks  
Pembrolizumab, Single dose every 6 weeks 
Route 
Intravenous 
Duration 
Up to 6 doses of ASP7517 in combination with pembrolizumab; 
with up to 4 doses (pembrolizumab) during the treatment period; 
a total of 17 doses of pembrolizumab for qualifying participants 
 
Monotherapy arm participants will receive up to 6 doses of ASP7517. The length of each cycle is 
28 days. 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. 
Pembrolizumab will be administered as an intravenous infusion over 30 min followed by ASP7517 
administration, at least 1 hour after pembrolizumab infusion through a dedicated intravenous line. 
The anticipated duration of the study for each participant, including Screening and the Observation 
Period, is up to approximately 3 years. 
 


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1.2 
Study Schema 
Figure 1 
Monotherapy: ASP7517 
 
 
 
 
 
 
 
Screen (Day -28 to -1) 
Treatment Period a 
Monotherapy 
ASP7517 IV every 28 days 
(1-cycle) for up to 6 cycles 
End of Treatment b 
• 
Safety follow-up visits (30, 60 
and 90 days after last dose 
administered in the treatment 
period) c 
• 
Visits for tumor imaging only 
every 8 weeks 
Observation Period d 
Survival Period e 
Consent 
EOT: end of treatment; iCPD: “immune” confirmed progressive disease; IV: intravenous iUPD: “immune” unconfirmed progressive disease 
a. 
Participants receiving ASP7517 monotherapy will receive a single dose of ASP7517 per cycle for a total of 6 cycles with each cycle as 28 days. 
b. EOT visit will be conducted for all participants after 7 days of EOT determination or prior to the initiation of new anticancer therapy, whichever occurs first. See 
footnote t in Table 1. 
c. 
After the EOT visit, participants will complete 30-, 60- and 90-day safety follow-up visits from the last dose of ASP7517 or prior to the initiation of new anticancer 
therapy.  
d. All participants will enter an observation period except those with iCPD, iUPD (per independent central review or local review) and who are not clinically stable or 
clinical progression is confirmed by the investigator. Participants in the Observation Period will be followed for up to 48 weeks until iCPD (confirmed by 
independent central review), initiation of a new anticancer therapy or meeting 1 of the discontinuation criteria, whichever occurs first. 
Outcomes will be 
assessed by 
telephone calls 
every 3 months 
for up to 
12 months 


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Figure 2 
Combination Therapy:  ASP7517 + Pembrolizumab 
 
 
Consent 
Treatment Period a 
Follow-up d 
Observation Period b 
Visits for disease assessment 
every 8 weeks  
Treatment Extension b 
Pembrolizumab IV every 
6 weeks up to a total of 
17 doses 
Survival Period e 
Screen (Day -28 to -1) 
Combination 
Therapya 
ASP7517 IV up to 6 
doses in combination 
with pembrolizumab 
IV up to 4 doses  
End of Treatment c 
EOT: end of treatment; iCPD: “immune” confirmed progressive disease; IV: intravenous; iUPD: “immune” unconfirmed progressive disease; PR: partial response; 
q: every; SD: stable disease 
a. 
In the combination treatment cohort, ASP7517 will be given on Day 1 of each 28-day cycle for up to 6 doses in combination with pembrolizumab administered 
every 6 weeks for up to 4 doses.  
b. All participants will enter an observation period except those with iCPD, iUPD (per independent central review or local review) and who are not clinically stable or 
clinical progression is confirmed by the investigator. Participants completing the combination therapy treatment period who enter the Observation Period with PR, 
CR or SD are allowed to continue to receive pembrolizumab alone up to a total of 17 doses of pembrolizumab), for those participants who, in the opinion of the 
investigator, are continuing to derive clinical benefit. In addition, subsequent to the Treatment period, all participants, except those with iCPD, iUPD (per 
independent central review or local review) and who are not clinically stable or clinical disease progression is confirmed by the investigator, will enter the 
Observation Period to monitor treatment response for up to 78 weeks until iCPD (confirmed by independent central review), initiation of a new anticancer therapy 
or meeting 1 of the Observation Period discontinuation criteria, whichever occurs first. If participant discontinues combination treatment of ASP7517 at any time 
prior to C5D15, then the participant should continue observation period up to 96 weeks. 
c. 
EOT visit will be conducted for all participants after 7 days of EOT determination or prior to the initiation of new anticancer therapy, whichever occurs first. See 
footnote s in Table 2. 
d. After EOT visit, participants will complete 30-, 60- and 90-day safety follow-up visits from the last dose of pembrolizumab or prior to the initiation of new 
anticancer therapy. 
e. 
All participants will be followed for survival and subsequent anti-cancer treatments following the conclusion of the Observation period. Outcomes will be assessed 
Safety follow-up 
Visits (30, 60 and 
90 days after last 
dose administered) 
Outcomes will be 
assessed by 
telephone calls 
every 3 months for 
up to 12 months 


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Figure 3 
ASP7517 Monotherapy Arm 
 
 
BOP2: Bayesian optimal phase 2; DLT: dose limiting toxicity; MTD: maximum tolerated dose; RP2D: recommended phase 2 dose; WT1: Wilms’ tumor protein 1 
Phase 1 Dose Escalation starting dose level of ASP7517 is 1 × 107 cells/dose, and the decision to escalate to the next dose level (1 × 108 cells/dose) will be made based in safety data 
review. Monotherapy dose expansion will be opened after the phase 1 monotherapy dose escalation has been completed. 


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Figure 4 
Combination Therapy ASP7517 + Pembrolizumab Arm 
 
 
BOP2: Bayesian optimal phase 2; CPI: checkpoint inhibitor; DESC: Dose Escalation and Safety Committee: DLT: dose limiting toxicity; MTD: maximum tolerated dose; 
RP2D: recommended phase 2 dose; WT1: Wilms’ tumor protein 1 
Phase 1 Dose Escalation starting dose level of ASP7517 is 1 × 107 cells/dose in combination and pembrolizumab, and the decision to escalate to the next dose level (1 × 108 cells/dose) 
will be made by the DESC. Combination therapy dose expansion will be opened after the phase 1 combination therapy dose escalation has been completed. 


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1.3 
Schedules of Assessments 
Table 1 
Schedule of Assessments – Dose Escalation Cohort 
Scr 
Treatmenta 
EOTt 
Cycle 1 
Cycle 2 
Cycles 3–4b 
Cycles 5–6c 
Visit Days 
-28 to -1
1 
2 
4 
8 
15 
1 
2 
4 
8 
15 
1 
8 
15 
1 
8 
15 
Window(days) 
0 
0 
0 
±1 
±1 
±1 
0 
±1 
±1 
±1 
±3 
±1 
±1 
±3 
±1 
±1 
+7
Signed ICF 
X 
Medical and Disease 
History 
X 
Physical 
Examinationd 
Xd 
Xd 
X 
X 
X 
X 
Xd 
X 
X 
X 
X 
Xd 
X 
X 
Xd 
X 
X 
Xd 
Vital Signs 
X 
Xe 
X 
X 
X 
X 
Xe 
X 
X 
X 
X 
Xe 
X 
X 
Xe 
X 
X 
X 
ECOG Performance 
X 
Xf 
X 
X 
X 
X 
Xf 
X 
X 
X 
Xf 
X 
X 
Xf 
X 
X 
X 
Chest X-ray 
Xg 
12-Lead ECGh
X 
Xh 
X 
Xh 
X 
Xh 
Xh 
Xh 
X 
Prior and 
Concomitant 
Medications 
Xi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy Test for 
WOCBP 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Clinical Laboratory 
Tests (chemistry, 
hematology, 
urinalysis)k
X 
Xf 
X 
X 
X 
X 
Xf 
X 
X 
X 
X 
Xf 
X 
X 
Xf 
X 
X 
X 
Coagulation Profile 
(PT/INR, D-dimer, 
fibrinogen)k 
X 
Xf 
X 
X 
X 
X 
Xf 
X 
X 
X 
X 
Xf 
Xf 
X 
Thyroid Profile Panell 
X 
X 
X 
Every 6 weeks 
X 
IRT Transaction 
Required 
X 
Xm 
X 
X 
X 
AE/SAE Assessment
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Table continued on next page 
Footnotes


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Scr 
Treatmenta 
EOTt 
Cycle 1 
Cycle 2 
Cycles 3–4b 
Cycles 5–6c 
Visit Days 
-28 to -1 
1 
2 
4 
8 
15 
1 
2 
4 
8 
15 
1 
8 
15 
1 
8 
15 
 
Window(days) 
 
0 
0 
0 
±1 
±1 
±1 
0 
±1 
±1 
±1 
±3 
±1 
±1 
±3 
±1 
±1 
+7 
PGxn 
 
Xn 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Buccal Swab for 
HLA Typing 
 
Xf 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pharmacokinetic:  
A7517o 
 
X 
See Table 6 for detailed sample time points 
X 
Pharmacokinetic: 
Pembrolizumabo 
 
X 
See Table 6 for detailed sample time points 
X 
Anti-WT1 antibody 
 
Xf 
 
 
 
 
Xf 
 
 
 
 
Xf 
 
 
Xf 
 
 
X 
Immune Response 
Biomarker (ELISpot) 
 
Xf 
 
 
X 
X 
Xf 
 
 
X 
X 
Xf 
X 
X 
Xf 
X 
X 
X 
Immune Response 
Biomarker (Tetramer)  
 
Xf 
 
 
 
X 
Xf 
 
 
 
X 
Xf 
 
X 
Xf 
 
X 
X 
Immune Cell 
Phenotyping 
 
Xf 
 
 
X 
X 
Xf 
 
 
X 
X 
Xf 
X 
X 
Xf 
X 
X 
X 
Cytokines 
 
Xf 
X 
X 
X 
X 
Xf 
X 
X 
X 
X 
Xf 
X 
X 
Xf 
X 
X 
X 
Circulating Tumor 
DNA 
 
Xf 
 
 
 
 
Xf 
 
 
 
 
Xf 
 
 
Xf 
 
 
X 
Archival Tumor 
Tissuep 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Radiographic Disease 
Assessmentq 
X 
Every 56 ± 7 days 
 
ASP7517 Dosingr  
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
X 
 
 
 
Pembrolizumab 
Dosings 
 
X 
 
 
 
 
 
 
 
 
Xs 
Every 6 weekss 
 
AE: adverse event; C: Cycle; CR: complete response; CT: computed tomography; D: Day; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; ELISpot: enzyme-
linked immunospot; EOT: end of treatment; FFPE: formalin-fixed, paraffin-embedded; HLA: human leukocyte antigen; ICF: informed consent form; IP: investigational product; IRT: 
interactive response technology; MRI: magnetic resonance imaging; PGx: pharmacogenomic; PR: partial response; PT/INR: prothrombin time/international normalized ratio; SAE: 
serious adverse event; Scr: screening; SD: stable disease; WOCBP: woman of childbearing potential; WT1: Wilms’ tumor 1 protein.  
Footnotes continued on next page  


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a. 
Cycles 1 through 6 represent ASP7517 monotherapy or combination of ASP7517 and pembrolizumab therapy; each cycle is 28 days.  
b. After the first 2 cycles, participants who have not met any individual treatment discontinuation criteria and are receiving clinical benefit (defined as radiological response or SD, or 
reduction of disease-related symptoms) will continue further treatment of ASP7517 in Cycles 3 and 4, as decided by the investigator. 
c. 
After the first 4 cycles, participants who achieve PR or SD may receive 2 doses of ASP7517 in Cycles 5 and 6. 
d. Height measurement performed at screening only. Height measurement may be performed at a subsequent visit if it was not done at screening. Weight measurement performed at 
screening and Day 1 of each cycle.  
e. 
The following vital sign assessment schedules apply: 
• 
At C1D1 and any visit when pembrolizumab and ASP7517 are administered together, vital signs are obtained predose (-1 h from start of pembrolizumab infusion), within 15 
min prior to start of the pembrolizumab infusion, 15 min (-5 to +10 min window) after the start of the pembrolizumab infusion, at the end of the pembrolizumab infusion (-5 to 
+10 min window), 30 min (± 10 min) after completion of the pembrolizumab infusion, within 15 min prior to the start of the ASP7517 infusion, every 15 min (-5 to +10 min 
window) during the ASP7517 infusion, at the end of the ASP7517 infusion (-5 to +10 min window), and postdose (+30 min, +1, +2, +3 and +4 h [± 10 min window each] 
from end of the ASP7517 infusion). 
• 
ASP7517 dosing only: Vital signs will be obtained within 15 min prior to start of the ASP7517 infusion, every 15 min (-5 to +10 min window) during the ASP7517 infusion, 
every 15 min (-5 to +10 min window) during the ASP7517 infusion, at the end of the ASP7517 infusion (-5 to + 10 min window), as well as 30 min (± 5 min), 1 h (± 10 min) 
and 2 h (± 10 min) after completion of the ASP7517 infusion. If participants are still available, additional optional vital sign assessments 3 h (± 10 min) and 4 h (± 10 min) 
after completion of the ASP7517 infusion will be obtained. 
• 
Pembrolizumab dosing only: Vital signs will be obtained within 15 min prior to start of the pembrolizumab infusion, 15 min (-5 to +10 min window) after the start of the 
pembrolizumab infusion (-5 to + 10 min window), at the end of the pembrolizumab infusion (-5 to + 10 min window) and at 30 min (± 10 min) after completion of the 
pembrolizumab infusion for participants in the combination therapy. 
f. 
Obtain predose. 
g. If chest X-ray is performed within to 2 weeks of screening (prior to ICF and performed as part of standard of care), then it does not need to be repeated. 
h. 12-lead ECGs will be recorded in triplicate (at least 2 min apart per time point) and transmitted electronically for central reading. ECGs may be repeated once during screening. On 
IP administration days, ECGs will be obtained: 
• 
At C1D1 and any visit when pembrolizumab and ASP7517 are administered together, ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h 
post dose of ASP7517. 
• 
ASP7517 dosing only: ECGs are obtained predose (-1 h from start of ASP7517 infusion) and 1 to 2 h post dose of ASP7517. 
• 
Pembrolizumab dosing only: ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h post dose of pembrolizumab. 
i. 
Includes medications taken within 28 days prior to C1D1. Include all anticancer treatment received 28 days prior to IP administration. 
j. 
Urine or serum pregnancy test will be performed in WOCBP. On treatment visit days, test must occur prior to IP administration.  
k. Laboratory tests will be analyzed by the institution’s local laboratory. However, sample results must also be submitted for centralized data entry. Laboratory test may be repeated 
during the screening period. 
Footnotes continued on next page 


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l. 
Thyroid panel including triiodothyronine or free triiodothyronine, free thyroxine and thyroid stimulating hormone will be measured prior to receiving pembrolizumab only for 
participants in the combination cohort (C1D1, C2D15, C4D1 and C5D15). If the thyroid panel is to be measured on same day of pembrolizumab dosing (ex. C4D1, 
pembrolizumab monotherapy dosing visit), the thyroid panel must be measured prior to receiving pembrolizumab. Thyroid panels assessed on C1D1 and C2D15 only apply 
for the combination therapy cohort. 
m. Enrollment or randomization will be done via IRT system after confirmation of eligibility and prior to dosing. 
n. Whole blood for optional PGx study may be collected at C1D1 prior to IP administration. 
o. See Table 6 for collection schedule for ASP7517 monotherapy and ASP7517 and pembrolizumab combination therapy. 
p. Archival tumor specimen at a minimum of 1 FFPE tumor tissue block with adequate viable tumor cells (preferred) OR a minimum of 20 FFPE unstained serial slides are 
required. 
q. Same technique (CT/MRI) used at screening should be utilized throughout the study. Imaging should include chest, abdomen and pelvis, as well as any other anatomical 
region appropriate for the participant’s disease. Scans performed prior to informed consent as standard of care are acceptable as screening scans, if done within 28 days prior 
to C1D1.  
r. 
In both the monotherapy and combination cohorts, each participant must remain at the site facility for 4 h following the participant’s first dose of ASP7517. For the next dose 
(2nd dose) or additional subsequent monotherapy with ASP7517, participants must remain at the site facility for at least 2 h after ASP7517 dosing.  
s. 
In the combination therapy arm, pembrolizumab will be administered as an intravenous infusion over 30 min followed by ASP7517 administration at least 1 h after 
pembrolizumab administration.  
t. 
If the participant will discontinue treatment due to meeting protocol criteria of CR after completion of Cycle 4 or a participant completes all 6 cycles of ASP7517, then all 
visits in the treatment cycle should be completed and the EOT visit will be performed 7 days (+ up to a 7-day window) after the last planned visit. 
• 
If participant has CR after completing Cycle 4, the EOT visit would be performed between C4D22 and C4D29. 
• 
If participant has SD or PR after completing Cycle 4, they are expected to complete all visits through C6D15 and the EOT visit would be performed between C6D22 and 
C6D29. 
• 
If the investigator decides to discontinue treatment prior to the completion of any cycle, the EOT visit will occur 7 days after the decision to discontinue treatment. 
• 
If new anticancer therapy is to be initiated, the EOT visit must occur prior to start of the new therapy, even if < 7 days from the decision to discontinue treatment. 
• 
For combination therapy participants that continue with pembrolizumab monotherapy, EOT visit will be performed 7 days after 17th dose of pembrolizumab or 7 days 
after decision to discontinue treatment, or prior to start of new anticancer therapy, whichever is earliest. 


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Table 2 
Schedule of Assessments for Dose Expansion Cohort 
Scr 
(-28 to -1) 
Treatmenta 
EOTs 
Cycle 1 
Cycle 2 
Cycles 3–4b 
Cycles 5–6c 
1 
4 
8 
15 
1 
4 
8 
15 
1 
15 
1 
15 
+7
Window(days) 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 3 
± 1 
Signed ICF 
X 
Medical and Disease 
History 
X 
Physical Examinationd 
Xd 
Xd 
X 
X 
X 
Xd 
X 
X 
X 
Xd 
X 
Xd 
X 
Xd 
Vital Signs 
X 
Xe 
X 
X 
X 
Xe 
X 
X 
X 
Xe 
X 
Xe 
X 
X 
ECOG Performance 
X 
Xf 
X 
X 
X 
Xf 
X 
X 
X 
Xf 
X 
Xf 
X 
X 
Chest X-ray 
Xg 
12-Lead ECGh
X 
Xh 
Xh 
Xh 
Xh 
X 
Prior and Concomitant 
Medications 
Xi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy Test for 
WOCBP 
Xj 
Xj 
Xj 
Xj 
Xj 
Xj 
Clinical Laboratory Tests 
(chemistry, hematology, 
urinalysis)k 
X 
Xf 
X 
X 
Xf 
X 
X 
X 
Xf 
X 
Xf 
X 
X 
Coagulation Profile 
(PT/INR, D-dimer, 
fibrinogen)k 
X 
Xf 
X 
X 
Xf 
X 
X 
Xf 
X 
Xf 
X 
X 
Thyroid Profile Panell 
X 
X 
X 
Every 6 weeks after C2D15 dose 
X 
PGxm 
Xm 
Buccal Swab for HLA 
Typing 
Xf 
AE/SAE Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetic:  A7517n 
X 
See Table 6 for sample time points 
X 
Pharmacokinetic: 
Pembrolizumabn 
X 
See Table 6 for sample time points 
X 
Anti-WT1 antibody 
Xf 
Xf 
Xf 
Xf 
X 
Table continued on next page 
Footnotes


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Scr 
(-28 to -1) 
Treatmenta 
EOTs 
Cycle 1 
Cycle 2 
Cycles 3–4b 
Cycles 5–6c 
 
 
1 
4 
8 
15 
1 
4 
8 
15 
1 
15 
1 
15 
+7 
Window(days) 
 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 3 
± 1 
 
Immune Response 
Biomarker (ELISpot) 
 
Xf 
 
X 
X 
Xf 
 
X 
X 
Xf 
X 
Xf 
X 
X 
Immune Response 
Biomarker (Tetramer) 
 
Xf 
 
 
X 
Xf 
 
 
X 
Xf 
X 
Xf 
X 
X 
Immune Cell Phenotyping 
 
Xf 
 
X 
X 
Xf 
 
X 
X 
Xf 
X 
Xf 
X 
X 
Cytokines 
 
Xf 
X 
X 
X 
Xf 
X 
X 
X 
Xf 
X 
Xf 
X 
X 
Circulating tumor DNA 
 
Xf 
 
 
 
Xf 
 
 
 
Xf 
 
Xf 
 
X 
Archival Tumor Tissueo 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor Tissue, Fresh 
Biopsy 
 
Xq 
 
 
 
 
 
 
Xr 
 
 
 
 
 
Radiographic Disease 
Assessmentp 
X 
Every 56 ± 7 days 
 
IRT Transaction Required 
X 
Xo 
 
 
 
X 
 
 
 
X 
 
X 
 
 
ASP7517 Dosing  
 
X 
 
 
 
X 
 
 
 
X 
 
X 
 
 
Pembrolizumab Dosing 
 
X 
 
 
 
 
 
 
X 
Every 6 weeks after C2D15 dose 
 
AE: adverse event; C: Cycle; CR: complete response; CT: computed tomography; D: Day; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; ELISpot: enzyme-
linked immunospot; EOT: end of treatment; FFPE: formalin-fixed, paraffin-embedded; HLA: human leukocyte antigen; ICF: informed consent form; IP: investigational product; IRT: 
interactive response technology; MRI: magnetic resonance imaging; PGx: pharmacogenomic; PR: partial response; PT/INR: prothrombin time/international normalized ratio; SAE: 
serious adverse event; Scr: screening; SD: stable disease; WOCBP: woman of childbearing potential; WT1: Wilms’ tumor 1 protein.  
a. 
Cycles 1 through 6 represent ASP7517 monotherapy or combination of ASP7517 and pembrolizumab therapy; each cycle is 28 days.  
b. After the first 2 cycles, participants who have not met any individual treatment discontinuation criteria and are receiving clinical benefit (defined as radiological response or SD, or 
reduction of disease-related symptoms) will continue further treatment of ASP7517 as decided by the investigator. 
c. 
After the first 4 cycles, participants who achieve PR or SD may receive 2 doses of ASP7517 in Cycles 5 and 6. 
d. Height measurement performed at screening only. Height measurement may be performed at a subsequent visit if it was not done at screening. Weight measurement performed at 
screening and Day 1 of each cycle.  
Footnotes continued on next page 
 


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e. 
The following vital sign assessment schedules apply: 
• 
At C1D1 and any visit when pembrolizumab and ASP7517 are administered together, vital signs are obtained predose (-1 h from start of pembrolizumab infusion), within 15 
min prior to start of the pembrolizumab infusion, 15 min (-5 to +10 min window) after the start of pembrolizumab infusion, at the end of pembrolizumab infusion (-5 to +10 
min window), 30 min (± 10 min) after completion of the pembrolizumab infusion, within 15 min prior to start of ASP7517 infusion, every 15 min (-5 to +10 min window) 
during ASP7517 infusion, at the end of ASP7517 infusion (-5 to +10 min window), and postdose (+30 min, +1, +2, +3 and +4 h [± 10 min window each] from end of the 
ASP7517 infusion). 
• 
ASP7517 dosing only: Vital signs will be obtained within 15 min prior to start of the ASP7517 infusion, every 15 min (-5 to +10 min window) during the ASP7517 infusion, 
at the end of the ASP7517 infusion (-5 to + 10 min window), as well as 30 min (± 5 min), 1 h (± 10 min) and 2 h (± 10 min) after completion of the ASP7517 infusion. If 
participants are still available, additional optional vital sign assessments 3 h (± 10 min) and 4 h (± 10 min) after completion of the ASP7517 infusion will be obtained. 
• 
Pembrolizumab dosing only: Vital signs will be obtained within 15 min prior to start of the pembrolizumab infusion, 15 min (-5 to +10 min window) after the start of the 
pembrolizumab infusion, at the end of the pembrolizumab infusion (-5 to + 10 min window) and at 30 min (± 10 min) after completion of the pembrolizumab infusion for 
participants in the combination therapy. 
f. 
Obtain predose. 
g. If chest X-ray is performed prior to 2 weeks of screening (prior to ICF and performed as part of standard of care), then it does not need to be repeated. 
h. During ASP7517 and pembrolizumab combination therapy, 12-lead ECGs will be recorded in triplicate (at least 2 min apart per time point) and transmitted electronically for 
central reading. After treatment with ASP7517 has been discontinued, 12-lead ECGs will be recorded as a single assessment (in triplicate if deemed necessary, at least 2 min apart 
per time point) and read locally. ECG may be repeated once during screening. On IP administration days, ECGs will be obtained: 
• 
At C1D1 and any visit when pembrolizumab and ASP7517 are administered together, ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h 
post dose. 
• 
ASP7517 dosing only: ECGs are obtained predose (-1 h from start of ASP7517 infusion) and 1 to 2 h post dose of ASP7517. 
• 
Pembrolizumab dosing only: ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h post dose of pembrolizumab. 
i. 
Includes medications taken within 28 days prior to C1D1. Include all anticancer treatment received 28 days prior to IP administration. 
j. 
Urine or serum pregnancy test will be performed in WOCBP. On treatment visit days, test must occur prior to IP administration.  
k. Laboratory tests will be analyzed by the institution’s local laboratory. However, sample results must also be submitted for centralized data entry. Laboratory test may be repeated 
during the screening period. 
l. 
Thyroid panel including triiodothyronine or free triiodothyronine, free thyroxine and thyroid stimulating hormone will be measured prior to receiving pembrolizumab only for 
participants in the combination cohort (C1D1, C2D15, C4D1 and C5D15). If the thyroid panel is to be measured on same day of pembrolizumab dosing (ex. C4D1, 
pembrolizumab monotherapy dosing visit), the thyroid panel must be measured prior to receiving pembrolizumab. 
m. Whole blood for optional PGx study may be collected at C1D1 prior to IP administration. 
n. See Table 6 for collection schedule for ASP7517 monotherapy and ASP7517 and pembrolizumab combination therapy. 
o. Archival tumor specimen at a minimum of 1 FFPE tumor tissue block with adequate viable tumor cells (preferred) OR a minimum of 20 FFPE unstained serial slides are required. 
Footnotes continued on next page 


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p. Same technique (CT/MRI) used at screening should be utilized throughout the study. Imaging should include chest, abdomen and pelvis, as well as any other anatomical region 
appropriate for the participant’s disease. Scans performed prior to informed consent as standard of care are acceptable as screening scans, if done within 28 days prior to C1D1.  
q. Participants in all expansion cohorts are required to provide a tumor specimen obtained within 56 days prior to first dose of IP. 
r. 
Participants in all expansion cohorts are required to provide an on-treatment tumor specimen collected ± 7 days of the C2D15 visit (or unscheduled) if predose biopsy is available 
and if medically feasible. 
s. 
If the participant will discontinue treatment due to meeting protocol criteria of CR after completion of Cycle 4 or a participant completes all 6 cycles of ASP7517, then all visits in 
the treatment cycle should be completed and the EOT visit will be performed 7 days (+ up to a 7-day window) after the last planned visit. 
• 
If participant has CR after completing Cycle 4, the EOT visit would be performed between C4D22 and C4D29. 
• 
If participant has SD or PR after completing Cycle 4, they are expected to complete all visits through C6D15 and the EOT visit would be performed between C6D22 and 
C6D29. 
• 
If the investigator decides to discontinue treatment prior to the completion of any cycle, the EOT visit will occur 7 days after the decision to discontinue treatment. 
• 
If new anticancer therapy is to be initiated, the EOT visit must occur prior to start of the new therapy, even if < 7 days from the decision to discontinue treatment. 
• 
For combination therapy participants that continue with pembrolizumab monotherapy, EOT visit will be performed 7 days after 17th dose of pembrolizumab or 7 days after 
decision to discontinue treatment, or prior to start of new anticancer therapy, whichever is earliest. 


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Table 3 
Schedule of Assessments for Safety Follow-up, Observation Period and Survival Follow-up Period for Participants who End the 
Treatment Early or Completed the Treatment Period 
Visit 
Observation Period 
Survival Follow-up 
Safety Follow-upᶠ 
Disease Assessment,  
Up to 48 weeksa 
 
30 days from 
 last dose  
60 days from  
last dose 
90 days from  
last dose 
Visits every 8 weeks ± 1 week 
from last planned scan  
Every 3 months 
Window (days) 
± 3 
± 3 
± 3 
 
± 7 
Physical Examination 
X 
X 
X 
 
 
Vital Signs 
X 
X 
X 
 
 
ECOG Performance 
X 
X 
X 
 
 
Concomitant Medications 
X 
X 
X 
X 
 
12-Lead ECG 
X 
X 
X 
 
 
Clinical Laboratory Tests (chemistry, hematology, coagulation, 
urinalysis) 
X 
X 
X 
X 
 
Pregnancy Test for WOCBP 
X 
X 
X 
 
 
AE/SAE Assessment 
X 
X 
X 
X 
 
Pharmacokinetic sample for cell kinetics (ASP7517) 
See Table 6 for sample time points 
Blood Sample for anti-WT1 antibody 
X 
X 
X 
Xb 
 
Blood Sample for Immune Response Biomarker (ELISpot)  
X 
X 
X 
Xc 
 
Blood Sample for Immune Response Biomarker (Tetramer)  
X 
X 
X 
Xb 
 
Blood Sample for Immune Cell Phenotyping 
X 
X 
X 
Xc 
 
Blood Sample for Cytokines 
X 
X 
X 
Xc 
 
Blood Sample for ctDNA 
X 
X 
X 
Xd 
 
Radiographic Disease Assessment 
 
 
 
X 
 
Survival Follow-upe 
 
 
 
 
X 
AE: adverse event; ctDNA: circulating tumor DNA; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; ELISpot: enzyme-linked immunospot; EOT: end of 
treatment; iCPD: “immune” confirmed progressive disease; iUPD: unconfirmed disease progression disease based on iRECIST; SAE: serious adverse event; WOCBP: woman of 
childbearing potential; WT1: Wilms’ tumor 1 protein.  
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a. For participants in ASP7517 monotherapy treatment arm. Participants in the Observation period will be followed until iCPD, iUPD who are not clinically stable, clinical disease 
progression, initiation of a new anticancer therapy or for a total of up to 48 weeks starting at EOT, whichever occurs first. 
b. Maximum of 8 samples collected during the Observation Period. Sample will be collected at the time of the disease assessment visit.  
c. Maximum of 4 samples collected during the Observation Period. Sample will be collected at the time of the disease assessment visit. 
d. Sample will be collected only at the time of discontinuation due to disease progression. 
e. Outcomes will be assessed by telephone calls every 3 months for up to 12 months. 
f. In Monotherapy Arm, Safety Follow-up is a part of 48 weeks of Observation period. Observation period starts after EOT. 
 
 
 


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Table 4 
Schedule of Assessments for Observation Period, Safety Follow-up and Survival Follow-up for Participants who Receive 
Pembrolizumab Monotherapy in the Observation Period 
Visit 
Observation Period 
Up to 96 weeksa 
Safety Follow-up 
Survival Follow-up 
 
Visits every 6 weeks (± 1 week) from last 
Pembrolizumab dose during combination treatment 
30 days from 
last dose  
60 days from 
last dose 
90 days from 
last dose 
Every 3 months 
Window (days) 
 
± 3 
± 3 
± 3 
± 7 
Physical Examination 
X 
X 
X 
X 
 
Vital Signs 
Xb 
X 
X 
X 
 
ECOG Performance 
 
X 
X 
X 
 
Concomitant Medications 
X 
X 
X 
X 
 
12-Lead ECG 
Xc 
X 
X 
X 
 
Clinical Laboratory Tests (chemistry, hematology, coagulation, 
urinalysis) 
Xc 
X 
X 
X 
 
Thyroid Profile Panel (triiodothyronine or free 
triiodothyronine, free thyroxine and thyroid stimulating 
hormone) 
Xc 
Xc 
 
 
 
Pregnancy Test for WOCBP 
Xc 
X 
X 
X 
 
AE/SAE Assessment 
X 
X 
X 
X 
 
Pharmacokinetic samples for cell kinetics (ASP7517) 
See Table 6 for schedule 
 
 
 
 
Pharmacokinetic sample for pembrolizumab 
See Table 6 for schedule 
 
 
 
 
Blood Sample for anti-WT1 antibody 
Xc,h 
 
 
 
 
Blood Sample for Immune Response Biomarker (ELISpot)  
Xc,g 
 
 
 
 
Blood Sample for Immune Response Biomarker (Tetramer)  
Xc,h 
 
 
 
 
Blood Sample for Immune Cell Phenotyping 
Xc,g 
 
 
 
 
Blood Sample for Cytokines 
Xc,g 
 
 
 
 
Blood Sample for ctDNA 
Xc,f 
 
 
 
 
Radiographic Disease Assessment 
Xd 
 
 
 
 
Pembrolizumab Dosing 
Xe 
 
 
 
 
Survival Follow-upi 
 
 
 
 
X 
AE: adverse event; C5D15: Cycle 5 Day 15; CR: complete response; ctDNA: circulating tumor DNA; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; 
ELISpot: enzyme-linked immunospot; iCPD: “immune” confirmed progressive disease; iUPD: unconfirmed disease progression disease based on iRECIST; PR: partial response; SAE: 
serious adverse event; SD: stable disease: WOCBP: woman of childbearing potential; WT1: Wilms’ tumor 1 protein.  
Footnotes continued on next page 


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a. 
For participants in ASP7517 and pembrolizumab treatment who have achieved CR, PR or SD and receiving pembrolizumab monotherapy. Pembrolizumab will be administered 
every 6 weeks for up to a total of 17 doses. Participants in the Observation period will be followed until iCPD, iUPD who are not clinically stable, clinical disease progression, 
initiation of a new anticancer therapy or for a total of up to 96 weeks, whichever occurs first. If participant discontinues pembrolizumab at any time during the 78-week 
Observation period, the participant will continue with Safety Follow-up visits, then resume Observation period visits every 6 weeks until iCPD, iUPD who are not clinically stable, 
clinical disease progression, initiation of a new anticancer therapy or for a total of up to 78 weeks from last dose of ASP7517, whichever occurs first. If participant discontinues 
combination treatment of ASP7517 at any time prior to C5D15, then the participant should continue observation period up to 96 weeks. 
b. Vital signs should be obtained prior to pembrolizumab infusion and within 30 min (± 10 min window) after completion of pembrolizumab infusion. 
c. 
Obtained predose. 
d. Disease assessment every 8 weeks. 
e. 
Pembrolizumab administered every 6 weeks for up to 17 doses total (for the study) for those participants who, in the opinion of the investigator, are continuing to derive clinical 
benefit. 
f. 
Sample collected at the time of discontinuation due to disease progression. 
g. Sample collected at the time of pembrolizumab administration of doses 5 and 7 (i.e., 2 samples are collected from the time the participant enters the Observation Period). 
h. Sample collected at the time of pembrolizumab administration of doses 5, 7, 9, 11 and 13 (i.e., 5 samples are collected from the time the participant enters the Observation Period).  
i. 
Outcomes will be assessed by telephone calls every 3 months for up to 12 months, starting from the 90-day safety follow-up or last visit prior to the start of new anti-cancer 
therapy. 
 
