Conditions: Ovarian Cancer NSCLC ESCC Solid Tumors
Keywords: NY-ESO-1 ASP0739 Solid Tumor NSCLC ESCC MRCL Ovarian Cancer R/R SS
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 16
Healthy volunteers: no

Brief summary:
The purpose of this study was to evaluate the safety, and tolerability of ASP0739, when administered as a single agent and in combination with pembrolizumab.

This study also evaluated the clinical response and other measures of anticancer activity of ASP0739 when administered as a single agent and in combination with pembrolizumab based on central and local assessment.

Detailed description:
The study comprised of 2 phases. Phase 1 (dose escalation) included participants with solid tumors known to express New York esophageal squamous cell carcinoma 1 (NY-ESO-1). Phase 2 (ASP0739 as single agent and in combination with pembrolizumab) included participants with relapsed/refractory Synovial Sarcoma (SS), myxoid/round cell liposarcoma (MRCL), and ovarian cancer who had not responded to Standard of Care (SOC) or were ineligible for standard therapy. Phase 2 single agent also included a cohort of participants with select solid tumors known to express NY-ESO-1 (melanoma, Non Small Cell Lung Cancer-adenocarcinoma \[NSCLC\], squamous cell and esophageal squamous cell carcinoma \[ESCC\]). Japanese participants were only enrolled into the monotherapy arm of the dose expansion cohort.

Arms:
arm 1: Participants with Relapsed/Refractory (R/R) solid tumors known to express New York esophageal squamous cell carcinoma 1 (NY-ESO-1) received intravenous (IV) infusion of ASP0739 (human embryonic kidney cell \[HEK293\] transfected with a lentiviral vector that is encoding the target antigen NY-ESO-1) at a dose of 1x10\^7 cells/milliliters (mL) at 4 to 6 mL/minute infusion rate on day 1 of each cycle for a total of 4 doses; an additional 2 doses was administered in participants with a partial response (PR) or stable disease (SD) (1 cycle= 28 days). . arm 2: Participants with R/R solid tumors known to express NY-ESO-1 received IV infusion of ASP0739 (HEK293 transfected with a lentiviral vector that is encoding the target antigen NY-ESO-1) at a dose of 1x10\^8 cells/mL at 4 to 6 mL/minute infusion rate on day 1 of each cycle for a total of 4 doses; an additional 2 doses was administered in participants with a PR or SD (1 cycle= 28 days). arm 3: Participants with synovial sarcoma (SS), myxoid/round cell liposarcoma (MRCL), ovarian cancer and other solid tumors known to express NY-ESO-1 (melanoma, non-small cell lung cancer \[NSCLC\] adenocarcinoma and squamous cell and esophageal squamous cell carcinoma \[ESCC\]) received IV infusion of ASP0739 (HEK293 transfected with a lentiviral vector that is encoding the target antigen NY-ESO-1) at a dose of 1x10\^8 cells/mL at 4 to 6 mL/minute infusion rate on day 1 of each cycle for a total of 4 doses; an additional 2 doses was administered in participants with a PR or SD (1 cycle= 28 days).

Interventions: intervention 1: ASP0739
Intervention descriptions: intervention 1: Intravenous (IV)

Protocol document:
SAP_002.pdf: 
Sponsor: Astellas Pharma Global Development, Inc. 
SAP DRAFT Version 1.7 
ISN/Protocol 0739-CL-0101 
22-Jun-2023 
Astellas 
Page 1 of 42 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
Version 1.7, dated 22-JUN-2023 
 
A Phase 1/2, Open-label Study Investigating the Safety, Tolerability and Efficacy of 
ASP0739 as a Single Agent and in Combination with Pembrolizumab in Patients with 
Advanced Solid Tumors Known to Express NY-ESO-1 
 
ISN/Protocol: 0739-CL-0101 
 
 
IND number: 26983 
 
 
Sponsor: 
 
Astellas Pharma Global Development, Inc. (APGD)  
1 Astellas Way 
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. 


Sponsor: Astellas Pharma Global Development, Inc. 
SAP DRAFT Version 1.7 
ISN/Protocol 0739-CL-0101 
22-Jun-2023 
Astellas 
Page 2 of 42 
Table of Contents 
I. 
LIST OF ABBREVIATIONS AND KEY TERMS ································
···········
 4 
1 
INTRODUCTION ································
································
··················
 8 
2 
TREATMENT PROTOCOL OBJECTIVES AND DESIGN ······························
 8 
2.1 
Study Objectives ································
································
···············
 8 
2.2 
Study Design ································
································
···················
 10 
2.3 
Randomization ································
································
·················
 12 
3 
SAMPLE SIZE································
································
·····················
 12 
4 
ANALYSIS SETS ································
································
·················
 13 
5 
ENDPOINTS ································
································
·······················
 14 
5.1 
Efficacy Endpoints ································
································
············
 14 
5.1.1 
Primary Efficacy Endpoints ································
····························
 15 
5.1.2 
Secondary Efficacy Endpoints ································
·························
 15 
5.2 
Safety Endpoints ································
································
··············
 21 
5.2.1 
Safety Endpoint: Dose-Limiting Toxicity (DLT) ································
····  21 
5.2.2 
Safety Endpoint: Maximum Tolerated Dose (MTD) and Recommended 
Phase 2 Dose (RP2D) ································
································
···  22 
5.2.3 
Safety Endpoint: Adverse Events (AEs) ································
··············
 22 
5.2.4 
Safety Endpoint: Laboratory Assessments ································
···········
 23 
5.2.5 
Safety Endpoint: Vital Signs ································
···························
 25 
5.2.6 
Safety Endpoint: Electrocardiogram (ECG) ································
··········
 25 
5.2.7 
Safety Endpoint: Eastern Cooperative Oncology Group Performance Status 
(ECOG PS) ································
································
···············
 26 
5.3 
Pharmacokinetic Variables ································
································
···  26 
5.4 
Pharmacodynamic Variables································
································
· 26 
5.5 
Other Variables ································
································
················
 26 
6 
STATISTICAL METHODOLOGY ································
···························
 27 
6.1 
General Considerations ································
································
·······  27 
6.2 
Study Population ································
································
··············
 27 
6.2.1 
Disposition of Participants ································
·····························
 27 
6.2.2 
Protocol Deviations ································
································
·····  28 
6.2.3 
Demographic and Other Baseline Characteristics ································
···  28 
6.2.4 
Disease History ································
································
··········
 29 


Sponsor: Astellas Pharma Global Development, Inc. 
SAP DRAFT Version 1.7 
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22-Jun-2023 
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Page 3 of 42 
6.2.5 
Previous and Concomitant Medications ································
··············
 29 
6.2.6 
Prior Radiation Therapy ································
································
 29 
6.2.7 
New and Prior Anti-Cancer Therapy ································
··················
 29 
6.3 
Study Drug ································
································
·····················
 29 
6.3.1 
Exposure ································
································
··················
 29 
6.4 
Analysis of Efficacy ································
································
··········
 30 
6.4.1 
Analysis of Primary Efficacy Endpoint ································
···············
 30 
6.4.2 
Analysis of Secondary Efficacy Endpoints ································
···········
 30 
6.5 
Analysis of Safety ································
································
·············
 31 
6.5.1 
Dose Limiting Toxicities ································
·······························
 31 
6.5.2 
Adverse Events ································
································
··········
 32 
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 Pharmacodynamics ································
·····························
 36 
6.8 
Additional Conventions ································
································
······  36 
6.8.1 
Analysis Windows ································
································
······  36 
6.8.2 
Imputation Rules for Incomplete Dates ································
···············
 37 
6.8.3 
Covid-19 Impact Assessment ································
··························
 38 
6.8.4 
Outliers ································
································
···················
 38 
7 
DOCUMENT REVISION HISTORY ································
·························
 39 
8 
REFERENCES ································
································
····················
 40 
9 
APPENDICES ································
································
·····················
 41 
Appendix 1 Key Contributors ································
································
···········
 41 
Author and Approver Signatures ································
································
·······  42 
 


Sponsor: Astellas Pharma Global Development, Inc. 
SAP DRAFT Version 1.7 
ISN/Protocol 0739-CL-0101 
22-Jun-2023 
Astellas 
Page 4 of 42 
I. 
LIST OF ABBREVIATIONS AND KEY TERMS 
List of Abbreviations 
Abbreviations  
Description of abbreviations  
AE 
adverse event 
AEsi 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT  
alanine aminotransferase  
APGD 
Astellas Pharma Global Development 
AST  
aspartate aminotransferase  
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 
BSA 
body surface area  
CI 
confidence interval 
Cmax 
maximum concentration 
CR  
complete response 
CSR 
clinical study report 
CTCAE  
Common Terminology Criteria for Adverse Events  
Ctrough 
concentration immediately prior to dosing at multiple dosing 
CV 
coefficient of variation 
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 
EOT 
end of treatment 
ESCC 
esophageal squamous cell carcinoma 
FAS 
full analysis set 


Sponsor: Astellas Pharma Global Development, Inc. 
SAP DRAFT Version 1.7 
ISN/Protocol 0739-CL-0101 
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Page 5 of 42 
Abbreviations  
Description of abbreviations  
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 
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 aet 
PR 
partial response per RECIST v1.1 
PS 
performance status 
PT 
preferred term 
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 


Sponsor: Astellas Pharma Global Development, Inc. 
SAP DRAFT Version 1.7 
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Abbreviations  
Description of abbreviations  
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 
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  
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 into a clinical trial.  NOTE: Once a participant 
has been enrolled, the clinical trial protocol applies to the 
participant.   
Investigational 
Product 
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 given to a participant, and continues until 
the last assessment after completing administration of the test drug 
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. 
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. 
 


Sponsor: Astellas Pharma Global Development, Inc. 
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Page 8 of 42 
1 
INTRODUCTION 
Due to early termination of the study, this Statistical Analysis Plan (SAP) contains parts of 
analysis described in the protocol based on the availability of data collected; and includes 
procedures for executing the statistical analysis to fulfill part of the objectives of the study. 
Tumor-related efficacy variables are evaluated by the Response Evaluation Criteria in Solid 
Tumors (RECIST) v1.1 and guidelines for response criteria for use in trials testing 
immunotherapeutics (iRECIST) by central review are not collected but investigator 
assessments will be collected. There is no combination treatments of ASP0739 and 
pembrolizumab as planned.  
The final SAP will be approved prior to database primary database lock. 
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 ASP0739 in 
participants with R/R solid tumors 
known to express NY-ESO-1 when 
administered as a single agent 
(phase 1 dose escalation), and in 
combination with 
pembrolizumab(1) in participants 
with R/R SS, MRCL and ovarian 
cancer (safety lead-in) 
● 
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(3) 
● 
To determine the RP2D and/or the 
MTD of ASP0739 when 
administered as a single agent 
(phase 1) 
● 
RP2D based on above 
● 
To evaluate the clinical response of 
ASP0739 when administered as a 
single agent and in combination 
with pembrolizumab(1) (phase 2) 
● 
Objective response rate per iRECIST (iORR) by 
Independent Central Review(2) 
Table continued next page 
 


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Objectives 
Endpoints 
Secondary 
● 
To evaluate other measures of 
anticancer activity of ASP0739 
when administered as a single 
agent and in combination with 
pembrolizumab(1) based on central 
and local assessment in participants 
with R/R SS, MRCL, or ovarian 
cancer (phase 2) 
 
 
 
● 
To obtain preliminary efficacy 
based on central and local 
assessment in participants with R/R 
solid tumors known to express NY-
ESO-1 (melanoma, NSCLC-
adenocarcinoma and squamous cell 
and ESCC) (phase 2) 
● 
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) 
 
 
● 
Objective response rate per iRECIST (iORR) 
Exploratory 
● 
To evaluate potential genomic, 
proteomic and/or other biomarkers 
that may correlate with treatment 
outcome when ASP0739 
administered as a single agent and 
in combination with 
pembrolizumab(1) 
● 
Exploratory biomarkers that may correlate with treatment 
outcome of ASP0739 as a single agent or in combination 
with pembrolizumab(1), including NY-ESO-1 expression  
● 
To evaluate pharmacodynamic 
activities of ASP0739 as a single 
agent and in combination with 
pembrolizumab(1) 
 
 
 
 
 
● 
To characterize the 
pharmacokinetic profile of 
ASP0739 when administered as a 
monotherapy and in combination 
with pembrolizumab(1) 
● 
Pharmacodynamic effects of ASP0739 such as changes in:  
o 
Cytokine expression and secretion (e.g., IFNg) 
o 
NY-ESO-1-specific T lymphocytes (e.g., cytotoxic T 
lymphocytes)  
o 
Immune cell populations (NKT cells, Treg cells, etc.)  
o 
Anti-NY-ESO-1 antibodies  
o 
Tumor microenvironment (CD8, PD-L1, etc.)  
 