 
 


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Table 5 
Schedule of Replication Competent Lentivirus for Dose Escalation Cohort and Dose Expansion Cohort 
Assessment 
C1D1 
3 Months After Treatment Initiation 
or at End of Treatment, Whichever is 
First 
6 Months after Treatment 
Initiation 
12 Months after Treatment 
Initiation 
18 Months after Treatment 
Initiation 
Window 
0 
± 7 days 
± 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 7.7.1]. 
b. Obtained predose. 
 


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Table 6 
Sample Collection Schedule-Dose Escalation Cohort and Dose Expansion Cohort 
Cycle 
Day 
Time Point
Window 
Dose Escalation 
Dose Expansion 
Pembrolizumab PKh 
ASP7517 PK 
Pembrolizumab PKh 
ASP7517 PK 
Cycle 1 
1 
Predose 
- 60 mina
X 
X 
X 
X 
End of pembrolizumab Infusion 
+ 15 minb
X 
X 
End of ASP7517 Infusion 
+ 15 minc
X 
X 
30 min post ASP7517 Infusion 
± 15 min 
X 
X 
1 h post ASP7517 Infusion 
± 15 min 
X 
X 
2 h post ASP7517 Infusion 
± 15 min 
X 
X 
5 h post ASP7517 Infusion 
± 15 min 
X 
X 
2 
24 h post ASP7517 Infusion 
± 60 min 
X 
Cycle 2 
1 
Predose 
- 60 mind
X 
X 
End of ASP7517 Infusion 
+ 15 minc
X 
Xg 
30 min post ASP7517 Infusion 
± 15 min 
X 
Xg 
1 h post ASP7517 Infusion 
± 15 min 
X 
Xg 
2 h post ASP7517 Infusion 
± 15 min 
X 
Xg 
5 h post ASP7517 Infusion 
± 15 min 
X 
Xg 
2 
24 h post ASP7517 Infusion 
± 60 min 
X 
15 
Predose 
- 60 mina
X 
End of pembrolizumab Infusion 
+ 15 minb
X 
Cycle 3 
1 
Predose 
- 60 mind
X 
End of ASP7517 Infusion 
+ 15 minc
X 
Cycle 4 
1 
Predose 
- 60 mina
X 
X 
Xg 
Xg 
End of pembrolizumab Infusion 
+ 15 minb
X 
Xg 
End of ASP7517 Infusion 
+ 15 minc
X 
Xg 
30 min post ASP7517 Infusion 
± 15 min 
X 
1 h post ASP7517 Infusion 
± 15 min 
X 
2 h post ASP7517 Infusion 
± 15 min 
X 
5 h post ASP7517 Infusion 
± 15 min 
X 
Table continued on next page 
Footnotes


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Cycle 
Day 
Time Point 
Window 
Dose Escalation 
Dose Expansion 
Pembrolizumab PKh 
ASP7517 PK 
Pembrolizumab PKh 
ASP7517 PK 
Cycle 5 
1 
Predose 
- 60 mind 
 
X 
 
 
End of ASP7517 Infusion 
+ 15 minc 
 
X 
 
 
15 
Predose 
- 60 mina 
X 
 
 
 
End of pembrolizumab Infusion 
+ 15 minc 
X 
 
 
 
Cycle 6 
1 
Predose 
- 60 mind 
 
X 
 
 
End of ASP7517 Infusion 
+ 15 minc 
 
X 
 
 
EOT 
EOT 
- 
- 
X 
X 
X 
X 
Safety Follow-up e 
30 days 
NA 
- 
 
X 
 
 
Observation Period 
Pembrolizumab 
Monotherapy:  
Doses 5 and 6 f  
1 
Predose 
- 60 mina 
X 
X 
X 
 
End of pembrolizumab Infusion 
+ 15 minb 
X 
 
X 
 
CR: complete response; EOT: end of treatment; NA: not applicable; PK: pharmacokinetics; . 
a. 
Within 60 min prior to pembrolizumab infusion. 
b. Within 15 min after the end of pembrolizumab infusion (before the infusion of ASP7517 on C1D1 and C4D1). 
c. 
Within 15 min after the end of ASP7517 infusion. 
d. Within 60 min prior to ASP7517 infusion. 
e. 
For participants in ASP7517 monotherapy arm and participants in ASP7517 and pembrolizumab combination therapy arm who end the treatment early or completed the treatment 
period [see Table 3]. 
f. 
For participants in ASP7517 and pembrolizumab combination therapy arm who receive pembrolizumab monotherapy in the Observation Period [see Table 4]. Doses 5 and 6 are 
the first 2 doses of pembrolizumab in the Observation Period when 6 cycles in the Treatment Period are completed. If the Treatment Period ends earlier than Cycle 6 and 
pembrolizumab monotherapy continues in the Observation Period, pembrolizumab PK is continued to the 6th dose of pembrolizumab from C1D1.   
g. Sample not collected in Stage 2 of Dose Expansion. 
h. Pembrolizumab PK samples only applicable for participants in the combination therapy arm. 
 


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2 
INTRODUCTION 
In this study (7517-CL-1101), ASP7517 is indicated as a single agent and in combination 
with pembrolizumab in participants with advanced solid tumors known to express the Wilms’ 
tumor protein 1 (WT1) antigen.  
Details about ASP7517 are provided in the Investigator’s Brochure. 
Details about pembrolizumab are provided in the summary of product characteristics/package 
insert of this product. 
2.1 
Study Rationale 
Accumulating evidence indicates that the WT1 gene plays an oncogenic function in 
leukemogenesis and tumorigenesis. The WT1 gene is highly expressed in leukemia and 
various types of solid tumors (e.g., melanoma, ovarian cancer and colon cancer) and is listed 
at the top of the ranking of tumor antigen [Sugiyama, 2010]. In addition, WT1 tumor antigen 
expression plays an important role in the progression of disease and prognosis of human 
malignancies [Qi, 2015; Sugiyama, 2010]. ASP7517 has effects against WT1 expressing 
tumors by inducing both natural killer 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 artificial 
Adjuvant Vector Cell (aAVC). In addition, nonclinical data suggest that ASP7517 is active in 
WT1 expressing tumor as described in Sections 4.1.1.2.5, 4.1.1.2.6 and 4.1.1.2.7 of the 
Investigator’s Brochure; therefore, ASP7517 treatment for solid tumors known to express 
WT1 may result in clinical benefit. 
2.2 
Background 
The WT1 gene was isolated as the gene responsible for a childhood renal neoplasm, Wilms’ 
tumor, which was thought to arise as a result of inactivation of both alleles of the WT1 gene 
located at chromosome 11p13 [Gessler et al, 1990]. This gene encodes a zinc finger 
transcription factor that plays an important role in cell growth and differentiation [Sugiyama, 
2001]. 
The WT1 gene is also expressed at high levels in almost all types of solid tumors, with its 
expression level serving as a significant prognostic factor. Cancers over-expressing WT1 
include melanoma, leukemia, breast cancer, ovarian cancer, glioblastoma, soft tissue sarcoma 
and colorectal cancer (CRC) [Bejrananda et al, 2010; Wagner et al, 2008; Nakatsuka et al, 
2006; Miyoshi et al, 2002; Menssen et al, 2000; Oji et al, 1999; Miwa et al, 1992]. 
In addition to its prognostic role in a variety of cancer types [Köbel et al, 2008; Sotobori et al, 
2006], WT1 is recognized as a promising target for immunotherapy based on its unique 
features [Dao et al, 2013; Cheever et al, 2009]. In addition, WT1 tumor antigen expression 
plays an important role in the disease progression of human malignancies [Qi, 2015; 
Sugiyama, 2010].  


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ASP7517 has effects against WT1-expressing tumors by inducing both natural killer (NK) 
cell activity (innate immunity) and WT1-specific T cell-dependent antitumor effects 
(adaptive immunity). 
Nonclinical pharmacology studies were performed to demonstrate that both the innate and 
adaptive immune system were activated by aAVC. Activation of innate immunity was 
demonstrated in a mouse lung metastatic cancer model, where NK cell depletion resulted in 
reduced antitumor effects. Activation of adaptive immunity was demonstrated in a second 
mouse model where mice were inoculated with AML tumor cells that either expressed WT1 
or did not express WT1. In this model, aAVC (NIH3T3)-WT1 (ASP7517 surrogate) 
prolonged survival in the mice inoculated with the WT1-expressing tumor cells. In addition, 
studies of ASP7517 surrogate demonstrated increase of the production of CD8+ T cells 
secreting IFNγ by WT1 peptide stimulation. For additional information on ASP7517 please 
refer to Investigator’s Brochure.  
2.2.1 
Melanoma 
Overall survival for advanced-stage melanoma of the skin has improved dramatically over 
the last decade from approximately 9 months before 2011 to at least 2 years in 2017 [Luke et 
al, 2017]. However, approximately 60% to 70% of patients that receive anti-programmed cell 
death protein 1 (anti-PD-1) therapy do not respond to treatment. Furthermore, acquired 
resistance is common, causing some patients who initially responded to the therapy to later 
experience disease progression. A recent study found that nearly 25% of patients with 
melanoma who initially had received an objective response had disease recurrence at 
follow-up (a median of 21 months) [Simeone & Ascierto, 2017]. Therefore, there is a high 
unmet need that persists for this patient population. 
2.2.2 
Colorectal Cancer 
CRC is one of the leading causes of cancer-related deaths worldwide [Fitzmaurice et al, 
2017]. Nearly 20% of CRC patients have metastasis at diagnosis [Christensen et al, 2018]. 
The treatment is palliative in the majority of these patients and the goal of treatment is to 
increase the quality of life and prolong overall survival (OS) [Weeks et al, 2012]. Stage 4 
CRC has a poor prognosis, with a less than 10% 5-year survival rate and a median survival 
time of approximately 5 months in patients who receive optimal supportive care without 
chemotherapy [Zacharakis et al, 2010]; and a 5-year survival rate less than 20% with 
chemotherapy, presenting the need of new therapy to address the high unmet need that 
persists for this patient population [American Cancer Society 2020; Siegel et al, 2014].  
2.2.3 
Ovarian Cancer 
Ovarian cancer is predominantly diagnosed in postmenopausal women, and due to the lack of 
symptoms in early stages, 75% of patients are diagnosed in advanced stages of the disease 
[Doubeni et al, 2016]. Most patients diagnosed with advanced ovarian cancer develop 
platinum resistant/refractory disease [Matsuo et al, 2010]. The median progression-free 
survival time for recurrent ovarian cancer is less than 6 months, and median overall survival 
is less than 15 months [Shimokawa et al, 2018]. Recurrent epithelial ovarian carcinoma is 


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generally considered an incurable disease and second-line chemotherapy may be 
administered for palliation of symptoms and extension of survival [Adams et al, 1998; 
Ozols, 1997].  
Based on the above, the majority of patients with melanoma, CRC and ovarian cancer are not 
cured with available therapies, underscoring the urgent need for new therapeutic alternatives 
that will improve the clinical outcomes of these patients. 
This study will include participants with locally progressive (unresectable) or metastatic solid 
tumor malignancies known to express WT1 antigen, including but not limited to melanoma, 
ovarian cancer and CRC, who have received all standard therapies (except CPI-naïve 
melanoma in phase 2). This study may contribute to an unmet medical need. 
2.3 
Risk/Benefit Assessment 
2.3.1 
ASP7517 Risk Assessment 
One study with ASP7517 in humans is currently ongoing (7517-CL-0101). The potential 
risks described in Table 7 and sections below are based on ASP7517 nonclinical studies. 
Also, study 7517-CL-0101 and clinical data from compounds with similar mechanism of 
action or composition risks information is available and discussed in this section.  
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. 
In the first-in-human ongoing clinical study (7517-CL-0101), there have been no dose 
limiting toxicities (DLTs) and 15 serious adverse events (SAE; 11 febrile neutropenia, 
1 pneumonia fungal, 1 atrial fibrillation, 1 delirium and 1 tumor-associated fever) reported 
(Data Snapshot/Extraction Point 31 May 2021). All reported SAEs were assessed as 
unrelated to the study product. 


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Table 7 
Potential Safety Concerns of ASP7517 based on Preclinical Studies 
Key Safety Targets 
Key Observations 
Relevance to 
Human Usage 
Liver 
Increased liver weight, increased AST and ALT,  
hepatocyte focal necrosis, mixed inflammatory cell 
infiltration (≥ 1 × 105 cells/kg, mononuclear cell 
aggregation (≥ 1 × 106 cells/kg, pigment laden 
macrophage infiltration (at ≥ 1 × 107 cells/kg) 
Potential risk 
Spleen 
Increased spleen weight (at ≥ 1 × 105 cells/kg); 
extramedullary hematopoiesis (≥ 1 × 106 cells/kg) 
Potential risk 
Emboli 
Emboli in the spleen and liver (≥ 1 × 105 cells/kg) 
Potential risk 
Kidney 
Increased creatinine, tubular basophilia, mononuclear cell 
infiltration (≥ 1 × 106 cells/kg) 
Potential risk 
Hematology 
Decreased platelet count 1 day after dose, increased 
platelet count 7 days after dose (≥ 1 × 105 cells/kg) 
Potential risk 
Pancreas 
Acinar cell necrosis, interstitial edema, mononuclear cell 
infiltration (≥ 1 × 107 cells/kg) 
Potential risk 
Urinary bladder 
Mononuclear cell infiltration (1 × 108 cells/kg) 
Low potential risk 
Submandibular gland 
Mononuclear cell infiltration (1 × 108 cells/kg) 
Low potential risk 
Epididymis 
Interstitial fibrosis and granuloma (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 
Not determined 
ALT: alanine aminotransferase; AST: aspartate aminotransferase; NOG: NOD.Cg-Prkdcscid Il2rgtm1Sug/Jic. 
2.3.1.1 Liver  
Preclinical studies demonstrated that 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 aspartate aminotransferase [AST] and alanine 
aminotransferase [ALT] 1 day after administration) and were completely reversed by 28 days 
after ASP7517 administration. The AEs in mice included increased liver weight, AST and 
ALT elevation, embolus, 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. 
2.3.1.2 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 


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physiological ranges by day 28. The standard assessment of hematology is recommended in 
clinical studies. 
2.3.1.3 Pancreas 
Edema was noted in gross pathology at doses of 1 × 107 cells/kg and higher doses 1 day after 
the sixth dose. This finding fully resolved by 7 or 28 days after the sixth dose. Histological 
assessment showed the presence of focal necrosis at a dose of 1 × 108 cells/kg 7 days after the 
second dose. After the sixth dose, acinar cell necrosis and interstitial edema on 1 day, and 
mononuclear cell infiltration and focal acinar cell necrosis on 7 days, were observed at 
1 × 107 cells/kg and higher doses. No edema or cell necrosis was observed 28 days after the 
sixth dose. 
The no-observed-adverse-effect-level for the toxicity in the pancreas was 1 × 106 cells/kg. 
These findings were partially or fully resolved 28 days after the second or the sixth dose. 
2.3.1.4 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. 
2.3.1.5 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 of 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. 
2.3.1.6 Infusion-related Reactions 
In nonclinical studies with ASP7517, IRRs/cytokine-release syndrome (CRS) was 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. 


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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 may 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]. Participants should be 
closely monitored for IRRs and CRS and appropriately managed per standard of care. 
2.3.1.7 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. Participants should be monitored closely for any 
signs or symptoms of allergic reaction or anaphylaxis and managed appropriately per 
standard of care. 
2.3.1.8 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 AEs 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]. 
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. In addition, the 
study medical monitor should be contacted to discuss event monitoring, follow up and study 
treatment management. 
2.3.1.9 Pembrolizumab Risk Assessment 
Refer to pembrolizumab package insert, summary of product characteristics monograph or 
local prescribing information for key safety information and potential toxicities. 


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Pembrolizumab may cause severe or life-threatening infusion-reactions including severe 
hypersensitivity or anaphylaxis. Signs and symptoms usually develop during or shortly after 
drug infusion and generally resolve completely within 24 hours of completion of infusion. 
Dose modification and toxicity management guidelines on pembrolizumab associated 
infusion reaction are provided in [Section 10.8 Appendix 8: Infusion Reaction Dose 
Modification and Treatment (Guidelines for ASP7517 and Pembrolizumab); Section 10.9 
Appendix 9: Monitoring of Pembrolizumab Potential Immune-related Adverse Events; 
Section 10.10 Appendix 10: Dose Modification and Toxicity Management for 
Immune-related AEs; and Section 10.11 Appendix 11 Dose Modification and Toxicity 
Management of Infusion Reactions Related to Pembrolizumab]. 
Note: There is a potential for an increase of rate and/or frequency on immune-related adverse 
events (irAEs) due to the overlap of immune therapy.  
2.3.2 
Risk Mitigation  
The study population is restricted to participants with advanced/metastatic solid tumors who 
have received, declined or had a contraindication to all therapy with established clinical 
benefit for their malignancy. Strict adherence to the eligibility criteria is essential to ensure 
investigators select appropriate participants for participation in the study.  
Additionally, the following precautions mitigate risk and protect participant safety: 
● Conservative criteria for interruption and/or discontinuation of study treatment. 
● The Dose Escalation and Safety Committee (DESC) will convene once a dose level 
cohort completes the dose limiting toxicity (DLT) observation period and the data are 
available for review. The committee’s decision on the dose level for the next cohort will 
be guided according to the Bayesian optimal interval (BOIN) Design based on DLTs 
observed in the DLT observation period. While safety data from the DLT observation 
period in the escalation cohorts are the minimum safety data needed for the committee 
meeting, all available safety findings, including those occurring after the designated 
DLT observation period that meet DLT criteria (“delayed DLT”), will be considered by 
the committee. 
● The safety in the expansion cohorts will be monitored using Bayesian logistic model and 
based on all DLT data obtained up to that time from both escalation cohorts and 
expansion cohorts and drug-related treatment-emergent adverse events (TEAEs) leading 
to death. Safety monitoring with these models will be started when an expansion cohort 
is opened. Enrollment in expansion cohorts may be held based on the criteria described 
in Section 9.5. 
The potential risk of irAEs and infusion-related reactions (IRRs) may be mitigated by closely 
monitoring participants’ symptoms, signs and clinical laboratory test results to facilitate early 
identification and management, as per the guidelines in Section 10.8 Appendix 8: Infusion 
Reaction Dose Modification and Treatment (Guidelines for ASP7517 and Pembrolizumab); 
Section 10.9 Appendix 9: Monitoring of Pembrolizumab Potential Immune-related Adverse 
Events; Section 10.10 Appendix 10: Dose Modification and Toxicity Management for 


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Immune-related AEs; and Section 10.11 Appendix 11: Dose Modification and Toxicity 
Management of Infusion Reactions Related to Pembrolizumab]. The management of such 
toxicities should be based on institutional standard of care and published guidelines, as 
appropriate based on investigator judgment, and on the protocol instructions regarding 
interruption or discontinuation of study drug treatment. 
2.3.3 
Benefit Assessment 
ASP7517 has effects against WT1 expressing tumors by stimulating innate and adaptive 
immunity and showed no significant safety findings in the preclinical pharmacology studies. 
In the repeated dose toxicity studies with mice, all major findings were reversible and 
monitorable; therefore, ASP7517 may provide benefit of effective and safe treatment in solid 
tumors with limited treatment option upon progression. 
Pembrolizumab is a humanized monoclonal antibody that targets programmed cell 
death protein 1 (PD-1) receptors on T lymphocytes targeting the negative regulators of the 
immune response rather than the tumor itself; thus, these agents are not specific to any type 
of malignancy therefore it has shown antitumor activity in various tumor types. 
Pembrolizumab has been approved to treat metastatic melanoma, non-small cell lung cancer 
and any unresectable or metastatic solid tumor with microsatellite instability and DNA 
mismatch repair deficiency. Pembrolizumab may improve the effect of ASP7517 since the 
inhibition of the binding of PD-1 to its ligands prevents immune evasion by cancer cells. As 
such, pembrolizumab would prime the immune system and make cancer cells more 
susceptible to the immune system which can be activated by ASP7517.  
Animal models suggest that ASP7517 treatment combinations with PD-1 pathway blockade 
may provide additive antitumor effect. 
The majority of patients treated with the current standard of care including with anti-PD-1 
monotherapies do not achieve objective responses, and most tumor regressions are partial 
rather than complete. The majority of patients with metastatic disease are not cured with 
available therapies, underscoring the urgent need for new therapies that will improve the 
clinical outcomes of these patients. 
2.3.4 
Overall Risk-Benefit Conclusion 
ASP7517 has effects against WT1 expressing tumors and showed no significant safety 
findings in the preclinical pharmacology studies. In the mice repeated dose toxicity studies of 
ASP7517, all major findings were reversible and monitorable and will not interfere with 
human clinical studies considering its potential benefit against the risk.  
Despite their clinical benefit, checkpoint inhibitors (CPIs) have side effects that are unique 
compared to traditional chemotherapy. The immune related side effects associated with CPIs 
can manifest in a number of organ systems, including gastrointestinal, endocrine, hepatic, and 
skin. With combination therapy of different CPIs, the toxicities are expected to overlap. 
Overall, the risk associated with participation in this clinical study of ASP7517 as single 
agent and in combination with pembrolizumab is considered to be acceptable for this 


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population of participants with advanced/metastatic solid tumors who have received, declined 
or had a contraindication to all therapy with established clinical benefit for their malignancy 
(except the CPI-naïve melanoma cohort in phase 2). 
In addition, the adequate study design with the strict adherence to the eligibility criteria, 
safety assessments, dosing and stopping/discontinuation rules is essential and will ensure 
participant safety on the study. 
3 
OBJECTIVES, ENDPOINTS  
Table 8 
Study Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
● 
To evaluate the safety and tolerability of 
ASP7517 when administered as a single agent 
and in combination with pembrolizumab 
● 
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 when administered as a single agent 
and in combination with pembrolizumab 
(phase 1) 
● 
DLTs 
● 
To evaluate the clinical response of ASP7517 
when administered as a single agent and in 
combination with pembrolizumab (phase 2) 
● 
Objective response rate per iRECIST 
(iORR) by independent central review 
Secondary 
● 
To evaluate other measures of anticancer 
activity of ASP7517 when administered as a 
single agent and in combination with 
pembrolizumab based on central and local 
assessment 
● 
Objective response rate per RECIST v1.1 
(ORR) 
● 
Disease control rate per iRECIST (iDCR) 
and RECIST v1.1 (DCR) 
● 
Progression-free survival per iRECIST 
(iPFS) and RECIST v1.1 (PFS) 
● 
Overall survival (OS) 
● 
Duration of response per iRECIST (iDOR) 
and RECIST v1.1 (DOR) 
Exploratory 
● 
To evaluate potential genomic, proteomic 
and/or other biomarkers that may correlate with 
treatment outcome when ASP7517 
administered as a single agent and in 
combination with pembrolizumab 
● 
Exploratory tumor and peripheral biomarkers 
that may correlate with treatment outcome of 
ASP7517 monotherapy or in combination with 
pembrolizumab 
Table continued on next page 


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Objectives 
Endpoints 
Exploratory (continued) 
● 
To evaluate pharmacodynamic activities of 
ASP7517 as a single agent and in combination 
with pembrolizumab 
● 
Pharmacodynamic effects of ASP7517 as a 
monotherapy or in combination with 
pembrolizumab, such as changes in: 
o 
Cytokine expression and secretion (e.g., 
IFNγ 
o 
WT1-specific T lymphocytes (e.g., 
cytotoxic T lymphocytes) 
o 
Immune cell populations (NKT cells, NK 
cells, etc.)  
o 
Anti-WT1 antibodies 
o 
Tumor microenvironment 
● 
To characterize the pharmacokinetic profile of 
ASP7517 when administered as a monotherapy 
and in combination with pembrolizumab 
● 
Cellular DNA load and kinetic parameter 
estimates (including AUC, Cmax, Ctrough and tmax) 
for ASP7517 as a monotherapy or in 
combination with pembrolizumab 
AE: adverse event; DLT: dose limiting toxicity; ECG: electrocardiogram; ECOG: Eastern Cooperative 
Oncology Group; IFNγ: interferon gamma; iRECIST: immune response evaluation criteria in solid tumors; 
MTD: maximum tolerated dose; NK: natural killer; NKT: natural killer T; RECIST: response evaluation criteria 
in solid tumors; RP2D: recommended phase 2 dose; SAE: serious adverse event; WT1: Wilms’ tumor protein 1. 
4 
STUDY DESIGN AND DOSE RATIONALE 
4.1 
Overall Study Design 
This study is a phase 1/2, open-label study of ASP7517 as monotherapy and in combination 
with pembrolizumab in selected participants with advanced solid tumors known to express 
WT1 antigen.  
This study consists of arms receiving ASP7517 monotherapy and arms receiving ASP7517 
and pembrolizumab combination therapy in phase 1 (dose escalation cohort) and phase 2 
(dose expansion cohort). Japan sites will participate only in the phase 2 monotherapy arm. 
Additional cohort may be added by a protocol amendment to further evaluate ASP7517 as a 
single agent and/or in combination with another anti-cancer agent.  
4.1.1 
Study Periods 
For participants in all arms/phases, the study consists of the following periods:  
● 
Screening: (up to 28 days) 
● 
Treatment (up to six 28-day cycles): 
o ASP7517 Monotherapy Arm: ASP7517 every 28 days 
o ASP7517 and Pembrolizumab Combination Therapy Arm: ASP7517 every 
28 days and pembrolizumab every 6 weeks in combination (up to 6 doses of 
ASP7517 in combination with up to 4 doses of pembrolizumab); 
● 
End of Treatment (EOT) Visit: Participants will complete an EOT visit within 
7 days of EOT determination or prior to initiation of new anticancer therapy 


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● 
Safety Follow-up: Participants will complete 30-day, 60-day and 90-day safety 
follow-up visits from the last dose of study drug or prior to the initiation of new 
anticancer therapy 
● 
Observation Period: 
o Observation Period for Monotherapy: All participants will enter an observation 
period after EOT, except those with iCPD, iUPD (per independent central 
review or local review) and who are not clinically stable or clinical progression 
is confirmed by the investigator. The observation period consists of safety 
follow-up visits (30, 60 and 90 days after last dose administered in the treatment 
period) and visits for only tumor imaging (every 8 weeks for up to 48 weeks). 
o Observation Period for Combination Therapy: Participants will enter an 
observation period 6 weeks from the last dose of pembrolizumab in combination 
with ASP7517 (up to 96 weeks and may receive pembrolizumab monotherapy 
up to a total of 17 doses every 6 weeks for qualifying participants).   
● 
Survival Follow-up: Telephone contact will be made every 3 months for up to 
12 months. 
4.1.2 
ASP7517 Monotherapy Arm in Dose Escalation Phase 1 Cohort 
For ASP7517 Monotherapy Arm in Dose Escalation portion participants will receive 1 dose 
of ASP7517 on Day 1 of each 28-day cycle for up to 6 doses. Following the first 2 cycles, 
participants who have not met any individual treatment discontinuation criteria and are 
receiving clinical benefit (defined as radiological response or stable disease [SD], or 
reduction of disease-related symptoms) may continue further treatment with ASP7517, as 
decided by the investigator. 
Participants who achieve confirmed complete response (CR) within the first 4 cycles will not 
receive further treatment with ASP7517, and participants who achieve partial response (PR) 
or SD after 4 doses may receive an additional 2 doses. An EOT visit will be conducted for all 
participants within 7 days of EOT determination or prior to the initiation of new anticancer 
therapy, whichever occurs first. 
The starting dose level is 1 × 107 cells/dose and the decision to escalate to the next dose level 
(1 × 108 cells/dose) will be made based on the assessment of safety variables, including the 
occurrence of dose limiting toxicities (DLTs). Dose level may be de-escalated to a lower dose 
level (1 × 106 cells/dose) based on the occurrence of DLTs. 
After the EOT visit, participants will complete 30-day, 60-day and 90-day safety follow-up 
visits from the last dose of ASP7517 or prior to the initiation of new anticancer therapy.  
All participants will enter an observation period except those with confirmed disease 
progression by immune response evaluation criteria in solid tumors (iRECIST) (iCPD), 
unconfirmed disease progression based on iRECIST (iUPD) (per independent central review 
or local review) and who are not clinically stable or clinical progression is confirmed by the 
investigator. Participants in the Monotherapy Arm Observation Period will be followed for 
up to 48 weeks starting at EOT until iCPD per independent central review, initiation of a new 


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anticancer therapy or meeting 1 of the Observation Period discontinuation criteria, whichever 
occurs first. Safety Follow-up period is included in Observation Period. 
All participants will be followed for survival, subsequent anticancer treatments and treatment 
outcomes following the conclusion of the Observation Period. 
Refer to [Section 4.1.5] for additional dose escalation cohort management details.  
4.1.3 
ASP7517 and Pembrolizumab Combination Therapy Arm in Dose Escalation 
Phase 1 Cohort 
In the combination treatment arm, ASP7517 will be given on Day 1 of each 28-day cycle for 
up to 6 doses in combination with pembrolizumab for up to 4 doses administered every 
6 weeks, starting from Day 1 of Cycle 1. For combination treatment, a 400 mg 
pembrolizumab infusion will be administered first, followed by an ASP7517 infusion at least 
1 hour after the completion of the pembrolizumab infusion. Following the first 2 cycles, 
participants who have not met any individual treatment discontinuation criteria and are 
receiving clinical benefit (defined as radiological response or SD, or reduction of 
disease-related symptoms) will continue further treatment with ASP7517 and pembrolizumab 
as decided by the investigator. Participants who achieve confirmed CR within the first 4 
cycles will not receive further treatment with ASP7517 at Cycle 5 and Cycle 6 (end of 
Treatment period) and participants who achieve PR or SD after 4 doses may receive 
additional 2 doses of ASP7517 in combination with pembrolizumab.   
Participants completing the Treatment period who enter the Observation Period with CR, PR 
or SD are allowed to continue on pembrolizumab alone up to a total of 17 doses for those 
participants who, in the opinion of the investigator, are continuing to derive clinical benefit. 
Subsequent to the Treatment period, all participants, except those with iCPD, iUPD who are 
not clinically stable or have clinical disease progression per independent central review or 
local review will enter the Observation Period to monitor treatment response. Participants in 
the Combination Arm Observation Period will be followed for up to 78 weeks starting at 
EOT until iCPD (confirmed by independent central review or local review), initiation of a 
new anticancer therapy or meeting 1 of the Observation Period discontinuation criteria, 
whichever occurs first. If participant discontinues combination treatment of ASP7517 at any 
time prior to C5D15, then the participant should continue observation period up to a total of 
96 weeks. 
After discontinuation of IP, all participants will complete an EOT visit, along with 30-, 60- 
and 90-day safety follow-up visits from the last dose of IP or prior to the initiation of new 
anticancer treatment.  
The initial dose escalation cohort of pembrolizumab combination with ASP7517 will use a 
starting dose of ASP7517 1 × 107 cells/dose.  
The decision to escalate to the next dose level (1 × 108 cells/dose) will be made based on the 
assessment of safety variables, including the occurrence of DLTs. A dose level of ASP7517 
may be de-escalated to a lower dose level (1 × 106 cells/dose) based on the occurrence of 


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DLTs. Refer to [Section 10.1.5.1 Dose Escalation and Safety Committee] for details about 
the DESC. 
All participants will be followed for survival, subsequent anticancer treatments and treatment 
outcomes following the conclusion of the Observation Period.  
4.1.4 
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 Cycle 1 Day 1 (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 the 
National Cancer Institute’s Common Terminology Criteria for Adverse Events 
(NCI-CTCAE), version 5.0.  
4.1.4.1 ASP7517 Monotherapy Arm DLTs 
● Non-hematologic AEs that are ≥ grade 3 and that do not resolve to ≤ grade 2 within 
72 hours of onset 
● Confirmed Hy’s law case 
● IRR that requires the infusion to be discontinued 
● Prolonged delay (> 2 weeks) in initiating Cycle 2 due to treatment-related toxicity 
● Any treatment-related toxicity that causes the participant to discontinue treatment during 
Cycle 1 
● Grade ≥ 3 thrombocytopenia accompanied by bleeding that requires transfusion or 
hospitalization 
● Grade ≥ 3 anemia requiring transfusion 
● Grade 3 febrile neutropenia with or without infection 
● Grade 5 treatment-related toxicity 
The following AEs will not be considered as DLTs in the ASP7517 monotherapy arm: 
● 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 
● 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 72 hours 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 
● Grade 3 irAEs that resolve to ≤ grade 1 within 72 hours of onset  
4.1.4.2 ASP7517 and Pembrolizumab Combination Therapy Arm DLTs 
● Grade ≥ 3 non-hematological AE that does not resolve to ≤ grade 2 within 72 hours of 
onset  


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● Grade ≥ 3 febrile neutropenia  
o Grade 3 febrile neutropenia is defined as absolute neutrophil count (ANC) 
< 1000/mm3 with a single temperature of > 38.3°C (101°F) or a sustained 
temperature of ≥ 38°C (100.4°F) for more than 1 hour. 
o Grade 4 febrile neutropenia is defined as ANC < 1000/mm3 with a single 
temperature of > 38.3°C (101°F) or a sustained temperature of ≥ 38°C (100.4°F) 
for more than 1 hour, with life-threatening consequences and urgent intervention 
indicated. 
● Grade ≥ 3 thrombocytopenia accompanied by bleeding that requires transfusion or 
hospitalization 
● Grade ≥ 3 anemia requiring transfusion 
● Grade ≥ 2 pneumonitis 
● Grade ≥ 2 encephalopathy, meningitis or motor or sensory neuropathy 
● Confirmed Hy’s law cases 
● Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 × upper limit 
of normal (ULN) in participants without liver metastases 
● AST or ALT > 8 × ULN in participants with liver metastases  
● Total bilirubin (TBL) > 3 × ULN (grade ≥ 3) 
● Guillain-Barré syndrome or myasthenic syndrome/myasthenia gravis 
● IRR that requires the infusion to be discontinued 
● Prolonged delay (> 2 weeks) in initiating Cycle 2 due to treatment-related toxicity 
● Any treatment-related toxicity that causes the participant to discontinue treatment during 
Cycle 1 
● Grade 5 treatment-related toxicity 
Participants experiencing a DLT will be discontinued from the study unless the participants 
are deriving clinical benefit from the study treatment in the opinion of the investigator; in 
those cases, after discussion with the sponsor, participants may be allowed to continue study 
treatment with ASP7517 upon resolution of the DLT event to ≤ grade 1 or baseline. 
Participants who are tolerating IP at a dose level that is being reviewed due to the occurrence 
of DLTs in another participant will not be automatically precluded from continued dosing 
during the safety review, and will be allowed to continue dosing for as long as tolerated 
unless directed otherwise as a result of the safety review by the DESC.  
DLTs Requiring Discontinuation of Treatment 
● 
If a study participant develops a grade 4 DLT after receiving Cycle 1, then the study 
participant should not receive Cycle 2 of the study product. 
● 
If a study participant develops a grade ≥ 3 non-hematological AE that does not resolve to 
≤ grade 2 within 72 hours of onset, it should be considered a DLT and the study 
participant should not receive Cycle 2 of the study product. 
If there is a delay in administration of Cycle 2 by > 4 weeks, it may result in discontinuation 
of Cycle 2 after discussion with the sponsor. 


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4.1.5 
Phase 1 Dose Escalation  
4.1.5.1 Safety Requirement for Monotherapy and Combination Therapy Dose 
Escalation 
After dosing with ASP7517, participants must be observed for safety for a minimum of 
4 hours in the dose escalation phase. The safety observation will consist of hourly AE 
observations. If new AEs are observed that are ≥ grade 3 during this time, participants should 
continue to be observed at the investigator’s discretion. The participant should be followed 
on an outpatient basis on planned visits during the DLT assessment period to closely monitor 
any AEs. 
The following vital sign assessment schedules apply: 
• At C1D1 and any visit when pembrolizumab and ASP7517 are administered together, 
vital signs are obtained predose (-1 h from start of pembrolizumab infusion), within 
15 min prior to start of the pembrolizumab infusion, 15 min (-5 to +10 min window) after 
the start of the pembrolizumab infusion, at the end of the pembrolizumab infusion 
(-5 to +10 min window), 30 min (± 10 min) after completion of the pembrolizumab 
infusion, within 15 min prior to the start of the ASP7517 infusion, every 15 min 
(-5 to +10 min window) during the ASP7517 infusion, at the end of the ASP7517 
infusion (-5 to +10 min window), and postdose (+30 min, +1, +2, +3 and +4 h [± 10 min 
window each] from end of the ASP7517 infusion). 
• ASP7517 dosing only: Vital signs will be obtained within 15 min prior to start of the 
ASP7517 infusion, every 15 min (-5 to +10 min window) during the ASP7517 infusion, 
every 15 min (-5 to +10 min window) during the ASP7517 infusion, at the end of the 
ASP7517 infusion (-5 to + 10 min window), as well as 30 min (± 5 min), 1 h (± 10 min) 
and 2 h (± 10 min) after completion of the ASP7517 infusion. If participants are still 
available, additional optional vital sign assessments 3 h (± 10 min) and 4 h (± 10 min) 
after completion of the ASP7517 infusion will be obtained. 
• Pembrolizumab dosing only: Vital signs will be obtained within 15 min prior to start of 
the pembrolizumab infusion, 15 min (-5 to +10 min window) after the start of the 
pembrolizumab infusion (-5 to + 10 min window), at the end of the pembrolizumab 
infusion (-5 to + 10 min window) and at 30 min (± 10 min) after completion of the 
pembrolizumab infusion for participants in the combination therapy. 
4.1.5.2 Phase 1 Dose Escalation Cohort for Monotherapy and Combination Therapy 
Arms 
The monotherapy and combination therapy dose escalation portion will evaluate escalating 
dose levels of ASP7517 in approximately 9 to 12 DLT-evaluable participants.  
Dose escalation will be guided according to the BOIN design [Liu & Yuan, 2015] to 
determine the next dose level based on DLT occurrence. After the planned number of 
evaluable participants has 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 


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3 to 4 evaluable participants for the initial assessment of each dose level. Refer to the 
Participant Replacement during Dose Escalation Cohort section for definition of evaluable 
participants. If the decision is made to remain at the current dose level, an additional 3 or 4 
evaluable participants may be enrolled at the current dose level. Three to 12 participants will 
be enrolled in the dose escalation cohort. A minimum of 6 participants must be enrolled at the 
dose level used to determine the maximum tolerated dose (MTD) and the recommended 
phase 2 dose (RP2D) of ASP7517. 
Study enrollment and study treatment will be temporarily interrupted during dose escalation 
of monotherapy or combination therapy arms pending review of the following: 
● 
Any death that is not related to disease progression occurring within 30 days of 
receiving IP 
● 
Occurrence of 2 grade ≥ 4 DLTs in 2 study participants 
● 
Any grade 4 hypersensitivity reaction/anaphylaxis 
Participant Replacement during Dose Escalation Cohort 
Participants may be replaced in the dose escalation cohort if: 
● 
Participant is discovered to have enrolled without fully satisfying eligibility criteria 
● 
Participant received less than the planned dose in Cycle 1 for reasons other than 
DLT 
● 
Participant has no DLT and withdraws from the study before the end of DLT 
evaluation period 
The decision regarding replacement of individual participants will be made by the sponsor 
with discussions with the treating investigator. 
Participants who experience DLTs in the dose escalation cohort will not be replaced. 
Refer to [Section 10.1.5.1 Dose Escalation and Safety Committee] for details about the 
DESC. 
Maximum Tolerated Dose 
The MTD determination will be based on at least 6 evaluable participants 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 for monotherapy and combination therapy. 
The dose level determined to be the MTD must have data from at least 6 participants. 
Determination of MTD will be done for monotherapy and combination therapy separately. 
Recommended Phase 2 Dose 
The sponsor, in conjunction with the DESC, will determine the RP2D of ASP7517 as a single 
agent and in combination with pembrolizumab 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.  


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The dose level determined to be the RP2D must have data from at least 6 participants. 
Determination of RP2D will be done for monotherapy and combination therapy separately. 
4.1.6 
Phase 2 Dose Expansion Cohort 
4.1.6.1 Monotherapy Arm Dose Expansion Cohort 
Monotherapy dose expansion will be opened after the phase 1 monotherapy arm dose 
escalation cohort has been completed and RP2D is established. If a confirmed response (PR 
based on iRECIST [iPR] or a CR based on iRECIST [iCR], per independent central review) 
is observed in a monotherapy arm dose escalation cohort, a tumor-specific dose expansion 
cohort may be opened in that tumor type after the phase 1 dose escalation has been 
completed. Once RP2D is determined; the melanoma expansion cohort may be opened (even 
if no response is observed in the dose escalation cohort). Participants with CPI refractory 
metastatic melanoma will be enrolled in the monotherapy dose escalation or expansion 
cohorts to allow for enrollment of this patient population in the combination arm dose 
expansion cohort. If antitumor activity was observed in dose escalation or melanoma dose 
expansion stage 1, expansion cohorts for CRC and ovarian cancer may be opened.  
Objective response rate per iRECIST (iORR), as confirmed per independent central review, 
is 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, 18 participants will be enrolled in a tumor-specific expansion cohort at each 
designated dose level (stage 1). If the iORR does not meet the optimal stopping boundaries 
(see table below), then an additional 25 participants will be enrolled for a total maximum 
sample size of 43 for that tumor type at each dose level (stage 2). Otherwise, the enrollment 
at that dose level will be closed. When the total number of participants reaches the maximum 
sample size of 43, it may be predicted that ASP7517 is efficacious if the number of responses 
is greater than or equal to 8.  
Optimized Stopping Boundaries for Monotherapy Arm 
Number of participants treated 
Stop if number of responses ≤  
18 
2 
If more than 1 dose level is open for enrollment within a selected tumor type, the newly 
enrolled participants with that tumor type will be randomly allocated to one 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 participants and dose level ‘y’ is newly opened for expansion, the next 
participant would be randomly allocated to dose level ‘x’ or ‘y’ with the ratio of 15:18.  
In case the enrollment for both the monotherapy arm escalation cohort and combination arm 
escalation cohort therapies opens together, participants will be randomized to either 
monotherapy or combination cohort in 1:1 ratio. 
When escalation and expansion cohorts are both open for enrollment, enrollment into 
escalation cohorts takes priority such that participants who are eligible for both will be 


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preferentially enrolled in the escalation cohorts. Additionally, enrollment in the expansion 
cohorts may be prematurely closed at the discretion of the sponsor. 
4.1.6.2 Combination Therapy Arm Dose Expansion Cohort 
The combination therapy arm dose expansion cohort will be opened after the phase 1 dose 
escalation cohort has been completed and MTD/RP2D of ASP7517 combination therapy has 
been determined. The metastatic melanoma CPI naïve cohort will be opened first. If 
5 confirmed responses (iPR or iCR per independent central review) are observed in 
metastatic melanoma CPI naïve participants, expansion cohorts for CRC, ovarian cancer and 
metastatic melanoma CPI refractory may be opened. In addition, if a confirmed response 
(iPR or iCR per independent central review) is observed in metastatic melanoma CPI 
refractory participants in the monotherapy arm, an expansion cohort for melanoma refractory 
participants may be opened for combination arm therapy, if not yet opened. 
For metastatic melanoma CPI naïve participants, initially 20 participants will be enrolled in 
an expansion cohort at each designated dose level (stage 1). If the iORR per independent 
central review does not meet the optimal stopping boundaries (see table below) for metastatic 
melanoma CPI naïve participants, then an additional 49 participants will be enrolled for a 
total maximum sample size of 69 at each dose level. When the total number of participants 
reaches the maximum sample size of 69, it may be predicted that the combination therapy 
with ASP7517 and pembrolizumab arm is effective if the number of responses is greater than 
or equal to 24. 
Optimized Stopping Boundaries for Metastatic Melanoma (CPI Naïve)  
Combination Therapy Arm 
Number of participants treated 
Stop if number of responses ≤  
20 
4 
CPI: checkpoint inhibitor 
For ovarian cancer, initially 19 participants will be enrolled in an expansion cohort at each 
designated dose level (stage 1). If the iORR per independent central review does not meet the 
optimal stopping boundaries (see table below) for ovarian cancer, then an additional 
36 participants will be enrolled for a total maximum sample size of 55 at each dose level. 
When the total number of participants reaches the maximum sample size of 55, it may be 
predicted that the combination therapy with ASP7517 arm is effective if the number of 
responses is greater than or equal to 13.  
Optimized Stopping Boundaries for Ovarian Cancer Combination Therapy Arm 
Number of participants treated 
Stop if number of responses ≤  
19 
3 
For CRC, initially 21 participants will be enrolled in an expansion cohort at each designated 
dose level (stage 1). If the iORR per independent central review does not meet the optimal 
stopping boundaries (see table below) for CRC, then an additional 39 participants will be 
enrolled for a total maximum sample size of 60 at each dose level. When the total number of 


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participants reaches the maximum sample size of 60, it may be predicted that the combination 
therapy with ASP7517 arm is effective if the number of responses is greater than or equal to 16.  
Optimized Stopping Boundaries for Colorectal Cancer Combination Therapy Arm 
Number of participants treated 
Stop if number of responses ≤  
21 
4 
For metastatic melanoma CPI refractory participants, initially 20 participants will be enrolled 
in an expansion cohort at each designated dose level (stage 1). If the iORR per independent 
central review does not meet the optimal stopping boundaries (see table below) for metastatic 
melanoma CPI refractory participants, then an additional 28 participants will be enrolled for a 
total maximum sample size of 48 at each dose level. When the total number of participants 
reaches the maximum sample size of 48, it may be predicted that the combination therapy 
with ASP7517 arm is effective if the number of responses is greater than or equal to 11.  
Optimized Stopping Boundaries for Metastatic Melanoma (CPI Refractory)  
Combination Therapy Arm 
Number of participants treated 
Stop if number of responses ≤  
20 
2 
CPI: checkpoint inhibitor 
If both monotherapy and combination therapy arms in the expansion cohorts are open for the 
same tumor type, randomization will be expanded to include both monotherapy and 
combination therapy arms and the randomization ratio will be based on the number of open 
slots still available at each dose level.  
Replacement of participants in phase 2 Dose Expansion Cohort 
If a participant in a phase 2 dose expansion cohort is not response evaluable (defined as the 
response analysis set [RAS]), an additional participant may be enrolled in that cohort based 
on sponsor discretion. 
UNIQUE to Japan Sites 
Japanese participants will be enrolled in the monotherapy arm of the dose expansion cohort. 
4.2 
Scientific Rationale for Study Design 
This study was designed to evaluate ASP7517 as monotherapy and in combination with 
pembrolizumab in selected participants with advanced solid tumors known to express WT1 
antigen. Antitumor efficacy of ASP7517 was demonstrated in preclinical AML model in 
which mice displayed significantly prolonged survival times. 
The rationale for evaluating the combination of ASP7517 and pembrolizumab is supported 
by preclinical in vivo studies obtained from mice models that show superior antitumor 
activity of combination therapy over monotherapy. Longer survival period was shown by 
aAVC-WT1 treatment in combination with anti-PD1 antibody relative to aAVC-WT1 alone. 
The prolonged survival time most likely results from WT1-specific antitumor effect induced 


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by aAVC (NIH3T3)-WT1. This suggests additive activity of ASP7517 with CPIs like 
pembrolizumab, which are known to restore immune system tumor surveillance, while 
ASP7517 functions by stimulating the immune system. Therefore, combination therapy may 
lead to higher rates of response in cancer patients compared to monotherapy. However, the 
combination may also increase the frequency or severity of toxicities, and thus, a dose 
escalation study is the appropriate setting to explore this combination.  
In this study, each participant will receive ASP7517 as monotherapy or in combination with 
pembrolizumab every 28 days.  
The design will closely monitor safety while efficiently assessing efficacy of ASP7517 dose 
levels of 1 × 107 cells/dose and 1 × 108 cells/dose as monotherapy and in combination with 
pembrolizumab fixed dose of 400 mg every 6 weeks.  
Tumor-specific expansion cohorts may be triggered by a confirmed response to ASP7517 or 
to the combination with pembrolizumab, or following the determination of RP2D. The types 
of cancer selected for the expansion cohorts were based on expression of WT1 in the tumor. 
Expansion will be initiated in melanoma (CPI naïve in the combination arm and CPI 
refractory in the monotherapy arm). A gated design in the expansion phase is being 
implemented to allow expansion into CRC and ovarian cancer. This gated design will allow 
early evaluation of response, avoiding a large number of participants being exposed to 
ineffective treatment. If antitumor activity is observed in dose escalation or melanoma dose 
expansion Stage 1, expansion cohorts for CRC and ovarian cancer may be opened. 
In the expansion phase of the combination arm, participants with metastatic melanoma are 
excluded if they received prior treatment with CPI. This will establish the efficacy of the 
combination of ASP7517 with pembrolizumab in CPI naïve participants. Also, there is no 
eligibility selection criteria for PD1 expression since it is not required per the pembrolizumab 
package insert for the tumor selected for the expansion phase. 
In addition, participants with HIV will be excluded since the compromised immune system 
may affect the immune response of ASP7517.  
Objective response rate (ORR) is selected as a suitable efficacy primary endpoint in such an 
early phase study because it can generally be assessed early and with a smaller sample size 
compared with survival studies. In addition, it provides an informative presentation of effect 
on tumor attributable to treatment since it is based on objective and quantitative assessment.  
Based on the above, this study is designed appropriately to assess safety and efficacy of 
ASP7517 as monotherapy and in combination with pembrolizumab in the selected 
participants. 
4.3 
Dose Rationale 
4.3.1 
ASP7517 
Nonclinical pharmacology data suggest ASP7517-surrogate shows prolonged survival when 
administered intravenously to the C1498-WT1 inoculated mouse AML model (per 30 g 
mouse), and prolonged survival was confirmed at the lowest dose level (5 × 102 cells/mouse) 


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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) for the first-in-human 7517-CL-0101 study, since the toxicology profile observed in 
the nonclinical studies was considered to be acceptable to initiate a clinical study at this dose 
level. In study 7517-CL-0101, 1 × 106 cells/dose and 1 × 107 cells/dose were completed with 
no DLT and determined to be safe by DESC. To date, 7 participants completed the DLT 
observation phase in the 1 × 108 cells/dose cohort without experiencing any DLTs, and 
DESC determined this dose level to be tolerable. Currently, additional participants are being 
enrolled in the 1 × 108 cells/dose cohort to confirm safety and tolerability. The starting dose 
of ASP7517 for study 7517-CL-1101 is selected to be 1 × 107 cells/dose for both 
monotherapy and combination therapy arms to balance protection of participant safety with 
efficient dose escalation. 
The dosing regimen of ASP7517 for this study will be treatments on Day 1 of each 28-day 
cycle, which is supported by nonclinical pharmacology and toxicology data. In mice 
immunized with specific antigen expressing aAVC at Day 0 and Day 28, NKT cells and 
T cells were stimulated after each administration, and recovery of toxicities were confirmed 
upon 28-day interval. Multiple administrations up to 6 doses are selected due to the 
immunosuppressive tumor microenvironment requiring repeated immune system reactivation 
to achieve response.  
4.3.2 
Pembrolizumab 
The planned dose of pembrolizumab for this study is 400 mg every 6 weeks. Recently, the 
manufacturer of pembrolizumab (Merck) has gained regulatory approval for a more 
convenient dosage in adults across all indications and regardless of tumor: 400 mg every 6 
weeks based on additional pharmacokinetic simulations [KEYTRUDA prescribing 
information, June 2020]. This schedule has demonstrated to provide equivalent exposure to 
the approved dosage of 200 mg every 3 weeks [Lala et al, 2018; Goldstein et al, 2017]  
The pharmacokinetic simulations study demonstrated that a dosage of 400 mg every 6 weeks 
provides adequate trough target engagement even for participants whose weights are higher 
than average, with occupancy of 97% for participants weighing 100 kg and 96% for those 
weighing 150 kg [Canadian Agency for Drugs and Technologies in Health, CADTH 
technology review, 2019]. 
4.4 
End of Study Definition  
The study start is defined as the date the first participant signs the informed consent form 
(ICF). End of study is defined as the last visit or scheduled procedure shown in the schedule 
of assessments for the last participant 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 participants enrolled in the country are no longer 
receiving IP. 


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5 
STUDY POPULATION 
All screening assessments must be completed and reviewed to confirm the potential 
participant 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 
Participant 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., HIPAA 
Authorization for U.S. sites) must be obtained from the participant prior to any study-
related procedures (including withdrawal of prohibited medication, if applicable). 
2. The participant is at least 18 years of age and legally an adult according to local 
regulation at the time of signing informed consent. 
3. Participant has locally-advanced (unresectable) or metastatic solid tumor malignancy that 
is confirmed by available pathology records or current biopsy. Participant must also have 
received all standard therapies (unless the therapy is contraindicated or intolerable) 
appropriate to provide clinical benefit in the opinion of the treating investigator for 
his/her specific tumor type. However, participants with metastatic melanoma who have 
not received CPIs (i.e., CPIs naive) may enroll in the phase 2 Combination Therapy Arm 
Dose Expansion Cohort to receive CPI: Pembrolizumab.   
4. Participant must be diagnosed with solid tumor known to express WT1 antigen such as, 
but not limited to melanoma, ovarian cancer or CRC (Examples of WT1 expressing 
cancers, please see literature reference by Sugiyama [2010]). 
5. Participant consents to provide an archival tumor specimen in a tissue block or unstained 
serial slides, if available, prior to study treatment. 
6. Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status 
of ≤ 2. 
7. Participant’s last dose of prior antineoplastic therapy, including any immunotherapy, was 
21 days or 5 half-lives, whichever is shorter, prior to initiation of IP administration. A 
participant with BRAF gene, epidermal growth factor receptor (EGFR) or anaplastic 
lymphoma kinase (ALK) mutation positive non-small cell lung carcinoma is allowed to 
remain on EGFR tyrosine kinase inhibitor (TKI) or ALK or BRAF inhibitor therapy until 
4 days prior to the start of IP administration. 
8. Participant has completed any radiotherapy (including stereotactic radiosurgery) at least 
2 weeks prior to IP administration. 
9. Participant’s AEs (excluding alopecia) from prior therapy have improved to grade 1 or 
baseline within 14 days prior to start of IP. 
10. Participant has adequate organ function prior to start of IP as indicated by the following 
laboratory values. If a participant has received a recent blood transfusion, the laboratory 
tests must be obtained ≥ 4 weeks after any blood transfusion: 


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Parameter 
Laboratory Value 
Hematological 
 
ANC 
≥ 1500/µL 
Platelets 
≥ 100000/µL 
Hemoglobin 
≥ 9 g/dL 
Renal 
 
Creatinine 
Either: 
a) ≤ institutional ULN, OR  
b) Estimated glomerular filtration rate* (eGFR) ≥ 45 mL/min/1.73m2 
if creatinine is > ULN 
*Using the Chronic Kidney Disease Epidemiology Collaboration 
(CKD-EPI) creatinine equation (2009); online calculator:  
https://www kidney.org/professionals/kdoqi/gfr_calculator 
Total bilirubin 
Either: 
a) ≤ 1.5 × ULN; or 
b) Direct bilirubin ≤ ULN and total bilirubin  
< 3 × ULN (for participants with Gilbert’s syndrome) 
AST (SGOT) and ALT (SGPT) 
≤ 2.5 × ULN 
ALT: alanine aminotransferase; ANC: absolute neutrophil count, AST: aspartate aminotransferase; 
CKD-EPI:  Chronic Kidney Disease Epidemiology Collaboration; eGFR: estimated glomerular filtration rate; 
SGOT: serum glutamic oxaloacetic transaminase; SGPT: serum glutamic pyruvic transaminase; ULN: upper 
limit of normal 
11. A female participant is eligible to participate if she is not pregnant (see [Section 10.2 
Appendix 2: Contraception Requirements]) and at least 1 of the following conditions 
applies: 
a. Not a woman of childbearing potential (WOCBP) (see [Section 10.2 Appendix 2: 
Contraception Requirements]) 
OR 
b. WOCBP who agrees to follow the contraceptive guidance (see [Section 10.2 
Appendix 2: Contraception Requirements]) from the time of informed consent 
through at least 6 months after the final IP administration. 
12. Female participant must agree not to breastfeed starting at screening and throughout the 
IP and for 180 days after the final IP administration. 
13. Female participant must not donate ova starting at screening and throughout the IP and 
for 180 days after the final IP administration. 
14. A male participant with female partner(s) of childbearing potential (including 
breastfeeding partner) must agree to use contraception (see [Section 10.2 Appendix 2 
Contraception Requirements]) throughout the treatment period and for at least 180 days 
after the final IP administration. 
15. Male participant must not donate sperm during the treatment period and for 180 days 
after the final IP administration. 
16. Male participant 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 the final IP administration. 
17. Participant agrees not to participate in another interventional study while receiving IP. 


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Additional Inclusion Criteria for Participants in the Expansion Cohorts: 
1. Participant meets one of the following: 
● Participant has the tumor type for which a confirmed response was observed in a 
monotherapy dose escalation cohort (monotherapy arm only) cohort; OR 
● For tumor specific expansion cohorts of ASP7517 or ASP7517 with pembrolizumab, 
participant has the applicable tumor type; CPI refractory metastatic melanoma 
(monotherapy and combination arms), CPI naïve melanoma (combination arm only), 
ovarian cancer, CRC. 
2. Participant has at least 1 measurable lesion per response evaluation criteria in solid 
tumors (RECIST) v1.1. Lesions situated in a previously irradiated area are considered 
measurable if progression has been demonstrated in such lesions.  
3. Participant consents to provide a tumor specimen in a tissue block or unstained serial 
slides obtained within 56 days prior to first dose of IP. If a recent tissue sample cannot be 
provided due to medical or safety concerns, enrollment into the study must be discussed 
with the medical monitor. 
4. Participant consents to undergoing a tumor biopsy (core tissue biopsy or excision) during 
the treatment period as indicated in the schedule of assessments if predose biopsy is 
available and if medically feasible. 
Waivers to the inclusion criteria will NOT be allowed. 
5.2 
Exclusion Criteria 
Participant will be excluded from participation in the study if any of the following apply: 
1. Participant weighs < 45 kg at screening.  
2. Participant has received investigational therapy (other than an investigational EGFR TKI 
in a participant with EGFR activating mutations or ALK or BRAF inhibitor in a 
participant with an ALK mutation) within 21 days or 5 half-lives, whichever is shorter, 
prior to start of IP. 
3. Participant requires or has received systemic steroid therapy or any other 
immunosuppressive therapy within 14 days prior to C1D1. Participants using a 
physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg 
per day of hydrocortisone up to 10 mg per day of prednisone) are allowed. 
4. Participant has symptomatic central nervous system (CNS) metastases or participant has 
evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans). 
Participants with previously treated CNS metastases are eligible, if they are clinically 
stable and have no evidence of CNS progression by imaging for at least 4 weeks prior to 
start of IP and are not requiring immunosuppressive doses of systemic steroids (> 30 mg 
per day of hydrocortisone or > 10 mg per day of prednisone or equivalent) for longer 
than 2 weeks. 
5. Participant has an active autoimmune disease. Participants with type 1 diabetes mellitus, 
endocrinopathies stably maintained on appropriate replacement therapy or skin disorders 
(e.g., vitiligo, psoriasis or alopecia) not requiring systemic treatment are allowed. 


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6. Participant was discontinued from prior immunomodulatory therapy due to a grade ≥ 3 
toxicity that was mechanistically related (e.g., immune related) to the agent in the 
judgment of the investigator.  
7. Participant has known history of serious hypersensitivity reaction to a known ingredient 
of ASP7517 or pembrolizumab or severe hypersensitivity reaction to treatment with 
another monoclonal antibody. 
8. Participant has a known history of human immunodeficiency virus. 
9. Participant with known history of positive hepatitis B surface antigen or isolated 
hepatitis B core antibody (including acute HBV or chronic HBV) or hepatitis C ([HCV] 
ribonucleic acid [RNA] detected by qualitative assay). Hepatitis C RNA testing is not 
required in participants with negative hepatitis C antibody testing. 
10. Participant has received a live vaccine against infectious diseases within 28 days prior to 
initiation of IP. 
11. Participant has a history of drug-induced pneumonitis (interstitial lung disease), a history 
of (non-infectious) pneumonitis that required steroids, radiation pneumonitis or currently 
has pneumonitis. 
12. Participant has an infection requiring systemic therapy within 14 days prior to IP. 
13. Participant has received a prior allogeneic bone marrow or solid organ transplant. 
14. Participant is expected to require another form of antineoplastic therapy while on IP. 
15. Participant has had a myocardial infarction or unstable angina within 6 months prior to 
the start of IP or currently has an uncontrolled illness including, but not limited to 
symptomatic congestive heart failure, clinically significant cardiac disease, unstable 
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would 
limit compliance with study requirements. 
16. Participant has a clinically significant abnormal electrocardiogram at screening in the 
investigator’s opinion. 
17. Participant has symptomatic cardiovascular disease within the preceding 12 months 
unless cardiology consultation and clearance has been obtained for study participation, 
including but not limited to the following: significant coronary artery disease (e.g., 
requiring angioplasty or stenting), acute myocardial infarction or unstable angina 
pectoris < 3 months prior screening, uncontrolled hypertension, clinically significant 
arrhythmia or congestive heart failure (New York Heart Association grade ≥ 3). 
18. Any condition that, in the investigator’s opinion, makes the participant unsuitable for 
study participation. 
19. Participant has had a major surgical procedure and has not completely recovered within 
28 days prior to the start of IP. 
20. Participant has a prior malignancy active (i.e., requiring treatment of intervention) within 
the previous 2 years prior to the screening visit, except for locally curable malignancies 
that have been apparently cured, such as basal or squamous cell skin cancer, superficial 
bladder cancer or carcinoma in situ of the cervix or breast. Participants 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. 


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21. Participant has International Normalized Ratio (INR) > 1.5 × ULN and/or activated 
partial thromboplastin time (aPTT) > 1.5 × institutional normal limits.   
Additional Exclusion Criteria for Participants in Combination Expansion Cohorts: 
1. Participants with metastatic CRC with documented microsatellite instability-high 
(MSI-H) or mismatch repair (MMR) deficient who have received prior treatment with 
PD-1 or programmed death-ligand (PD-L1) inhibitors such as nivolumab or 
pembrolizumab. 
2. For CPI naïve metastatic melanoma participants who have received to PD-1 or PD-L1 
inhibitors, such as nivolumab or pembrolizumab. 
3. Participant with metastatic ovarian cancer with documented MSI-H or MMR deficient 
who have received PD-1or PD-L1 inhibitors, such as nivolumab or pembrolizumab. 
Waivers to the exclusion criteria will NOT be allowed. 
5.3 
Lifestyle Considerations 
Not applicable. 
5.4 
Screen Failures 
A screen failure is defined as a potential participant who signed the ICF, but did not meet one 
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 28-day screening period without the need to 
register the participant as a screen failure. If the participant meets exclusion criteria that 
cannot resolve during the screening period, or more than 28 days elapse from the date of 
signing the ICF, the participant must be documented as a screen failure. In order to re-screen 
after prior screen failure, a new ICF must be signed and the participant entered into screening 
with a new participant identification number. Rescreening is only allowed once for an 
individual participant. 


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6 
INVESTIGATIONAL PRODUCT(S) AND OTHER STUDY 
TREATMENT(S) 
6.1 
Investigational Product(s) and Other Study Treatments 
Administered 
Table 9 
Investigational Product(s) 
Name 
ASP7517 
Pembrolizumab for Combination 
Therapy Arm 
Use 
Test product 
Test product 
Dosage Form 
Suspension for injection 
Solution for injection 
Physical Description 
Opalescent and white to slightly 
yellowish-white suspension 
Clear to slightly opalescent, colorless to 
slightly yellow solution 
Unit Dose Strength 
1 x 107 cells/mL 
100 mg/vial 
Packaging and Labeling 
Clear single use vial 
Clear single use vial 
Route of Administration 
Intravenous infusion 
Intravenous infusion 
 
Administration Frequency 
Administered intravenously every 28 days 
Administered intravenously every 6 weeks 
IMP or Non-IMP 
IMP  
IMP 
Sourcing 
Provided centrally by sponsor  
Provided centrally by sponsor unless 
otherwise designated 
IMP: Investigational Medicinal Product 
Refer to the pharmacy manual for detailed information regarding preparation, handling and 
storage of ASP7517. 
For pembrolizumab, refer to the prescribing information for detailed information regarding 
preparation, handling and storage [KEYTRUDA prescribing information, June 2020]. 
6.1.1 
Investigational Product Administration 
ASP7517 will be diluted with normal saline to approximately 50 mL and administered by 
intravenous infusion at 4 to 6 mL/min infusion rate through a dedicated intravenous line. 
Pembrolizumab will be administered at a dose of 400 mg via 30-min intravenous infusion 
every 6 weeks beginning on C1D1. Sites should make every effort to target infusion timing to 
be as close to 30 min as possible. However, given the variability of infusion pumps from site 
to site, a window between -5 min and +10 min is permitted (i.e., infusion time is 30 min 
(-5 min/+10 min). The pembrolizumab infusion should be completed at least 1 hour prior to 
ASP7517 injection for participants in ASP7517 and pembrolizumab combination therapy 
arms.  
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 APGD or sponsor’s designee in accordance with APGD or sponsor’s 
designee standard operating procedures (SOPs), current Good Manufacturing Practice (GMP) 
guidelines, International Council for Harmonisation of Technical Requirements for 


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Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines and 
applicable local laws/regulations. 
Each carton and 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. 
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 participants 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 handling, storage and 
accountability of the IP. 
6.3 
Randomization 
This is an open-label study. Participant 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 the phase 2 
dose expansion. 
In case the enrollment for both monotherapy escalation arm and combination therapy 
escalation arm opens together, participants will be randomized to either monotherapy or 
combination arm in 1:1 ratio. 
For phase 2 enrollment, if more than 1 dose level is open for enrollment within a selected 
disease type, the newly enrolled participants 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 participants and dose level ‘y’ is newly 


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opened for expansion of A7517 monotherapy for melanoma, the next participant would be 
randomly allocated to dose level ‘x’ or ‘y’ with the ratio of 15:18. 
If both monotherapy and combination therapy expansion arms are open for the same tumor 
type, randomization will be expanded to include both monotherapy and combination therapy 
arms and the randomization ratio will be based on the number of open slots still available at 
each dose level. 
UNIQUE to Japan Sites 
Japanese participants will be enrolled in the monotherapy arm of the dose expansion cohort. 
6.4 
Investigational Product and Other Study Treatment 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. 
6.5 
Dose Modification 
Dose modifications of ASP7517 are not allowed at the individual participant level without 
prior consultation with the sponsor’s medical monitor. Any participants who do not receive a 
subsequent dose within the scheduled time window in the schedules of assessments [Table 1 
and Table 2] can only resume treatment after discussion with the medical monitor. Any 
participant experiencing a grade 3 treatment-related AE after receiving a dose of ASP7517 
may receive the subsequent scheduled dose of ASP7517 only after the observed grade 3 
treatment-related 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). 
Refer to the appendices and approved pembrolizumab package insert, summary of product 
characteristics monograph or local product information supplied by the manufacturer for the 
recommended treatment modifications for pembrolizumab. 
6.6 
Continued Access to Investigational Product After the End of the 
Study  
ASP7517 will be given up to a maximum of 6 cycles. ASP7517 and pembrolizumab will not 
be made available after conclusion of the study to participants who are still receiving and 
benefitting from study treatment in countries where the product does not have marketing 
approval and is not commercially available, as the treatment with ASP7517 does not have 
authorization to be administered after the study is complete.   
Pembrolizumab will be administrated per the product insert treatment instructions and further 
treatment beyond the study period is allowed. 


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6.7 
Treatment of Overdose  
In the event of suspected ASP7517 overdose, the participant should receive supportive care 
and monitoring. The medical monitor/expert should be contacted as applicable. 
For this study, an overdose of pembrolizumab will be defined as any dose of 1000 mg or 
≥ 5 times the indicated dose.  
No specific information is available on the treatment of overdose of pembrolizumab. In the 
event of overdose, the participant should be observed closely for signs of toxicity. 
Appropriate supportive treatment should be provided if clinically indicated. 
In the event of suspected pembrolizumab overdose, refer to the approved package insert, 
summary of product characteristics or local product information supplied by the manufacturer 
for the IP.  
Refer to [Section 10.3.7 Reporting Procedures for Special Situations] for reporting 
requirements for suspected overdose or other medication error.  
6.8 
Concomitant Therapy 
The following treatments are prohibited during the study: 
● 
Investigational agents other than ASP7517 and pembrolizumab 
● 
Steroids and other immunosuppressive therapy: The use of immunosuppressive agents 
and immunosuppressive doses of systemic steroids (> 30 mg per day of hydrocortisone 
or > 10 mg per day of prednisone or equivalent) are not allowed during IP unless 
needed to manage AEs related to IP. The use of topical, ocular, intra-articular, 
intranasal and inhalational corticosteroids (with minimal systemic absorption) is 
allowed. Physiologic replacement doses of systemic corticosteroids (≤ 30 mg per day of 
hydrocortisone or ≤ 10 mg per day of prednisone or equivalent) are permitted. 
Corticosteroids for prophylaxis (e.g., contrast dye allergy) or for brief treatment of 
conditions not related to IP (e.g., delayed-type hypersensitivity reaction caused by a 
contact allergen) are also allowed. 
● 
Vaccines: Live vaccines are prohibited while the participant is receiving IP and for 
30 days after last dose of IP. Examples of live vaccines include, but are not limited to, 
the following: measles, mumps, rubella, chicken pox, yellow fever, seasonal flu, H1N1 
flu, rabies, Bacillus Calmette-Guerin and typhoid vaccine. 
● 
Other anticancer treatment: The use of other anticancer therapy (e.g., chemotherapy, 
hormonal therapy, immunotherapy, radiotherapy, biological therapy, targeted therapy) 
is not allowed during IP; however, participants with metastatic castration resistant 
prostate cancer who do not have orchiectomy should continue androgen deprivation 
therapy during the study. 
● 
Palliative (limited field) radiation therapy: for bone metastases is allowed. IP should be 
interrupted during radiation therapy. The use of bisphosphonates and receptor activator 
of nuclear factor kappa-B ligand inhibitors for bone metastases is allowed if initiated 


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prior to screening. Surgical treatment of isolated or symptomatic lesions for palliation 
or curative management is also allowed. 
Refer to [Section 10.5 List of Excluded Concomitant Medications] for a detailed list of drug 
classes and/or specific medications that are prohibited during participation in the study. 
7 
STUDY PROCEDURES AND ASSESSMENTS 
● 
Study procedures and their timing are summarized in the schedules of assessments 
[Table 1 through Table 4]. Adherence to the study design requirements, including those 
specified in the schedule of assessments, is essential and required for study conduct. 
Prospective protocol waivers or exemptions are not allowed. 
● 
Any change, divergence or departure from the study design or procedures identified in 
the protocol is considered a protocol deviation. All deviations from the protocol are to be 
recorded. 
● 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study treatment. 
● 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
● 
Procedures conducted as part of the participant’s routine clinical management (e.g., 
imaging, blood count) and obtained before signing of the ICF may be utilized for 
screening or baseline purposes provided the procedures met the protocol-specified 
criteria and were performed within the time frame defined in the schedule of 
assessments. 
7.1 
Efficacy Assessments 
Disease response and progression will be evaluated in this study using the RECIST v1.1 and 
iRECIST criteria as assessed by independent central review and investigator.  
Tumor assessments will be performed at screening and at every 8 weeks (± 1 week) from 
C1D1 until confirmed disease progression by iRECIST (iCPD). Scans will be read on site 
and also submitted in digital format for independent central review. Procedures for 
independent imaging central review will be described in a separate imaging charter. The 
assessment will include tumor measurements for target lesions, non-target lesions, and 
assessment for any new lesions. An overall assessment will be characterized for time point 
evaluation.  
Computed tomography (CT) or magnetic resonance imaging (MRI) scans are preferred for 
this study and to ensure comparability, the same technique (CT/MRI) used at screening 
should be utilized throughout the study. The same method should be employed and assessed 
by the same individual on each occasion, when possible. Imaging should include chest, 
abdomen and pelvis as well as any other anatomical region appropriate for the participant’s 
disease. 