 
● 
Cellular DNA load and kinetic parameter estimates 
(including AUC, Cmax, Ctrough and tmax) for ASP0739 as a 
monotherapy or in combination with pembrolizumab(1) 
AE: adverse event; CD8: cluster of differentiation 8; DCR: disease control per RECIST v1.1; DLT: dose 
limiting toxicity; DOR: duration of response per RECIST v1.1; ECG: electrocardiogram; ECOG: Eastern 
Cooperative Oncology Group; ESCC: esophageal squamous cell carcinoma; iDCR: disease control per 
iRECIST; iDOR: duration of response per iRECIST; IFNg; interferon gamma; iORR: objective response rate 
per iRECIST; iPFS: progression-free survival per iRECIST; iRECIST: immune response evaluation criteria in 
solid tumors; MRCL: myxoid/round cell liposarcoma; NKT: natural killer T; NSCLC: non-small cell lung 
cancer; NY-ESO-1: New York esophageal squamous cell carcinoma 1; ORR: objective response rate per 
RECIST v1.1; OS: overall survival; PD-L1: programmed death-ligand 1; PFS: progression-free survival per 
RECIST v1.1; R/R: relapsed/refractory; RECIST: response evaluation criteria in solid tumors; RP2D: 
recommended phase 2 dose; SAE: serious adverse event; SS: synovial sarcoma; Note: (1) There will be no 
treatment in combination with Pembrolizumab due to early termination of the study. (2) There will be no 
Independent Central Review data. (3) There will be no serum, coagulation, and physical exam data.  


Sponsor: Astellas Pharma Global Development, Inc. 
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Page 10 of 42 
2.2 
Study Design 
This is a phase 1, open-label study of ASP0739 in participants with R/R solid tumors known 
to express NY-ESO-1 and a phase 2 study of single agent and combination therapy with 
pembrolizumab in participants with R/R SS, MRCL or ovarian cancer.  
Phase 1 (dose escalation) will have participants with solid tumors known to express NY-
ESO-1 and phase 2 (dose expansion) of ASP0739 single agent and combination therapy with 
pembrolizumab will have participants with R/R SS, MRCL, or ovarian cancer who have not 
responded to SOC or are ineligible for standard therapy. Phase 2 single agent will also 
include a cohort of participants with select solid tumors known to express NY-ESO-1 
(melanoma, NSCLC-adenocarcinoma and squamous cell and ESCC). 
Both study phases consist of the following periods:  
● 
Screening: (up to 28 days)  
● 
Treatment with ASP0739 (up to 6 doses every 28-days) and for participants in 
combination cohorts with pembrolizumab on C1D1, and then every 6 weeks, until 
disease progression, unacceptable toxicity or up to 17 doses (4 doses in combination with 
ASP0739 and up to 13 doses as a single agent if participant is continuing to derive 
clinical benefit in the opinion of the investigator) End of Treatment (EOT) visit after 
completion of IP: Within 7 days of EOT determination or prior to the initiation of new 
anticancer therapy, whichever occurs first  
● 
Safety follow-up visits at 30, 60 and 90 days from the last dose of ASP0739 or prior to 
the initiation of new anticancer therapy  
● 
Follow-up visits every 2 months for up to 1 year or until progression or start of a new 
anticancer therapy or death (whichever occurs first)  
● 
Survival follow-up for up to 1 year by telephone calls every 3 months after the start of a 
new anticancer treatment or progression after ASP0739 and/or pembrolizumab treatment 
Details of the schedule of clinical assessments are available in the protocol. 
Part 1: Phase 1 Single Agent Dose Escalation 
The single agent dose escalation portion will evaluate escalating dose levels of ASP0739 in 
approximately 3 to 12 DLT-evaluable participants. 
ASP0739 in Combination with Pembrolizumab Safety Lead-in  
Enrollment in the combination therapy safety lead-in will start once phase 1 single agent dose 
escalation is completed and the RP2D is defined.  
The combination therapy safety lead-in portion will evaluate the RP2D of ASP0739 with a 
fixed dose of 400 mg pembrolizumab in 6 to 9 participants with at least 6 DLT-evaluable 
participants.  
Phase 2 Single Agent  
Once RP2D is determined, the phase 2 single agent cohorts may be opened in R/R SS, 
MRCL, ovarian cancer, and other solid tumors known to express NY-ESO-1 (melanoma, 


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NSCLC-adenocarcinoma and squamous cell and ESCC). If a confirmed response (partial 
response based on iRECIST [iPR] or complete response based on iRECIST [iCR], per 
independent central review) occurs in other solid tumors known to express NY-ESO-1, a 
tumor-specific dose expansion cohort may be opened in that tumor type.  
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]. For R/R 
SS, MRCL, and ovarian cancer, initially 18 participants will be enrolled in each 
tumor-specific expansion cohort (stage 1). If the iORR does not meet the optimal stopping 
boundaries (see Section 6.9), then an additional 25 participants (stage 2) may be enrolled for 
a total maximum sample size of 43 participants. When the total number of participants 
reaches the maximum sample size of 43, it may be predicted that ASP0739 is effective if the 
number of responses is greater than or equal to 8. 
Phase 2 Combination of ASP0739 + Pembrolizumab 
Once safety lead-in is completed and 2 radiographic responses, complete response (CR) or 
partial response (PR), are observed by local or central review, the phase 2 combination 
cohorts may be opened in the respective tumor type where the responses were observed.  
For R/R SS, initially 22 participants will be enrolled in an expansion cohort (stage 1). If the 
iORR does not meet the optimal stopping boundaries (see Section 6.9) for R/R SS, then an 
additional 38 participants (stage 2) may be enrolled for a total maximum sample size of 60. 
When the total number of participants reaches the maximum sample size of 60, it may be 
predicted that ASP0739 in combination with pembrolizumab is effective if the number of 
responses is greater than or equal to 18.  
For R/R MRCL, initially, 22 participants will be enrolled in an expansion cohort (stage 1). If 
the iORR does not meet the optimal stopping boundaries (see Section 6.9) for R/R MRCL, 
then an additional 38 participants (stage 2) may be enrolled for a total maximum sample size 
of 60. When the total number of participants reaches the maximum sample size of 60, it may 
be predicted that ASP0739 in combination with pembrolizumab is effective if the number of 
responses is greater than or equal to 18.  
For R/R ovarian cancer, initially, 10 participants will be enrolled in an expansion cohort 
(stage 1). If the iORR does not meet the optimal stopping boundaries (see Section 6.9) for 
R/R ovarian cancer, then an additional 19 participants (stage 2) may be enrolled for a total 
maximum sample size of 29. When the total number of participants reaches the maximum 
sample size of 29, it may be predicted that ASP0739 in combination with pembrolizumab is 
effective if the number of responses is greater than or equal to 4.  
If both single agent and combination therapy expansion cohorts are open for the same tumor 
type, participants will be randomized to either single agent or combination therapy cohorts 
and the randomization ratio will be based on the number of open slots still available at each 
cohort.  


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Replacement of Participants in Phase 2 Dose Expansion 
If a participant in phase 2 is not response evaluable (defined as the response analysis set 
[RAS]), then an additional participant may be enrolled in that cohort based on sponsor 
discretion.  
2.3 
Randomization  
Assignment and Allocation 
Priority for enrollment will be given to the safety lead-in portion of the ASP0739 and 
pembrolizumab combination arm when both phase 2 single agent dose expansion and 
combination therapy safety lead-in are open.  
If both single agent and combination therapy expansion cohorts are open for the same tumor 
type, participants will be randomized to either single agent or combination therapy cohorts 
and the randomization ratio will be based on the number of open slots still available at each 
cohort. 
3 
SAMPLE SIZE 
ASP0739 Single Agent  
A total of approximately 181 participants may be enrolled in single agent treatment.  
Phase 1 Single Agent Dose Escalation:  
The sample size of approximately 12 participants for the dose escalation phase 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, a minimum of 6 evaluable and up 
to 12, should provide adequate information for the dose escalation and safety objectives of 
the study.  
Phase 2 Single Agent Dose Expansion:  
It is estimated that up to approximately 169 participants may be enrolled in the single agent 
arms. The iORR is monitored using the BOP2 design.  
For each indication (SS, MRCL or ovarian), with assumptions mentioned in the statistical 
hypotheses section below, the statistical power would be approximately at least 0.80 while 
controlling the type I error rate at 0.05 (1-sided).  
The sample size of approximately 40 participants for other solid tumors known to express 
NY-ESO-1 is not based on statistical power calculation. A minimum of 10 participants per 
tumor type will be enrolled. If less than approximately 6 participants within each tumor type 
of melanoma, NSLCC-adenocarcinoma or squamous cell and ESCC are NY-ESO-1 positive 
based on analysis of the most recent tissue sample, additional participants may be added so 
that there are approximately 6 NY-ESO-1 positive participants.  
ASP0739 Combination with Pembrolizumab:  
A total of approximately 158 participants may be enrolled in combination therapy.  


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Combination Therapy Safety Lead-in:  
The sample size of approximately 6 to 9 participants for safety lead-in 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 safety objectives of the study.  
Phase 2 Combination Therapy:  
It is estimated that up to approximately 149 participants may be enrolled in the combination 
therapy arms. The iORR is monitored using the BOP2 design.  
For each indication, with assumptions mentioned in the statistical hypotheses section below, 
the statistical power would be approximately at least 0.80 while controlling the type I error 
rate at 0.05 (1-sided).  
Statistical Hypotheses: 
Phase 2 Single Agent (SS, MRCL, Ovarian):  
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.  
Solid tumors known to express NY-ESO-1 (melanoma, NSCLC-adenocarcinoma and 
squamous cell as well as ESSC):  
There is no formal statistical hypothesis for this cohort.  
Phase 2 Combination Therapy: 
SS:  
H0: iORR is 20%, at which the treatment is deemed as unacceptable.  
H1: iORR is at least 35%, at which the treatment is deemed as acceptable.  
MRCL:  
H0: iORR is 20%, at which the treatment is deemed as unacceptable.  
H1: iORR is at least 35%, at which the treatment is deemed as acceptable.  
Ovarian:  
H0: iORR is 5%, at which the treatment is deemed as unacceptable.  
H1: iORR is at least 20%, at 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. Pharmacodynamics analysis 


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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 participant 
number. 
For each dose level, 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 and 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 one dose of IP and have at least one 
post baseline primary efficacy measurement. 
Safety Analysis Set (SAF) 
All participants who take at least 1 dose of IP. 
Pharmacokinetic Analysis 
Set (PKAS) 
The PKAS consists of the administered population for which 
pharmacokinetics data are available for at least one 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 
The endpoints that are described in statistical methodology (Section 6) are described in this 
section. 
5.1 
Efficacy Endpoints 
Tumor-related efficacy variables are evaluated by the Response Evaluation Criteria in Solid 
Tumors (RECIST) v1.1 and guidelines for response criteria for use in trials testing 
immunotherapeutics (iRECIST) (Seymour, L., et al., 2017).  


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5.1.1 
Primary Efficacy Endpoints 
5.1.1.1 Primary Efficacy Endpoint: 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 complete response (iCR) or partial response (iPR) per 
iRECIST. Although iORR by independent central review is not included, other endpoints 
assessment 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 Secondary Efficacy Endpoint: 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. The same analysis conducted for 
[Section 5.1.1.1 Primary Efficacy Endpoint: Objective Response Rate per iRECIST (iORR)] 
will be conducted for the endpoints of:  
● 
ORR with confirmed response by investigator assessment 
● 
ORR with unconfirmed response by investigator assessment 
5.1.2.2 Secondary Efficacy Endpoint: 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.  
5.1.2.3 Secondary Efficacy Endpoint: 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 stable disease (SD) per RECIST v1.1. 
5.1.2.4 Secondary Efficacy Endpoint: 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 
 


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5.1.2.5 Secondary Efficacy Endpoint: Progression-free Survival per iRECIST (iPFS) 
iPFS is defined as the time from the date of first dose until death from any cause or 
radiographic disease progression assessed per iRECIST by investigator assessment.  
If unconfirmed disease progression per iRECIST (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 (ACT): 
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 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) 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 therapy (ACT): 
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 
Table continued on next page 


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iPFS 
 
 
Situation  
Date of Event or Censor 
Outcome  
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 
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 as 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 cannot be censored at “NE”. If NE is the only previous assessment, then 
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 Secondary Efficacy Endpoint: 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.  
 


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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 (ACT): 
Radiographical progression documented per 
RECIST v1.1 
Date of radiological disease 
progression 
Event 
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 therapy (ACT): 
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 as 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 cannot be censored at “NE”. If NE is the only previous assessment, then 
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 Secondary Efficacy Endpoint: 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 
calculated only for the subgroup of participants with confirmed response iCR/iPR per 
iRECIST for investigator assessment.  


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Table 4 
iDOR Definition 
iDOR 
 
 
Situation  
Date of Event or Censor 
Outcome 
Participant did not receive new anti-cancer therapy (ACT) 
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); 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); 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 (ACT) 
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); c) the next timepoint responses are 
all iUPD, and iCPD never occurs; 
Date of last radiological assessment 
before start of new ACT 
Censor 
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); 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 
 


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Missing 2 scheduled imaging assessments: 
Missing 2 scheduled imaging assessments is defined as the gap between two imaging 
assessments as 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 cannot be censored at “NE”. If NE is the only previous assessment, then 
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 Secondary Efficacy Endpoint: 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 for investigator assessment.   
Table 5 
DOR Definition 
DOR 
 
 
Situation  
Date of Event or Censor 
Outcome 
Participant did not receive new anti-cancer therapy (ACT) 
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 (ACT) 
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 is more than 140 days (2.5 times the scheduled imaging assessment interval 
[2.5 x 56 days]). 


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5.2 
Safety Endpoints 
Safety and tolerability, to determine MTD and RP2D, are the primary endpoints of the study. 
Safety endpoints are DLTs, adverse events (AEs), laboratory measurements, vital signs, 
ECGs, physical examinations, and ECOG (Eastern Cooperative Oncology Group) 
performance status (PS). Safety will be assessed by evaluation of the following variables: 
5.2.1 
Safety Endpoint: 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 C1D1 in the dose escalation cohort 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 National Cancer Institute’s Common Terminology Criteria for Adverse Events 
(NCI-CTCAE). Participants experiencing DLTs, who in the opinion of the investigator are 
deriving clinical benefit from the study treatment (e.g., marked reduction in tumor burden), 
may be allowed to continue study treatment with ASP0739 upon resolution of the event to 
≤ grade 1 or baseline, upon discussion with the sponsor. Participants experiencing DLTs 
during the single agent dose escalation portion will not be replaced. 
5.2.1.1 Safety Endpoint: ASP0739 Single Agent Dose-Limiting Toxicities (DLTs) 
For participants in the single agent (dose escalation) ASP0739 arm, DLTs are defined in the 
protocol in Section 4.1. 
Participants who are tolerating the 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. 
5.2.1.2 Safety Endpoint: ASP0739 Safety Lead-In Dose-Limiting Toxicities (DLTs) 
A DLT is defined as any of the listed events that occur within 28 days starting with the first 
dose on C1D1 in the safety lead-in cohort and that is considered to be possibly, probably or 
definitely related to IP. Confirmation of DLTs will be made by the DESC. The severity of 
AEs will be assessed according to NCI-CTCAE. Participants experiencing DLTs, who in the 
opinion of the investigator are deriving clinical benefit from the study treatment (e.g., marked 
reduction in tumor burden), may be allowed to continue study treatment with ASP0739 upon 
resolution of the event to ≤ grade 1 or baseline, upon discussion with the sponsor. 
Participants experiencing DLTs during the combination safety lead-in portion will not be 
replaced. 
5.2.1.3 Safety Endpoint: ASP0739 Dose-Limiting Toxicities (DLTs) 
For participants in the ASP0739, DLTs are defined in the protocol in Section 4.1.  
Participants who are tolerating the IP at a dose level that is being reviewed due to the 
occurrence of DLTs in another participant will not be automatically precluded from 


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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.   
5.2.2 
Safety Endpoint: 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. 
Recommended Phase 2 Dose (RP2D) 
The sponsor, in conjunction with the DESC, will determine the RP2D of ASP0739 as a single 
agent taking into consideration the safety and efficacy data, as well as other available data, 
such as pharmacokinetics and pharmacodynamics of ASP0739. The RP2D will not exceed 
the MTD. 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 dose level determined to be the RP2D must have data from at least 6 participants. 
Determination of RP2D will be done for monotherapy. 
5.2.3 
Safety Endpoint: Adverse Events (AEs) 
An AE is any untoward medical occurrence in a participant or clinical study participant, 
temporally associated with the use of study IP and other study treatments, whether or not 
considered related to the study IP and other study treatments. 
A treatment-emergent adverse event (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 or 
with missing assessment of the causal relationship.  
If the adverse event occurs on Day 1 and the onset check box is marked “Onset after first 
dose of study IP” or the onset check box is left blank, then the adverse event will be 
considered treatment emergent. If the adverse event occurs on Day 1 and the onset check box 
is marked “Onset before first dose of study IP”, then the adverse event will not be considered 
treatment emergent. If a participant experiences an event both during the pre-investigational 
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 


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collected that begin within 30 days after taking the last dose of study IP will also be counted 
as TEAE. 
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.  
AE data will be listed. 
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 
 
5.2.4 
Safety Endpoint: Laboratory Assessments 
For quantitative clinical laboratory measurements (hematology and biochemistry), 
descriptive statistics will be used to summarize results and change from baseline by dose 
level and overall and by time point. Shifts from baseline to the worst grade based on 
NCI-CTCAE v5.0 in laboratory tests will also be tabulated.  
Laboratory data will be listed. 
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 
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 
Table continued on next page 


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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. 
5.2.5 
Safety Endpoint: Vital Signs 
Vital signs will include: 
● 
Systolic and diastolic blood pressures (mmHg) 
● 
Pulse rate (beats/minute)  
● 
Respiratory rate (breaths/minute) 
● 
Body temperature (degrees C) 
● 
Height (m) (Height measurement performed at screening only) and weight (kg) 
5.2.6 
Safety Endpoint: Electrocardiogram (ECG) 
12-lead ECGs will be recorded in triplicate at the scheduled time points (at least 2 minutes 
apart per time point). Each ECG tracing will be taken 5 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. 
The routine 12-lead ECG results will be summarized by dose level and by time point.  
Interpretations of routine 12-lead ECG results will be summarized by dose level and by time 
point.  
12-lead ECG data interpretations and quantitative values will be listed. 


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5.2.7 
Safety Endpoint: 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 and kinetic parameter estimates of ASP0739 will be evaluated for each 
cohort as outlined in the Protocol in the Schedule of Assessments. 
Cellular DNA load and kinetic parameters for ASP0739 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 ASP0739 including 
calculation of AUC (including AUClast, AUC28d, AUCinf, Cmax, Ctrough and tmax) using standard 
noncompartmental analysis. For pharmacokinetic parameters, tmax, n, median, minimum and 
maximum will be calculated.  
5.4 
Pharmacodynamic Variables 
Pharmacodynamic effects of ASP0739 as monotherapy will be assessed with immune cell 
populations (NKT cells, Treg cells, etc.).  
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 (CV) 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%.  
Summaries based on FAS and RAS (e.g., disposition, baseline, and efficacy data) will be 
presented by planned treatment, unless specifically stated otherwise. Safety analysis and 
other summaries based on SAF, PKAS or PDAS will be presented by actual dose level 
received.  
Baseline is defined as the last available measurement prior to the first dose of IP.  
Unless otherwise specified, all summaries will be presented overall, by dose level, and by 
phase. 
All data processing, summarization, and analyses will be performed using Statistical Analysis 
Software (SAS)® Version 9.4 or higher on Linux. Specifications for table, figure, and listing 
(TLF) 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). 
For the definition of subgroups of interest, please refer to Section 6.8.  
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, by 
dose level, phase, and overall  
● 
Number and percentage of participants completed and discontinued treatment, by 
primary reason for treatment discontinuation for SAF, by dose level, phase, and overall 
● 
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 
by dose level, phase, and overall  


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● 
Number and percentage of participants completed and discontinued the study during the 
observation period, by primary reason for post-study period discontinuation for SAF by 
dose level, phase, and overall  
● 
Number and percentage of participants completed and discontinued the study during the 
observation period, by primary reason for post-study period discontinuation for SAF by 
dose level, phase, and overall  
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 participant enrolled. The number and percentage of participants meeting 
any criteria will be summarized for each criterion and overall, by dose level, phase, 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 - Clinical study procedure conducted prior to subject signing informed consent. 
PD6 - Event not reported within the expected turn-around time per protocol reporting 
requirements. 
PD7 - 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, and overall for SAF. 
Descriptive statistics for age, weight, body surface area (BSA), and height at study entry will 
be presented. Frequency tabulations for sex, ethnicity, age group (defined in Section 6.8), 
race, region, and baseline ECOG will be presented. This will be done for SAF and RAS, by 
dose level, phase, and overall.   
Medical history and conditions existing at baseline will be coded in MedDRA 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 IP. 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 World Health Organization Drug Dictionary (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, 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, and overall 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 
New and Prior Anti-Cancer Therapy  
Frequency tabulations of participants with prior and with 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  
● 
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% 