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Imaging should be done every 8 weeks from C1D1 regardless of treatment interruption or 
delays and through the follow-up period as applicable. Scans performed prior to informed 
consent as standard of care are acceptable as screening scans if done within 28 days prior to 
C1D1. If a biopsy of a target lesion is performed, the baseline scan should be repeated, if 
possible. 
Confirmatory scans for CR or PR should be done at least 4 weeks after the date of the scan 
that CR or PR was first observed. Confirmatory scans for PD must occur at least 4 weeks 
after the date of the scan that PD was first observed but no longer than 8 weeks. 
7.2 
Safety Assessments 
7.2.1 
Laboratory Assessments 
● 
See [Section 10.6 Appendix 6: Clinical Laboratory Assessments] for the list of clinical 
laboratory tests to be performed and refer to the schedules of assessments [Table 1 
through Table 4] for timing and frequency. 
● 
The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study as an AE. The laboratory reports 
must be filed with the source documents.  
● 
Clinical significance of out-of-range laboratory findings is to be determined and 
documented by the investigator or subinvestigator who is a qualified physician. 
Abnormal laboratory findings associated with the underlying disease are not considered 
clinically significant unless judged by the investigator to be more severe than expected 
for the participant's condition. 
7.2.2 
Vital Signs 
● 
Oral temperature, pulse rate, respiratory rate, and blood pressure will be assessed as 
specified in the schedules of assessments [Table 1 through Table 4]. 
● 
Blood pressure and pulse measurements will be assessed with a completely automated 
device. Manual techniques will be used only if an automated device is not available. 
● 
Blood pressure and pulse measurements should be preceded by at least 5 min of rest for 
the participant in a quiet setting without distractions (e.g., television, cell phones). 
● 
Vital signs will be measured in a semi-supine position after 5 min rest and will include 
temperature, systolic and diastolic blood pressure, and pulse.  
● 
The following vital sign assessment schedules apply: 
o At C1D1 and any visit when pembrolizumab and ASP7517 are administered 
together, vital signs are obtained predose (-1 hour from start of pembrolizumab 
infusion), within 15 min prior to start of the pembrolizumab infusion, 15 min (-5 to 
+10 min window) after the start of the pembrolizumab infusion, at the end of the 
pembrolizumab infusion (-5 to +10 min window), 30 min (± 10 min) after 
completion of the pembrolizumab infusion, within 15 min prior to the start of the 
ASP7517 infusion, every 15 min (5 to +10 min window) during the ASP7517 
infusion, at the end of the ASP7517 infusion (-5 to +10 min window), and postdose 
(+30 min, +1, +2, +3 and +4 hours [± 10 min window each] from end of the 
ASP7517 infusion).  


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o ASP7517 dosing only: Vital signs will be obtained within 15 min prior to start of the 
ASP7517 infusion, every 15 min (-5 to +10 min window) during the ASP7517 
infusion, every 15 min (-5 to +10 min window) during the ASP7517 infusion, at the 
end of the ASP7517 infusion (-5 to + 10 min window), as well as 30 min (± 5 min), 
1 hour (± 10 min) and 2 hours (± 10 min) after completion of the ASP7517 infusion. 
If participants are still available, additional optional vital sign assessments 3 hours 
(± 10 min) and 4 hours (± 10 min) after completion of the ASP7517 infusion will be 
obtained. 
o Pembrolizumab dosing only: Vital signs will be obtained within 15 min prior to start 
of the pembrolizumab infusion, 15 min (-5 to +10 min window) after the start of the 
pembrolizumab infusion (-5 to +10 min window), at the end of the pembrolizumab 
infusion (-5 to +10 min window) and at 30 min (± 10 min) after completion of the 
pembrolizumab infusion for participants in the combination therapy. 
7.2.3 
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 through Table 4]. 
Height and body weight will be measured at the screening visit, and the body weight 
measurement will be repeated at Day 1 of each cycle. Height measurement may be performed 
at a subsequent visit if it was not done at screening. 
7.2.4 
Electrocardiogram  
A standard 12-lead ECG will be performed at the screening visit for purposes of assessing 
participant eligibility. ECG can be repeated during the screening period.  
For Dose Escalation: 
12-lead ECGs will be recorded in triplicate (at least 2 min apart per time point) and 
transmitted electronically for central reading. ECGs may be repeated once during screening. 
On IP administration days, ECGs will be obtained: 
• At C1D1 and any visit when pembrolizumab and ASP7517 are administered together, 
ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h 
post dose of ASP7517. 
• ASP7517 dosing only: ECGs are obtained predose (-1 h from start of ASP7517 
infusion) and 1 to 2 h post dose of ASP7517. 
• Pembrolizumab dosing only: ECGs are obtained predose (-1 h from start of 
pembrolizumab infusion) and 1 to 2 h post dose of pembrolizumab. 
For Dose Expansion: 
During ASP7517 and pembrolizumab combination therapy, 12-lead ECGs will be recorded in 
triplicate (at least 2 min apart per time point) and transmitted electronically for central 
reading. After treatment with ASP7517 has been discontinued, 12-lead ECGs will be 
recorded as a single assessment (in triplicate if deemed necessary, at least 2 min apart per 


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time point) and read locally. On IP administration days, ECG will be obtained predose and 1 
to 2 hours post dose. ECG may be repeated once during screening. 
ECGs will be recorded after the participant has been in a resting, supine position for at least 
5 min. Further details of the procedure will be separately specified in the procedural manual. 
7.2.5 
Imaging  
Chest X-ray or 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. 
7.2.6 
ECOG Performance Status 
The ECOG Scale [Oken et al, 1982] will be used to assess performance status [Table 10] at 
time points outlined in the schedules of assessments [Table 1 through Table 4]. 
Table 10 
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 
7.2.7 
Order of Assessments  
The following order should be followed when more than one assessment is required at a time 
point with blood sampling for pharmacokinetics/metabolic profiling being collected nearest 
to the scheduled time point:  
● 
ECG 
● 
Vital signs 
● 
Blood collection 
7.3 
Adverse Events and Other Safety Aspects 
The definitions of an AE or SAE can be found in [Sections 10.3.1 and 10.3.2], respectively. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate or the 
participant's legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting and 
recording events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study IP or procedures, or that 
caused the participant to discontinue the IP or procedures and/or study [see Section 10.3 


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Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up and Reporting].  
The method of recording, evaluating, and assessing causality of AE and SAE and the 
procedures for completing and transmitting SAE reports are provided in [Section 10.3 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up and Reporting]. 
7.3.1 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information 
All SAEs will be collected from the signing of the ICF until the follow-up visit at the time 
points specified in the schedule of assessments [Table 1 through Table 4] and reported on the 
eCRF. 
All AEs will be collected from the signing of the ICF until the follow-up visit at the time 
points specified in the schedule of assessments [Table 1 through Table 4] and reported on the 
eCRF.  
If the NCI CTCAE grade/grade of an SAE/AE changes, the event should be relisted on the 
eCRF with the new NCI CTCAE grade/grade and new onset date. 
If the NCI CTCAE grade/grade decreases, the SAE/AE should be relisted on the eCRF with 
the new NCI CTCAE grade/grade and new onset date. The exception is ongoing predose 
events that continue post-dose and improve post-dose. Such events should not be re-listed. 
If the NCI CTCAE grade/grade of an SAE reduces, the details of the AE should be provided 
on the SAE worksheet for the medical assessor to be able to assess the course of the event. 
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in [Section 10.3 Appendix 3: Adverse 
Events: Definitions and Procedures for Recording, Evaluating, Follow-up and Reporting]. 
The investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available. 
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the investigator learns of any SAE, including a death, at any time 
after a participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study IP or study participation, the investigator must promptly 
notify the sponsor.  
7.3.2 
Method of Detecting Adverse Events and Serious Adverse Events 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about AE 
occurrences. 
7.3.3 
Follow-up of Adverse Events and Serious Adverse Events 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs (and AEs of special interest [as defined in 


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Section 7.3.6]) will be followed until resolution, stabilization, the event is otherwise 
explained, or the participant is lost to follow-up (as defined in [Section 8.3]). Further 
information on follow-up procedures is provided in [Section 10.3 Appendix 3: Adverse 
Events: Definitions and Procedures for Recording, Evaluating, Follow-up and Reporting]. 
If after the protocol-defined AE collection period (see [Section 7.3.1 Time Period for 
Collecting Adverse Event and Serious Adverse Event 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 the sponsor. 
7.3.4 
Regulatory Reporting Requirements for Serious Adverse Events 
● 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a study IP under clinical investigation are met. 
● 
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study IP under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRB/IEC and investigators. 
● 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
● 
An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the 
IRB/IEC, if appropriate according to local requirements. 
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 (S)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 


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thrombocytopenia will not be reported as an SAE. These procedures are collected per the 
eCRF’s completion guidelines. 
7.3.6 
Adverse Events of Special Interest  
irAEs are considered AEs of special interest. Participants should be evaluated carefully for 
potential IRRs as described in [Section 2.3.1.6 Infusion-related Reactions]. In the event a 
participant is diagnosed with an IRR, then it should be reported as an AE using the diagnosis 
rather than the list of symptoms. Additional information on the AE of IRR will be collected 
on the AE eCRF. 
If the IRR is also classified as serious, they are to be collected via the SAE/Special Situation 
worksheet and reported within 24 hours as described in [Section 10.3.6 Reporting of Serious 
Adverse Events]. 
7.3.7 
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 reported as protocol deviations and/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 on the eCRF. If the AE meets the 
definition of an SAE, the SAE is to be reported as described in [Section 10.3.6 Reporting 
Procedures for Serious Adverse Events] and the details of the associated special situation are 
to be included in the clinical description on the special situation worksheet or pregnancy 
reporting form.  
The special situations are: 
● 
Pregnancy 
● 
Lactation 
● 
Medication error, overdose and use outside protocol 
● 
Misuse/abuse 
● 
Occupational exposure 
● 
(Suspicion of) Transmission of infectious agent 
● 
Suspected drug-drug interaction 
Instructions and procedures for reporting special situations are provided in [Section 10.3.7 
Reporting Procedures for Special Situations].  
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 for the dose escalation and expansion cohorts. Sampling time points are as shown in 
the schedule of assessments [Table 6].  


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Serum concentrations of pembrolizumab will be evaluated in the combination therapy arm as 
outlined in the schedule of assessments [Table 6]. 
Refer to the laboratory manual for detailed information regarding sampling, processing, 
shipping and storage instructions. 
7.5 
Pharmacodynamics 
Samples for exploratory pharmacodynamics and biomarker analyses of APS7517 will be 
collected according to the schedules of assessments [Table 1 and Table 3].  
The samples described in [Sections 7.5.1 Blood Samples, 7.5.2 Tumor Tissue Samples and 
7.5.3 Buccal Swab Samples] 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. 
Refer to the laboratory manual for detailed information regarding sampling, processing, 
shipping and storage instructions. 
7.5.1 
Blood Samples 
Blood samples will be 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 9.4.5.1 Analysis of Exploratory Biomarker(s)]. Examples of these 
biomarkers include, but are not limited to, anti-WT1 antibodies, 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 
genes that may modify treatment effect.  
7.5.2 
Tumor Tissue Samples 
The tumor tissue will be used for biomarker analyses as described in [Section 9.4.5.1 
Analysis of Exploratory Biomarkers(s)]. Examples of biomarkers include, but are not limited 
to, expression of WT1, expression and mutation of genes that may modify treatment effect, 
tumor mutational burden, changes in the tumor microenvironment and changes in immune 
related molecules. Examples include, but are not limited to, CD4 T-cells, CD8 T-cells, etc. 
Archival tumor tissue sample: All participants are required to submit (if available) an 
archival tumor tissue sample in the form of a formalin-fixed, paraffin-embedded (FFPE) 
block or unstained slides will be collected. If unstained slides are submitted, a minimum of 
20 slides (4 to 5-microns thick) is necessary. 


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Baseline tumor tissue sample: Participants in all expansion cohorts are required to consent 
to provide a tumor tissue sample (both an FFPE block and frozen sample) obtained within 
56 days prior to first dose of study treatment. If the participant has both an FFPE block AND 
frozen tissue specimen taken within 56 days prior to the first dose of study treatment, a new 
biopsy is not required. 
On-treatment tumor tissue sample: Participants in all expansion cohorts are required to 
consent to provide an on-treatment tumor tissue sample (both an FFPE block and frozen 
sample). On-treatment tumor tissue sample is to be collected ± 7 days of the C2D15 visit (or 
unscheduled). 
Details on sample collection, labeling, and shipment procedures will be provided in a 
separate laboratory manual.  
7.5.3 
Buccal Swab Samples 
Buccal swab samples will be used to genotype the human leukocyte antigen (HLA) gene 
complex. Knowledge of the specific HLA gene complex in each participant may help 
understand/explain observed differences in efficacy or treatment effect. The buccal swab will 
be used for biomarker analyses as described in [Section 9.4.5.1 Analysis of Exploratory 
Biomarker(s)].  
7.6 
Pharmacogenomics  
Pharmacogenomic (PGx) research may be conducted in the future to analyze or determine 
genes of relevance to clinical response, pharmacokinetics, toxicity/safety, efficacy and/or 
disease. A 4 to 6 mL sample of whole blood for possible banked PGx analysis will be 
collected as indicated in the schedules of assessments [Table 1 and Table 2] Samples will be 
shipped to a sponsor-designated sample banking contract research organization (CRO). 
Details on sample collection, labeling, storage and shipment procedures will be provided in a 
separate laboratory manual. 
See [Section 10.7 Appendix 7: Pharmacogenomic Analysis with Banked Sample] for further 
details on the banking procedures.  
7.7 
Other Assessments 
7.7.1 
Replication Competent Lentivirus 
Blood samples will be collected and used to monitor the presence of replication competent 
lentivirus. Sampling time points are as shown in the schedule of assessments [Table 5]. If 
there is a positive result during the first 18 months of assessments, additional follow-up 
assessments may be required. 
7.8 
Total Amount of Blood 
The total amount of blood for each participant will vary depending on the course of their 
disease, duration on treatment and local laboratory requirements. At any time during the 


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study, if any laboratory abnormalities are found for a participant, additional blood may be 
drawn for safety monitoring. 
The maximum amount of blood collected within 24 hours is approximately 112 mL when an 
optional PGx sample is collected and 108 mL when an optional PGx sample is not collected.   
● 
Dose Escalation Cohorts:  
For monotherapy with ASP7517 
o 
Approximately 108 mL of blood will be collected during the Cycle 1 with optional 
PGx sample, and 104 mL without optional PGx sample  
o 
Approximately 90 mL of blood will be collected during Cycle 2 
o 
Approximately 74 mL of blood will be collected at Cycle 3 
o 
Approximately 82 mL of blood will be collected at Cycle 4 
o 
Approximately 74 mL of blood will be collected at Cycle 5 
o 
Approximately 74 mL of blood will be collected at Cycle 6 
o 
Approximately 36 mL of blood will be collected at EOT depending on the local lab. 
o 
Approximately 104 mL of blood will be collected during the Survival follow-up 
period 
o 
Approximately 34 mL of blood will be collected at the visit during the observation 
period 
For combination therapy with ASP7517 and pembrolizumab 
o Approximately 112 mL of blood will be collected during Cycle 1 with the optional 
PGx sample, and 108 mL without the optional PGx sample 
o Approximately 94 mL of blood will be collected during Cycle 2 
o Approximately 74 mL of blood will be collected at Cycle 3 
o Approximately 86 mL of blood will be collected at Cycle 4 
o Approximately 78 mL of blood will be collected at Cycle 5 
o Approximately 74 mL of blood will be collected at Cycle 6 
o Approximately 38 mL of blood will be collected at EOT depending on the local lab. 
o Approximately 40 mL of blood will be collected at the visit during the observation 
period. 
● 
Dose Expansion Cohorts:  
For monotherapy with ASP7517 
o 
Approximately 104 mL of blood will be collected during the Cycle 1 with optional 
PGx sample, and 100 mL without optional PGx sample 
o 
Approximately 84 mL of blood will be collected during Cycle 2 
o 
Approximately 56 mL of blood will be collected at Cycle 3 
o 
Approximately 60 mL of blood will be collected at Cycle 4  
o 
Approximately 56 mL of blood will be collected at Cycle 5 
o 
Approximately 56 mL of blood will be collected at Cycle 6 
o 
Approximately 36 mL of blood will be collected at EOT depending upon the local 
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o 
Approximately 102 mL of blood will be collected during the Survival follow-up 
period 
o 
Approximately 34 mL of blood will be collected at the visit during the observation 
period 
For combination therapy with ASP7517 and pembrolizumab 
o Approximately 108 mL of blood will be collected during Cycle 1 with the optional 
PGx sample, and 104 mL without the optional PGx sample 
o Approximately 84 mL of blood will be collected during Cycle 2 
o Approximately 56 mL of blood will be collected at Cycle 3 
o Approximately 64 mL of blood will be collected at Cycle 4 
o Approximately 56 mL of blood will be collected at Cycle 5 
o Approximately 56 mL of blood will be collected at Cycle 6 
o Approximately 38 mL of blood will be collected at EOT depending on the local lab. 
o Approximately 38 mL of blood will be collected at the visit during the observation 
period. 
In addition, approximately 20 mL of blood could be collected for an RCL sample during this 
study. 
8 
PARTICIPANT DISCONTINUATION 
Refer to [Section 10.1.9 Study and Site Start and Closure] regarding discontinuation of study 
sites or of the study as a whole.  
8.1 
Discontinuation of Individual Participant(s) from Study Treatment  
A discontinuation from treatment is defined as a participant who enrolled in the study and for 
whom study treatment is permanently discontinued for any reason.  
The participant 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 participant from study treatment or to terminate a 
participant’s involvement in the study at any time if the participant’s clinical condition 
warrants it. 
The reason for discontinuation from study treatment must be documented in the participant’s 
medical records. 
A participant must discontinue study treatment for any of the following reasons: 
● 
Participant requests to stop treatment.  
● 
Any clinical AE, laboratory abnormality or intercurrent illness, in the opinion of the 
investigator, indicates continued treatment is not in the best interest of the participant. 
● 
Participant is found to have significantly deviated from any one of the inclusion or 
exclusion criteria after enrollment (participants having clinical benefit and no DLT may 
be kept in the study after discussion with the medical monitor). 
● 
Participant not achieving response (CR or PR) and the participant is no longer deriving 
clinical benefit, in the opinion of the investigator. 


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● 
Participant begins other anti-cancer therapies. 
● 
Participant is in need of receiving prohibited concomitant treatment(s) based on 
Investigator’s clinical opinion.  
● 
Participant experiences disease relapse/progression. 
● 
Investigator/subinvestigator determines that the continuation of the study treatment will 
be detrimental to the participant. 
● 
Participant is lost to follow-up despite reasonable efforts by the investigator to locate the 
participant. 
● 
Female participant becomes pregnant.  
● 
Death. 
8.2 
Discontinuation of Individual Participant(s) from Study 
All participants who discontinue study treatment will remain in the study and must continue 
to be followed for protocol-specific follow-up procedures as outlined in the schedules of 
assessments [Table 3 to Table 6]. The only exception to this is when the participant 
specifically withdraws consent for any further contact with him/her or persons previously 
authorized by the participant to provide this information. 
All participants who discontinue study treatment are to be followed for up to 12 months after 
their end of treatment, death or the final analysis, whichever occurs first per the schedules of 
assessments [Table 3 to Table 4]. 
8.3 
Lost to Follow-up 
Every reasonable effort is to be made to contact any participant lost to follow-up during the 
course of the study to complete study-related assessments, record outstanding data and 
retrieve IP. These contact attempts should be documented in the participant’s medical record. 
9 
STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
The hypotheses for the primary efficacy endpoint for each indication and dose level are given 
as follows: 
Monotherapy Dose Expansion: 
H0:  iORR is 10%, at which the treatment is deemed as unacceptable. 
H1:  iORR is at least 25%, at which the treatment is deemed as acceptable. 
Combination Therapy Dose Expansion: 
Metastatic Melanoma CPI Naïve  
H0:  iORR is 25%, at which the treatment is deemed as unacceptable.  
H1:  iORR is at least 40%, at which the treatment is deemed as acceptable. 


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Metastatic Melanoma CPI Refractory 
H0:  iORR is 13%, at which the treatment is deemed as unacceptable.  
H1:  iORR is at least 28%, at which the treatment is deemed as acceptable. 
Ovarian 
H0:  iORR is 15%, at which the treatment is deemed as unacceptable.  
H1:  iORR is at least 30%, at which the treatment is deemed as acceptable. 
Colorectal Cancer 
H0:  iORR is 18%, at which the treatment is deemed as unacceptable.  
H1:  iORR is at least 33%, at which the treatment is deemed as acceptable. 
9.2 
Sample Size Determination 
Phase 1 Dose Escalation: 
The sample size of approximately 24, including 12 from monotherapy and 12 from 
combination therapy, is not based on a statistical power calculation. The number of 
participants enrolled will be dependent on the DLT incidence. The estimated number of 
participants should provide adequate information for the dose escalation and safety objectives 
of the study. 
Phase 2 Dose Expansion: 
It is estimated that up to approximately 361 participants may be enrolled in the monotherapy 
and combination therapy arms (approximately 129 participants for monotherapy and 
232 participants for combination therapy). The iORR is monitored using the BOP2 design.  
Monotherapy 
For each indication, with assumptions mentioned in the statistical hypotheses section, the 
statistical power would be approximately 0.80 while controlling the type I error rate at 
0.05 (1-sided).  
Combination Therapy 
For each indication, with assumptions mentioned in the statistical hypotheses section, the 
statistical power would be approximately 0.80 while controlling the type I error rate at 
0.05 (1-sided). 


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9.3 
Populations for Analyses 
The following populations are defined:  
Population 
Description 
Enrolled  
All participants who sign the informed consent form are allocated to 
treatment 
Full Analysis Set (FAS) 
All participants who are enrolled and receive at least one dose of study 
treatment.  
Response Analysis Set (RAS) 
The RAS will consist of all participants who are enrolled and receive at 
least 1 dose of IP and have at least 1 post baseline primary efficacy 
measurement. 
Safety Analysis Set (SAF) 
All participants who take at least one dose of IP. 
Pharmacokinetic analysis set 
(PKAS) 
The PKAS consists of the administered population for which 
pharmacokinetics data are available for at least 1 time point. Additional 
participants may be excluded from the PKAS at the discretion of the 
pharmacokineticist. 
Pharmacodynamic analysis set 
(PDAS) 
The PDAS will include the participants from the administered population 
for whom sufficient pharmacodynamic measurements were collected. The 
PDAS will be used for all analyses of pharmacodynamic data. 
DLT Evaluation Analysis Set 
(DEAS) 
The DEAS is defined as all participants in SAF by excluding participants 
who meet any of the following criteria: 
● 
Participant is discovered to have enrolled without fully satisfying 
eligibility criteria. 
● 
Participant received less than the planned dose in Cycle 1 for 
reasons other than DLT. 
● 
Participant has no DLT and withdraws from the study before the end 
of DLT evaluation period 
The DEAS will be used for the analysis of DLT data. 
DLT: dose limiting toxicity 
9.4 
Statistical Analyses 
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. Changes from the planned 
analyses in the final SAP that impact the statistical analyses will be justified in the clinical 
study report (CSR). 
9.4.1 
General Considerations 
In general, data will be summarized 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 participants with no missing data (i.e., will add 
up to 100%). 
Baseline will be defined as the last non-missing observation prior to first administration of 
IP, unless otherwise specified.  
Demographics and baseline characteristics will be summarized by monotherapy and 
combination therapy arms, and dose level, and overall for all treated participants. 


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The number and percentage of participants who completed and discontinued treatment and 
reasons for treatment discontinuation will be presented for all enrolled participants and for 
participants in the safety analysis set (SAF) by monotherapy and combination therapy arms, 
and dose level, and overall. Similar tables for screening disposition, observation period 
disposition and follow-up disposition will also be presented for all treated participants by 
monotherapy and combination therapy arms, and dose level, and overall. All disposition 
details and dates of first and last evaluations for each participant will be listed.  
Previous and concomitant treatment and medical history will be listed. Investigational 
product exposure will be summarized by descriptive statistics and will be listed. 
9.4.2 
Analysis of Efficacy  
Binary efficacy endpoint analysis will be conducted on RAS while time to event endpoints 
will be conducted on FAS. The interpretation of results of the primary efficacy endpoint will 
be based on RAS. Efficacy analyses will be summarized by monotherapy and combination 
therapy and dose level. Tumor related analyses are summarized based on RECIST v1.1 and 
iRECIST. 
9.4.2.1 Analysis of Primary Endpoint  
9.4.2.1.1 
Primary Analysis 
Objective Response Rate per iRECIST (iORR) 
iORR is defined as the proportion of participants for each dose level whose best overall 
response is rated as confirmed iCR or iPR per iRECIST by independent central review. iORR 
for each dose level will be calculated and its 95% confidence interval will be constructed by 
Clopper-Pearson method. 
9.4.2.2 Sensitivity Analysis 
The same analysis of the primary endpoint as described in [Section 9.4.2.1.1 Primary 
Analysis] will be conducted for the following: 
● 
iORR with unconfirmed response by independent central review 
● 
iORR with confirmed response by investigator assessment 
● 
iORR with unconfirmed response by investigator assessment 
9.4.2.3 Analysis of Secondary Endpoints  
Objective Response Rate per RECIST v1.1 (ORR): 
ORR is defined as the proportion of participants for each dose level whose best overall 
response is rated as CR or PR per RECIST v1.1. The same analysis of the primary endpoint 
as described in [Section 9.4.2.1.1 Primary Analysis] will be conducted for the following: 
● 
ORR with confirmed response by independent central review 
● 
ORR with unconfirmed response by independent central review 
● 
ORR with confirmed response by investigator assessment 
● 
ORR with unconfirmed response by investigator assessment 


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Disease Control Rate per iRECIST (iDCR): 
iDCR is defined as the proportion of participants for each dose level whose best overall 
response is rated as confirmed iCR, iPR or stable disease (iSD) per iRECIST. iDCR for dose 
level will be calculated and its 95% confidence interval will be constructed by 
Clopper-Pearson method by independent central review and investigator assessment. 
Disease Control Rate per RECIST v1.1 (DCR): 
DCR is defined as the proportion of participants for each dose level whose best overall 
response is rated as confirmed CR, PR or SD per RECIST v1.1. DCR for dose level will be 
calculated and its 95% confidence interval will be constructed by Clopper-Pearson method by 
independent central review and investigator assessment. 
Overall Survival (OS): 
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 participant 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). The distribution of OS will be estimated for each dose level using Kaplan-Meier 
methodology. 
Progression-free Survival per iRECIST (iPFS): 
iPFS is defined as the time from the start of the study treatment until death from any cause or 
radiographic disease progression assessed per iRECIST by independent central review and 
investigator assessment, whichever occurs first. The distribution of iPFS will be estimated for 
each dose level using Kaplan-Meier methodology. 
Progression-free Survival per RECIST v1.1 (PFS): 
PFS is defined as the time from the start of the study treatment until death from any cause or 
radiographic disease progression assessed per RECIST v1.1 by independent central review 
and investigator assessment, whichever occurs first. The distribution of PFS will be estimated 
for each dose level using Kaplan-Meier methodology. 
Duration of Response per iRECIST (iDOR): 
iDOR will be calculated only for the subgroup of participants with confirmed response 
iCR/iPR per iRECIST by independent central review and investigator assessment. The 
distribution of iDOR will be estimated for each dose level using Kaplan-Meier methodology. 
Duration of Response per RECIST v1.1 (DOR): 
DOR will be calculated only for the subgroup of participants with confirmed response CR/PR 
per RECIST v1.1 by independent central review and investigator assessment. The distribution 
of DOR will be estimated for each dose level using Kaplan-Meier methodology. 
9.4.3 
Analysis of Safety 
Safety analyses will be conducted on the SAF. Safety analyses will be summarized by 
monotherapy and combination therapy arms, and dose level and overall. 


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9.4.3.1 Adverse Events  
AEs will be coded using MedDRA and graded using NCI-CTCAE v5.0. 
A TEAE is defined as an AE observed after starting administration of the IP until 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 participants with TEAEs, drug-related TEAEs, serious 
TEAEs, drug-related serious TEASs, TEAEs leading to withdrawal of treatment and drug 
related 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 participant.  
AE data will be listed. 
9.4.3.2 Laboratory Assessments  
For quantitative clinical laboratory measurements (hematology and biochemistry), descriptive 
statistics will be used to summarize results and change from baseline by monotherapy and 
combination therapy arms, and dose level, and overall and time point. Shifts from baseline to 
the worst grade based on NCI CTCAE 5.0 in laboratory tests will also be tabulated. 
Laboratory data will be listed. 
9.4.3.3 Vital Signs  
Descriptive statistics will be used to summarize vital sign results and changes from baseline 
for participants in the SAF by dose level and time point.  
Vital signs data will be listed. 
9.4.3.4 Electrocardiogram 
9.4.3.4.1 
Routine 12-lead Electrocardiogram 
The routine 12-lead ECG results will be summarized by monotherapy and combination 
therapy arms, dose level and time point. 
Interpretations of routine 12-lead ECG results will be summarized by monotherapy and 
combination therapy arms, dose level and time point. 
12-lead ECG data interpretations and quantitative values will be listed. 
9.4.3.5 Eastern Cooperative Oncology Group Performance Status 
Summary statistics (number and percent of participants) 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. 


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9.4.3.6 Concentration-response Relationship Analysis  
Exploratory analysis between pharmacokinetic parameter and clinical measures (e.g., 
efficacy or safety) may be performed. 
9.4.4 
Analysis of Pharmacokinetics 
Cellular DNA load and kinetic parameters for ASP7517 pharmacokinetics 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. Participants with sufficient 
cellular DNA samples will have kinetic parameter estimates for ASP7517 including 
calculation of AUC (including AUClast, AUC28d, AUCinf), Cmax, Ctrough and tmax using standard 
noncompartmental analysis. For pharmacokinetic parameter, tmax, only n, median, minimum 
and maximum will be calculated. 
Descriptive statistics of pembrolizumab pharmacokinetics may be tabulated. 
9.4.5 
Analysis of Pharmacodynamics 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 participants may be performed. 
9.4.5.1 Analysis of Exploratory Biomarker(s) 
Associations between biomarkers and clinical results (efficacy, safety or pharmacodynamics) 
may be performed on participants 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 analyses, such as 
alternative modeling approaches, may be conducted. All analyses described in this section are 
based on availability of the data.  
9.5 
Interim Analysis 
Safety, pharmacokinetic and other clinical data will be reviewed on an ongoing basis to 
determine if the study will proceed on 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. If the response rate does not meet the optimal stopping 
boundaries, then stage 2 will be opened. 
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: 
1. If the posterior mean of the safety event rate is higher than 30% as indicated by Bayesian 
logistic model across all tumor types at a given dose level for monotherapy or 


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combination therapy, then enrollment may be held in all expansion cohorts at that dose 
level and at higher dose levels for that therapy.  
2. Additionally, if the posterior mean of the safety event rate is higher than 30% as 
indicated by Bayesian logistic model in a specific tumor type at a dose level for 
monotherapy or combination therapy, enrollment of that dose level and any higher 
dose-level may be held for that tumor type and that therapy.  
9.6 
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/time point. 
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.  


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10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Appendix 1: Ethical, Regulatory and Study Oversight 
Considerations 
10.1.1 Regulatory and Ethical Considerations 
● 
This study will be conducted in accordance with the protocol and with the following: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
o Applicable ICH Good Clinical Practice (GCP) Guidelines 
o Applicable laws and regulations 
● 
The protocol, protocol amendments, ICF, Investigator’s Brochure, and other relevant 
documents (e.g., advertisements) must be submitted to an IRB/IEC by the investigator 
and reviewed and approved by the IRB/IEC before the study is initiated. 
● 
Any amendments to the protocol will require IRB/IEC approval before implementation 
of changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants. 
● 
The investigator will be responsible for the following: 
o 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 
o Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
o Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local regulations 
10.1.2 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. 
10.1.3 Informed Consent of Participants 
10.1.3.1 Informed Consent Process 
● 
The investigator or his/her representative will explain the nature of the study to the 
participant and answer all questions regarding the study. 
● 
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 
50, local regulations, ICH guidelines, Health Insurance Portability and Accountability 
Act requirements, where applicable, and the IRB/IEC or study center. 


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● 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF. 
● 
Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
● 
A copy of the ICF(s) must be provided to the participant. 
10.1.3.2 Supply of New and Important Information Influencing the Participant’s 
Consent and Revision of the Written Information 
● 
The investigator or his/her representative will immediately inform the participant 
verbally whenever new information becomes available that may be relevant to the 
participant’s consent or may influence the participant’s willingness to continue 
participating in the study (e.g., report of serious adverse drug reaction). The 
communication must be documented in the participant’s medical records and whether the 
participant is willing to remain in the study or not must be confirmed and documented.  
● 
The investigator must update the participant’s ICF and submit it for approval to the 
IRB/IEC. The investigator or his/her representative must obtain written informed consent 
from the participant on all updated ICFs throughout their participation in the study. The 
investigator or his/her designee must reconsent participants with the updated ICF even if 
relevant information was provided verbally. The investigator or his/her representative 
who obtained the written informed consent and the participant should sign and date the 
ICF (or for Japan Region place a personal seal). A copy of the signed (or for Japan 
Region sealed) ICF will be given to the participant and the original will be placed in the 
participant’s medical record. An entry must be made in the participant’s records 
documenting the reconsent process. 
10.1.4 Data Protection 
Individual participant medical information obtained as a result of this study is considered 
confidential and disclosure to third parties is prohibited unless the participant provides 
written consent or approval. Additional medical information may be given only after 
approval of the participant to the investigator or to other appropriate medical personnel 
responsible for the participant's well-being. 
The sponsor shall not disclose any confidential information on participants 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 participant’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 participant's right to protection against invasion of privacy. Only a 
participant identification number will identify participant 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. 