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o >80% 
o Unknown 
● 
Number and percentage of participants with dose adjustments or 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 survival and other time-to-event analyses). Best overall responses are summarized 
based on iRECIST and RECIST 1.1. Efficacy analyses will be summarized by dose level, 
phase, and overall. Swimmer plots will be produced displaying participants’ overall disease 
response experience, spider plots to display percent change in tumor size, and waterfall plots 
to display maximum tumor shrinkage rate. 
6.4.1 
Analysis of Primary Efficacy Endpoint 
6.4.1.1 Analysis of Primary Efficacy Endpoint: Objective Response Rate per iRECIST 
(iORR) 
iORR for each dose level will be calculated and its 95% confidence interval will be 
constructed by Clopper-Pearson method for the endpoints of: 
● 
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 Analysis of Secondary Efficacy Endpoint: Objective Response Rate per 
RECIST v1.1 (ORR) 
ORR for each dose level 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 Analysis of Secondary Efficacy Endpoint: 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 
6.4.2.3 Analysis of Secondary Efficacy Endpoint: 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 


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6.4.2.4 Analysis of Secondary Efficacy Endpoint: Overall Survival (OS) 
OS data will be listed. 
6.4.2.5 Analysis of Secondary Efficacy Endpoint: Progression-Free Survival per 
iRECIST (iPFS) 
iPFS data will be listed. 
6.4.2.6 Analysis of Secondary Efficacy Endpoint: Progression-Free Survival per 
RECIST v1.1 (PFS) 
PFS data will be listed. 
6.4.2.7 Analysis of Secondary Efficacy Endpoint: Duration of Response per iRECIST 
(iDOR) 
iDOR data will be listed. 
6.4.2.8 Analysis of Secondary Efficacy Endpoint: Duration of Response per RECIST 
v1.1 (DOR) 
DOR data 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, 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: 
Action 
Number of Participants Treated at 
Current Dose Level 
3 
4 
5 
6 
7 
8 
9 
Escalate dose if number of 
participants with DLT ≤ 
0 
0 
1 
1 
1 
1 
2 
Stay at current dose level if 
number of participants with 
DLT = 
1 
1 
NA 
2 
2 
2 
3 
De-escalate if number of 
participants with DLT = 
2 
2 
2 or 3 
3 
3 or 4 3 or 4 
4 
Stop if number of participants 
with DLT ≥ 
3 
3 
4 
4 
5 
5 
5 
DLT: dose limiting toxicity 
 


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6.5.2 
Adverse Events 
For the purpose of safety assessments in this study, events recorded during the pre-
investigational period will be classified as Baseline Signs and Symptoms. All AEs recorded 
on treatment including within 30 days from the last study treatment and SAEs on treatment 
including within 90 days of the last study treatment will be summarized.  
Summaries and listings of SAEs and Serious TEAEs include SAEs upgraded by the sponsor 
based on review of the Sponsor’s list of Always Serious terms if any upgrade was done. 
The coding dictionary for this study will be Medical Dictionary for Regulatory Activities 
(MedDRA). It will be used to summarize AEs by SOC and PT. AEs will be graded using 
National Cancer Institute’s Common Terminology Criteria for AEs (NCI-CTCAE).  
An overview table will include the following details by dose level, phase, and overall: 
● 
Number and percentage of participants with TEAEs 
● 
Number and percentage of participants with IP-related TEAEs 
● 
Number and percentage of participants with TEAE leading to death 
● 
Number and percentage of participants with IP-related TEAE leading to death 
● 
Number and percentage of participants with serious TEAEs and Astellas upgraded 
serious TEAE 
● 
Number and percentage of participants with serious IP-related TEAEs and Astellas 
upgraded serious IP-related TEAE 
● 
Number and percentage of participants with TEAEs leading to permanent 
discontinuation of study IP 
● 
Number and percentage of participants with IP-related TEAEs leading to permanent 
discontinuation of study IP 
● 
Number and percentage of deaths 
The number and percentage of participants with TEAEs, as classified by SOC and PT will be 
summarized by dose level, phase, and overall. Summaries will be provided for: 
● 
DLTs within the DLT observation period 
● 
All DLTs 
● 
TEAEs 
● 
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  
● 
TEAEs excluding serious adverse events that equal to or exceed a threshold of 10% in 
any dose level   
● 
Common TEAEs that equal to or exceed a threshold of 10% in any dose level  
● 
TEAEs leading to death 
● 
IP-related TEAE leading to death 
● 
CTCAE Grade 3 or higher TEAEs 
● 
IP-related CTCAE Grade 3 or higher TEAEs  


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In addition, 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, 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 (including < Grade 3 and ≥ Grade 3). 
The same summary will be done for IP-Related TEAEs. 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 list of adverse events to be summarized may change during the course of the study due to 
ongoing pharmacovigilance. 
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, and overall.  
6.5.4 
Clinical Laboratory Evaluation 
The baseline visit is the last measurement taken prior to initial study IP administration.   
Quantitative clinical laboratory variables, i.e., hematology, biochemistry, coagulation and 
urinalysis will be summarized using mean, standard deviation, minimum, maximum and 
median by phase and dose level at each visit. Additionally, a within-participant change will 
be calculated as the post-baseline measurement minus the baseline measurement and 
summarized in the same way.  
The number and percentage of participants in relevant categories will be summarized for 
each dose level, phase, and overall at each visit. 
Frequency tabulations of qualitative clinical laboratory variables (urinalysis) will be 
presented by dose level, phase, and overall at each visit.  
Laboratory results will also be graded using NCI-CTCAE, where possible. 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.  
Laboratory results will be listed.  


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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 (TBL), Aspartate 
Transaminase (AST) and their combination are defined. The participant’s highest value 
during the investigational period will be used.   
Parameter 
Criteria 
ALT 
> 3xULN 
> 5xULN 
> 10xULN 
> 20xULN 
AST 
> 3xULN 
> 5xULN 
> 10xULN 
> 20xULN 
ALT or AST 
> 3xULN 
> 5xULN 
> 10xULN 
> 20xULN 
TBL 
> 2xULN 
ALP 
> 1.5xULN 
ALT and/or AST AND TBL (*)  
(ALT and/or AST > 3xULN) and 
(TBL > 2xULN) 
ALT and/or AST AND TBL AND ALP (*) 
(ALT and/or AST > 3xULN) and TBL > 
2xULN 
and ALP < 2xULN 
ALT: alanine aminotransferase; ALP: alkaline phosphatase; AST: aspartate aminotransferase; TBL: total 
bilirubin; ULN: upper limit of normal  
(*) Combination of values measured within same sample 
The number and percentage of participants with potentially clinically significant values in 
liver enzymes and total bilirubin during the investigational period will be presented by dose 
level, phase, and overall. 
6.5.5 
Vital Signs 
The baseline value is the last measurement taken prior to the first IP administration.   
Vital signs (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse, body 
temperature and weight) will be summarized using mean, standard deviation, minimum, 
maximum and median by dose level, phase, and overall.  Additionally, a within-participant 
change will be calculated per visit as the post-baseline measurement minus the baseline 
measurement and summarized by visit. 
Tables for potentially clinically significant vital signs will be generated using baseline value 
and highest post-baseline value for each participant. 
The following criteria are defined as clinically significant for each parameter: 


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Vital Sign Variable 
Criteria 
SBP 
≥180 mmHg AND ≥20 mmHg change from baseline 
DBP 
≥105 mmHg AND ≥15 mmHg change from baseline 
Pulse Rate 
≥120 bpm AND ≥15 bpm change from baseline 
Vital signs data will be displayed in listings. 
6.5.6 
Electrocardiograms (ECGs) 
The three values of each ECG parameter within a time point from the central reviewer will be 
averaged to determine time-specific parameter for a participant and used in summaries. 
ECG variables will be summarized using mean, standard deviation, minimum, maximum and 
median for each dose level, phase, and overall at each treatment visit and time point, 
including changes from baseline.  
Number and percentage of participants with normal and abnormal results as assessed by 
central review for the overall interpretation will be tabulated by dose level, phase, and overall 
at each treatment visit and time point. A shift analysis table showing shift in overall ECG 
interpretation from baseline to each time point will be provided. The worst of the three 
overall ECG interpretations will be used as the time-specific overall ECG interpretation for a 
participant. 
The QT interval corrected for heart rate by Fridericia’s formula, QTcF, is defined as: QTc (F) 
= QT/(RR)0.33, where RR interval is inversely proportional to heart rate (approximately RR = 
60/heart rate). 
The QTcF interval will be summarized using frequency tables for each treatment visit and 
time point for values of clinical importance using the range criteria below. 
 
QTc Interval Criteria Value (msec) 
Cumulative Category 
Interval Category 
Normal 
Borderline 
Prolonged 
Clinically significant 
≤ 450 
> 450 
> 480 
> 500 
≤ 450 
> 450 to  ≤ 480 
> 480 to ≤ 500 
> 500 
 
The QTcF interval will also be summarized by the frequencies of participants with a change 
from baseline of clinical importance using the criteria identified below. These summaries will 
be provided for each treatment visit and time point.   
Variable 
Change from Baseline 
Cumulative Category 
Interval Category 
QTc Interval (msec) 
<0  
≥ 0 
> 30 
> 60  
<0  
≥ 0 to ≤ 30 
> 30 to ≤ 60 
> 60  
 


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Number and percent of participants with 12 lead ECG abnormalities as well as number and 
percent of participants whose 12 lead ECG reading changed from normal at baseline to 
abnormal will be tabulated by dose level, phase, and overall at each treatment visit and time 
point.  
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, and overall by visit. 
6.6 
Analysis of Pharmacokinetics 
Cellular DNA load and kinetic parameters of ASP0739 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 plots 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 
ASP0739 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. 
Kinetic parameters will be plotted against dose to make an assessment of their relationship. 
6.7 
Analysis of Pharmacodynamics 
Immune cell phenotyping biomarkers will be summarized by change from baseline at each 
time point by both absolute number and percentage.  
6.8 
Additional Conventions 
6.8.1 
Analysis Windows 
No visit window will be used; nominal visit date will be considered date of visit.   