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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. 
10.1.5 Committee(s) Structure 
10.1.5.1 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 phase 2 expansion cohorts. 
For full information regarding the membership, operations and logistics of the committee 
please refer to DESC Charter.  
10.1.6 Dissemination of Clinical Study Data 
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 lock. 
10.1.7 Data Quality Assurance 
● 
All participant data relating to the study will be recorded on the eCRF unless transmitted 
to the sponsor or designee electronically in an external data file (e.g., central laboratory 
data). The investigator is responsible for verifying that data entries on the eCRF are 
accurate and correct by physically or electronically signing the eCRF. 
● 
Guidance on completion of eCRFs will be provided in a separate eCRF Completion 
Guideline. 
● 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
● 
Monitoring details describing strategy (e.g., risk-based initiatives in operations and 
quality such as Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities and requirements, including handling of 


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noncompliance issues and monitoring techniques (central, remote, or on-site monitoring) 
are provided in the Monitoring Plan. 
● 
The sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 
● 
The sponsor assumes accountability for actions delegated to other individuals (e.g., 
Contract Research Organizations). 
● 
Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator according to ICH or applicable local regulatory 
requirements, whichever is longer, after study completion. No records may be destroyed 
during the retention period without the written approval of the sponsor. No records may 
be transferred to another location or party without written notification to the sponsor. 
10.1.8 Source Documents 
1. Source data must be available at the study site to document the existence of the 
participants 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 participant.  
2. The investigator must maintain accurate documentation (source data) that supports the 
information entered on the eCRF. 
3. 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 clinical outcome assessment and/or drug accountability.  
4. 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 participant file and be 
available for archiving.  
5. Study monitors will perform ongoing source data review and verification, as required by 
region, to confirm that data entered into the eCRF by authorized site personnel are 
accurate, complete, and verifiable from source documents; that the safety and rights of 
participants are being protected; and that the study is being conducted in accordance with 
the currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements. 


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UNIQUE to Japan Region: 
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, participant files and study-related records kept at either a pharmacy, 
a laboratory, or medical technical office, as well as participant 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 one 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 
10.1.9 Study and Site Start and Closure 
The study start date is the date the first participant signs the ICF for the study.  
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 


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The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but 
are not limited to: 
For study termination: 
● 
Discontinuation of further study test product development 
For site termination: 
● 
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines 
● 
Inadequate or no recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator 
● 
Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, the sponsor or designee shall promptly 
inform the Investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified by 
the applicable regulatory requirements. The Investigator shall promptly inform the participant 
and should assure appropriate participant therapy and/or follow-up. 
10.1.10 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 product 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.  
10.1.11 Insurance of Participants and Others (UNIQUE to Japan) 
If a participant suffers any study-related injury, the sponsor will compensate the participant 
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 participant 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.  


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2. When the participant 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. 
10.1.12 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, eCRFs and source 
documents. Direct access to these documents will be required by the auditors. 
To support quality around participant safety and reliability of study results, quality tolerance 
limits (QTLs) are defined and monitored. QTLs represent the acceptable variation of study 
data, taking into consideration the current state of medical and statistical knowledge about the 
variables to be analyzed, as well as the statistical design of the study. It is a level, point, or 
value associated with a parameter that should trigger an evaluation if a deviation is detected 
to determine if there is a possible systematic issue (i.e., a trend has occurred). The QTLs 
defined for this study are provided below.  
Table 11 
Quality Tolerance Limits 
QTL #: Name and Parameter 
Definition 
Parameter Justification 
QTL1: Eligibility: % or 
randomized participants not 
meeting 
key criteria 
Proportion (%) of randomized 
participants with per-defined key 
inclusion/exclusion criteria 
deviation(s) that lead to 
exclusion 
from the per protocol population 
A high number of participants not 
meeting the entrance criteria can 
have a negative impact on the 
interpretation of the primary 
analysis and overall validity of the 
trial results 
QTL2: Late SAE reporting: % of 
SAEs reported > 1 days 
Proportion (%) of SAEs reported 
more than one day after site 
awareness 
Late SAE reporting may be an 
indicator of insufficient safety event 
reporting, missing safety events, 
and/or poor protocol compliance 
QLT: quality tolerance limit; SAE: serious adverse event 
Additional information regarding the QTL limit and limit justification, as well as associated activities can be 
found in STL-3458 QTL monitoring plan. 
 


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QTL Management Activities: 
● 
For control of risks associated with “QTL1: Eligibility,” refer to [Section 7.1 Efficacy 
Assessments]. For control of risks associated with “QTL2: Late SAE reporting,” refer to 
[Section 7.3 Adverse Events and Other Safety Aspects] and [Section 10.3 Adverse 
Events: Definitions and Procedures for Recording, Evaluating, Follow-up and 
Reporting].  


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10.2 
Appendix 2: 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 schedule of assessments. Pregnancy 
test results must confirm that the participant 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): 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o 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 one 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 one 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 participant’s medical records, medical examination or medical history interview. 
CONTRACEPTION GUIDANCE FOR FEMALE PARTICIPANTS OF 
CHILDBEARING POTENTIAL 
Female participants of childbearing potential are eligible for participation in the study if they 
agree to use one 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 after the final 
IP administration.a 
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 


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o Oral 
o Intravaginal 
o Transdermal 
● 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
o Oral 
o Injectable 
o Implantable 
● 
Other combined (estrogen- and progesterone-containing) methods 
o Vaginal ring 
o Injectable 
o Implantable 
o Intrauterine hormone-releasing system or intrauterine device 
o 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 participant. 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 participants participating 
in clinical studies. 
CONTRACEPTION GUIDANCE FOR MALE PARTICIPANTS WITH PARTNER(S) 
OF CHILDBEARING POTENTIAL 
Male participants 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 participants 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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10.3 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up and Reporting 
10.3.1 Definition of Adverse Events 
AE Definition: 
An AE is any untoward medical occurrence in a participant or clinical study participant, 
temporally associated with the use of study IP, whether or not considered related to the study 
IP. 
“Adverse event” means any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. 
NOTE: 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 study IP. This includes events related to the comparator and events related to the 
(study) procedures. 
Events Meeting the AE Definition 
● 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (i.e., not related to progression of 
underlying disease). 
● 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
● 
New conditions detected or diagnosed after study IP administration even though it may 
have been present before the start of the study. 
Events NOT Meeting the AE Definition 
● 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
● 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 
● 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads 
to the procedure is the AE. 
● 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
● 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.  


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10.3.1.1 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 participant’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. 
10.3.1.2 Potential Cases of Drug-induced Liver Injury 
Refer to [Section 10.4 Appendix 4: 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 [Section 10.4 Appendix 4: 
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 [Section 10.3.6 Reporting 
Procedures for Serious Adverse Events]. 
10.3.2 Definition of Serious Adverse Events 
An SAE is defined as any untoward medical occurrence that, at any dose: 
● 
Results in death 
● 
Is life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
● 
Requires inpatient hospitalization or prolongation of existing hospitalization 
o 
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the physician’s 
office or outpatient setting. Complications that occur during hospitalization are AEs. 
If a complication prolongs hospitalization or fulfills any other serious criteria, the 
event is serious. When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious. 
o 
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 


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● 
Results in persistent or significant disability/incapacity 
o 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
o 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle), which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption. 
● 
Is a congenital anomaly/birth defect 
● 
Other situations: 
o 
Medical or scientific judgment should be exercised in deciding whether SAE 
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 participant or may require medical or surgical intervention to prevent 
one of the other outcomes listed in the above definition. These events should usually 
be considered serious. 
o 
Examples of such events include invasive or malignant cancers, 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. 
If an event is not an AE per definition in [Section 10.3.1 Definition of Adverse Events], then 
it cannot be an SAE even if serious conditions are met (e.g., hospitalization for 
signs/symptoms of the disease under study, death due to progression of disease).  
10.3.3 Assessment of Causality 
● 
The investigator is obligated to assess the relationship between study IP and each 
occurrence of each AE/SAE. 
● 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
● 
The investigator will use clinical judgment to determine the relationship. 
● 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study IP administration will 
be considered and investigated. 
● 
The investigator will also consult the Investigator’s Brochure and/or Product 
Information, for marketed products, in his/her assessment. 
● 
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
● 
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 make an assessment of causality for every event before the 
initial transmission of the SAE data to the sponsor. 


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● 
The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment. 
● 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
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 participant been administered IP?  
● 
Plausibility (i.e., could the event been caused by the suspect IP? Consider biologic and/or 
pharmacologic mechanism, half-life, literature evidence, drug class, preclinical and study 
data, etc.) 
● 
Dechallenge/dose reduction/rechallenge:  
o Dechallenge: Did the (S)AE resolve or improve after only stopping the dose of the 
suspect drug without any treatment? 
o Dose reduction: Did the (S)AE resolve or improve after reducing the dose of the 
suspect drug? 
o Rechallenge: Did the (S)AE reoccur if the suspected drug was reintroduced after 
having been stopped?  
● 
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  
● 
Temporal relationship between exposure to the IP and (S)AE onset and/or resolution. 
Did the (S)AE occur in a reasonable temporal relationship to the administration of the 
IP?  
● 
Finally, judging which are more likely based on all the above contents, factors of 
reasonable possibility or confounding factors, comprehensive judgment of plausible will 
be provided.  
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. While it is very important that the 
investigator always assesses causality for every event before the initial transmission of the 
SAE data to the sponsor, the initial report should be submitted without delay (i.e., within 
24 hours of awareness). 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 


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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.  
10.3.4 Assessment of Severity  
AEs, including abnormal clinical laboratory values, will be graded using the National Cancer 
Institute-common terminology criteria for adverse event (NCI-CTCAE) guidelines, 
version 5.0. The items that are not stipulated in the NCI-CTCAE, version 5.0 will be assessed 
according to the criteria below and entered into the eCRF:  
Table 12 
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. 
10.3.5 Recording and Follow-up of AEs and/or SAEs 
AE and SAE Recording 
● 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. 
● 
The investigator will then record all relevant AE/SAE information in the eCRF. 
● 
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to the sponsor in lieu of completion of the eCRF. 
● 
There may be instances when copies of medical records for certain cases are requested 
by the sponsor. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to the sponsor. 
● 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 


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Follow-up of AEs and SAEs 
● 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor 
to elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
● 
If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide the sponsor with a copy of any post mortem findings 
including histopathology. 
● 
New or updated information will be recorded in the originally completed eCRF. 
● 
The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information. 
10.3.6 Reporting Procedures for Serious Adverse Events 
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/product defect 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 
UNIQUE to Japan Sites: 
In the case of a SAE, 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 OYOBI 
FUGUAI HOUKOKUSHO or JUTOKUNA YUUGAIJISHOU HOUKOKUSHO containing 


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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.  
For contact details, see [Contact Details of Sponsor's Key Personnel]. Fax or email the 
JUTOKUNA YUUGAIJISHOU OYOBI FUGUAI 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 [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). 
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  
● 
Participant number, sex and age 
● 
Date of report 
● 
Description of the SAE (event and seriousness criteria)  
● 
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., SUSAR reporting) according to current local/regional 
regulatory requirements. The sponsor or sponsor's designee will submit expedited safety 
reports to competent authorities 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. 


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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 participant. 
10.3.7 Reporting Procedures for Special Situations 
10.3.7.1 Contraceptive Guidance and Collection of Pregnancy Information 
If a female participant 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 [Section 10.3.6 Reporting Procedures for Serious Adverse 
Events] using the SAE worksheet or pregnancy form as a special situation and in the eCRF.  
The investigator will attempt to collect pregnancy information on any female partner of a 
male participant who becomes pregnant during the study dosing period or within 180 days 
from the discontinuation of dosing and report the information to the sponsor according to the 
timelines in [Section 10.3.6 Reporting Procedures for Serious Adverse Events] using the 
special situation worksheet or pregnancy form.  
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 
participant as an AE in the eCRF or SAE per [Section 10.3.6 Reporting Procedures for 
Serious Adverse Events]. Participant pregnancy outcomes listed below are to be reported as 
SAEs: 
● 
Spontaneous abortion/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) 
● 
Benign hydatidiform mole 
● 
Blighted ovum 
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. 
10.3.7.2 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 participant), overdose or “off-label use” (i.e., use 
outside of the target disease defined in the protocol) is suspected, refer to [Section 6.7 


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Treatment of Overdose]. 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 10.3.6 
Reporting Procedures for Serious Adverse Events] together with the details of the medication 
error, overdose and/or “off-label use.” 
10.3.7.3 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. 
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 [Section 10.3.6 Reporting Procedures for 
Serious Adverse Events] together with details of the misuse or abuse of the IP. 
10.3.7.4 Occupational Exposure 
If occupational exposure (e.g., inadvertent exposure to the IP of study site personnel while 
preparing it for administration to the participant) 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. 
10.3.7.5 (Suspicion of) Transmission of Infectious Agent  
If transmission of an infectious agent 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) 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 10.3.6 Reporting Procedures for Serious Adverse Events] together with the details of 
the suspected transmission of infectious agent.  
10.3.7.6 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 [Section 10.3.6 Reporting 
Procedures for Serious Adverse Events] together with details of the suspected drug-drug 
interaction. 
10.3.7.7 Reporting Procedures for Product Defect 
When investigator-confirmed death or SAE caused by a defect of a regenerative medicine 
product occurs, or when the investigator judges there is a risk that the product defect caused a 
SAE, the (suspected) product defect is to be reported to sponsor. 


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The investigator must complete and submit a product defect 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 product defect worksheet is to be 
reported as described in [Section 10.3.6 Reporting Procedures for Serious Adverse Events]. 
10.3.8 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 participants, who will be required to sign an updated 
ICF in order to continue in the study. 
UNIQUE to Japan Region: 
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 participants, in compliance with 
[Section 10.1.3.2 Supply of New and Important Information Influencing the Participant’s 
Consent and Revision of the Written Information]. 
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 the rest of the world (within 24 
hours of awareness). 
10.3.8.1 Collection of Defect Information in Stage of Manufacture, Delivery and Storage 
Provision of information from QA to Pharmacovigilance (PV): 
● 
If QA determines that there is a significant quality issue in the defect information 
collected after shipment of the investigational products, QA will send it to PV. When it 
is judged as a significant quality issue, the impact on the participant is also evaluated by 
QA, therefore PV evaluates the provided information and reports it to the 
Pharmaceutical and Medical Devices Agency (PMDA).  


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Provision of information from the PV department to the QA department: 
● 
When the defect information is reported to PV from the investigational sites, PV will 
send it to QA. If QA obtains the follow-up information, QA will send it to PV and PV 
will submit the additional report to PMDA. 
10.3.9 Urgent Safety Measures 
A 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, IRB/IEC, where applicable, in order to protect participants 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.  
When the sponsor receives a safety issue from any source (either Japan or worldwide) that 
requires a USM to be implemented, then the sponsor will report that safety information to all 
study sites in Japan and the rest of world (within 24 hours of awareness).  
10.3.10 Reporting Urgent Safety Measures 
In the event of a potential USM, the investigator must contact the study physician and/or (for 
Japan region) an Astellas team member (within 24 hours of awareness). Full details of the 
potential USM are to be recorded in the participant’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 participants. 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 
competent authorities 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. 


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10.4 
Appendix 4: 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 participant 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 alkaline phosphatase 
[ALP], ALT, AST and TBL). Testing should be repeated within 72 hours of notification of 
the test results. For studies for which a central laboratory is used, alerts will be generated by 
the central laboratory regarding moderate and severe liver abnormality to inform the 
investigator and study team. Participants 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 13 
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 participant 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 > 5 × ULN and† (TBL > 2 × ULN in participants with liver metastases) 
● 
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 


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the liver abnormality case report form (LA-CRF). Participants with confirmed abnormal liver 
function testing should be followed as described below. 
Confirmed moderately abnormal liver function tests should be repeated 2 to 3 times weekly, 
and then weekly or less if abnormalities stabilize or the IP has been discontinued and the 
participant is asymptomatic.  
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 participants 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 participants, 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 participant’s history, other testing may be appropriate including:  
o Acute viral hepatitis (A, B, C, D, E or other infectious agents) 
o Ultrasound or other imaging to assess biliary tract disease 
o 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 liver function tests, such as viral hepatitis, 
preexisting or acute liver disease, or exposure to other agents associated with liver injury, the 
participant may be discontinued from study treatment. The investigator may determine that it 
is not in the participant’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) 


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● 
ALT or AST > 5 × ULN and† (TBL > 2 × ULN in participants with liver metastases) 
● 
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 participant with moderate or severe hepatic laboratory 
tests is not possible, study treatment should be discontinued. 
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 participants 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 participants showing such AT elevations, often with ATs much greater than 
3 × ULN, one 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. 


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10.5 
Appendix 5: List of Excluded Concomitant Medications 
10.5.1 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 is prohibited, with the exception of immune-related AEs. 
10.5.2 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. 
 


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10.6 
Appendix 6: Clinical Laboratory Assessments 
Laboratory tests will be performed according to the schedule of assessments. 
Table 14 
Clinical Laboratory Tests 
Panel/Assessments 
Parameters to be Analyzed 
Hematology 
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) or CO2† 
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  
Thyroid Panel 
Triiodothyronine or free triiodothyronine 
Free thyroxine 
Thyroid stimulating hormone 
eCRF: electronic case report form; hCG: human chorionic gonadotrophin. 
† If testing is not available, this test is not mandatory. 
* Local results will be collected and entered into the eCRF. 
 


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10.7 
Appendix 7: Pharmacogenomic Analysis With Banked Sample  
INTRODUCTION 
PGx research aims to provide information regarding how naturally occurring differences in a 
participant’s gene and/or expression of genes based on genetic variation may impact what 
treatment options are best suited for the participant. 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, 
toxicity or disease may be better understood. As many diseases may be influenced by one or 
more genetic variations, PGx research may identify which genes are involved in determining 
the way a participant 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 and/or disease. 
By analyzing genetic variations, it may be possible to predict an individual participant’s 
response to treatment in terms of efficacy and/or toxicity and/or disease. 
PARTICIPANT PARTICIPATION 
Participants who have consented to participate in this study will participate in the PGx 
substudy. Participants 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 
Participants who consent to participate in this substudy will provide approximately 4 mL 
sample of whole blood/buccal swab per Astellas’ instructions. Each sample will be identified 
by the unique participant 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 and/or disease.  
DISPOSAL OF PGx SAMPLES/DATA 
All PGx samples collected will be stored for a period of up to 15 years following study 
database lock. If there is no requirement for analysis, the whole blood sample will be 
destroyed after the planned storage period. The participant has the right to withdraw consent 
at any time. When a participant’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 PARTICIPANTS 
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 
participants, 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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10.8 
Appendix 8:  Infusion Reaction Dose Modification and Treatment (Guidelines for ASP7517 and Pembrolizumab)  
Table 15 
Infusion Reaction Dose Modification and Treatment (Guidelines for ASP7517 and Pembrolizumab) 
NCI CTCAE Grade 
Treatment 
Premedication at Subsequent Dosing 
Grade 1 
Mild reaction; infusion interruption not 
indicated; intervention not indicated 
• 
Increase monitoring of vital signs as medically indicated until the participant 
is deemed medically stable in the opinion of the investigator. 
None 
Grade 2 
Requires therapy or infusion 
interruption but responds promptly to 
symptomatic treatment (e.g., 
antihistamines, NSAIDs, narcotics, 
intravenous fluids); prophylactic 
medications indicated for ≤ 24 h. 
• 
Stop Infusion. 
• 
Additional appropriate medical therapy may include but is not limited to: 
• 
Intravenous fluids 
• 
Antihistamines 
• 
NSAIDs 
• 
Acetaminophen 
• 
Narcotics 
• 
Increase monitoring of vital signs as medically indicated until the participant 
is deemed medically stable in the opinion of the investigator. 
• 
If symptoms resolve within 1 h of stopping drug infusion, the infusion may 
be restarted at 50% of the original infusion rate (e.g., from 100 mL/h. to 50 
mL/h). Otherwise, dosing will be held until symptoms resolve and the 
participant should be premedicated for the next scheduled dose. 
Participants who develop grade 2 toxicity despite adequate premedication 
should be permanently discontinued from further study drug treatment 
(pembrolizumab only) 
Pembrolizumab only: Participant may be 
premedicated 1.5 h  
(± 30 min) prior to infusion of pembrolizumab 
with: 
Diphenhydramine 50 mg po (or equivalent dose 
of antihistamine). 
Acetaminophen 500 to 1000 mg po (or 
equivalent dose of analgesic). 
 
Contact the study medical monitor regarding 
ASP7517 dose management   
Table continued on next page 


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NCI CTCAE Grade 
Treatment 
Premedication at Subsequent Dosing 
Grades 3 or 4 
Grade 3: 
Prolonged (i.e., not rapidly responsive 
to symptomatic medication and/or 
brief interruption of infusion); 
recurrence of symptoms following 
initial improvement; hospitalization 
indicated for other clinical sequelae 
(e.g., renal impairment, pulmonary 
infiltrates) 
Grade 4: 
Life-threatening; pressor or ventilator 
support indicated 
• 
Stop Infusion. 
• 
Additional appropriate medical therapy may include, but is not limited to: 
o 
Epinephrine* 
o 
Intravenous fluids 
o 
Antihistamines 
o 
NSAIDs 
o 
Acetaminophen 
o 
Narcotics 
o 
Oxygen 
o 
Pressors 
o 
Corticosteroids 
• 
Increase monitoring of vital signs as medically indicated until the participant 
is deemed medically stable in the opinion of the investigator.  
• 
Once the participant has been stabilized, collect blood for cytokine/ 
chemokine panel (ad hoc collection for shipment to central lab). 
• 
If the reaction is suggestive of anaphylaxis, collect blood (standard red 
top tube) for serum total tryptase level (levels typically peak within 3 h 
after the onset of symptoms). Serum should be frozen if the assay cannot 
be performed promptly at the local laboratory. 
• 
Hospitalization may be indicated. 
* In cases of anaphylaxis, epinephrine should be used immediately. 
Participant is permanently discontinued from further study drug 
treatment. 
Any grade 4 hypersensitivity reaction/anaphylaxis, 
study treatment should be discontinued  
Appropriate resuscitation equipment should be available at the bedside and a physician readily available during the period of drug administration. For further information, please 
refer to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE) at http://ctep.cancer.gov. 
NCI: National Cancer Institute; NSAID: non-steroidal anti-inflammatory drug 


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10.9 
Appendix 9:  Monitoring of Pembrolizumab Potential Immune-related Adverse Events  
Table 16 
Monitoring of Pembrolizumab Potential Immune-related Adverse Events 
Potential irAE 
Closely monitor participants’ symptoms for prompt diagnosis and management. 
Pneumonitis 
New cough, worsening cough, shortness of breath, or chest pain 
Colitis 
Changes in bowel habits; abdominal pain; blood or mucus in stool; nausea 
Hepatitis 
Yellowing of skin or whites of eyes; pain on right side of abdomen; dark urine (color of tea); nausea or vomiting; bleeding or 
bruising more easily than usual; loss of appetite; drowsiness 
Endocrinopathies 
Persistent or unusual headaches, changes in vision, rapid heartbeat, increased sweating, feeling very tired or weak, achy 
muscles, change in weight (gain or loss), feeling lightheaded or feeling faint, feeling more hungry or thirsty than usual, loss 
of hair, mood changes such as reduced sex drive or increased irritability, forgetfulness, feeling cold, constipation, deeper 
voice, urinating more frequently than usual, nausea or vomiting, abdominal pain 
Motor/sensory neuropathy; Encephalitis; 
Myasthenic syndrome/myasthenic gravis or 
Guillain-Barre syndrome 
Numbness or tingling, weakness, confusion, headache, forgetfulness, changes in mood or behavior, fever, increased 
sensitivity to light, neck stiffness 
Ocular Inflammation 
Changes in vision (blurry vision; double vision; other vision changes), eye pain, eye redness, eyelid swelling 
Pancreatitis 
Nausea or vomiting, abdominal pain 
Infection 
Fever, other signs of infection 
Musculoskeletal inflammation 
New or worsening joint symptoms, muscle weakness or pain 
irAE: immune-related adverse event  


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10.10 Appendix 10: Dose Modification and Toxicity Management for Immune-related AEs  
AEs associated with pembrolizumab exposure may represent an immune-related response. These irAEs may occur shortly after the first dose or several 
months after the last dose of pembrolizumab treatment and may affect more than one body system simultaneously. Therefore, early recognition and 
initiation of treatment is critical to reduce complications. Based on existing clinical study data, most irAEs were reversible and could be managed with 
interruptions of pembrolizumab, administration of corticosteroids and/or other supportive care. For suspected irAEs, ensure adequate evaluation to 
confirm etiology or exclude other causes. Additional procedures or tests such as bronchoscopy, endoscopy, skin biopsy may be included as part of the 
evaluation. Dose modification and toxicity management guidelines for irAEs associated with pembrolizumab are provided in Table 17. 
Based on 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 (see [Section 2.3.1.8 Other]) and managed as required per standard of care. In case of such events, ensure adequate 
evaluation to confirm etiology or exclude other causes. In addition, the study medical monitor should be contacted to discuss event monitoring, follow up 
and study treatment management. 
Table 17 
Dose Modification and Toxicity Management Guidelines for Immune-related Adverse Events Associated with Pembrolizumab 
General instructions: 
1. Severe and life-threatening immune-related adverse events (irAEs) should be treated with intravenous corticosteroids followed by oral steroids. Other immunosuppressive 
treatment should begin if the irAEs are not controlled by corticosteroids.  
2. Pembrolizumab must be permanently discontinued if the irAE does not resolve or the corticosteroid dose is not ≤10 mg/day within 12 weeks of the last pembrolizumab 
treatment.  
3. The corticosteroid taper should begin when the irAE is ≤ Grade 1 and continue at least 4 weeks. 
4. If pembrolizumab has been withheld, pembrolizumab may resume after the irAE decreased to ≤ Grade 1 after corticosteroid taper. 
Table continued on next page 
 


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irAEs 
Toxicity grade  
(CTCAE v5.0) 
Action with pembrolizumab 
Corticosteroid and/or other 
therapies  
Monitoring and follow-up  
Pneumonitis  
Grade 2 
Withhold  
• 
Administer corticosteroids 
(initial dose of 1 to 2 mg/kg 
prednisone or equivalent) 
followed by taper 
• 
Add prophylactic antibiotics for 
opportunistic infections 
• 
Monitor participants for signs and 
symptoms of pneumonitis 
• 
Evaluate participants with suspected 
pneumonitis with radiographic imaging 
and initiate corticosteroid treatment 
Recurrent Grade 2,  
Grade 3 or 4  
Permanently discontinue 
Diarrhea/Colitis  
Grade 2 or 3 
Withhold 
• 
Administer corticosteroids 
(initial dose of 1 to 2 mg/kg 
prednisone or equivalent) 
followed by taper 
• 
Monitor participants for signs and 
symptoms of enterocolitis (i.e., 
diarrhea, abdominal pain, blood or 
mucus in stool with or without fever) 
and of bowel perforation (i.e., 
peritoneal signs and ileus) 
• 
Participants with ≥ Grade 2 diarrhea 
suspecting colitis should consider GI 
consultation and performing endoscopy 
to rule out colitis 
• 
Participants with diarrhea/colitis should 
be advised to drink liberal quantities of 
clear fluids. If sufficient oral fluid 
intake is not feasible, fluid and 
electrolytes should be substituted via IV 
infusion 
Recurrent Grade 3 or Grade 4 
Permanently discontinue 
Table continued on next page 


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irAEs 
Toxicity grade (CTCAE 
v5.0) 
Action with pembrolizumab 
Corticosteroid and/or other 
therapies 
Monitoring and follow-up 
AST or ALT elevation or 
Increased Bilirubin 
Grade 2 a 
Withhold 
•
Administer corticosteroids
(initial dose of 0.5 to 1 mg/kg
prednisone or equivalent)
followed by taper
•
Monitor with liver function tests
(consider weekly or more frequently
until liver enzyme value returned to
baseline or is stable)
Grade 3 b or 4 c 
Permanently discontinue 
•
Administer corticosteroids
(initial dose of 1 to 2 mg/kg
prednisone or equivalent)
followed by taper
Type 1 diabetes mellitus 
(T1DM) or Hyperglycemia 
New onset T1DM or 
Grade 3 or 4 
hyperglycemia associated 
with evidence of -cell 
failure 
Withhold d 
•
Initiate insulin replacement
therapy for participants with
T1DM
•
Administer anti-hyperglycemic
in participants with 
hyperglycemia 
•
Monitor participants for hyperglycemia
or other signs and symptoms of
diabetes
Hypophysitis 
Grade 2 
Withhold 
•
Administer corticosteroids and
initiate hormonal replacements
as clinically indicated
•
Monitor for signs and symptoms of
hypophysitis (including hypopituitarism
and adrenal insufficiency)
Grade 3 or 4 
Withhold or permanently 
discontinue d 
Hyperthyroidism 
Grade 2 
Continue 
•
Treat with non-selective beta-
blockers (e.g., propranolol) or
thionamides, as appropriate
•
Monitor for signs and symptoms of
thyroid disorders
Grade 3 or 4 
Withhold or permanently 
discontinue d 
Hypothyroidism 
Grade 2, 3, 4 
Continue 
•
Initiate thyroid replacement
hormones (e.g., levothyroxine
or liothyronine) per standard of
care
•
Monitor for signs and symptoms of
thyroid disorders
Table continued on next page 
Footnotes


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irAEs 
Toxicity grade (CTCAE 
v5.0) 
Action with 
pembrolizumab 
Corticosteroid and/or other 
therapies  
Monitoring and follow-up  
Nephritis: 
grading according to 
increased creatinine or acute 
kidney injury 
Grade 2 
Withhold 
• 
Administer corticosteroids 
(prednisone 1 to 2 mg/kg or 
equivalent) followed by taper 
• 
Monitor changes of renal function 
Grade 3 or 4 
Permanently discontinue 
Myocarditis 
Grade 1 or 2 
Withhold 
• 
Based on severity of AE 
administer corticosteroids 
• 
Ensure adequate evaluation to confirm 
etiology and/or exclude other causes 
Grade 3 or 4 
Permanently discontinue 
All Other immune-related 
AEs 
Persistent Grade 2 
Withhold 
• 
Based on severity of AE 
administer corticosteroids 
• 
Ensure adequate evaluation to confirm 
etiology or exclude other causes 
Grade 3 
Withhold or discontinue 
based on the event e  
Recurrent Grade 3 or 
Grade 4  
Permanently discontinue 
a AST/ALT: > 3.0 - 5.0 × ULN if baseline normal; > 3.0 - 5.0 × baseline, if baseline abnormal;  
bilirubin: > 1.5 - 3.0 × ULN if baseline normal; > 1.5 - 3.0 × baseline if baseline abnormal 
b AST/ALT: > 5.0 to 20.0 × ULN, if baseline normal; > 5.0 - 20.0 × baseline, if baseline abnormal; bilirubin: > 3.0 - 10.0 × ULN if baseline normal; > 3.0 - 10.0 × baseline if 
baseline abnormal 
c AST/ALT: > 20.0 × ULN, if baseline normal; > 20.0 × baseline, if baseline abnormal;  
bilirubin: > 10.0 × ULN if baseline normal; > 10.0 × baseline if baseline abnormal 
d The decision to withhold or permanently discontinue pembrolizumab is at the discretion of the investigator or treating physician. If control achieved or ≤ Grade 2, pembrolizumab 
may be resumed. 
e Events that require discontinuation include but are not limited to: Guillain-Barre Syndrome, encephalitis, Stevens-Johnson Syndrome and toxic epidermal necrolysis. 
AE: adverse event; ALT: alanine aminotransferase; AST: aspartate aminotransferase; CTCAE: common terminology criteria for adverse events; GI: gastrointestinal; irAE: immune-
related adverse event; ULN: upper limit of normal 


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10.11 Appendix 11: Dose Modification and Toxicity Management of Infusion Reactions Related to Pembrolizumab 
Pembrolizumab may cause severe or life-threatening infusion-reactions including severe hypersensitivity or anaphylaxis. Signs and symptoms usually 
develop during or shortly after drug infusion and generally resolve completely within 24 hours of completion of infusion. Dose modification and toxicity 
management guidelines on pembrolizumab associated infusion reaction are provided in Table 18.  
Table 18 
Pembrolizumab Infusion Reaction Dose Modification and Treatment Guidelines 
NCI-CTCAE Grade 
Treatment 
Premedication at Subsequent Dosing 
Grade 1 
Mild reaction; infusion interruption 
not indicated; intervention not 
indicated 
• 
Increase monitoring of vital signs as medically indicated until the participant is 
deemed medically stable in the opinion of the investigator. 
None 
Grade 2 
Requires therapy or infusion 
interruption but responds promptly 
to symptomatic treatment (e.g., 
antihistamines, NSAIDs, narcotics, 
IV fluids); prophylactic medications 
indicated for ≤ 24 h. 
• 
Stop Infusion. 
• 
Additional appropriate medical therapy may include but is not limited to: 
• 
IV fluids 
• 
Antihistamines 
• 
NSAIDs 
• 
Acetaminophen 
• 
Narcotics 
• 
Increase monitoring of vital signs as medically indicated until the participant is 
deemed medically stable in the opinion of the investigator. 
• 
If symptoms resolve within 1 h of stopping drug infusion, the infusion may be 
restarted at 50% of the original infusion rate (e.g., from 100 mL/h. to 50 mL/h). 
Otherwise dosing will be held until symptoms resolve and the participant should be 
premedicated for the next scheduled dose. 
Participants who develop Grade 2 toxicity despite adequate premedication should 
be permanently discontinued from further study drug treatment 
Participant may be premedicated 1.5 h  
(± 30 min) prior to infusion of pembrolizumab 
with: 
Diphenhydramine 50 mg po (or equivalent dose 
of antihistamine). 
Acetaminophen 500 to 1000 mg po (or 
equivalent dose of analgesic). 
Table continued on next page 
 


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NCI-CTCAE Grade 
Treatment 
Premedication at Subsequent Dosing 
Grades 3 or 4 
 
Grade 3: 
Prolonged (i.e., not rapidly 
responsive to symptomatic 
medication and/or brief interruption 
of infusion); recurrence of 
symptoms following initial 
improvement; hospitalization 
indicated for other clinical sequelae 
(e.g., renal impairment, pulmonary 
infiltrates) 
Grade 4: 
Life-threatening; pressor or 
ventilator support indicated 
• 
Stop Infusion. 
• 
Additional appropriate medical therapy may include but is not limited to: 
• 
Epinephrine† 
• 
IV fluids 
• 
Antihistamines 
• 
NSAIDs 
• 
Acetaminophen 
• 
Narcotics 
• 
Oxygen 
• 
Pressors 
• 
Corticosteroids 
• 
Increase monitoring of vital signs as medically indicated until the participant is 
deemed medically stable in the opinion of the investigator. 
• 
Hospitalization may be indicated. 
†In cases of anaphylaxis, epinephrine should be used immediately. 
Participant is permanently discontinued from further study drug treatment. 
 
Appropriate resuscitation equipment should be available at the bedside and a physician readily available during the period of drug administration. For further information, please 
refer to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE) at http://ctep.cancer.gov 
NCI: National Cancer Institute; NSAID: nonsteroidal anti-inflammatory drug 
 


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10.12 Appendix 12: 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 participant level during any crisis (e.g., natural disaster, pandemic).   
BENEFIT-RISK RATIONALE 
Maintaining the safety of clinical study participants 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 Schedule of Assessments (Table 1 to Table 5) unless the site 
principal investigator (PI) 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 participant, 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 4 due to a 
crisis. 
INFORMED CONSENT 
Participants 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 participant to provide written 
consent prior to implementation, the PI or designee will obtain oral agreement from the 
participant followed by written documentation as soon as is feasible. A separate addendum to 
the study informed consent will be provided to document the participant’s consent of the 
changes. 
PARTICIPANT PROCEDURES ASSESSMENT 
Sites with participants 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 participant travel to/from the study site nearly impossible 
● 
Site facilities have been closed for clinical study conduct.  
● 
Site has been restricted to treating participants 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 participant with respect to time and travel.  
● 
Participant(s) have temporarily relocated from the current study site to an alternate 
study site to avoid placing a burden on the participant with respect to travel.  


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● 
Participant(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.  
● 
Participant has risk factors for which traveling to the site pose an additional risk to 
the participant’s health and safety.  
Adherence to the original protocol as reflected in the Schedule of Assessments (Section 1.3) 
is expected, where plausible, in the case of a crisis. The alternate measures as noted in 
Table 19 to Table 23 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 participants participating in the study at a time of 
crisis. 
If one or more of the alternate measures noted below is implemented for a participant, the site 
should document in the participant’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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ALTERNATIVE SCHEDULES OF ASSESSMENTS IN RESPONSE TO A CRISIS 
Table 19 
Study Interruption: Schedule of Assessments – Dose Escalation Cohort 
Alternate 
Approach(es) 
Treatmenta 
EOTt 
Cycle 1 
Cycle 2 
Cycles 3–4b 
Cycles 5–6c 
Visit Days 
1 
2 
4 
8 
15 
1 
2 
4 
8 
15 
1 
8 
15 
1 
8 
15 
Window(days) 
0 
0 
0 
±1 
±1 
±1 
0 
±1 
±1 
±1 
±3 
±1 
±1 
±3 
±1 
±1 
+7
Physical 
Examinationd 
Vital Signs 
Except for IP 
administration days, 
exams can be 
performed at a local 
facility and results 
submitted to PI  
Xe 
X 
X 
X 
X 
Xe 
X 
X 
X 
X 
Xe 
X 
X 
Xe 
X 
X 
X 
ECOG Performance 
Except for IP 
administration days, 
can be completed by 
remote/telemedicine 
visit 
Xf 
X 
X 
X 
X 
Xf 
X 
X 
X 
Xf 
X 
X 
Xf 
X 
X 
X 
12-Lead ECGh
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. 
Xh 
X 
Xh 
X 
Xh 
Xh 
Xh 
X 
Prior and 
Concomitant 
Medications 
Remote/Virtual/Telemedicine Visits allowed for non-dosing visits. Please refer to protocol schedule of assessments 
Every Visit 
Table continued on next page 
Footnotes


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Alternate 
Approach(es) 
Treatmenta 
EOTt 
Cycle 1 
Cycle 2 
Cycles 3–4b 
Cycles 5–6c 
Visit Days 
1 
2 
4 
8 
15 
1 
2 
4 
8 
15 
1 
8 
15 
1 
8 
15 
Window(days) 
0 
0 
0 
±1 
±1 
±1 
0 
±1 
±1 
±1 
±3 
±1 
±1 
±3 
±1 
±1 
+7
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 
Xj 
Xj 
Xj 
Xj 
Xj 
Clinical Laboratory 
Tests (chemistry, 
hematology, 
urinalysis)k,ᶠ
Except for IP administration days, collection of samples at local facility acceptable if results can be made available to investigative site 
Coagulation Profile 
(PT/INR, D-dimer, 
fibrinogen)k 
Except for IP 
administration days, 
collection of samples 
at local facility 
acceptable if results 
can be made available 
to investigative site 
Xf 
X 
X 
X 
X 
Xf 
X 
X 
X 
X 
Xf 
Xf 
X 
Thyroid Profile 
Panell 
Test to be completed 
for IP administration 
days in the clinic. 
EOT lab testing can 
be performed at a 
local clinic per 
protocol requirement, 
and results submitted 
to PI for evaluation 
X 
X 
Every 6 weeks 
X 
IRT Transaction 
Required 
None 
Xm 
X 
X 
X 
AE/SAE 
Assessment
Completion by phone contact allowed for non-dosing visits with further assessment at local clinic if needed. 
Every Visit 
PGxn 
None 
Xn 
Table continued on next page 
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Alternate 
Approach(es) 
Treatmenta 
EOTt 
Cycle 1 
Cycle 2 
Cycles 3–4b 
Cycles 5–6c 
Visit Days 
 
1 
2 
4 
8 
15 
1 
2 
4 
8 
15 
1 
8 
15 
1 
8 
15 
 
Window(days) 
 
0 
0 
0 
±1 
±1 
±1 
0 
±1 
±1 
±1 
±3 
±1 
±1 
±3 
±1 
±1 
+7 
Buccal Swab for 
HLA Typing 
None 
Xf 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pharmacokinetic:  
A7517o 
None 
X 
See Table 6 in the Protocol for detailed sample time points 
X 
Pharmacokinetic: 
Pembrolizumabo 
None: 
X 
See Table 6 for detailed sample time points 
X 
Anti-WT1 antibody 
None 
Xf 
 
 
 
 
Xf 
 
 
 
 
Xf 
 
 
Xf 
 
 
X 
Immune Response 
Biomarker 
(ELISpot) 
None  
Xf 
 
 
X 
X 
Xf 
 
 
X 
X 
Xf 
X 
X 
Xf 
X 
X 
X 
Immune Response 
Biomarker 
(Tetramer)  
None:  
Xf 
 
 
 
X 
Xf 
 
 
 
X 
Xf 
 
X 
Xf 
 
X 
X 
Immune Cell 
Phenotyping 
None:  
Xf 
 
 
X 
X 
Xf 
 
 
X 
X 
Xf 
X 
X 
Xf 
X 
X 
X 
Cytokines 
None: 
Xf 
X 
X 
X 
X 
Xf 
X 
X 
X 
X 
Xf 
X 
X 
Xf 
X 
X 
X 
Circulating Tumor 
DNA 
None:  
Xf 
 
 
 
 
Xf 
 
 
 
 
Xf 
 
 
Xf 
 
 
X 
Archival Tumor 
Tissuep 
To be provided from 
archival tumor sample 
available  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Radiographic 
Disease 
Assessmentq 
Assessment to be 
done per protocol 
requirements. Outside 
of the window 
assessments need to 
be escalated to 
Astellas Medical 
Monitor 
Every 56 ±7 days 
 
ASP7517 Dosingr  
None.  
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
X 
 
 
 
Pembrolizumab 
Dosings 
None  
X 
 
 
 
 
 
 
 
 
Xs 
Every 6 weekss 
 
Footnotes appear on next page 


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AE: adverse event; C: Cycle; CR: complete response; CT: computed tomography; D: Day; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; ELISpot: enzyme-
linked immunospot; EOT: end of treatment; FFPE: formalin-fixed, paraffin-embedded; HLA: human leukocyte antigen; ICF: informed consent form; IP: investigational product; IRT: 
interactive response technology; MRI: magnetic resonance imaging; PGx: pharmacogenomic; PI: principal investigator; PR: partial response; PT/INR: prothrombin time/international 
normalized ratio; SAE: serious adverse event; Scr: screening; SD: stable disease; WOCBP: woman of childbearing potential; WT1: Wilms’ tumor 1 protein.  
a. 
Cycles 1 through 6 represent ASP7517 monotherapy or combination of ASP7517 and pembrolizumab therapy; each cycle is 28 days.  
b. After the first 2 cycles, participants who have not met any individual treatment discontinuation criteria and are receiving clinical benefit (defined as radiological response or SD, or 
reduction of disease-related symptoms) will continue further treatment of ASP7517 in cycles 3 and 4, as decided by the investigator. 
c. 
After the first 4 cycles, participants who achieve PR or SD may receive 2 doses of ASP7517 in Cycles 5 and 6. 
d. Height measurement performed at screening only. Height measurement may be performed at a subsequent visit if it was not done at screening. Weight measurement performed at 
screening and Day 1 of each cycle.  
e. 
The following vital sign assessment schedules apply: 
● 
At C1D1 and any visit when pembrolizumab and ASP7517 are administered together, vital signs are obtained predose (-1 h from start of pembrolizumab infusion), within 15 
min prior to start of the pembrolizumab infusion, 15 min (-5 to +10 min window) after the start of the pembrolizumab infusion, at the end of the pembrolizumab infusion (-5 to 
+10 min window), 30 min (± 10 min) after completion of the pembrolizumab infusion, within 15 min prior to the start of the ASP7517 infusion, every 15 min (5 to +10 min 
window) during the ASP7517 infusion, at the end of the ASP7517 infusion (-5 to +10 min window), and postdose (+30 min, +1, +2, +3 and +4 h [± 10 min window each] 
from end of the ASP7517 infusion).  
● 
ASP7517 dosing only: Vital signs are obtained within 15 min prior to start of the ASP7517 infusion, every 15 min (-5 to +10 min window) during the ASP7517 infusion, 
every 15 min (-5 to +10 min window) during the ASP7517 infusion, at the end of the ASP7517 infusion (-5 to +10 min window), as well as 30 min (± 5 min), 1 h (±10 min) 
and 2 h (± 10 min) after completion of the ASP7517 infusion. If participants are still available, additional optional vital sign assessments 3 h (± 10 min) and 4 h (± 10 min) 
after completion of the ASP7517 infusion will be obtained.  
● 
Pembrolizumab dosing only: Vital signs will be obtained 15 min prior to the start of the pembrolizumab infusion, 15 min (-5 to +10 min window) after the start of the 
pembrolizumab infusion (-5 to +10 min window), at the end of the pembrolizumab infusion (-5 to + 10 min window) and at 30 min (±10 min) after completion of the 
pembrolizumab infusion for participants in the combination therapy. 
f. 
Obtain predose. 
g. If chest X-ray is performed within to 2 weeks of screening (prior to ICF and performed as part of standard of care), then it does not need to be repeated. 
h. 12-lead ECGs will be recorded in triplicate (at least 2 min apart per time point) and transmitted electronically for central reading. ECGs may be repeated once during screening. On 
IP administration days, ECGs will be obtained: 
● 
At C1D1 and any visit when pembrolizumab and ASP7517 are administered together, ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h 
post dose of ASP7517. 
● 
ASP7517 dosing only: ECGs are obtained predose (-1 h from start of ASP7517 infusion) and 1 to 2 h post dose of ASP7517. 
● 
Pembrolizumab dosing only: ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h post dose of pembrolizumab. 
i. 
Includes medications taken within 28 days prior to C1D1. Include all anticancer treatment received 28 days prior to IP administration. 
j. 
Urine or serum pregnancy test will be performed in WOCBP. On treatment visit days, test must occur prior to IP administration.  
k. Laboratory tests will be analyzed by the institution’s local laboratory. However, sample results must also be submitted for centralized data entry. Laboratory test may be repeated 
during the screening period. 
Footnotes continued on next page  


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l. 
Thyroid panel including triiodothyronine or free triiodothyronine, free thyroxine and thyroid stimulating hormone will be measured prior to receiving pembrolizumab only for 
participants in the combination cohort (C1D1, C2D15, C4D1 and C5D15). If the thyroid panel is to be measured on same day of pembrolizumab dosing (ex. C4D1, 
pembrolizumab monotherapy dosing visit), the thyroid panel must be measured prior to receiving pembrolizumab. Thyroid panels assessed on C1D1 and C2D15 only apply for the 
combination therapy cohort. 
m. Enrollment or randomization will be done via IRT system after confirmation of eligibility and prior to dosing. 
n. Whole blood for optional PGx study may be collected at C1D1 prior to IP administration. 
o. See Table 6 for collection schedule for ASP7517 monotherapy and ASP7517 and pembrolizumab combination therapy. 
p. Archival tumor specimen at a minimum of 1 FFPE tumor tissue block with adequate viable tumor cells (preferred) OR a minimum of 20 FFPE unstained serial slides are required. 
q. Same technique (CT/MRI) used at screening should be utilized throughout the study. Imaging should include chest, abdomen and pelvis, as well as any other anatomical region 
appropriate for the participant’s disease. Scans performed prior to informed consent as standard of care are acceptable as screening scans, if done within 28 days prior to C1D1.  
r. 
In both the monotherapy and combination cohorts, each participant must remain at the site facility for 4 h following the participant’s first dose of ASP7517. For the next dose (2nd 
dose) or additional subsequent monotherapy with ASP7517, participants must remain at the site facility for at least 2 h after ASP7517 dosing.  
s. 
In the combination therapy arm, pembrolizumab will be administered as an intravenous infusion over 30 min followed by ASP7517 administration at least 1 h after pembrolizumab 
administration.  
t. 
If the participant will discontinue treatment due to meeting protocol criteria of CR after completion of Cycle 4 or a participant completes all 6 cycles of ASP7517, then all visits in 
the treatment cycle should be completed and the EOT visit will be performed 7 days (+ up to a 7-day window) after the last planned visit. 
⚫ 
If participant has CR after completing Cycle 4, the EOT visit would be performed between C4D22 and C4D29. 
⚫ 
If participant has SD or PR after completing Cycle 4, they are expected to complete all visits through C6D15 and the EOT visit would be performed between C6D22 and 
C6D29. 
⚫ 
If the investigator decides to discontinue treatment prior to the completion of any cycle, the EOT visit will occur 7 days after the decision to discontinue treatment. 
⚫ 
If new anticancer therapy is to be initiated, the EOT visit must occur prior to start of the new therapy, even if < 7 days from the decision to discontinue treatment. 
⚫ 
For combination therapy participants that continue with pembrolizumab monotherapy, EOT visit will be performed 7 days after 17th dose of pembrolizumab or 7 days after 
decision to discontinue treatment, or prior to start of new anticancer therapy, whichever is earliest.  
 


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Table 20 
Study Interruption: Schedule of Assessments for Dose Expansion Cohort 
Alternate Approach(es) 
 Treatmenta 
EOTs 
Cycle 1 
Cycle 2 
Cycles 
3–4b 
Cycles 
5-6c
1 
4 
8 
15 
1 
4 
8 
15 
1 
15 
1 
15 
+7
Window(days) 
0 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±3 
±1 
±3 
±1 
Physical Examinationd 
For Cycle 1, each Cycle D1 are IP administration days. Other visits can be obtained at local facility and results submitted to PI 
Vital Signs ͤ 
Except for IP administration days, other exams can be performed at a local facility and results submitted to PI 
ECOG Performance ᶠ 
Except for IP administration days, can be completed by remote/telemedicine visit 
12-Lead ECGh
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. 
Xh 
Xh 
Xh 
Xh 
X 
Prior and Concomitant 
Medications 
Remote/Virtual/Telemedicine 
Visits allowed for non-dosing 
visits. Please refer to protocol 
schedule of assessments Every 
Visit 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy Test for 
WOCBP 
Test must be completed prior to 
dosing, however EoT test may be 
performed at local clinical and 
result submitted to PI 
Xj 
Xj 
Xj 
Xj 
Xj 
Clinical Laboratory Tests 
(chemistry, hematology, 
urinalysis)k 
Except for IP administration 
days, collection of samples at 
local facility acceptable if results 
can be made available to 
investigative site 
Xf 
X 
X 
Xf 
X 
X 
X 
Xf 
X 
Xf 
X 
X 
Table continued on next page 
Footnotes


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Alternate Approach(es) 
 Treatmenta 
EOTs 
Cycle 1 
Cycle 2 
Cycles 
3–4b 
Cycles 
5-6c
1 
4 
8 
15 
1 
4 
8 
15 
1 
15 
1 
15 
+7
Window(days) 
0 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±3 
±1 
±3 
±1 
Coagulation Profile 
(PT/INR, D-dimer, 
fibrinogen)k 
Except for IP administration 
days, collection of samples at 
local facility acceptable if results 
can be made available to 
investigative site 
Xf 
X 
X 
Xf 
X 
X 
Xf 
X 
Xf 
X 
X 
Thyroid Profile Panell 
Except for IP administration 
days, the lab testing can be 
performed at a local clinic per 
protocol requirement 
communicated by the PI and 
results submitted to PI for 
evaluation 
X 
X 
Every 6 weeks after C2D15 dose 
X 
PGxm 
None 
Xm 
Buccal Swab for HLA 
Typing 
None 
Xf 
AE/SAE Assessment 
Completed by phone contact allowed for non-dosing visits with further assessment at local clinic if needed. 
Every visit 
Pharmacokinetic: 
A7517n 
None 
X 
See Table 6 for sample time points 
X 
Pharmacokinetic: 
Pembrolizumabn 
None 
X 
See Table 6 for sample time points 
X 
Anti-WT1 antibody 
None 
Xf 
Xf 
Xf 
Xf 
X 
Immune Response 
Biomarker (ELISpot) 
None 
Xf 
X 
X 
Xf 
X 
X 
Xf 
X 
Xf 
X 
X 
Immune Response 
Biomarker (Tetramer) 
None 
Xf 
X 
Xf 
X 
Xf 
X 
Xf 
X 
X 
Immune Cell 
Phenotyping 
None 
Xf 
X 
X 
Xf 
X 
X 
Xf 
X 
Xf 
X 
X 
Cytokines 
None 
Xf 
X 
X 
X 
Xf 
X 
X 
X 
Xf 
X 
Xf 
X 
X 
Table continued on next page 
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Alternate Approach(es) 
 Treatmenta 
EOTs 
Cycle 1 
Cycle 2 
Cycles 
3–4b 
Cycles 
5-6c 
 
 
1 
4 
8 
15 
1 
4 
8 
15 
1 
15 
1 
15 
+7 
Window(days) 
 
0 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±3 
±1 
±3 
±1 
 
Circulating tumor DNA 
None 
Xf 
 
 
 
Xf 
 
 
 
Xf 
 
Xf 
 
X 
Archival Tumor Tissueo 
To be provided from archival 
tumor sample available 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor Tissue, Fresh 
Biopsy 
None 
Xq 
 
 
 
 
 
 
Xr 
 
 
 
 
 
Radiographic Disease 
Assessmentp 
Assessment to be done per 
protocol requirements. Outside of 
the window assessments need to 
be escalated to Astellas Medical 
Monitor 
Every 56 ±7 days 
 
ASP7517 Dosing  
None 
X 
 
 
 
X 
 
 
 
X 
 
X 
 
 
Pembrolizumab Dosing 
None 
X 
 
 
 
 
 
 
X 
Every 6 weeks after C2D15 dose 
 
AE: adverse event; C: Cycle; CR: complete response; CT: computed tomography; D: Day; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; ELISpot: enzyme-
linked immunospot; EOT: end of treatment; FFPE: formalin-fixed, paraffin-embedded; HLA: human leukocyte antigen; ICF: informed consent form; IP: investigational product; IRT: 
interactive response technology; MRI: magnetic resonance imaging; PGx: pharmacogenomic; PI: principal investigator; PR: partial response; PT/INR: prothrombin time/international 
normalized ratio; SAE: serious adverse event; Scr: screening; SD: stable disease; WOCBP: woman of childbearing potential; WT1: Wilms’ tumor 1 protein.  
a. 
Cycles 1 through 6 represent ASP7517 monotherapy or combination of ASP7517 and pembrolizumab therapy; each cycle is 28 days.  
b. After the first 2 cycles, participants who have not met any individual treatment discontinuation criteria and are receiving clinical benefit (defined as radiological response or SD, or 
reduction of disease-related symptoms) will continue further treatment of ASP7517 as decided by the investigator. 
c. 
After the first 4 cycles, participants who achieve PR or SD may receive 2 doses of ASP7517 in Cycles 5 and 6. 
d. Height measurement performed at screening only. Height measurement may be performed at a subsequent visit if it was not done at screening. Weight measurement performed at 
screening and Day 1 of each cycle.  
e. 
The following vital sign assessment schedules apply: 
● 
At C1D1 and any visit when pembrolizumab and ASP7517 are administered together, vital signs are obtained predose (-1 h from start of pembrolizumab infusion), within 15 
min prior to start of the pembrolizumab infusion, 15 min (-5 to +10 min window) after the start of the pembrolizumab infusion, at the end of the pembrolizumab infusion (-5 to 
+10 min window), 30 min (± 10 min) after completion of the pembrolizumab infusion, within 15 min prior to the start of the ASP7517 infusion, every 15 min (5 to +10 min 
window) during the ASP7517 infusion, at the end of the ASP7517 infusion (-5 to +10 min window), and post-dose (+30 min, +1, +2, +3 and +4 h [± 10 min window each] 
from end of the ASP7517 infusion).  
Footnotes continued on next page 


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● 
ASP7517 dosing only: Vital signs are obtained within 15 min prior to start of the pembrolizumab infusion, every 15 min (-5 to +10 min window) during the ASP7517 
infusion, , every 15 min (-5 to +10 min window) during the ASP7517 infusion, at the end of the ASP7517 infusion (-5 to + 10 min window), as well as 30 min (± 5 min), 1 h 
(± 10 min) and 2 h (± 10 min) after completion of the ASP7517 infusion. If participants are still available, additional optional vital sign assessments 3 h (± 10 min) and 4 h 
(± 10 min) after completion of the ASP7517 infusion will be obtained.  
● 
Pembrolizumab dosing only: Vital signs will be obtained within 15 min prior to start of the pembrolizumab infusion, 15 min (-5 to +10 min window) after the start of the 
pembrolizumab infusion (-5 to +10 min window), at the end of the pembrolizumab infusion (-5 to + 10 min window) and at 30 min (± 10 min) after completion of the 
pembrolizumab infusion for participants in the combination therapy. 
f. 
Obtain predose on dosing days. 
g. If chest X-ray is performed prior to 2 weeks of screening (prior to ICF and performed as part of standard of care), then it does not need to be repeated. 
h. During ASP7517 and pembrolizumab combination therapy, 12-lead ECGs will be recorded in triplicate (at least 2 min apart per time point) and transmitted electronically for 
central reading. After treatment with ASP7517 has been discontinued, 12-lead ECGs will be recorded as a single assessment (in triplicate if deemed necessary, at least 2 min apart 
per time point) and read locally. ECG may be repeated once during screening. On IP administration days, ECGs will be obtained: 
• 
At C1D1 and any visit when pembrolizumab and ASP7517 are administered together, ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h 
post dose of ASP7517. 
• 
ASP7517 dosing only: ECGs are obtained predose (-1 h from start of ASP7517 infusion) and 1 to 2 h post dose of ASP7517. 
• 
Pembrolizumab dosing only: ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h post dose of pembrolizumab. 
i. 
Includes medications taken within 28 days prior to C1D1. Include all anticancer treatment received 28 days prior to IP administration. 
j. 
Urine or serum pregnancy test will be performed in WOCBP. On treatment visit days, test must occur prior to IP administration.  
k. Laboratory tests will be analyzed by the institution’s local laboratory. However, sample results must also be submitted for centralized data entry. Laboratory test may be repeated 
during the screening period. 
l. 
Thyroid panel including triiodothyronine or free triiodothyronine, free thyroxine and thyroid stimulating hormone will be measured prior to receiving pembrolizumab only for 
participants in the combination cohort. If the thyroid panel is to be measured on same day of pembrolizumab dosing (ex. C4D1, pembrolizumab monotherapy dosing visit), the 
thyroid panel must be measured prior to receiving pembrolizumab. Thyroid panels assessed on C1D1 and C2D15 only apply for the combination therapy cohort. 
m. Whole blood for optional PGx study may be collected at C1D1 prior to IP administration. 
n. See Table 6 for collection schedule for ASP7517 monotherapy and ASP7517 and pembrolizumab combination therapy. 
o. Archival tumor specimen at a minimum of 1 FFPE tumor tissue block with adequate viable tumor cells (preferred) OR a minimum of 20 FFPE unstained serial slides are required. 
p. Same technique (CT/MRI) used at screening should be utilized throughout the study. Imaging should include chest, abdomen and pelvis, as well as any other anatomical region 
appropriate for the participant’s disease. Scans performed prior to informed consent as standard of care are acceptable as screening scans, if done within 28 days prior to C1D1.  
q. Participants in all expansion cohorts are required to provide a tumor specimen obtained within 56 days prior to first dose of IP. 
r. 
Participants in all expansion cohorts are required to provide an on-treatment tumor specimen collected ± 7 days of the C2D15 visit (or unscheduled) if predose biopsy is available 
and if medically feasible. 
Footnotes continued on next page 


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s. 
If the participant will discontinue treatment due to meeting protocol criteria of CR after completion of Cycle 4 or a participant completes all 6 cycles of ASP7517, then all visits in 
the treatment cycle should be completed and the EOT visit will be performed 7 days (+ up to a 7-day window) after the last planned visit. 
• 
If participant has CR after completing Cycle 4, the EOT visit would be performed between C4D22 and C4D29. 
• 
If participant has SD or PR after completing Cycle 4, they are expected to complete all visits through C6D15 and the EOT visit would be performed between C6D22 and 
C6D29. 
• 
If the investigator decides to discontinue treatment prior to the completion of any cycle, the EOT visit will occur 7 days after the decision to discontinue treatment. 
• 
If new anticancer therapy is to be initiated, the EOT visit must occur prior to start of the new therapy, even if < 7 days from the decision to discontinue treatment. 
• 
For combination therapy participants that continue with pembrolizumab monotherapy, EOT visit will be performed 7 days after 17th dose of pembrolizumab or 7 days after 
decision to discontinue treatment, or prior to start of new anticancer therapy, whichever is earliest. 
 


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Table 21 
Study Interruption: Schedule of Assessments for Safety Follow-up, Observation Period and Survival Follow-up Period for 
Participants who End the Treatment Early or Completed the Treatment Period 
Visit 
Alternate Approach(es) 
Observation Period 
Survival 
Follow-up 
Safety Follow-upᶠ 
Disease Assessment, 
Up to 48 weeksa 
Window (days) 
30 days from 
 last dose 
60 days from 
last dose 
90 days from 
last dose 
Visits every 8 weeks 
±1 week from last planned 
scan  
Every 3 months 
±3 
±3 
±3 
±7 
Physical Examination 
Can be obtained at local facility and 
results submitted to PI 
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 
ECOG Performance 
Can be completed by phone contact 
X 
X 
X 
Concomitant Medications 
Can be completed by phone contact 
X 
X 
X 
12-Lead ECG
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. 
X 
X 
X 
Clinical Laboratory Tests (chemistry, 
hematology, coagulation, urinalysis) 
Collection of samples at local facility 
acceptable if results can be made 
available to investigative site 
X 
X 
X 
Pregnancy Test for WOCBP 
Test may be performed at local clinical 
and result 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 
Pharmacokinetic sample for cell 
kinetics (ASP7517) 
None 
See Table 6 for sample time points 
Blood Sample for anti-WT1 antibody 
None 
X 
X 
X 
Xb 
Blood Sample for Immune Response 
Biomarker (ELISpot)  
None 
X 
X 
X 
Xc 
Blood Sample for Immune Response 
Biomarker (Tetramer)  
None 
X 
X 
X 
Xb 
Table continued on next page 
Footnotes


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Visit 
Alternate Approach(es) 
Observation Period 
Survival 
Follow-up 
Safety Follow-upᶠ 
Disease Assessment, 
Up to 48 weeksa 
Window (days) 
30 days from 
 last dose 
60 days from 
last dose 
90 days from 
last dose 
Visits every 8 weeks 
±1 week from last planned 
scan  
Every 3 months 
±3 
±3 
±3 
±7 
Blood Sample for Immune Cell 
Phenotyping 
None 
X 
X 
X 
Xc 
Blood Sample for Cytokines 
None 
X 
X 
X 
Xc 
Blood Sample for ctDNA 
None 
X 
X 
X 
Xd 
Radiographic Disease Assessment 
Assessment to be done per protocol 
requirements. Outside of the window 
assessments need to be escalated to 
Astellas Medical Monitor 
X 
Survival Follow-upe 
Can be completed by phone contact per 
protocol design. 
X 
AE: adverse event; ctDNA: circulating tumor DNA; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; ELISpot: enzyme-linked immunospot; EOT: end of 
treatment; iCPD: “immune” confirmed progressive disease; iUPD: unconfirmed disease progression disease based on iRECIST; SAE: serious adverse event; WOCBP: woman of 
childbearing potential; WT1: Wilms’ tumor 1 protein.  
a.
For participants in ASP7517 monotherapy treatment arm. Participants in the Observation period will be followed until iCPD, iUPD who are not clinically stable, clinical disease
progression, initiation of a new anticancer therapy or for a total of up to 48 weeks starting at EOT, whichever occurs first.
b.
Maximum of 5 samples collected during the Observation Period. Sample will be collected at the time of the disease assessment visit.
c.
Maximum of 1 sample collected during the Observation Period. Sample will be collected at the time of the disease assessment visit.
d.
Sample will be collected only at the time of discontinuation due to disease progression.
e.
Outcomes will be assessed by telephone calls every 3 months for up to 12 months.
f.
In the Monotherapy Arm, Safety Follow-up is a part of the 48 weeks Observation period. Observation period starts after EOT.


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Table 22 
Study Interruption: Schedule of Assessments for Observation Period, Safety Follow-up and Survival Follow-up for Participants 
who Receive Pembrolizumab Monotherapy in the Observation Period 
Visit 
Alternate Approach(es) 
Observation Period 
Up to 96weeksa 
Safety Follow-up 
Survival 
Follow-up 
Visits every 6 weeks (±1 week) from last 
Pembrolizumab dose during combination 
treatment 
30 days 
from last 
dose 
60 days 
from last 
dose 
90 days 
from last 
dose 
Every 3 
months 
Window (days) 
±3 
±3 
±3 
±7 
Physical Examination 
Can be obtained at local facility and results submitted to PI 
X 
X 
X 
X 
Vital Signs 
Exams can be performed at a local clinic per SOC and 
results submitted to PI for evaluation 
Xb 
X 
X 
X 
ECOG Performance 
Can be completed by phone contact 
X 
X 
X 
Concomitant Medications 
Can be completed by phone contact 
X 
X 
X 
X 
12-Lead ECG
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. 
Xc 
X 
X 
X 
Clinical Laboratory Tests 
(chemistry, hematology, 
coagulation, urinalysis) 
Collection of samples at local facility acceptable if results 
can be made available to investigative site 
Xc 
X 
X 
X 
Thyroid Profile Panel 
(triiodothyronine or free 
triiodothyronine, free thyroxine 
and thyroid stimulating 
hormone) 
Collection of samples at local facility acceptable if results 
can be made available to investigative site 
Xc 
Xc 
Pregnancy Test for WOCBP 
Test may be performed at local clinical and result submitted 
to PI 
Xc 
X 
X 
X 
AE/SAE Assessment 
Completed by phone contact allowed with further 
assessment at local clinic if needed 
X 
X 
X 
X 
Pharmacokinetic samples for cell 
kinetics (ASP7517) 
None 
See Table 6 in the Protocol for schedule 
Pharmacokinetic sample for 
pembrolizumab 
None 
See Table 6 in the Protocol for schedule 
Blood Sample for anti-WT1 
antibody 
None 
Xc,h 
Table continued on next page 
Footnotes


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Visit 
Alternate Approach(es) 
Observation Period 
Up to 96weeksa 
Safety Follow-up 
Survival 
Follow-up 
 
Visits every 6 weeks (±1 week) from last 
Pembrolizumab dose during combination 
treatment 
30 days 
from last 
dose  
60 days 
from last 
dose 
90 days 
from last 
dose 
Every 3 
months 
Window (days) 
 
 
±3 
±3 
±3 
±7 
Blood Sample for Immune 
Response Biomarker (ELISpot)  
None 
Xc,g 
 
 
 
 
Blood Sample for Immune 
Response Biomarker (Tetramer)  
None 
Xc,h 
 
 
 
 
Blood Sample for Immune Cell 
Phenotyping 
None 
Xc,g 
 
 
 
 
Blood Sample for Cytokines 
None 
Xc,g 
 
 
 
 
Blood Sample for ctDNA 
None 
Xc,f 
 
 
 
 
Radiographic Disease 
Assessment 
Assessment to be done per protocol requirements. Outside 
of the window assessments need to be escalated to Astellas 
Medical Monitor 
Xd 
 
 
 
 
Pembrolizumab Dosing 
Assessment to be done per protocol requirements. Outside 
of the window assessments need to be escalated to Astellas 
Medical Monitor 
Xe 
 
 
 
 
Survival Follow-upi 
Can be completed by phone contact per protocol design. 
 
 
 
 
X 
AE: adverse event; C5D15: Cycle 5 Day 15; CR: complete response; ctDNA: circulating tumor DNA; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; 
ELISpot: enzyme-linked immunospot; iCPD: “immune” confirmed progressive disease; iUPD: unconfirmed disease progression disease based on iRECIST; PR: partial response; SAE: 
serious adverse event; SD: stable disease: WOCBP: woman of childbearing potential; WT1: Wilms’ tumor 1 protein.  
a. 
For participants in ASP7517 and pembrolizumab treatment who have achieved CR, PR or SD and receiving pembrolizumab monotherapy. Pembrolizumab will be administered 
every 6 weeks for up to a total of 17 doses. Participants in the Observation period will be followed until iCPD, iUPD who are not clinically stable, clinical disease progression, 
initiation of a new anticancer therapy or for a total of up to 78 weeks, whichever occurs first. If participant discontinues combination treatment of ASP7517 at any time prior to 
C5D15, then the participant should continue observation period up to 96 weeks. 
b. Vital signs should be obtained prior to pembrolizumab infusion and within 30 min (± 10 min window) after completion of pembrolizumab infusion. 
c. 
Obtained predose. 
d. Disease assessment every 8 weeks. 
e. 
Pembrolizumab administered every 6 weeks for up to 17 doses total (for the study) for those participants who, in the opinion of the investigator, are continuing to derive clinical 
benefit. 
f. 
Sample collected at the time of discontinuation due to disease progression. 
g. Sample collected at the time of pembrolizumab administration of doses 5 and 7. 
Footnotes continued on next page 


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h. Sample collected at the time of pembrolizumab administration of doses 5, 7, 9, 11 and 13. 
i. 
Outcomes will be assessed by telephone calls every 3 months for up to 12 months, starting from the 90-day safety follow-up or last visit prior to the start of new anti-cancer 
therapy. 


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Table 23 
Study Interruption: Schedule of Replication Competent Lentivirus for Dose Escalation Cohort and Dose Expansion Cohort 
Assessment 
Alternate 
Approach(es) 
C1D1 
3 Months After Treatment 
Initiation or at End of 
Treatment, Whichever is First 
6 Months after 
Treatment Initiation 
12 Months after 
Treatment Initiation 
18 Months after 
Treatment 
Initiation 
Window 
 
0 
±7 days 
±1 month 
±1 month 
+1 month 
Blood Sample for RCLa 
None: to collect at the 
first time participant 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 7.7.1]. 
b. Obtained predose. 
 