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6.8.2 
Imputation Rules for Incomplete Dates 
Missing or partial start and stop dates of adverse events, concomitant medications, and new 
anti-cancer therapy will be imputed according to Astellas standards using the following 
algorithm: 
● 
Imputation rules for partial or missing stop dates: 
o 
If the month and year are present, then impute as the last day of that month.  
o 
If only the year is present, impute as December 31 of that year. 
o 
If the stop date is entirely missing, assume the event or medication is ongoing. 
● 
Imputation rules for partial or missing start dates: 
Start Date 
Stop Date 
Complete: 
yyyymmdd 
Partial: yyyymm 
Partial: yyyy 
missing 
< 1st  
dose 
≥ 1st 
dose 
< 1st dose 
yyyymm 
≥ 1st 
dose 
yyyymm 
< 1st 
dose 
yyyy 
≥ 1st 
dose 
yyyy 
Partial: 
yyyymm 
= 1st dose  
yyyymm 
2 
1 
2 
1 
n/a 
1 
1 
≠ 1st dose  
yyyymm 
2 
2 
2 
2 
2 
Partial: 
yyyy 
= 1st dose  
yyyy 
3 
1 
3 
1 
n/a 
1 
1 
≠ 1st dose  
yyyy 
3 
3 
3 
3 
3 
Missing 
4 
1 
4 
1 
4 
1 
1 
1 = Impute as the date of first dose; 2 = Impute as the first of the month; 3 = Impute as January 1 of the year; 
4 = Impute as January 1 of the stop year 
 
For survival and other time-to-event endpoints, missing or incomplete death date will be 
imputed as the earliest feasible date on or after the date last known to be alive as the 
examples shown in the table below. 
Incomplete date of death or 
new anti-cancer therapy 
Date Last Known to be Alive/Not Started 
New Treatment 
Imputed Date 
?? APR 2020 
31 MAR 2020 
01 APR 2020 
14 ??? 2020 
31 MAR 2020 
14 APR 2020 
?? ??? 2020 
31 MAR 2020 
31 MAR 2020 
?? APR ???? 
31 MAR 2020 
01 APR 2020 
14 APR ???? 
31 MAR 2020 
14 APR 2020 
?? ??? ???? 
31 MAR 2020 
31 MAR 2020 
 


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6.8.3 
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 Covid-19, the listing shows if an assessment was not 
performed due to Covid-19, 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 Covid-19 are also included. 
For non-visit-based assessments affected by Covid-19, 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. 
6.8.4 
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 
 
1.1 
15FEB2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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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) 
Liu S and Yuan Y. Bayesian optimal interval designs for phase I clinical trials. J R Stat Soc Ser C 
Appl Stat. 2015;64:507-23. 
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, 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. 
Zhou H, Lee JJ, Yuan Y. BOP2: Bayesian optimal design for phase II clinical trials with simple and 
complex endpoints. Stat Med. 2017;36(21):3302-14. 
 


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9 
APPENDICES 
Appendix 1 Key Contributors 
Primary Author  
 
Phastar, Inc. (Biometrics) 
 
Phastar, Inc. (Biometrics) 
Key Contributors 
The following contributed to or reviewed this Statistical Analysis Plan as relevant to their 
indicated discipline or role. 
 
Data Science 
 
Immuno-Oncology 
Development 
 
Data Science 
 
CPED 
 
CPED 
 
Clinical Science 
 
Data Science 
  
Regulatory Affairs 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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Author and Approver Signatures 
 (E-signatures are attached at end of document)  
 is the study statistician for this study and the primary author of this 
Statistical Analysis Plan. 
 
 
 
/Global Data Science is the global statistical lead 
(GSTATL) for this project and biostatistics peer reviewer of this Statistical Analysis Plan. 
 
 
 
This Statistical Analysis Plan was approved by: 
 
  
Global Data Science 
 
 
 
This Statistical Analysis Plan was approved by: 
 
 
 
 
 
 
PPD
PPD
PPD
PPD

Prot_000.pdf: 
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Version 5.0 Incorporating Substantial Amendment 4  
A Phase 1/2 Open-label Study Investigating the Safety, 
Tolerability and Efficacy of ASP0739 as a Single Agent and in 
Combination with Pembrolizumab in Patients with Advanced 
Solid Tumors known to Express NY-ESO-1 
 
ISN/Protocol 0739-CL-0101 
Version 5.0 
Incorporating Substantial Amendment 4 [See Section 12] 
24 Aug 2022 
 
IND 26983 
IND Grantor: CBER 
 
Sponsor: 
Astellas Pharma Global Development Inc. 
1 Astellas Way 
Northbrook, IL 60062, US 
 
 
 
 
Protocol History: 
Version 1.0 [06 Nov 2020] 
Version 2.0 Incorporating Substantial Amendment 1 [01 Feb 2021] 
Version 3.0 Incorporating Substantial Amendment 2 [01 Jul 2021] 
Version 4.0 Incorporating Substantial Amendment 3 [04 Jan 2022] 
 
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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Version 5.0 Incorporating Substantial Amendment 4  
Table of Contents 
SIGNATURES ································
································
································
 8 
CONTACT DETAILS OF SPONSOR’S KEY PERSONNEL ································
·····  10 
1 
PROTOCOL SUMMARY ································
································
·······  11 
1.1 
Synopsis ································
································
························
 11 
1.2 
Study Schema ································
································
··················
 21 
1.3 
Schedules of Assessments ································
································
····  25 
2 
INTRODUCTION ································
································
·················
 38 
2.1 
Study Rationale ································
································
················
 38 
2.2 
Background ································
································
····················
 38 
2.2.1 
Synovial Sarcoma and Myxoid/Round Cell Liposarcoma ··························
 39 
2.2.2 
Ovarian Cancer ································
································
··········
 39 
2.3 
Risk/Benefit Assessment ································
································
·····  40 
2.3.1 
Risk Assessment ································
································
·········  40 
2.3.1.1 
ASP0739 Risk Assessment ································
·······················
 40 
2.3.1.2 
Pembrolizumab Risk Assessment ································
················
 43 
2.3.2 
Risk Mitigation ································
································
··········
 43 
2.3.3 
Benefit Assessment ································
································
·····  44 
2.3.4 
Overall Risk-Benefit Conclusion ································
······················
 45 
3 
OBJECTIVES AND ENDPOINTS ································
····························
 46 
4 
STUDY DESIGN AND DOSE RATIONALE ································
················
 47 
4.1 
Overall Study Design ································
································
·········  47 
4.2 
Scientific Rationale for Study Design ································
······················
 59 
4.3 
Dose Rationale ································
································
················
 60 
4.3.1 
ASP0739································
································
··················
 60 
4.3.2 
Pembrolizumab ································
································
··········
 61 
4.4 
End of Study Definition ································
································
······  62 
5 
STUDY POPULATION ································
································
··········
 62 
5.1 
Inclusion Criteria ································
································
··············
 62 
5.2 
Exclusion Criteria ································
································
·············
 64 
5.3 
Lifestyle Considerations ································
································
······  66 
5.4 
Screen Failures ································
································
················
 66 


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5.4.1 
Rescreening ································
································
··············
 66 
6 
INVESTIGATIONAL PRODUCT(S) ································
·························
 67 
6.1 
Investigational Product(s) Administered ································
···················
 67 
6.1.1 
Investigational Product Administration ································
···············
 67 
6.2 
Preparation/Handling/Storage/Accountability ································
·············
 67 
6.2.1 
Packaging and Labeling ································
································
 67 
6.2.2 
Handling, Storage and Accountability ································
················
 68 
6.3 
Randomization ································
································
·················
 68 
6.3.1 
Assignment and Allocation································
·····························
 68 
6.4 
Investigational Product Compliance ································
························
 69 
6.5 
Dose Modification ································
································
············
 69 
6.6 
Continued Access to Investigational Product After the End of the Study ··············
 69 
6.7 
Treatment of Overdose ································
································
·······  69 
6.8 
Concomitant Therapy ································
································
·········  70 
7 
STUDY PROCEDURES AND ASSESSMENTS ································
············
 71 
7.1 
Efficacy Assessments ································
································
·········  71 
7.2 
Safety Assessments ································
································
···········
 72 
7.2.1 
Laboratory Assessments ································
································
 72 
7.2.2 
Vital Signs ································
································
················
 72 
7.2.3 
Physical Examination ································
································
···  72 
7.2.4 
Electrocardiogram ································
································
·······  73 
7.2.5 
Imaging ································
································
···················
 73 
7.2.6 
ECOG Performance Status ································
·····························
 73 
7.2.7 
Order of Assessments ································
································
···  74 
7.3 
Adverse Events and Other Safety Aspects ································
·················
 74 
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 ···············
 75 
7.3.3 
Follow-up of Adverse Events and Serious Adverse Events ························
 75 
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 ································
··········
 76 
7.3.6 
Adverse Events of Special Interest ································
····················
 76 
7.3.7 
Special Situations ································
································
········  76 


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7.4 
Pharmacokinetics ································
································
··············
 77 
7.5 
Pharmacodynamics/Biomarker ································
······························
 77 
7.5.1 
Blood Samples ································
································
···········
 77 
7.5.2 
Tumor Tissue Samples ································
································
··  78 
7.5.3 
Buccal Swab Samples ································
································
···  78 
7.6 
Pharmacogenomics ································
································
···········
 78 
7.7 
Other Assessments ································
································
············
 79 
7.7.1 
Replication Competent Lentivirus ································
·····················
 79 
7.8 
Total Amount of Blood ································
································
·······  79 
8 
PARTICIPANT DISCONTINUATION ································
······················
 79 
8.1 
Discontinuation of Individual Participant(s) from Study Treatment ····················
 79 
8.2 
Discontinuation of Individual Participant(s) from Study ································
· 80 
8.3 
Lost to Follow-up ································
································
·············
 80 
9 
STATISTICAL CONSIDERATIONS ································
·························
 80 
9.1 
Statistical Hypotheses ································
································
········  80 
9.2 
Sample Size Determination ································
································
··  81 
9.3 
Populations for Analyses ································
································
·····  82 
9.4 
Statistical Analyses ································
································
···········
 83 
9.4.1 
General Considerations ································
································
· 83 
9.4.2 
Analysis of Efficacy ································
································
·····  83 
9.4.2.1 
Analysis of Primary Endpoint ································
····················
 83 
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································
································
·····  85 
9.4.3.2 
Laboratory Assessments ································
··························
 85 
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 ································
 86 
9.4.4 
Analysis of Pharmacokinetics ································
··························
 86 
9.4.5 
Analysis of Pharmacodynamics ································
·······················
 86 
9.4.5.1 
Analysis of Exploratory Biomarker(s) ································
··········
 87 


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9.5 
Interim Analysis ································
································
···············
 87 
9.6 
Additional Conventions ································
································
······  87 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ································
································
·············
 88 
10.1 
Appendix 1: Ethical, Regulatory and Study Oversight Considerations ·················
 88 
10.1.1 
Regulatory and Ethical Considerations ································
···············
 88 
10.1.2 
Financial Disclosure ································
································
····  88 
10.1.3 
Informed Consent of Participants································
······················
 88 
10.1.3.1 
Informed Consent Process ································
························
 88 
10.1.3.2 
Supply of New and Important Information Influencing the 
Participant’s Consent and Revision of the Written Information ·············
 89 
10.1.4 
Data Protection ································
································
··········
 89 
10.1.5 
Committee(s) Structure ································
································
· 90 
10.1.5.1 
Tolerability Evaluation Meeting ································
·················
 90 
10.1.5.2 
Dose Escalation and Safety Committee ································
·········  90 
10.1.6 
Dissemination of Clinical Study Data································
·················
 90 
10.1.7 
Data Quality Assurance ································
································
· 91 
10.1.8 
Source Documents ································
································
······  91 
10.1.9 
Study and Site Start and Closure ································
······················
 93 
10.1.10 
Arrangement for Use of Information and Publication of the Study ···············
 93 
10.1.11 
Insurance of Participants and Others (UNIQUE to Japan) ·························
 94 
10.1.12 
Quality Assurance ································
································
·······  94 
10.2 
Appendix 2: Contraception Requirements ································
·················
 95 
10.3 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up and Reporting ································
······················
 97 
10.3.1 
Definition of Adverse Events ································
··························
 97 
10.3.1.1 
Abnormal Laboratory Findings ································
··················
 98 
10.3.1.2 
Potential Cases of Drug-induced Liver Injury ································
··  98 
10.3.2 
Definition of Serious Adverse Events································
·················
 98 
10.3.3 
Assessment of Causality ································
································
 99 
10.3.4 
Assessment of Severity ································
·······························
 101 
10.3.5 
Recording and Follow-Up of AEs and/or SAEs ································
···  101 
10.3.6 
Reporting Procedures for Serious Adverse Events ································
 102 
10.3.7 
Reporting Procedures for Special Situations ································
·······  104 
10.3.7.1 
Contraceptive Guidance and Collection of Pregnancy Information ·······  104 


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10.3.7.2 
Medication Error, Overdose and “Off-label Use” ···························
 104 
10.3.7.3 
Misuse/Abuse ································
································
····  105 
10.3.7.4 
Occupational Exposure ································
·························
 105 
10.3.7.5 
(Suspicion of) Transmission of Infectious Agent ····························
 105 
10.3.7.6 
Suspected Drug-drug Interaction ································
··············
 105 
10.3.7.7 
Reporting Procedures for Product Defect ································
·····  105 
10.3.8 
Supply of New Information Affecting the Conduct of the Study ················
 106 
10.3.8.1 
Collection of Defect Information in Stage of Manufacture, Delivery 
and Storage ································
································
·······  106 
10.3.9 
Urgent Safety Measures ································
······························
 107 
10.3.10 
Reporting Urgent Safety Measures ································
··················
 107 
10.4 
Appendix 4: Liver Safety Monitoring and Assessment ································
· 108 
10.5 
Appendix 5: List of Excluded Concomitant Medications ······························
 111 
10.5.1 
Concomitant Medications ································
····························
 111 
10.5.2 
Other Investigational Agents ································
·························
 111 
10.6 
Appendix 6: Clinical Laboratory Assessments ································
··········
 112 
10.7 
Appendix 7: Pharmacogenomic Analysis with Banked Sample ·······················
 114 
10.8 
Appendix 8: Infusion Reaction Dose Modification and Treatment (Guidelines 
for ASP0739 and Pembrolizumab) ································
························
 116 
10.9 
Appendix 9: Monitoring of Pembrolizumab Potential Immune-related Adverse 
Events································
································
·························
 118 
10.10 
Appendix 10: Dose Modification and Toxicity Management for Immune-related 
Adverse Events ································
································
··············
 119 
10.11 
Appendix 11: Dose Modification and Toxicity Management of Infusion 
Reactions Related to Pembrolizumab ································
·····················
 123 
10.12 
Appendix 12: Clinical Study Continuity ································
·················
 125 
10.13 
List of Abbreviations and Definition of Key Study Terms ·····························
 145 
11 
REFERENCES ································
································
··················
 149 
12 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ····························
 153 
13 
SPONSOR SIGNATURE ································
································
······  156 
 


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List of In-text Tables  
Table 1 
Schedule of Assessments – Dose Escalation Cohort and Safety Lead-in 
Combination Cohort ································
································
··········
 25 
Table 2 
Schedule of Assessments for Dose Expansion Monotherapy and Combination 
Therapy Cohort ································
································
················
 29 
Table 3 
Schedule of Assessments for Follow-up Periods ································
··········
 33 
Table 4 
Schedule of Replication Competent Lentivirus for Dose Escalation Cohort, 
Dose Expansion Cohort and Safety Lead-in Cohort ································
······  35 
Table 5 
Sample Collection Schedule- Dose Escalation Cohort, Dose Expansion Cohort 
and Safety Lead-in Cohort ································
································
···  36 
Table 6 
Summary of Potential Safety Concerns for ASP0739 ································
····  40 
Table 7 
Study Objectives and Endpoints ································
·····························
 46 
Table 8 
Dose Levels (Phase 1 Dose Escalation) ································
····················
 49 
Table 9 
Investigational Product(s) ································
································
····  67 
Table 10 
ECOG Performance Status ································
································
···  73 
Table 11 
Grading Scale Defining the Severity of an Adverse Event ·····························
 101 
Table 12 
Moderate and Severe Liver Abnormalities ································
···············
 108 
Table 13 
Clinical Laboratory Tests ································
································
··  112 
Table 14 
Infusion Reaction Dose Modification and Treatment (Guidelines for ASP0739 
and Pembrolizumab) ································
································
········  116 
Table 15 
Monitoring of Pembrolizumab Potential Immune-related Adverse Events ··········
 118 
Table 16 
Dose Modification and Toxicity Management Guidelines for Immune-related 
Adverse Events Associated with Pembrolizumab ································
·······  119 
Table 17 
Pembrolizumab Infusion Reaction Dose Modification and Treatment Guidelines ··  123 
Table 18 
Study Interruption: Schedule of Assessments – Dose Escalation Cohort and 
Safety Lead-in Combination Cohort ································
······················
 127 
Table 19 
Study Interruption: Schedule of Assessments – Dose Expansion Monotherapy 
and Combination Therapy Cohort ································
·························
 134 
Table 20 
Study Interruption: Schedule of Assessments – Schedule of Assessments for 
Follow-up Periods ································
································
···········
 141 
Table 21 
Study Interruption: Schedule of Assessments – Schedule of Replication 
Competent Lentivirus for Dose Escalation Cohort, Dose Expansion Cohort and 
Safety Lead-in Cohort ································
································
······  143 
 
List of In-text Figures 
Figure 1 
Study Schema ································
································
··················
 21 
Figure 2 
Study Design Schema ································
································
········  23 
 


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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 
ASP0739 as a Single Agent and in Combination with Pembrolizumab in Patients with 
Advanced Solid Tumors known to Express NY-ESO-1 
ISN/Protocol 0739-CL-0101 
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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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CONTACT DETAILS OF SPONSOR’S KEY PERSONNEL 
24-hour Contact for 
Serious Adverse Events 
 
See [Section 10.3.6 
Reporting Procedures for 
Serious Adverse Events] 
Please fax or email the serious adverse events/special 
situations worksheet to: 
Astellas Pharma Global Development Inc.  
Global/US Pharmacovigilance 
North America fax number: +1-888-396-3750 
North America alternate fax number: +1-847-317-1241 
International fax number: +44-800-471-5263 
Email: safety-us@astellas.com 
Specific to Japan: 
JUTOKUNA YUUGAIJISHOU OYOBIFUGUAI 
HOUKOKUSHO or JUTOKUNA YUUGAIJISHOU 
HOUKOKUSHO and the special situations worksheet to: 
Astellas Pharma Inc. - Japan 
Pharmacovigilance 
Fax number: 03-3243-5747 
Email: rk-safety-jp@jp.astellas.com  
Medical Monitor/Study 
Physician 
 
 
Astellas Pharma Global Development, Inc. (APGD) 
1 Astellas Way, Northbrook, Illinois 60062 USA 
 
 
 
PPD
PPD


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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 ASP0739 as a 
Single Agent and in Combination with Pembrolizumab in Patients with Advanced Solid Tumors 
known to Express NY-ESO-1 
Planned Study Period/Duration:  
From approximately 2Q2021 to 2Q2025 
Planned Total Number of Study Sites and Location(s):   
Approximately 30 study sites 
North America and Japan 
Study Objectives and Endpoints:  
Objective(s) 
Endpoint(s) 
Primary 
● 
To evaluate the safety and tolerability of 
ASP0739 in participants with R/R solid tumors 
known to express NY-ESO-1 when administered 
as a single agent (phase 1 dose escalation), and 
in combination with pembrolizumab in 
participants with R/R SS, MRCL and ovarian 
cancer (safety lead-in) 
● 
Safety and tolerability as noted by: DLTs, 
AEs, SAEs, laboratory test results (serum 
chemistry, hematology, coagulation, 
urinalysis, and pregnancy test), ECGs, vital 
signs, physical exams and ECOG 
performance status scores 
● 
To determine RP2D of ASP0739 when 
administered as a single agent 
● 
RP2D based on above 
● 
To evaluate the clinical response of ASP0739 
when administered as a single agent and in 
combination with pembrolizumab in participants 
with R/R SS, MRCL and ovarian cancer 
(phase 2) 
● 
Objective response rate per iRECIST (iORR) 
by Independent Central Review 
Secondary 
 
● 
To evaluate other measures of anticancer 
activity of ASP0739 when administered as a 
single agent and in combination with 
pembrolizumab based on central and local 
assessment in participants with R/R SS, MRCL 
or ovarian cancer (phase 2) 
● 
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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Objective(s) 
Endpoint(s) 
Secondary (continued) 
• 
To obtain preliminary efficacy based on central 
and local assessment in participants with R/R 
solid tumors known to express NY-ESO-1 
(melanoma, NSCLC-adenocarcinoma and 
squamous cell and ESCC) (phase 2) 
● 
Objective response rate per iRECIST 
(iORR) 
Exploratory 
• 
To evaluate potential genomic, proteomic and/or 
other biomarkers that may correlate with 
treatment outcome when ASP0739 is 
administered as a single agent and in combination 
with pembrolizumab 
• 
Exploratory biomarkers that may correlate 
with treatment outcome of ASP0739 as a 
single agent or in combination with 
pembrolizumab, including NY-ESO-1 
expression 
• 
To evaluate pharmacodynamic activities of 
ASP0739 as a single agent and in combination 
with pembrolizumab 
• 
Pharmacodynamic effects of ASP0739, such 
as changes in: 
o 
Cytokine expression and secretion 
(e.g., IFNg) 
o 
NY-ESO-1-specific T lymphocytes 
(e.g., cytotoxic T lymphocytes) 
o 
Immune cell populations (NKT 
cells, Treg cells, etc.) 
o 
Anti-NY-ESO-1 antibodies 
o 
Tumor microenvironment (CD8, 
PD-L1, etc.) 
• 
To evaluate pharmacokinetics of ASP0739 when 
administered as a single agent and in combination 
with pembrolizumab 
• 
Cellular DNA load and kinetic parameter 
estimates (including AUC, Cmax, Ctrough and 
tmax) for ASP0739 as a single agent or in 
combination with pembrolizumab 
AE: adverse event; CD8: cluster of differentiation 8; DCR: disease control per RECIST v1.1; DLT: dose 
limiting toxicity; DOR: duration of response per RECIST v1.1; ECG: electrocardiogram; ECOG: Eastern 
Cooperative Oncology Group; ESCC: esophageal squamous cell carcinoma; iDCR: disease control per 
iRECIST; iDOR: duration of response per iRECIST; IFNg; interferon gamma; iORR: objective response rate 
per iRECIST; iPFS: progression-free survival per iRECIST; iRECIST: immune response evaluation criteria 
in solid tumors; MRCL: myxoid/round cell liposarcoma; NKT: natural killer T; NSCLC: non-small cell lung 
cancer; NY-ESO-1: New York esophageal squamous cell carcinoma 1; ORR: objective response rate per 
RECIST v1.1; OS: overall survival; PD-L1: programmed death-ligand 1; PFS: progression-free survival per 
RECIST v1.1; R/R: relapsed/refractory; RECIST: response evaluation criteria in solid tumors; RP2D: 
recommended phase 2 dose; SAE: serious adverse event; SS: synovial sarcoma 