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INVESTIGATIONAL MEDICINAL PRODUCT SUPPLY 
If any of the conditions outlined above in the Participants Procedures Assessment are met, the 
following mitigating strategies will be employed, as needed, to ensure continuity of IMP 
supply to the participants:   
● 
Increase stock of IMP on site to reduce number of shipments required, if site storage 
condition will allow, however each shipment will be closely monitored by Astellas. 
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 participant 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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10.13 List of Abbreviations and Definition of Key Study Terms 
List of Abbreviations 
Abbreviations 
Description of abbreviations 
aAVC 
artificial adjuvant vector cell 
ADL 
activities of daily living 
AE 
adverse event 
ALK 
anaplastic lymphoma kinase 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
anti-PD-1 
anti-programmed cell death protein 1 
AST 
aspartate aminotransferase 
AT 
aminotransferases 
AUC 
area under the concentration-time curve 
AUCinf 
area under the concentration-time curve from the time of dosing extrapolated to 
time infinity 
AUClast 
area under the concentration-time curve from the time of dosing up to the time 
of the last measurable concentration 
AUC28d 
area under the concentration-time curve from time zero to Day 28 
BOIN 
Bayesian optimal interval 
BOP2 
Bayesian optimal phase 2 
C1D1 
Cycle 1 Day 1 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
Cmax 
maximum concentration 
CNS 
central nervous system 
CPI 
checkpoint inhibitor 
CR 
complete response 
CRC 
colorectal cancer 
CRO 
contract research organization 
CRS 
cytokine-release syndrome 
CSR 
clinical study report 
CT 
computed tomography 
CTCAE 
common terminology criteria for adverse events 
ctDNA 
circulating tumor DNA 
Ctrough 
concentration immediately prior to dosing at multiple dosing 
DCR 
disease control rate per RECIST v1.1 
DESC 
Dose Escalation and Safety Committee 
DLT 
dose limiting toxicity 
DOR 
duration of response per RECIST v1.1 
DPD 
Data Protection Directive 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 


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Abbreviations 
Description of abbreviations 
eCRF 
electronic case report form 
eGFR 
epidermal growth factor receptor 
ELISpot 
enzyme-linked immunospot 
EOT 
end of treatment 
FAS 
full analysis set 
FFPE 
formalin-fixed, paraffin embedded 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practices 
HLA 
human leukocyte antigen 
HRT 
hormone replacement therapy 
ICF 
informed consent form 
ICH  
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
iCPD 
“immune” confirmed progressive disease 
iCR 
complete response based on iRECIST 
iDCR 
disease control rate per iRECIST 
iDOR 
duration of response per iRECIST 
IEC 
Independent Ethics Committee 
IFNγ 
interferon gamma 
IMP 
investigational medicinal product 
INR 
international normalized ratio 
iORR 
objective response rate per iRECIST 
IP 
investigational product 
iPFS 
progression-free survival per iRECIST 
iPR 
partial response based on iRECIST 
irAE 
immune-related AE 
IRB 
Institutional Review Board 
iRECIST 
immune response evaluation criteria in solid tumors 
IRR 
infusion-related reactions 
IRT 
interactive response technology 
iSD 
stable disease per iRECIST 
ISN 
international study number 
iUPD 
unconfirmed disease progression disease based on iRECIST 
LA-CRF 
liver abnormality case report form 
LFT 
liver function test 
MMR 
mismatch repair 
MRI 
magnetic resonance imaging 
MSI-H 
microsatellite instability-high 
MTD 
maximum tolerated dose 
NCI-CTCAE 
National Cancer Institute’s Common Terminology Criteria for Adverse Events 
NK 
natural killer 


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Abbreviations 
Description of abbreviations 
NKT 
natural killer T 
ORR 
objective response rate per RECIST v1.1 
OS 
overall survival 
PD-1 
programmed cell death protein 1 
PD-L1 
programmed death-ligand 
PFS 
progression-free survival per RECIST v1.1 
PGx 
pharmacogenomic 
PI 
principal investigator 
PKAS 
pharmacokinetic analysis set 
PMDA 
Pharmaceutical and Medical Devices Agency 
po 
by mouth 
PR 
partial response 
PT/INR 
prothrombin time/international normalized ratio 
PV 
pharmacovigilance 
QA 
quality assurance 
QC 
quality control 
QTL 
quality tolerance limit 
RAS 
response analysis set 
RCL 
replication competent lentivirus 
RECIST 
response evaluation criteria in solid tumors 
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 
t½ 
terminal elimination half-life 
TBL 
total bilirubin 
TEAE 
treatment-emergent adverse event 
TKI 
tyrosine kinase inhibitor 
tmax 
time of maximum concentration  
ULN 
upper limit of normal 
WOCBP 
woman of childbearing potential 
WT1 
Wilms’ tumor protein 1 


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Definition of Key Study Terms 
Terms 
Definition of Terms 
Baseline  
Assessments of participants 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 participant into a study. Note: Once a participant has 
received the IP or placebo, the protocol applies to the participant.  
Investigational 
Product 
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 participant, and continues until the last 
assessment after completing administration of the test product or 
comparative drug. 
Randomization 
The process of assigning participants 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 participants into groups at 
a differential rate; for example, 3 participants may be assigned to a treatment 
group for every one assigned to the control group. 
Screening 
A process of active consideration of potential participants for randomization 
in a study. 
Screen failure 
Potential participant who signed the ICF, but did not meet one or more 
criteria required for participation in the study and was not randomized. 
Screening period 
Period of time before entering the investigational period, usually from the 
time when a participant signs the consent form until just before the test 
product or comparative drug (sometimes without randomization) is given to 
a participant.  
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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11 
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12 
ATTACHMENT 1: PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Protocol 7517-CL-1101 A Phase 1/2, Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP7517 as a Single Agent and in 
Combination with Pembrolizumab in Patients with Advanced Solid Tumors Known to Express WT1 Antigen 
Substantial Amendment 6, 10 Feb 2022 
This amendment is considered to be substantial 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. 
Overall Rationale for the Amendment: 
The purpose of this amendment is to clarify that the patient population in the monotherapy arm of the dose expansion cohort will include Japanese 
participants. 
Summary of Changes 
Table 1 
Substantial Changes 
Section Number 
Description of Change 
Brief Rationale 
1.1, 4.1.6.2 and 6.3.1 
Clarify that Japanese participants will enroll in the monotherapy 
arm of the dose expansion cohort. 
To clarify that the patient population in the 
monotherapy arm of the dose expansion cohort will 
include Japanese participants 
5.1 
Revise inclusion criterion 1 for Additional Inclusion Criteria for 
Participants in the Expansion Cohorts 
To clarify a target population for ASP7517 
monotherapy 
7.8 
Updated total amount of blood collectioned 
 
 


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Table 2 
Nonsubstantial Changes 
Section Number 
Description of Change 
Brief Rationale 
1.1, 1.2, 1.3, 4.1.1, 
4.1.3, 10.12 
Update the maximum pembrolizumab treatment to up to an 
additional 17 doses 
This revision is made for clarification in the event that 
participants in the combination therapy cohorts 
discontinue ASP7517 treatment early. 
1.3 (Tables 1 and 2), 
10.12 (Tables 19 and 
20) 
Add Thyroid Profile Panel assessments on C1D1 and C2D15 (for 
combination therapy cohorts) 
Accounts for thyroid monitoring required for 
pembrolizumab administration 
1.3 (Tables 1 and 2), 
10.12 (Tables 19 and 
20) 
Update 12-lead ECG footnotes to clarify timing of ECG 
monitoring when ASP7517 and pembrolizumab are administered 
together or separately 
This revision is made for clarification. 
7.5.2 
Add that a participant with both an FFPE block and a frozen tissue 
specimen taken within 56 days prior to the first dose of study 
treatment does not need to provide a new biopsy 
This revision is made for clarification. 
10.6 
Remove blast count and cell count from Table 14 
This parameter is not applicable to this study. 
10.6 
Add a footnote to clarify testing for HCO3 
This revision is made for clarification. 
10.8, 10.11 
Remove no subsequent dosing from premedication at subsequent 
dosing for Grades 3 or 4 in Tables 15 and 18 
This revision is made for clarification. 
Throughout 
Minor administrative-type changes (e.g., typos, format, numbering 
and consistency throughout the protocol) and change subject and 
patient to participant throughout 
To provide clarifications to the protocol and to ensure 
complete understanding of study procedures. 
 
 


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13 
SPONSOR SIGNATURE 
Astellas Signatories 
(Electronic signatures are attached at the end of the document.) 
 
 
 
Medical Science 
 
 
 
Data Science  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Global Protocol Format v9.0 
PPD
PPD

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STATISTICAL ANALYSIS PLAN
Version 2.0, dated 6-JUN-2024
A Phase 1/2, Open-label Study Investigating the Safety, Tolerability and Efficacy of 
ASP7517 as a Single Agent and in Combination with Pembrolizumab in Patients with 
Advanced Solid Tumors Known to Express WT1 Antigen
ISN/Protocol: 7517-CL-1101
IND number: 025239
Sponsor:
Astellas Pharma Global Development, Inc. (APGD) 
2375 Waterview Drive
Northbrook, IL 60062, US
This confidential document is the property of the sponsor.  No unpublished information 
contained in this document may be disclosed without prior written approval of the sponsor.


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Table of Contents 
I. 
LIST OF ABBREVIATIONS AND KEY TERMS ··········································· 4 
1 
INTRODUCTION ·················································································· 7 
2 
TREATMENT PROTOCOL OBJECTIVES AND DESIGN ······························ 7 
2.1 
Study Objectives ··············································································· 7 
2.2 
Study Design ···················································································· 8 
2.3 
Randomization ················································································· 11 
3 
SAMPLE SIZE····················································································· 11 
4 
ANALYSIS SETS ················································································· 12 
5 
ENDPOINTS ······················································································· 13 
5.1 
Efficacy Endpoints ············································································ 13 
5.1.1 
Primary Efficacy Endpoints ···························································· 13 
5.1.2 
Secondary Efficacy Endpoints ························································· 13 
5.2 
Safety Endpoints ·············································································· 20 
5.3 
Pharmacokinetic Variables ··································································· 25 
5.4 
Pharmacodynamic Variables································································· 25 
5.5 
Other Variables ················································································ 25 
6 
STATISTICAL METHODOLOGY ··························································· 26 
6.1 
General Considerations ······································································· 26 
6.2 
Study Population ·············································································· 26 
6.2.1 
Disposition of Participants ····························································· 26 
6.2.2 
Protocol Deviations ····································································· 27 
6.2.3 
Demographic and Other Baseline Characteristics ··································· 27 
6.2.4 
Disease History ·········································································· 28 
6.2.5 
Previous and Concomitant Medications ·············································· 28 
6.2.6 
Prior Radiation Therapy ································································ 28 
6.2.7 
Non-Medication Therapy ······························································· 28 
6.2.8 
Prior and New Anti-Cancer Therapy ·················································· 28 
6.3 
Study Drug ····················································································· 28 
6.3.1 
Exposure ·················································································· 28 
6.4 
Analysis of Efficacy ·········································································· 29 
6.4.1 
Analysis of Primary Efficacy Endpoint ··············································· 29 


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6.4.2 
Analysis of Primary Efficacy Endpoints ·············································· 29 
6.5 
Analysis of Safety ············································································· 30 
6.5.1 
Dose Limiting Toxicities ······························································· 30 
6.5.2 
Adverse Events ·········································································· 31 
6.5.3 
Adverse Events of Special Interest (AEsi) ··········································· 33 
6.5.4 
Clinical Laboratory Evaluation ························································ 33 
6.5.5 
Vital Signs ················································································ 34 
6.5.6 
Electrocardiograms (ECGs) ···························································· 35 
6.5.7 
Pregnancies ··············································································· 36 
6.5.8 
Eastern Cooperative Oncology Group (ECOG) Performance Status ·············· 36 
6.6 
Analysis of Pharmacokinetics ······························································· 36 
6.6.1 
Estimation of Pharmacokinetic Parameters ·········································· 36 
6.7 
Analysis of Exploratory Endpoints ························································· 36 
6.8 
Subgroups of Interest ····································· Error! Bookmark not defined. 
6.9 
Interim Analysis (and Early Discontinuation of the Clinical Study) ···················· 36 
6.10 
Additional Conventions ······································································ 36 
6.10.1 
Analysis Windows ······································································ 36 
6.10.2 
Imputation Rules for Incomplete Dates ··············································· 37 
6.10.3 
Covid-19 Impact Assessment ·························································· 38 
6.10.4 
Outliers ··················································································· 38 
7 
DOCUMENT REVISION HISTORY ························································· 39 
8 
REFERENCES ···················································································· 40 
9 
APPENDICES ····················································································· 41 
9.1 
Appendix 1: Key Contributors and Approvers ············································ 41 
9.2 
Appendix 2 Author and Approver Signatures ············································· 42 
 


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I. 
LIST OF ABBREVIATIONS AND KEY TERMS 
List of Abbreviations 
Abbreviations  
Description of abbreviations  
aAVC 
artificial adjuvant vector cell 
AE 
adverse event 
AEsi 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT  
alanine aminotransferase  
ANC 
absolute neutrophil count 
APGD 
Astellas Pharma Global Development 
ASCM 
analysis set classification meeting 
ATC 
anatomical therapeutic chemical 
AST  
aspartate aminotransferase  
AUC 
area under the concentration-time curve 
BMI 
body mass index 
BOIN 
Bayesian optimal interval 
BOP2 
Bayesian optimal phase 2 
CI 
confidence interval 
Cmax 
maximum concentration 
CR  
complete response 
CRC 
colorectal cancer 
CSR 
clinical study report 
CTCAE  
Common Terminology Criteria for Adverse Events  
Ctrough 
concentration immediately prior to dosing at multiple dosing 
DCR
disease control rate per RECIST v1.1
DEAS
DLT evaluation analysis set
DESC 
dose escalation and safety committee 
DBP
diastolic blood pressure
DLT
dose limiting toxicity
DOR
duration of response per RECIST v1.1
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF
electronic case report form
ELISpot
enzyme-linked immunospot
EOT
end of treatment
FAS
full analysis set
ICH 
International Conference on Harmonization 
iCR 
complete response per iRECIST 
iDCR
disease control rate per iRECIST
iDOR
duration of response per iRECIST
INR
international normalize ratio
iORR
objective response rate per iRECIST
IP
investigational product
iPFS
progression-free survival per iRECIST
iPR 
partial response per iRECIST 
irAE
immune-related adverse event


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Abbreviations  
Description of abbreviations  
iRECIST 
immune response evaluation criteria in solid tumors 
IRR 
infusion related reactions 
iSD 
stable disease per iRECIST 
iUPD 
unconfirmed disease progression per iRECIST 
MedDRA  
Medical Dictionary for Regulatory Activities  
MTD 
maximum tolerated dose 
NCI  
National Cancer Institute  
ORR  
objective response rate per RECIST v1.1 
OS 
overall survival 
PD 
progressive disease 
PDAS 
pharmacodynamics analysis set 
PKAS 
pharmacokinetic analysis set 
PR 
partial response per RECIST v1.1 
PS 
performance status 
PT 
preferred term 
QT 
Q-T interval from electrocardiogram 
QTc 
QT interval corrected for heart rate 
QTcF 
Fridericia-corrected QT interval 
RAS 
response analysis set 
RBC 
red blood cell 
RCL 
replication competent lentivirus 
RDI 
relative dose intensity 
RECIST 
response evaluation criteria in solid tumors 
RP2D
recommended phase 2 dose
SAE 
serious adverse event 
SAF
safety analysis set
SAP 
statistical analysis plan 
SAS 
Statistical Analysis Software
SBP
systolic blood pressure
SD 
stable disease 
SOC
system organ class
TBL 
total bilirubin 
TEAE
treatment emergent adverse event
TLF
tables, listings and figures
tmax 
time to maximum concentration 
ULN 
upper limit of normal 
WBC
white blood cell
WHO-DD
World Health Organization Drug Dictionary
 
 
 


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List of Key Terms 
Terms 
Definition of terms 
Baseline 
Observed values/findings which are regarded observed starting point for 
comparison.   
End of Study 
This date reflects when a participant completes follow-up. 
Enroll 
To register or enter into a clinical trial.  NOTE: Once a participant has 
been enrolled, the clinical trial protocol applies to the participant.   
Intervention 
The drug, therapy or process under investigation in a clinical study that is 
believed to have an effect on outcomes of interest in a study.  (e.g., 
health-related quality of life, efficacy, safety, pharmacoeconomics).   
Investigational period 
Period of time where major interests of protocol objectives are observed, 
and where the test drug or comparative drug (sometimes without 
randomization) is usually given to a participant, and continues until the 
last assessment after completing administration of the test drug 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. 
Screen failure 
Potential participant who did not meet 1 or more criteria required for 
participation in a trial. 
Screening 
A process of active consideration of potential participants for enrollment 
in a trial. 
Screening period 
Period of time before entering the investigational period, usually from the 
time of starting a participant signing consent until just before the test drug 
or comparative drug (sometimes without randomization) is given to a 
participant.   
Study period 
Period of time from the first site initiation date to the last 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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1 
INTRODUCTION 
This Statistical Analysis Plan (SAP) contains technical and detailed elaboration of the 
principal features of the analysis described in the protocol, and includes procedures for 
executing the statistical analysis to fulfill the objectives of the study.  
The final SAP will be approved prior to database hardlock. 
Changes to the planned analyses in the final SAP that impact the statistical analyses will be 
documented in the Clinical Study Report (CSR). 
2 
TREATMENT PROTOCOL OBJECTIVES AND DESIGN 
2.1 
Study Objectives 
 
Objectives 
Endpoints 
Primary 
 
To evaluate the safety and 
tolerability of ASP7517 when 
administered as a single agent and 
in combination with 
pembrolizumab 
 
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 when 
administered as a single agent and 
in combination with 
pembrolizumab (phase 1) 
 
DLTs 
 
To evaluate the clinical response of 
ASP7517 when administered as a 
single agent and in combination 
with pembrolizumab (phase 2) 
 
Objective response rate per iRECIST (iORR) by 
independent central review(1) 
Secondary 
 
To evaluate other measures of 
anticancer activity of ASP7517 
when administered as a single 
agent and in combination with 
pembrolizumab based on central 
and local assessment 
 
Objective response rate per RECIST v1.1(ORR) 
 
Disease control rate per iRECIST (iDCR) and RECIST v1.1 
(DCR) 
 
Progression-free survival per iRECIST (iPFS) and RECIST 
v1.1 (PFS) 
 
Overall survival (OS) 
 
Duration of response per iRECIST (iDOR) and RECIST 
v1.1 (DOR)
 
 
 
 
 
 
 
 
 
 
 
 
 


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Objectives 
Endpoints 
Exploratory 
 
To evaluate potential genomic, 
proteomic and/or other biomarkers 
that may correlate with treatment 
outcome when ASP7517 
administered as a single agent and 
in combination with 
pembrolizumab 
 
Exploratory tumor and peripheral biomarkers that may 
correlate with treatment outcome of ASP7517 monotherapy 
or in combination with pembrolizumab 
 
To evaluate pharmacodynamic 
activities of ASP7517 as a single 
agent and in combination with 
pembrolizumab 
 
Pharmacodynamic effects of ASP7517 as a monotherapy or 
in combination with pembrolizumab, 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.)  
o 
Anti-WT1 antibodies  
o 
Tumor microenvironment 
 
To characterize the 
pharmacokinetic profile of 
ASP7517 when administered as a 
monotherapy and in combination 
with pembrolizumab 
 
Cellular DNA load and kinetic parameter estimates 
(including AUC, Cmax, Ctrough and tmax) for ASP7517 as a 
monotherapy or in combination with pembrolizumab 
 
AE: adverse event; DLT: dose limiting toxicity; ECG: electrocardiogram; ECOG: Eastern Cooperative 
Oncology Group; IFNg: interferon gamma; iRECIST: immune response evaluation criteria in solid tumors; 
MTD: maximum tolerated dose; NK: natural killer; NKT: natural killer T; RECIST: response evaluation criteria 
in solid tumors; RP2D: recommended phase 2 dose; SAE: serious adverse event; WT1: 
 
(1) There will be no Independent Central Review data.  
 
2.2 
Study Design 
This study is a phase 1/2, open-label study of ASP7517 as monotherapy and in combination 
with pembrolizumab in selected patients with advanced solid tumors known to express WT1 
antigen.  
This study consists of arms receiving ASP7517 monotherapy and arms receiving ASP7517 
and pembrolizumab combination therapy in phase 1 (dose escalation cohort) and phase 2 
(dose expansion cohort). 
Additional cohorts may be added by a protocol amendment to further evaluate ASP7517 as a 
single agent and/or in combination with another anti-cancer agent.  
For participants in all arms/phases, the study consists of the following periods:  
 Screening: (up to 28 days)  
 Treatment (up to six 28-day cycles):  
o ASP7517 Monotherapy Arm: ASP7517 every 28 days  
 
 
 
 
 
 
 
 
  
 
 


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o ASP7517 and Pembrolizumab Combination Therapy Arm: ASP7517 every 28 
days and pembrolizumab every 6 weeks in combination (up to 6 doses of 
ASP7517 in combination with a total of 4 doses of pembrolizumab);  
 End of Treatment (EOT) Visit: Participants will complete an EOT visit within 7 days 
of EOT determination or prior to initiation of new anticancer therapy 
 Safety Follow-up: Participants will complete 30-day, 60-day and 90-day safety 
follow-up visits from the last dose of study drug or prior to the initiation of new 
anticancer therapy  
 Observation Period. 
o Observation Period for Monotherapy: All participants will enter an 
observation period after EOT, except those with iCPD, iUPD (per independent 
central review or local review) and who are not clinically stable or clinical 
progression is confirmed by the investigator. The observation period consists 
of safety follow-up visits (30, 60 and 90 days after last dose administered in 
the treatment period) and visits for only tumor imaging (every 8 weeks for up 
to 48 weeks). 
o Observation Period for Combination Therapy: Participants will enter an 
observation period 6 weeks from the last dose of pembrolizumab in 
combination with ASP7517 (up to 78 weeks and may receive pembrolizumab 
monotherapy up to 13 doses every 6 weeks for qualifying participants) 
 Survival Follow-up: Telephone contact will be made every 3 months for up to 12 
months 
Details of the schedule of clinical assessments are available in the protocol. 
Phase 1 Dose Escalation Cohort for Monotherapy and Combination Therapy Arms 
The monotherapy and combination therapy dose escalation portion will evaluate escalating 
dose levels of ASP7517 in approximately 9 to 12 dose limiting toxicity (DLT)-evaluable 
participants.  
Phase 2 Monotherapy Arm Dose Expansion Cohort  
Monotherapy dose expansion will be opened after the phase 1 monotherapy arm dose 
escalation cohort has been completed. If a confirmed response (partial response based on 
iRECIST [iPR] or complete response based on iRECIST [iCR], per independent central 
review) occurs in a monotherapy arm dose escalation cohort (for melanoma, ovarian cancer 
and CRC only), a tumor-specific dose expansion cohort may be opened in that tumor type, at 
the dose level in which the confirmed response was observed and phase 1 dose escalation has 
been completed. Once RP2D is determined, the melanoma expansion cohort may be opened 
(if not already opened due to an observed response in a dose escalation cohort). Participants 
with CPI refractory metastatic melanoma will be enrolled in the monotherapy dose escalation 
or expansion cohorts to allow for enrollment of this patient population in the combination 
 
 
 
 


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arm dose expansion cohort. If antitumor activity was observed in dose escalation or 
melanoma dose expansion stage 1, expansion cohorts for CRC and ovarian cancer may be 
opened. If a confirmed response (PR based on iRECIST [iPR] or a CR based on iRECIST 
[iCR], per independent central review) occurs in a monotherapy arm dose escalation cohort 
for any other tumor type, a tumor-specific dose expansion cohort may be opened in that 
tumor type at the dose level in which the confirmed response was observed and phase 1 dose 
escalation has been completed. 
Objective response rate per iRECIST (iORR), as confirmed per independent central review, 
is 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. 
If the iORR does not meet the optimal stopping boundaries after stage 1 (detailed in section 
6.9), then additional participants may be enrolled for that tumor type at each dose level (stage 
2). Otherwise, the enrollment at that dose level will be closed.  
Phase 2 Combination Therapy Arm Dose Expansion Cohort  
The combination therapy arm dose expansion cohort will be opened after the phase 1 dose 
escalation cohort has been completed. The metastatic melanoma CPI naïve cohort will be 
open. If 5 confirmed responses (iPR or iCR per independent central review) are observed in 
metastatic melanoma CPI naïve participants, expansion cohorts for CRC, ovarian cancer, and 
metastatic melanoma CPI refractory may be opened. In addition, if a confirmed response 
(iPR or iCR per independent central review) is observed in metastatic melanoma CPI 
refractory participants in the monotherapy arm, an expansion cohort for melanoma refractory 
participants may be opened for combination arm therapy, if not yet opened. 
As in all cohorts, if the iORR per independent central review does not meet the optimal 
stopping boundaries after stage 1(see section 6.9) for metastatic melanoma CPI naïve 
participants, then additional participants may be enrolled up to the maximum total sample 
size for that tumor type.  
Similarly, for all other tumor types, if the iORR per independent central review does not meet 
the optimal stopping boundaries for that tumor type after stage 1 (see section 6.9) , then 
additional participants may be enrolled up to the total maximum sample size at each dose 
level.  
If both monotherapy and combination therapy arms in the expansion cohorts are open for the 
same tumor type, randomization will be expanded to include both monotherapy and 
combination therapy arms and the randomization ratio will be based on the number of open 
slots still available at each dose level. 
Replacement of Participants in Phase 2 Dose Expansion Cohort  
If a participant in a phase 2 dose expansion cohort is not response evaluable (defined as the 
response analysis set [RAS]), an additional participant may be enrolled in that cohort based 
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2.3 
Randomization  
Priority for enrollment will be given to the phase 1 dose escalation portion before the phase 2 
dose expansion. 
In case the enrollment for both monotherapy escalation arm and combination therapy 
escalation arm opens together, participants will be randomized to either monotherapy or 
combination arm in 1:1 ratio. 
For phase 2 enrollment, if more than 1 dose level is open for enrollment within a selected 
disease type, the newly enrolled participants 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 
opened for expansion of ASP7517 monotherapy for melanoma, the next participant would be 
 
If both monotherapy and combination therapy expansion arms are open for the same tumor 
type, randomization will be expanded to include both monotherapy and combination therapy 
arms and the randomization ratio will be based on the number of open slots still available at 
each dose level. 
3 
SAMPLE SIZE 
Phase 1 Dose Escalation: 
The sample size of approximately 24, including 12 from monotherapy and 12 from 
combination therapy, is not based on a statistical power calculation. The number of 
participants enrolled will be dependent on the DLT incidence. The estimated number of 
participants should provide adequate information for the dose escalation and safety objectives 
of the study. 
Phase 2 Dose Expansion:  
It is estimated that up to approximately 361 participants may be enrolled in the monotherapy 
and combination therapy arms (approximately 129 participants for monotherapy and 232 
participants for combination therapy). The iORR is monitored using the BOP2 design. For 
each indication, with assumptions mentioned in the Statistical Hypotheses below, the 
statistical power would be approximately 0.80 while controlling the type I error rate at 0.05 
(1-sided).  
 Monotherapy 
Statistical Hypotheses: 
H0: iORR is 10%, under which the treatment is deemed as unacceptable.  
H1: iORR is at least 25%, under which the treatment is deemed as acceptable.  
Combination Therapy  
 
 
  
 
 
 
  
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 


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Statistical Hypotheses: 
Metastatic Melanoma CPI Naïve  
H0: iORR is 25%, under which the treatment is deemed as unacceptable.  
H1: iORR is at least 40%, under which the treatment is deemed as acceptable.  
Metastatic Melanoma CPI Refractory  
H0: iORR is13%, under which the treatment is deemed as unacceptable.  
H1: iORR is at least 28%, under which the treatment is deemed as acceptable.  
Ovarian Cancer  
H0: iORR is 15%, under which the treatment is deemed as unacceptable.  
H1: iORR is at least 30%, under which the treatment is deemed as acceptable.  
Colorectal Cancer  
H0: iORR is 18%, under which the treatment is deemed as unacceptable.  
H1: iORR is at least 33%, under which the treatment is deemed as acceptable. 
4 
ANALYSIS SETS 
In accordance with International Conference on Harmonization (ICH) recommendations in 
guidelines E3 and E9, the following analysis sets will be used for the analyses. Full Analysis 
Set (FAS) and Response Analysis Set (RAS) will be used for efficacy analysis. Safety 
Analysis Set (SAF) will be used for the analyses of safety variables. Pharmacokinetic 
Analysis Set (PKAS) will be used for pharmacokinetic analyses. The biomarker 
pharmacodynamics analysis set (PDAS) will be used for all analyses of pharmacodynamics 
data. The data from all participants who were enrolled in the study will be included in the 
data listings. All enrolled participants are those who signed the informed consent form and 
were assigned a subject number. 
For each dose level group, the number and percentage of participants will be characterized 
for all treated participants and by each analysis set. 
Population
Description
Enrolled 
All participants who sign the informed consent form are allocated to 
treatment. 
Full Analysis Set (FAS)
All participants who are enrolled and receive at least one dose of study 
treatment. 
Response Analysis Set (RAS)
The response analysis set will consist of all participants who are 
enrolled and receive at least 1 dose of IP and have at least 1 post 
baseline primary efficacy measurement. 
Safety Analysis Set (SAF) 
All participants who take at least 1 dose of IP. 


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Pharmacokinetic Analysis Set 
(PKAS) 
The PKAS consists of the administered population for which 
pharmacokinetics data are available for at least 1 time point. Additional 
participants may be excluded from the PKAS at the discretion of the 
pharmacokineticist. 
Pharmacodynamic Analysis Set 
(PDAS) 
The PDAS will include the participants from the administered population for 
whom sufficient pharmacodynamic measurements were collected. The 
PDAS will be used for all analyses of pharmacodynamic data. 
DLT Evaluation Analysis Set 
(DEAS) 
The DEAS is defined as all participants in SAF excluding participants who 
meet any of the following criteria:  
 
Participant is discovered to have enrolled without fully satisfying 
eligibility criteria.  
 
Participant received less than the planned dose in cycle 1 for 
reasons other than DLT.  
 
Participant has no DLT and withdraws from the study before the 
end of DLT evaluation period. The DEAS will be used for the 
analysis of DLT data. 
5 
ENDPOINTS 
5.1 
Efficacy Endpoints 
Tumor-related efficacy variables are evaluated by the Response Evaluation Criteria in Solid 
Tumors (RECIST) 1.1 and guidelines for response criteria for use in trials testing 
immunotherapeutics (iRECIST) (Seymour, L., et al., 2017).   
5.1.1 
Primary Efficacy Endpoints 
will not be collected; 
investigator assessed endpoints will be presented. 
5.1.1.1 Objective Response Rate per iRECIST (iORR) 
iORR is defined as the proportion of participants for each dose level whose best overall 
response is rated as confirmed iCR or iPR per iRECIST. Endpoints will include:  
 iORR with confirmed response by investigator assessment 
 iORR with unconfirmed response by investigator assessment 
5.1.2 
Secondary Efficacy Endpoints 
5.1.2.1 Objective Response Rate per RECIST (ORR) 
ORR is defined as the proportion of participants for each dose level whose best overall 
response is rated as CR or PR per RECIST v1.1 for the endpoints of: 
 ORR with confirmed response by investigator assessment 
 ORR with unconfirmed response by investigator assessment 
5.1.2.2 Disease Control Rate per iRECIST (iDCR) 
iDCR is defined as the proportion of participants for each dose level whose best overall 
response is rated as confirmed iCR, iPR or stable disease (iSD) per iRECIST.  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 


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5.1.2.3 Disease Control Rate per RECIST v1.1 (DCR) 
DCR is defined as the proportion of participants for each dose level whose best overall 
response is rated as confirmed CR, PR or SD per RECIST v1.1. 
5.1.2.4 Overall Survival (OS) 
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 participant 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).  
Table 1 
OS Definition 
Situation  
Date of Event or Censor 
Outcome 
Death before or on analysis cutoff date  
Date of death 
Event 
Death after analysis cutoff date  
Analysis cutoff date 
Censor 
Last known alive is before or on cutoff 
date 
Last known alive date 
Censor 
Last known alive is after cutoff date 
Analysis cutoff date 
Censor 
OS = Date of Event or Censor  Date of First Dose +1 
5.1.2.5 Progression-free Survival per iRECIST (iPFS) 
iPFS is defined as the time from the start of the study treatment until death from any cause or 
radiographic disease progression assessed per iRECIST by investigator assessment, 
whichever occurs first.  
If iUPD occurs but iSD, iPR, or iCR is observed any time subsequent to iUPD, iUPD status 
will be disregarded for determination of iPFS. 
Table 2 
iPFS Definition 
iPFS 
 
 
Situation  
Date of Event or Censor 
Outcome  
No evaluable post-baseline imaging 
assessments, no death  
Date of first dose (Day 1) 
Censor  
Participant did not receive new anti-cancer therapy: 
iCPD 
First date where iUPD criteria 
are met 
Event  
No iCPD, but death recorded on eCRF 
Date of death 
Event 
No iCPD nor death and not in one of the 
following cases :a)if the participant stops 
protocol treatment because they were not 
judged to be clinically stable, b) no further 
response assessments are done (because of 
participant refusal, protocol non-
compliance, or participant death); c) the 
Date of last radiological 
assessment 
Censor  


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iPFS 
 
 
Situation  
Date of Event or Censor 
Outcome  
next timepoint responses are all iUPD, and 
iCPD never occurs; 
No iCPD nor death and is in one of the 
following cases : a)if the participant stops 
protocol treatment because they were not 
judged to be clinically stable, b) no further 
response assessments are done (because of 
participant refusal, protocol non-
compliance, or participant death); c) the 
next timepoint responses are all iUPD, and 
iCPD never occurs; 
First date where iUPD criteria 
are met 
Event 
Participant received new anti-cancer (ACT) therapy: 
No progression before new ACT 
Date of last radiological 
assessment before start of 
new anti-cancer therapy  
Censor  
iCPD before new ACT 
First date where iUPD criteria 
are met 
Event  
iUPD before new ACT and not in one of 
the following cases : a)if the participant 
stops protocol treatment because they were 
not judged to be clinically stable, b) no 
further response assessments are done 
(because of participant refusal, protocol 
non-compliance, or participant death); c) 
the next timepoint responses are all iUPD, 
and iCPD never occurs;
Date of last radiological 
assessment before start of 
new anti-cancer therapy  
Censor 
iUPD before new ACT and is in one of the 
following cases : a)if the participant stops 
protocol treatment because they were not 
judged to be clinically stable, b) no further 
response assessments are done (because of 
participant refusal, protocol non-
compliance, or participant death); c) the 
next timepoint responses are all iUPD, and 
iCPD never occurs;
First date where iUPD criteria 
are met 
Event 
Missed >=2 scheduled radiological 
assessments 
 
 
If last assessment prior to missing >= 2 
scans is iUPD 
First date where iUPD criteria 
are met 
Event 
If last assessment prior to missing >= 2 
scans is not iUPD and no progression or 
death after missing >=2 scans
Date of last radiological 
assessment 
Censor 


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iPFS 
 
 
Situation  
Date of Event or Censor 
Outcome  
No post-baseline tumor imaging prior to 
missing 2 scans and progression or death 
after missing >=2 scans 
Date of first dose (Day 1) 
Censor 
No post-baseline tumor imaging prior to 
missing 2 scans and no progression or death 
after missing >=2 scans 
Date of last radiological 
assessment 
Censor 
If radiographical progression or death 
occurs after missing 2 scheduled 
radiological assessments and last 
assessment prior to missing >= 2 scans is 
not iUPD 
Date of last radiological 
assessment before missing 2 
scans 
Censor 
iPFS = Date of Event or Censor  Date of First Dose +1 
Missing 2 scheduled imaging assessments: 
Missing 2 scheduled imaging assessments is defined as the gap between two imaging 
assessments being more than 140 days (2.5 times the scheduled imaging assessment interval 
(2.5 x 56 days)). Imaging assessments after first iUPD will be excluded from PFS derivation. 
Note: Participant 
iPFS will be censored at Day 1. 
To apply the cut-off date to iPFS is to exclude those tumor assessments after cut-off date and 
anti-cancer therapy date after cut-off date in the analysis. 
5.1.2.6 Progression-free Survival per RECIST v1.1 (PFS) 
PFS is defined as the time from the start of the study treatment until death from any cause or 
radiographic disease progression assessed per RECIST v1.1 by investigator assessment, 
whichever occurs first.  
 