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Study Population:   
Phase 1 (Dose Escalation) 
Adult participants with solid tumors relapsed/refractory (R/R) to standard of care (SOC) and 
known to express New York esophageal squamous cell carcinoma 1 (NY-ESO-1). 
Phase 2  
Adult participants with synovial sarcoma (SS), myxoid/round cell liposarcoma (MRCL) or ovarian 
cancer R/R to SOC who have not received prior checkpoint inhibitor therapy will receive ASP0739 
as single agent and in combination with pembrolizumab (after a lead-in safety evaluation). 
Adult participants with R/R solid tumors known to express NY-ESO-1 (melanoma, non-small cell 
lung cancer [NSCLC]-adenocarcinoma and squamous cell, and esophageal squamous cell 
carcinoma [ESCC]) will receive ASP0739 as single agent.  
Number of Participants:  
A total of approximately 339 participants may be enrolled in the study. 
ASP0739 Single Agent 
A total of approximately 181 participants may be enrolled in single agent treatment. 
Phase 1 (Dose Escalation) 
Approximately 12 participants with R/R solid tumors known to express NY-ESO-1. 
Phase 2 
Approximately 43 participants with R/R SS, 43 participants with R/R MRCL and 43 participants 
with R/R ovarian cancer will be enrolled once phase 1 single agent dose escalation is completed 
and the recommended phase 2 dose (RP2D) is defined. 
In a separate cohort, approximately 40 participants with R/R solid tumors known to express 
NY-ESO-1 (melanoma, NSCLC-adenocarcinoma and squamous cell and ESCC) will be enrolled 
for preliminary efficacy assessment.  
ASP0739 Combination with Pembrolizumab 
A total of approximately 158 participants may be enrolled in combination therapy.  
Safety Lead-in: Enrollment will start upon completion of phase 1 single agent dose escalation and 
confirmation of RP2D. Approximately 6 to 9 participants with R/R SS, MRCL or ovarian cancer 
may be enrolled to assess the safety of combination therapy prior to enrolling the specified number 
of participants for efficacy evaluation in each tumor type that is opened. 
Phase 2: Approximately 60 participants with R/R SS, 60 participants with R/R MRCL and 
29 participants with R/R ovarian cancer may be enrolled in a same cancer type cohort where 2 local 
or central radiographic responses (complete response per iRECIST [iCR] or partial response per 
iRECIST [iPR]) were observed with single agent and the safety lead-in is completed. Groups of 
participants will enroll in parallel and independently in each cohort. 
Study Design Overview:   
This is a phase 1, open-label study of ASP0739 in participants with R/R solid tumors known to 
express NY-ESO-1 and a phase 2 study of single agent and combination therapy with 
pembrolizumab in participants with R/R SS, MRCL or ovarian cancer. 
Phase 1 (dose escalation) in participants with solid tumors known to express NY-ESO-1 and phase 
2 of ASP0739 single agent and combination therapy with pembrolizumab in R/R SS, MRCL and 
ovarian cancer who have not responded to SOC or are ineligible for standard therapy.  


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Phase 2 single agent will also include a cohort of participants with select solid tumors known to 
express NY-ESO-1 (melanoma, NSCLC-adenocarcinoma and squamous cell and ESCC). 
Both study phases consist of the following periods:   
● 
Screening (up to 28 days) 
● 
Treatment with ASP0739 (up to 6 doses every 28-days) and for participants in combination 
cohorts with pembrolizumab on cycle 1 day 1 (C1D1), and then every 6 weeks, until disease 
progression, unacceptable toxicity or up to 17 doses  
● 
EOT visit after completion of investigational product (IP): Within 7 days of EOT 
determination or prior to the initiation of new anticancer therapy, whichever occurs first 
● 
Safety follow-up visits at 30, 60 and 90 days from the last dose of treatment or prior to the 
initiation of new anticancer therapy 
● 
Follow-up visits every 2 months for up to 1 year or until progression or start of a new 
anticancer therapy or death (whichever occurs first) 
● 
Survival follow-up for up to 1 year by telephone calls every 3 months after the start of a new 
anticancer treatment or progression after ASP0739 and/or pembrolizumab treatment 
ASP0739 Single Agent 
Participants will receive an intravenous infusion of ASP0739 (human embryonic kidney cells 
[HEK293] transfected with a lentiviral vector that is encoding the target antigen NY-ESO-1). 
Participants will receive 1 dose every 28-day cycle for up to 4 doses; an additional 2 doses may be 
administered in participants with PR or stable disease (SD). Following the first 2 cycles, 
participants who have not met any individual treatment discontinuation criteria and are receiving 
clinical benefit may continue further treatment with ASP0739, as decided by the investigator. 
The starting dose is 1 × 107 cells/dose and the decision to dose escalate to the next dose level  
(1 × 108 cells/dose) or to dose reduce (1 × 106 cells/dose) to a lower dose level will be made based 
on the assessment of safety variables, including the occurrence of dose-limiting toxicities (DLTs).  
Dose Levels (Phase 1 dose escalation)  
Dose Level 
Dose 
0 
1 × 107 cells/dose 
+1 
1 × 108 cells/dose 
ASP0739 Combination with Pembrolizumab 
The RP2D of ASP0739 determined from the phase 1 dose escalation phase will be combined with 
pembrolizumab 400 mg for the safety lead-in with approximately 6 to 9 participants. If the RP2D is 
selected at the same dose level as the maximum tolerated dose (MTD) based on the phase 1 dose 
escalation portion, the combination safety lead-in will start at one dose level lower than the MTD. 
Participants will receive 1 dose of ASP0739 every 28-day cycle for a total of 4 doses; an additional 
2 doses may be administered for participants with PR or SD. Following the first 2 cycles, 
participants who have not met any individual treatment discontinuation criteria and are receiving 
clinical benefit may continue further treatment with ASP0739 and pembrolizumab, as decided by 
the investigator. Participants will also receive pembrolizumab 400 mg on C1D1, then every 6 
weeks, until disease progression, unacceptable toxicity or for up to a total of 17 doses or until one 
of the discontinuation criteria is met. For combination treatment, a 400 mg pembrolizumab infusion 
will be administered first, followed by an ASP0739 infusion at least 1 hour after the completion of 
the pembrolizumab infusion. 


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Phase 1 Single Agent Dose Escalation: 
The single agent dose escalation phase will evaluate escalating dose levels of ASP0739 in 
approximately 3 to 12 DLT-evaluable participants.  
The dose escalation phase will assess safety and tolerability of ASP0739 during cycle 1. 
Participants will receive up to 6 doses of ASP0739 via intravenous infusion separated by 28 days. 
Dosing will occur on day 1 of each cycle. After the first dose of ASP0739, participants must be 
observed for safety for a minimum of 4 hours. If new adverse events (AEs) are observed that are 
greater than grade 3 during this time, participants should continue to be observed until the AEs are 
less than grade 3.  
Dose escalation will be guided according to the Bayesian Optimal Interval (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 phase will enroll 3 to 
4 evaluable participants for the initial assessment of each dose level. 
Enrollment in the single agent dose escalation cohorts will be staggered such that there will be a 
minimum of 28 calendar days between the treatment initiation of the first and second participants 
and 14 calendar days between the second and the third participant at the same dose level for all 
escalation cohorts. In the absence of toxicity, additional participants may be treated at a dose level 
without any formal stagger. An interval of 28 calendar days will separate study treatment initiation 
of the last patient in a dose cohort from the first participant treatment in sequential dose cohort. 
ASP0739 in Combination with Pembrolizumab Safety Lead-in 
Enrollment in the combination therapy safety lead-in will start once phase 1 single agent dose 
escalation is completed and the RP2D is defined. 
The combination therapy safety lead-in portion will evaluate the RP2D of ASP0739 with a fixed 
dose of 400 mg pembrolizumab in 6 to 9 participants with at least 6 DLT-evaluable participants. If 
the RP2D is selected at the same dose level as the MTD based on the phase 1 dose escalation 
portion, the combination safety lead-in will start at one dose level lower than the MTD.  
Safety lead-in will be guided according to the BOIN design [Liu & Yuan, 2015] to determine if the 
RP2D of ASP0739 with a fixed dose of 400 mg pembrolizumab is tolerable and based on DLT 
occurrence after 28 days. After the planned number of evaluable participants has completed the 
DLT observation period of 28 days for a given dose level, safety for that dose level will be 
assessed. Safety lead-in will enroll 3 to 4 evaluable participants for the initial assessment of RP2D. 
A minimum of 6 participants must be enrolled at the dose level used to determine the RP2D.  
Enrollment in the safety lead-in cohort will be staggered such that there will be a minimum of 
28 calendar days between the treatment initiation of the first and second participants and 
14 calendar days between the second and the third participants at the same dose level for the safety 
lead-in cohort. In the absence of toxicity, additional participants may be treated at a dose level 
without any formal stagger. An interval of 28 calendar days will separate study treatment initiation 
of the last patient in a dose cohort from the first participant treatment in sequential dose cohort.  
Study Enrollment Interruption:  
Study enrollment will be temporarily interrupted 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 


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Participant Replacement during Dose Escalation/Safety Lead-in:  
Participants may be replaced in the safety lead-in or dose escalation cohort if: 
● 
Participant is discovered to have enrolled without fully satisfying eligibility criteria 
● 
Participant did not receive 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 
Recommended Phase 2 Dose 
The sponsor, in conjunction with the DESC, will determine the RP2D of ASP0739 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 
ASP0739.  
The dose level determined to be the RP2D must have data from at least 6 participants. 
Dose Escalation 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 for the phase 1 dose 
escalation and phase 2 safety lead-in. 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 expansion and phase 2 expansion 
cohorts for single agent and combination therapy with pembrolizumab. 
While safety data from the DLT observation period in the escalation cohorts are the minimum 
safety data needed for the DESC meeting, all available safety findings will be considered by the 
DESC. The DESC will assess whether a longer DLT observation period is warranted based on 
emerging data. Additionally, only when determining the RP2D, the DESC may choose a more 
conservative dosing decision than the MTD selected by BOIN design, based on evaluation of the 
safety data and other available data. 
The decision on the dose level for the next cohort will be based on the BOIN design. In addition, 
MTD will be determined by BOIN from at least 6 participants. The RP2D dose for expansion will 
not be higher than the MTD. If the RP2D is selected at the same dose level as the MTD based on 
the phase 1 dose escalation portion, the combination safety lead-in will start at one dose level lower 
than the MTD. 
Phase 2 Single Agent 
Once RP2D is determined, the phase 2 single agent cohorts may be opened in R/R SS, MRCL, 
ovarian cancer and other solid tumors known to express NY-ESO-1 (melanoma, NSCLC-
adenocarcinoma and squamous cell and ESCC). If a confirmed response (iPR or iCR, per 
independent central review or local assessment) occurs in other solid tumors known to express NY-
ESO-1, a tumor-specific dose expansion cohort may be opened in that tumor type.  
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]. For R/R SS, 
MRCL and ovarian cancer, initially 18 participants will be enrolled in each tumor-specific 
expansion cohort (stage 1). If the iORR does not meet the optimal stopping boundaries (see table 
below), then an additional 25 participants (stage 2) may be enrolled for a total maximum sample 