Table 3 
PFS Definition 
PFS 
 
 
Situation  
Date of Event or Censor 
Outcome  
No evaluable post-baseline imaging 
assessments, no death  
Date of first dose (Day 1) 
Censor  
Participant did not receive new anti-cancer therapy: 
Radiographical progression documented per 
RECIST v1.1 
Date of radiological disease 
progression 
Event  
 
 
  
 
  
 
 
 
 
 


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PFS 
 
 
Situation  
Date of Event or Censor 
Outcome  
No radiographical progression, but death 
recorded on eCRF 
Date of death 
Event 
Neither radiographical progression nor 
death 
Date of last disease 
assessment 
Censor  
Participant received new anti-cancer (ACT) therapy: 
Radiographical progression documented per 
RECIST v1.1 after new ACT 
Date of last radiological 
assessment before start of 
new anti-cancer therapy  
Censor  
Radiographical progression documented per 
RECIST v1.1 before new ACT 
Date of radiological disease 
progression 
Event  
No radiographical progression before new 
ACT but death recorded  
Date of last radiological 
assessment before start of 
new anti-cancer therapy  
Censor 
No radiographical disease progression nor 
death 
Date of last radiological 
assessment before start of 
new anti-cancer therapy  
Censor  
Missed >=2 scheduled radiological 
assessments 
 
 
If radiographical progression or death 
occurs after missing 2 scheduled 
radiological assessments 
Date of last radiological 
assessment before missing 2 
scans 
Censor 
PFS = Date of Event or Censor  Date of First Dose +1 
Missing 2 scheduled imaging assessments: 
Missing 2 scheduled imaging assessments is defined as the gap between two imaging 
assessments being more than 140 days (2.5 times the scheduled imaging assessment interval 
(2.5 x 56 days)). Imaging assessments after first iUPD will be excluded in PFS derivation. 
Note: Participant 
PFS will be censored at Day 1. 
To apply the cut-off date to PFS is to exclude those tumor assessments after cut-off date and 
anti-cancer therapy date after cut-off date in the analysis. 
5.1.2.7 Duration of Response per iRECIST (iDOR) 
iDOR is defined as the time from the date of the first response iCR/iPR (whichever is first 
recorded) to the date of radiographical progression or date of censoring. iDOR will be 
 
 
  
 
  
 
 
 
 
 


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calculated only for the subgroup of participants with confirmed response iCR/iPR per 
iRECIST separately for investigator assessment.  
 
Table 4 
iDOR Definition 
iDOR 
 
 
Situation  
Date of Event or Censor 
Outcome  
Participant did not receive new anti-cancer therapy 
iCPD  
First date where iUPD criteria 
are met 
Event 
No iCPD nor death and NOT in one of the 
following cases : a) the participant stops 
protocol treatment because they were not 
judged to be clinically stable, b) no further 
response assessments are done (because of 
participant refusal, protocol non-
compliance, or participant death); c) the 
next timepoint responses are all iUPD, and 
iCPD never occurs; 
Date of last radiological 
assessment 
Censor 
No iCPD nor death and is in one of the 
following cases : a) the participant stops 
protocol treatment because they were not 
judged to be clinically stable, b) no further 
response assessments are done (because of 
participant refusal, protocol non-
compliance, or participant death); c) the 
next timepoint responses are all iUPD, and 
iCPD never occurs;
First date where iUPD criteria 
are met 
Event 
Participant received new anti-cancer therapy 
No progression before new ACT 
Date of last radiological 
assessment before start of 
new ACT 
Censor 
iCPD before new ACT 
First date where iUPD criteria 
are met 
Event 
iUPD before new ACT and NOT in one of 
the following cases : a) the participant stops 
protocol treatment because they were not 
judged to be clinically stable, b) no further 
response assessments are done (because of 
participant refusal, protocol non-
compliance, or participant death); c) the 
next timepoint responses are all iUPD, and 
iCPD never occurs;
Date of last radiological 
assessment before start of 
new ACT 
Censor 


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iDOR 
 
 
Situation  
Date of Event or Censor 
Outcome  
Participant did not receive new anti-cancer therapy 
iUPD before new ACT and is in one of the 
following cases : a) the participant stops 
protocol treatment because they were not 
judged to be clinically stable, b) no further 
response assessments are done (because of 
participant refusal, protocol non-
compliance, or participant death); c) the 
next timepoint responses are all iUPD, and 
iCPD never occurs; 
First date where iUPD criteria 
are met 
Event 
Missed >=2 scheduled radiological assessments 
If last assessment prior to missing >= 2 
scans is iUPD 
First date where iUPD criteria 
are met 
Event 
If last assessment prior to missing >= 2 
scans is not iUPD and no progression after 
missing >=2 scans 
Date of last radiological 
assessment 
Censor 
If radiographical progression occurs after 
missing 2 scheduled radiological 
assessments and last assessment prior to 
missing >= 2 scans is not iUPD 
Date of last radiological 
assessment before missing 2 
scans 
Censor 
iDOR = Date of Event or Censor  Date of First iCR/iPR +1 
Missing 2 scheduled imaging assessments: 
Missing 2 scheduled imaging assessments is defined as the gap between two imaging 
assessments being more than 140 days (2.5 times the scheduled imaging assessment interval 
(2.5 x 56 days)). Imaging assessments after first iUPD will be excluded in DOR derivation. 
Note: Participant 
DOR/iDOR will be censored at Day 1. 
To apply the cut-off date to DOR/iDOR is to exclude those tumor assessments after cut-off 
date and anti-cancer therapy date after cut-off date in the analysis. 
5.1.2.8 Duration of Response per RECIST v1.1 (DOR) 
DOR is defined as the time from the date of the first response CR/PR (whichever is first 
recorded) to the date of radiographical progression or date of censoring. DOR will be 
calculated only for the subgroup of participants with confirmed response CR/PR per RECIST 
v1.1, separately for investigator assessment.  
 
 
  
 
  
 
 
 
 
 


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Table 5 
DOR Definition 
DOR 
 
 
Situation  
Date of Event or Censor 
Outcome  
Participant did not receive new anti-cancer therapy 
Radiographical progression documented per 
RECIST v1.1 
Date of radiological PD 
Event 
No radiographical progression  
Date of last radiological 
assessment 
Censor 
Participant received new anti-cancer therapy 
Radiographical progression documented per 
RECIST v1.1 after new ACT 
Date of last radiological 
assessment before start of 
new anti-cancer therapy  
Censor  
Radiographical progression documented per 
RECIST v1.1 before new ACT 
Date of radiological PD 
Event 
No radiographical progression 
Date of last radiological 
assessment before start of 
new anti-cancer therapy 
Censor 
Missed >=2 scheduled radiological assessments 
If radiographical progression or death 
occurs after missing 2 scheduled 
radiological assessments 
Date of last radiological 
assessment before missing 2 
scans 
Censor 
DOR = Date of Event or Censor  Date of First CR/PR +1 
Missing 2 scheduled imaging assessments: 
Missing 2 scheduled imaging assessments is defined as the gap between two imaging 
assessments being more than 140 days (2.5 times the scheduled imaging assessment interval 
(2.5 x 56 days)). 
5.2 
Safety Endpoints 
Safety and tolerability (determine MTD) are the primary endpoints of the study. Safety 
endpoints are adverse events (AEs), laboratory measurements, vital signs, physical 
examination and ECOG performance status (PS). Safety will be assessed by evaluation of the 
following variables: 
5.2.1.1 Dose-Limiting Toxicity (DLT) 
A DLT is defined as any of the listed events that occur within 28 days starting with the first 
dose on cycle 1 day 1 (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 the 


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-
CTCAE).  
5.2.1.2 ASP7517 Monotherapy Arm Dose-Limiting Toxicities (DLTs) 
For participants in the ASP7517 monotherapy DLT is defined in the protocol in section 4.1. 
5.2.1.3 ASP7517 and Pembrolizumab Combination Therapy Arm Dose-Limiting 
Toxicities (DLTs) 
For participants in the ASP7517 and Pembrolizumab combination therapy arm, DLT is 
defined in the protocol in section 4.1.  
Participants who are tolerating IP at a dose level that is being reviewed due to the occurrence 
of DLTs in another participant will not be automatically precluded from continued dosing 
during the safety review, and will be allowed to continue dosing for as long as tolerated 
unless directed otherwise as a result of the safety review by the DESC. 
Dose escalation within individual participants will not be allowed. 
5.2.1.4 Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) 
Maximum Tolerated Dose 
The MTD determination will be based on at least 6 evaluable participants 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 for monotherapy and combination therapy.  
The dose level determined to be the MTD must have data from at least 6 participants. 
Determination of MTD will be done for monotherapy and combination therapy separately. 
Recommended Phase 2 Dose 
The sponsor, in conjunction with the DESC, will determine the RP2D of ASP7517 as a single 
agent and in combination with pembrolizumab 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 participants. 
Determination of RP2D will be done for monotherapy and combination therapy separately. 
5.2.1.5 Adverse Events (AEs) 
AEs will be coded using MedDRA v26.0 and graded using NCI CTCAE.  
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 at least possible relationship (possibly or probably related) to 
study treatment as assessed by the investigator or with missing assessment of the causal 
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The number and percentage of participants with TEAEs, IP-related TEAEs, serious TEAEs, 
IP-related serious TEASs, TEAEs leading to withdrawal of treatment and IP related 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 participant.  If 
an AE is observed with different relationships to study drug then the AE will be counted 
under its maximum relationship only. In case the AE relationship is not reported, it will be 
treated as the maximum relationship. 
dose of study IP
considered treatment emergent. If the adverse event occurs on Day 1 and the onset check box 
IP
treatment emergent. If a participant experiences an event both during the preinvestigational 
period and during the investigational period, the event will be considered as TEAE only if it 
has worsened in severity (i.e. it is reported with a new start date). All adverse events 
collected that begin within 30 days after taking the last dose of study IP will also be counted 
as TEAE. 
Immune-related AE (irAE) and infusion related reactions (IRR) will be considered as 
Adverse Events of Special Interest (AEsi). The list of events classified as AEsi may change 
during the study due to ongoing pharmacovigilance. 
Time to first onset of irAE will follow the following algorithm: 
Situation 
Date of Event or Censor 
Outcome 
AE of interest observed
Date of first onset
Event
No AE of interest observed 
and treatment ongoing
Date of data cutoff 
Censor 
No AE of interest observed 
and treatment 
discontinued
Date of last dose + 30 days 
Censor 
Time to First Onset = Date of Event or Censor  Date of First Dose +1 
5.2.1.6 Laboratory Assessments 
Clinical laboratory variables for hematology, chemistry including liver function test, 
coagulation, urinalysis, and bone marrow will be collected during the conduct of the study as 
listed in Table 6 below. 
Additional laboratory tests should be performed according to institutional standard of care. 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 6 
Laboratory Assessments 
Clinical Laboratory Tests 
Panel/Assessments
Parameters to be Analyzed 
NCI-CTCAE Grading (Hyper/Hypo) 
CBC with 
Differential 
Hematocrit (Hct)  
Hemoglobin (Hgb)  
Platelet count  
Red blood cell count (RBC) 
White blood cell count (WBC)  
White blood cell count differential 
Absolute neutrophil count 
Absolute lymphocyte count 
NA 
Both 
Hypo 
NA 
Both 
NA 
Hypo 
Both 
 
Biochemistry 
Sodium (Na) 
Potassium (K) 
Chloride (Cl) 
Bicarbonate (HCO3) 
Blood urea nitrogen (BUN) 
Creatinine (Cr) 
Glucose (Gl) 
Calcium (Ca) 
Phosphorus 
Magnesium (Mg) 
Albumin (Alb) 
Total protein (T Prot) 
Alkaline phosphatase (ALP) 
Lactate dehydrogenase (LDH) 
Creatine phosphokinase (CPK) 
Liver function tests including*: 
Bilirubin total (TBL) 
Alanine aminotransferase (ALT) 
Aspartate aminotransferase 
(AST) 
Both 
Both 
NA 
NA 
NA 
Hyper 
Both 
Both 
NA 
Both 
Hypo 
NA 
Hyper 
NA 
Hyper 
 
Hyper 
Hyper 
Hyper 
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Panel/Assessments
Parameters to be Analyzed 
NCI-CTCAE Grading (Hyper/Hypo) 
Urinalysis 
Color 
Appearance 
Specific gravity 
pH 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocyte esterase 
Nitrite 
Protein 
Urobilinogen 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
NA 
Urine/Serum 
Pregnancy Test * 
hCG (Positive/Negative) 
NA 
Coagulation Profile 
(PT/INR, D-Dimer, 
Fibrinogen) 
Activated partial thromboplastin 
time (aPTT) 
International normalized ratio (INR) 
Prothrombin time (sec) (PT) 
Fibrinogen  
D-Dimer  
 
Hyper 
Hyper 
NA 
NA 
NA 
eCRF: electronic case report form; hCG: human chorionic gonadotrophin. 
* Local results will be collected and entered into the eCRF. 
 
5.2.1.7 Vital Signs 
Vital signs will include: 
 Systolic and diastolic blood pressures (mmHg) 
 Pulse rate (beats/minute)  
 Respiratory Rate (breaths/min) 
 Body temperature (degrees C) 
 Height (m) (Height measurement performed at screening only) and weight (kg) 
5.2.1.8 Electrocardiogram (ECG) 
12-lead ECGs will be recorded in triplicate at the scheduled time points. Each ECG tracing 
will be taken 2 minutes apart. ECGs will be read at the site for clinical decision making and 
transmitted to a central reviewer. Data from the central reviewer will be used in summary 
presentations. 
 
 
 
 
 


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5.2.1.9 Eastern Cooperative Oncology Group Performance Status (ECOG PS) 
The ECOG Scale [Oken et al., 1982] will be used to assess performance status at time points 
outlined in the Protocol in the Schedule of Assessments. 
5.3 
Pharmacokinetic Variables 
Cellular DNA load of ASP7517and serum concentrations of Pembrolizumab will be 
evaluated for each cohort as outlined in the Protocol in the Schedule of Assessments. 
5.4 
Pharmacodynamic Variables 
Pharmacodynamic effects of ASP7517 as monotherapy or in combination with 
pembrolizumab will be assessed with: 
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.)  
o Anti-WT1 antibodies  
o Tumor microenvironment variables 
5.5 
Other Variables 
 
Duration of exposure (days) 
o Duration of exposure to a study drug will be calculated in days, using the following 
formula: 
o (Last date of exposure  date of first dose) + 1; where last date of exposure= initial 
infusion date of the last cycle + 27 or death date if death occurs within last cycle. 
- 
When the start or stop date is missing, then the exposure will be treated 
as missing. 
 
Cumulative actual dose (# of cells) 
o Total amount of IP administered to the participant from first dose date to last dose 
date 
 
Number of cycles initiated  
o Total number of cycles with non-zero dosing in the cycle 
 
Planned dose intensity 
o Planned dose/planned number of cycles 
 
Actual dose intensity 
o Defined as the cumulative actual dose divided by number of cycles  
 
Relative dose intensity (RDI; %) 
o Actual Dose Intensity 
-----------------------------  x 100 
Planned Dose Intensity 
 
 
 
 
 
 


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6 
STATISTICAL METHODOLOGY 
6.1 
General Considerations 
For continuous variables, descriptive statistics will include the number of participants (n), 
mean, standard deviation, median, minimum and maximum. When needed, the use of other 
percentiles (e.g.10%, 25%, 75% and 90%) will be reported in the relevant section. In 
addition, for plasma concentrations and continuous PK parameters, the coefficient of 
variation and the geometric mean will also be calculated. Frequencies and percentages will be 
displayed for categorical data. Percentages by categories will be based on the number of 
participants with no missing data, i.e. will add up to 100%. Kaplan-Meier estimates will be 
calculated for time-to-event variables and median survival time will be estimated with 2-
sided 90% confidence intervals (CI). 
Baseline is defined as the last available measurement prior to the first dose of study drug.  
Unless otherwise specified, all summaries will be presented overall, by dose level received, 
and by phase. Separate displays will be presented for monotherapy and combination therapy 
cohort unless specified otherwise. 
All data processing, summarization, and analyses will be performed using SAS® Version 9.4 
or higher on Linux. Specifications for table, figure, and data listing formats can be found in 
the TLF specifications for this study. 
Study day will be calculated in reference to the first dose date. For assessments conducted 
before the first dose, study day will be calculated as (assessment date  first dose date). For 
assessments conducted on or after the first dose, study day will be calculated as (assessment 
date  first dose date + 1). 
6.2 
Study Population 
6.2.1 
Disposition of Participants 
The following participant data will be presented: 
 
Number and percentage of participants with informed consent, discontinued before 
allocation to treatment, allocated to treatment (overall only) 
 
Number and percentage of participants allocated to treatment in each analysis set  
 
Number and percentage of participants completed and discontinued treatment, by 
primary reason for treatment discontinuation for SAF 
 
Number and percentage of participants completed and discontinued the study, by 
primary reason for study discontinuation for SAF by dose level 
 
Number and percentage of participants completed and discontinued the study at 30-, 60-, 
and 90-day follow-up, by primary reason for post-study period discontinuation for SAF  
 
Number and percentage of participants completed and discontinued the study during the 
observation period, by primary reason for post-study period discontinuation for SAF  
 
  
 
 
 


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Number and percentage of participants completed and discontinued the study during the 
survival follow-up period, by primary reason for post-study period discontinuation for 
SAF  
 
For the combination therapy arm, separate summaries for ASP7517 and Pembrolizumab 
will be provided for End of Treatment disposition. 
All disposition details and dates of first and last evaluations for each participant will be listed. 
6.2.2 
Protocol Deviations 
Protocol deviations as defined in the study protocol (Section 8.1.6 Protocol Deviations) will 
be assessed for all participants enrolled. The number and percentage of participants meeting 
any criteria will be summarized for each criterion and overall, by dose level, phase, tumor 
type, and overall as well as by study site. Participants deviating from a criterion more than 
once will be counted once for the corresponding criterion. Any participants who have more 
than one protocol deviation will be counted once in the overall summary. A data listing will 
be provided by site and participant. 
The protocol deviation criteria will be uniquely identified in the summary table and listing. 
The unique identifiers will be as follows: 
PD1 - Entered into the study even though they 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. 
PD5  Informed Consent: Clinical study procedures conducted prior to subject signing 
informed consent. 
PD6  Safety Reporting: Events not reported within the expected turn-around time per 
protocol reporting requirements. 
PD7  Procedures and Tests: Missed safety or efficacy assessments related to primary or key 
secondary endpoints. 
6.2.3 
Demographic and Other Baseline Characteristics 
Demographics and baseline characteristics will be summarized with descriptive statistics. 
Number and percentage of participants allocated to treatment in each country and site will be 
presented by dose level, phase, tumor type, and overall for SAF and FAS. 
Descriptive statistics for age, weight, and height at study entry will be presented. Frequency 
tabulations for sex, ethnicity, age group (>=65 years and <65 years of age), race, region, and 
baseline ECOG will be presented. This will be done for FAS and RAS. 
Medical history and conditions existing at baseline will be coded in MedDRA v26.0 and 
summarized by System Organ Class (SOC) and Preferred Term (PT) as well as by PT alone, 
by treatment group and overall for the SAF. Baseline conditions are defined as those ongoing 
 
 


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at the time of informed consent or arise following the time of informed consent and before 
the first dose of study drug. For ongoing medical conditions, Common Terminology Criteria 
for Adverse Events (CTCAE) grade will be provided in listing. 
6.2.4 
Disease History 
Frequency tabulations will be presented for disease history including tumor subtype and prior 
anti-cancer therapies.  
6.2.5 
Previous and Concomitant Medications 
Previous medications include medications taken within 28 days prior to cycle 1 day 1 and all 
anticancer treatment received 28 days prior to IP administration. Previous medications are 
coded with WHO-DD, and will be summarized in descending percentage order by Preferred 
WHO Name (Ingredients), as well as by therapeutic subgroup (ATC 2nd level) and chemical 
subgroup (ATC 4th level) and preferred WHO name by dose level, phase, tumor type, and 
overall for the SAF. 
Concomitant medications include medications taken after the first dose of study drug up until 
the 90 days follow-up visit. As with previous medication, concomitant medication will be 
summarized by dose level, phase, tumor type, and overall, in descending percentage order by 
Preferred WHO Name (Ingredients), as well as by therapeutic subgroup (ATC 2nd level) and 
chemical subgroup (ATC 4th level) and preferred WHO name for the SAF. Participants 
taking the same medication multiple times will be counted once per medication and 
investigational period. A medication which can be classified into several chemical and/or 
therapeutic subgroups is presented in all chemical and therapeutic subgroups. 
6.2.6 
Prior Radiation Therapy  
Frequency tabulations of participants with prior radiation therapy will be presented for SAF. 
6.2.7 
Non-Medication Therapy 
Frequency tabulations of participants with non-medication therapy and reason for use will be 
presented by dose level, phase, tumor type, and overall for SAF. Number of non-medication 
therapy received per participant will be summarized using descriptive statistics. 
6.2.8 
Prior and New Anti-Cancer Therapy  
Frequency tabulations of participants with prior or new anti-cancer therapy will be presented 
for SAF. 
6.3 
Study Drug 
6.3.1 
Exposure 
The following information on drug exposure will be presented with descriptive statistics (n, 
mean, standard deviation, median, minimum, maximum) for the SAF: 
 
Duration of exposure (days) 
 
Cumulative actual dose (# of cells) 
 
Number of cycles initiated  
   


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Planned dose intensity 
 
Actual dose intensity 
 
Relative dose intensity (RDI; %); in addition to descriptive statistics, frequency 
tabulations will be presented for RDI for the following categories: 
o <50% 
o 50% to <=80% 
o >80% 
o Unknown 
Number and percentage of participants with dose adjustments, or interruptions and reasons 
for dose adjustments and interruptions will be presented for the SAF. 
6.4 
Analysis of Efficacy  
Efficacy analysis will be conducted on the FAS and RAS (RAS for response-related analyses, 
FAS for overall survival and other time-to-event analyses). Tumor related analyses are 
summarized based on RECIST 1.1 and iRECIST. Efficacy analyses will be summarized by 
dose level, phase, and tumor type. 
overall disease response experience, and waterfall plots to display maximum tumor shrinkage 
rate. 
6.4.1 
Analysis of Primary Efficacy Endpoint 
6.4.1.1 Objective Response Rate per iRECIST (iORR) 
iORR with confirmed response by investigator assessment will be calculated for each group 
and its 95% confidence interval will be constructed by Clopper-Pearson method. To assess 
sensitivity, iORR will also be estimated and its 95% confidence interval will be constructed 
by Clopper-Pearson method for the endpoints: 
 iORR with confirmed response by investigator assessment 
 iORR with unconfirmed response by investigator assessment 
6.4.2 
Analysis of Secondary Efficacy Endpoints 
6.4.2.1 Objective Response Rate per RECIST v1.1(ORR) 
ORR for each group will be calculated and its 95% confidence interval will be constructed by 
Clopper-Pearson method for the endpoints of: 
 ORR with confirmed response by investigator assessment 
 ORR with unconfirmed response by investigator assessment 
6.4.2.2 Disease Control Rate per iRECIST (iDCR) 
iDCR for each group will be calculated and its 95% confidence interval will be constructed 
by Clopper-Pearson method by investigator assessment for the endpoints of: 
 iDCR with confirmed response by investigator assessment 
 iDCR with unconfirmed response by investigator assessment 
   
 
 
 
 
 
 
 
 
 
 
 
 
 


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6.4.2.3 Disease Control Rate per RECIST v1.1 (DCR) 
DCR for each group will be calculated and its 95% confidence interval will be constructed by 
Clopper-Pearson method by investigator assessment for the endpoints of: 
 DCR with confirmed response by investigator assessment 
 DCR with unconfirmed response by investigator assessment 
6.4.2.4 Overall Survival (OS) 
OS will be estimated and summarized for each dose level and treatment group using Kaplan-
Meier methodology for investigator assessments of radiological scans. OS will be also listed.  
6.4.2.5 Progression-Free Survival per iRECIST (iPFS) 
iPFS will be estimated and summerized for each group using Kaplan-Meier methodology for 
investigator assessments of radiological scans. iPFS will be listed. 
6.4.2.6 Progression-Free Survival per RECIST v1.1 (PFS) 
PFS will be estimated and summarized for each group using Kaplan-Meier methodology for 
investigator assessments of radiological scans. PFS will be listed.  
6.4.2.7 Duration of Response per iRECIST (iDOR) 
iDOR will be listed. 
6.4.2.8 Duration of Response per RECIST v1.1 (DOR) 
DOR will be listed . 
6.5 
Analysis of Safety 
Safety analyses will be conducted using the SAF. Safety analyses will be summarized by 
dose level, phase, tumor type, and overall. 
6.5.1 
Dose Limiting Toxicities 
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: 
 
 




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The number and percentage of participants with TEAEs, as classified by SOC and PT will be 
summarized by dose level, phase, tumor type, and overall. Summaries will be provided for: 
 
DLTs within the DLT observation period 
 
TEAEs 
 
Deaths 
 
IP related TEAEs  
 
Serious TEAEs and Astellas upgraded serious TEAE  
 
IP related serious TEAEs and IP related Astellas upgraded serious TEAE  
 
TEAEs leading to permanent discontinuation of study IP  
 
IP related TEAEs leading to permanent discontinuation of study IP  
 
CTCAE Grade 3 or higher TEAEs 
 
IP-related CTCAE Grade 3 or higher TEAEs  
 
TEAEs excluding serious adverse events that equal to or exceed a threshold of 5% in any 
dose level   
 
common TEAEs that equal to or exceed a threshold of 5% in any dose level  
 
Late SAEs occurring beyond 30 days from last study treatment 
The number and percentage of participants with TEAEs, and TEAEs leading to death, as 
classified by PT only, will be summarized by dose level, phase, tumor type, and overall. 
AE summary tables will include participant counts as opposed to AE counts. If a participant 
experiences more than one episode of a particular AE, that participant will be counted only 
once for that event. If a participant has more than one AE that code to the same preferred 
term, the participant will be counted only once for that preferred term. Similarly, if a 
participant has more than one AE within a body system, the participant will be counted only 
once in that body system.   
The number and percentage of participants with TEAEs, as classified by SOC and PT will 
also be summarized by NCI-CTCAE severity grade, and by relationship to study drug. In the 
participant count, if a participant has multiple TEAEs with the same SOC or PT, but with 
differing severity grade or relationship, then the participant will be counted only once with 
the worst severity grade and highest degree of relationship, however, if any of the severity 
grade or relationship values are missing then the participant will be counted only once with 
missing severity grade or relationship. 
The number and percentage of participants with TEAEs, as classified by SOC and PT will be 
summarized by dose level for SAF.  
All AEs, deaths, SAEs, withdrawals due to adverse events, and AEs for re-screened 
participants will be displayed in listings.  
The list of adverse events to be summarized may change during the course of the study due to 
ongoing pharmacovigilance. 
           
  


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6.5.3 
Adverse Events of Special Interest (AEsi) 
The number and percentage of participants with Adverse Events of Special Interest (AEsi) 
such as IRR, irAE, and as classified by SOC and PT, will be summarized by dose level, 
phase, tumor type, and overall.  
 
6.5.4 
Clinical Laboratory Evaluation 
The baseline visit is the last measurement taken prior to initial study IP administration.   
Frequency tabulations of qualitative clinical laboratory variables will be presented at each 
visit.  
Laboratory results will also be graded using NCI-CTCAE, where possible. Following the 
Table 6 in section 5.2.1.6, parameters that have criteria available for both low and high 
values, i.e., hypo- and hyper-, will be summarized for both criteria. The same participant can 
be counted for both values if the participant has different laboratory values meeting each 
criterion. NCI-CTCAE grade of laboratory evaluations will be summarized by number and 
percentage of participants for each visit. Shift tables of NCI-CTCAE grade change from 
baseline to worst post-baseline grade will also be presented. The number and percentage of 
participants with grade 3 or 4 laboratory test results will be summarized by dose level, phase, 
tumor type, and overall, and laboratory parameter (the name of the adverse event associated 
with the abnormal laboratory test result) will be presented. 
Laboratory results will be listed.  
6.5.4.1 Liver Safety Assessment 
The following potentially clinically significant criteria in liver function tests for Alkaline 
Phosphatase (ALP), Alanine Transaminase (ALT), total bilirubin, Aspartate Transaminase 
(AST) and their combination are defined.  The participant
investigational period will be used.   
 
 
 
 
 






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6.5.7 
Pregnancies 
A detailed listing of all pregnancies will be provided. 
6.5.8 
Eastern Cooperative Oncology Group (ECOG) Performance Status 
Number and percent of participants for each category of the ECOG performance status at 
each assessment time will be provided. The change from baseline to EOT score will also be 
summarized. Negative change scores indicate an improvement. Positive change scores 
indicate a decline in performance.  
ECOG will also be summarized using shift table from baseline to post-baseline score for each 
dose level, phase, tumor type, and overall by visit. 
6.6 
Analysis of Pharmacokinetics 
Cellular DNA load and kinetic parameters of ASP7517, as well as serum concentration of 
pembrolizumab will be summarized by using descriptive statistics including n, mean, 
standard deviation, minimum, median, maximum, coefficient of variation (CV), geometric 
mean, and geometric CV. Spaghetti and mean time-course of cellular DNA load will be 
constructed. 
6.6.1 
Estimation of Pharmacokinetic Parameters 
Participants with sufficient cellular DNA samples will have kinetic parameter estimates for 
ASP7517 including calculation of AUC, Cmax, and tmax. for each cycle estimated by the 
pharmacokineticist using a non-compartmental analysis method in reference to Manual for 
Non-Compartmental Analysis of Pharmacokinetic Data from Studies using PhoenixTM® 
WinNonlin® (Certara, Saint Louis, Missouri, US) software version 6.4 or higher. 
Exploratory analysis between pharmacokinetic parameters and clinical measures (e.g., 
efficacy or safety) may be performed. 
6.7 
Analysis of Exploratory Endpoints 
Biomarkers/Pharmacodynamics 
Immune cell phenotyping biomarkers will be summarized by change from baseline at each 
time point by both absolute number and percentage.  
 
6.8 
Interim Analysis (and Early Discontinuation of the Clinical Study) 
No interim analysis to be performed.   
6.9 
Additional Conventions 
6.9.1 
Analysis Windows 
No visit window will be used; nominal visit date will be considered date of visit. 




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6.9.3 
COVID-19 Impact Assessment 
Assessments affected by the COVID-19 pandemic will be listed for visit-based assessments 
and for non-visit-based assessments.  
For visit-based assessments affected by the COVID-19 pandemic, the listing shows if an 
assessment was not performed due to the COVID-19 pandemic, if it was out of window, if 
the assessment was performed at an alternative location or if it was a virtual assessment. 
Other information and comments reported on assessments affected by the COVID-19 
pandemic are also included. 
For non-visit-based assessments affected by the COVID-19 pandemic, participants who 
experience any of the following items: treatment discontinuation due to COVID-19, COVID-
19 medical history, COVID-19 adverse event, hospitalization due to COVID-19, dose 
changing due to COVID-19, or COVID-19 death, will be listed.   
Any events including discontinuation of treatment, medical history, adverse events, 
hospitalization, dose changing, or death, which are related to COVID-19, will be identified in 
the corresponding listing. 
6.9.4 
Outliers 
All values will be included in the analyses. 


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7 
DOCUMENT REVISION HISTORY  
Version
Date 
Changes 
Comment/rationale for change 
1.0 
 
Original Document 
 
2.0 
15-SEP-
2023 
Endpoints by Independent Central 
Review have been removed in 
sections 5.1 Efficacy Endpoints and 
6.4 Analysis of Efficacy. 
 
In Section 6.4.2 Analysis of Primary 
Efficacy Endpoints, OS, iPFS, PFS 
will be summarized and listed; iDOR, 
and DOR will be listed only. Select 
analyses have been removed from 
Section 6.7 Analysis of Exploratory 
Endpoints. 
 
Section 6.8 Subgroups of Interested 
has been removed. 
 
Time to first AE analyses were 
removed. 
 
 
Signature page 
Appendix 1: Key Contributors and 
Approvers 
Appendix 2: Author and Approver 
Signatures
Independent Central Review 
data is no longer being collected. 
 
 
 
Early termination of study and 
number of analyses has been 
reduced. 
 
 
 
 
Subgroup analyses no longer 
being performed. 
 
with Kaplan-Meier method and 
summary no longer being 
performed. 
 
 
 
  
 
 


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8 
REFERENCES 
ICH Harmonized Tripartite Guideline E 3. Structure and Content of Clinical Study Reports, 
November 1995. (www.ich.org; Guidelines; "Efficacy" Topics) 
ICH Harmonized Tripartite Guideline E 9. Statistical Principles for Clinical Trials, February 1998. 
(www.ich.org; Guidelines; "Efficacy" Topics) 
Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative 
Oncology Group. Am J Clin Oncol. 1982;5:649-655. 
Seymour, L., Bogaerts, J., Perrone, A., et al. iRECIST: guidelines for response criteria for use in trials 
testing immunotherapeutics. The Lancet Oncology. 2019: 18:e143-e152. 


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9 
APPENDICES 
9.1 
Appendix 1: Key Contributors and Approvers 
 
 
  
 
 
Data Science 
    
 
Medical Science 
 
Data Science 
 
CPED 
 
CPED 
  
Data Science 
  
Regulatory Affairs 
 
Data Science 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


Sponsor: Astellas Pharma Global Development, Inc.
SAP Final Version 2.0
ISN/Protocol 7517-CL-1101
06-Jun-2024
Astellas
Page 42 of 42
9.2
Appendix 2
Author and Approver Signatures
Prepared by:
Approved by:
E-signatures are attached at end of document
Date:
Date (DD MMM YYYY)
Approved by:
E-signatures are attached at end of document
Date:
 
Date (DD MMM YYYY)
PPD
PPD
PPD