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size of 43. When the total number of participants reaches the maximum sample size of 43, it may 
be predicted that ASP0739 is effective if the number of responses is greater than or equal to 8.  
Optimized Stopping Boundaries for SS, MRCL and Ovarian Cancer 
Number of participants treated 
Stop if number of responses ≤  
18 
2 
MRCL: myxoid/round cell liposarcoma; SS: synovial sarcoma 
For the melanoma/NSCLC/ESCC cohort, after a minimum of 10 participants per tumor type are 
enrolled, if less than approximately 6 participants for each tumor type of melanoma, 
NSCLC-adenocarcinoma or squamous cell carcinoma or ESCC are NY-ESO-1 positive upon 
analysis of the most recent tissue sample, then additional participants may be enrolled into the 
tumor type with less than approximately 6 NY-ESO-1 positive participants. 
UNIQUE to Japan Sites: 
Japanese participants will only be enrolled into the monotherapy arm of the dose expansion cohort. 
Phase 2 Single Agent Dose Expansion Cohort with Japanese Safety Lead-in 
After the phase 1 dose escalation cohort has been completed, the phase 2 single agent dose 
expansion cohort with Japanese safety lead-in may be opened. The Japanese safety lead-in will 
enroll 3 to 8 safety evaluable participants to confirm Japanese tolerability of the RP2D of 
ASP0739. Japanese participants must be managed under hospitalization for 7 days from C1D1 
through C1D8 during the Japanese safety lead-in. Prior to hospital discharge, the investigator must 
ensure participant safety by performing medical tests and procedures listed on Day 8 of Cycle 1. 
During the Japanese safety lead-in, an interval of 7 days will separate study treatment initiation for 
the second participant from the first participant. In the absence of toxicity, additional participants 
may be treated without any formal stagger. 
The tolerability of ASP0739 single agent therapy RP2D will be assessed during the DLT 
observation period, which is from C1D1 to C1D28. Quantitative assessment of DLTs will be 
performed referring to the concept of a BOIN design with the target DLT rate of 30% and optimal 
interval of (0.236, 0.359) to determine if the ASP0739 single agent therapy RP2D is tolerable and 
is based on a DLT occurrence after 28 days. The tolerability evaluation rule is as follows:  
 
Number of Participants evaluable for DLT Assessment 
3 
4 
5 
6 
7 
8 
[Tolerable] 
If the number of participants with DLTs is equal or 
less than the number given in the corresponding cell, 
the ASP0739 single agent therapy RP2D can be 
determined to be tolerable. 
0 
0 
1 
1 
1 
1 
[Stay] 
If the number of participants with DLTs is equal to the 
number given in the corresponding cell, enrollment is 
continued until the maximum number of participants is 
reached. 
1 
1 
NA 
2* 
2* 
2* 
[Not tolerable] 
If the number of participants with DLTs is equal or 
greater than the number given in the corresponding 
cell, the ASP0739 single agent therapy RP2D is 
determined to be intolerable. 
2 
2 
2 
3 
3 
3 
DLT: dose limiting toxicity; NA: not applicable; RP2D: recommended phase 2 dose; TEM: tolerability 
evaluation meeting  
*When the number of participants for DLT assessment reaches the maximum number of participants and the 
recommended action is Stay, the tolerability of the dose will be assessed comprehensively at the TEM. 


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A minimum of 3 evaluable participants must be enrolled at the dose level used to determine the 
tolerability of RP2D in Japanese participants. Three to four safety evaluable participants are 
enrolled as initial assessment. If the evaluation is to be continued based on DLT occurrence, 
additional 3 to 4 safety evaluable participants are enrolled. After the tolerability of RP2D is 
confirmed in Japanese participants, additional Japanese participants may be enrolled into dose 
expansion part continuously. 
 
Tolerability Evaluation Meeting 
A Tolerability Evaluation Meeting (TEM) consisting of sponsor representatives and investigators 
will convene once the number of Japanese participants (defined in the protocol) completes the DLT 
observation period and data are available for review. TEM members should consider all available 
safety findings when making their evaluations and decisions. Additional details regarding 
responsibilities, membership requirements and safety review time points are included in the TEM 
Charter. 
Replacement of Participants in Japanese Safety Lead-in 
Participants may be replaced in the safety lead-in if: 
● 
The participant is discovered to have enrolled without fully satisfying the eligibility criteria. 
● 
The participant received less than the planned dose in C1 for reasons other than a DLT. 
● 
The participant has experienced 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 safety lead-in 
will not be replaced. 
The 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 
ASP0739 upon resolution of the DLT event to ≤ grade 1 or baseline. 
A participant who meets the stopping criteria will not receive study drug at C2. Additionally, at the 
TEM, the aggregate safety data are reviewed if any study stopping rules below have been met: 
● 
If a study participant develops a grade 4 DLT after receiving C1 
● 
If a study participant develops a grade ≥ 3 non-hematological AE that does not resolve to 
≤ grade 2 within 72 hours of onset 
Note: This event should be considered a DLT. 
● 
If there is a delay in administration of C2 by > 4 weeks, it may result in discontinuation of 
treatment after discussion with the sponsor. 
Study enrollment and study treatment of the Japanese safety lead-in will be temporarily interrupted 
if any of the following events occur in a participant: 
● 
Any death that is not related to disease progression occurring within 30 days of receiving 
ASP0739 
● 
Occurrence of 2 grade ≥ 4 DLTs in 2 participants 
● 
Any grade 4 hypersensitivity reaction/anaphylaxis 
Phase 2 Combination of ASP0739 + Pembrolizumab  
Once safety lead-in is completed and 2 radiographic responses (iCR or iPR) are observed in the 
phase 2 dose expansion monotherapy cohort by local or central review, the phase 2 combination 
cohorts may be opened in the respective tumor type where the responses were observed. 


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For R/R SS, initially 22 participants will be enrolled in an expansion cohort (stage 1). If the iORR 
does not meet the optimal stopping boundaries (see table below) for R/R SS, then an additional 
38 participants (stage 2) may be enrolled for a total maximum sample size of 60. When the total 
number of participants reaches the maximum sample size of 60, it may be predicted that ASP0739 
in combination with pembrolizumab is effective if the number of responses is greater than or equal 
to 18.  
Optimized Stopping Boundaries for SS 
Number of participants treated 
Stop if number of responses ≤  
22 
3 
SS: synovial sarcoma 
For R/R MRCL, initially, 22 participants will be enrolled in an expansion cohort (stage 1). If the 
iORR does not meet the optimal stopping boundaries (see table below) for R/R MRCL, then an 
additional 38 participants (stage 2) may be enrolled for a total maximum sample size of 60. When 
the total number of participants reaches the maximum sample size of 60, it may be predicted that 
ASP0739 in combination with pembrolizumab is effective if the number of responses is greater 
than or equal to 18.  
Optimized Stopping Boundaries for MRCL 
Number of participants treated 
Stop if number of responses ≤  
22 
3 
MRCL: myxoid/round cell liposarcoma 
For R/R ovarian cancer, initially, 10 participants will be enrolled in an expansion cohort (stage 1). 
If the iORR does not meet the optimal stopping boundaries (see table below) for R/R ovarian 
cancer, then an additional 19 participants (stage 2) may be enrolled for a total maximum sample 
size of 29. When the total number of participants reaches the maximum sample size of 29, it may 
be predicted that ASP0739 in combination with pembrolizumab is effective if the number of 
responses is greater than or equal to 4.  
Optimized Stopping Boundaries for Ovarian Cancer 
Number of participants treated 
Stop if number of responses ≤  
10 
0 


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If both single agent and combination therapy expansion cohorts are open for the same tumor type, 
participants will be randomized to either single agent or combination therapy cohorts and the 
randomization ratio will be based on the number of open slots still available at each cohort.  
Replacement of Participants in Phase 2 Dose Expansion  
If a participant in phase 2 is not response evaluable (defined as the response analysis set [RAS]), 
then an additional participant may be enrolled in that cohort based on sponsor discretion. 
Treatment Groups and Duration: 
Monotherapy 
Arm/IP Name 
ASP0739 
Use 
Test product 
Dose 
1 × 107 cells/dose, 1 × 108 cells/dose 
Frequency 
Single dose on day 1 every 4 weeks  
Route 
Intravenous 
Duration 
Up to 6 doses  
Combination Therapy: 
Arm/IP Name 
ASP0739 and pembrolizumab 
Use 
Test product 
Dose 
1 × 107 cells/dose, 1 × 108 cells/dose (ASP0739); 400 mg 
(pembrolizumab) 
Frequency 
ASP0739, single dose on day 1, and then every 4 weeks  
Pembrolizumab, single dose on day 1, and then every 6 weeks 
Route 
Intravenous 
Duration 
Up to 6 doses of ASP0739 in combination with pembrolizumab; 
with up to 4 doses (pembrolizumab) during the treatment period; a 
total of 17 doses of pembrolizumab for qualifying participants 
 






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Figure 2 
Study Design Schema 
 
Footnotes appear on next page 


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CR: complete response per iRECIST; DLT: dose limiting toxicity; ESCC: esophageal squamous cell carcinoma; iRECIST: immune response evaluation criteria in solid tumors; 
MRCL: myxoid/round cell liposarcoma; MTD: maximum tolerated dose; NSCLC: non-small cell lung cancer; NY-ESO-1: New York esophageal squamous cell carcinoma 1; PR: 
partial response per iRECIST; RP2D: recommended phase 2 dose; R/R: relapsed/refactory; SS: synovial sarcoma  
*Melanoma, NSCLC-adenocarcinoma and squamous cell lung and ESCC. 


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1.3 
Schedules of Assessments 
Table 1 
Schedule of Assessments – Dose Escalation Cohort and Safety Lead-in Combination Cohort 
 
Scr 
Treatmenta 
Pembro 
Mono 
EOTe,y 
Cycle 1 
Cycle 2 
Cycles 3–4b 
Cycles 5–6c 
Doses  
5-17d 
Visit Days 
-28 to  
-1 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
8 
15 
22 
1 
8 
15 
22y 
Every 6 
weeks 
 
Window (days) 
 
 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
+ 7 
Signed ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and Disease 
History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examinationf 
Xf 
Xf 
X 
 
X 
X 
X 
Xf 
X 
 
X 
X 
X 
Xf 
X 
X 
X 
Xf 
X 
X 
X 
Xf 
Xf 
Vital Signsg 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG Performance 
X 
Xh 
X 
 
X 
X 
X 
Xh 
X 
 
X 
Xh 
X 
Xh 
X 
X 
X 
Xh 
X 
X 
X 
Xh 
X 
MUGA or ECHO 
Xi 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-Lead ECGj 
X 
Xj 
 
 
X 
X 
 
Xj 
 
 
X 
Xj 
 
Xj 
 
 
 
Xj 
 
 
 
 
X 
Prior and Concomitant 
Medications 
Xk 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy Test for 
WOCBP 
X 
Xl 
 
 
 
 
 
Xl 
 
 
 
 
 
Xl 
 
 
 
Xl 
 
 
 
Xl 
Xj 
Clinical Laboratory 
Tests (chemistry, 
hematology, urinalysis)m 
X 
Xh 
X 
 
X 
X 
X 
Xh 
X 
 
X 
X 
X 
Xh 
X 
X 
X 
Xh 
X 
X 
X 
Xh 
X 
Coagulation Profile 
(PT/INR, fibrinogen)m 
X 
Xh 
X 
 
X 
X 
X 
Xh 
X 
 
X 
X 
X 
Xh 
 
 
 
Xh 
 
 
 
Xh 
X 
Thyroid Profile Panelm,n 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
Every 6 weeks after C2D15 dose 
 
PGxo 
 
Xo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Buccal Swab for HLA 
Typing 
 
Xh 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE/SAE Assessment 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Table continued on next page 


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Scr 
Treatmenta 
Pembro 
Mono 
EOTe,y 
Cycle 1 
Cycle 2 
Cycles 3–4b 
Cycles 5–6c 
Doses  
5-17d 
Visit Days 
-28 to  
-1 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
8 
15 
22 
1 
8 
15 
22y 
Every 6 
weeks 
 
Window (days) 
 
 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
+ 7 
Pharmacokinetic: 
ASP0739p 
See Table 5 for detailed sample time points 
Pharmacokinetic: 
Pembrolizumabp 
See Table 5 for detailed sample time points 
Anti-NY-ESO-1 
antibody 
 
Xh 
 
 
 
 
 
Xh 
 
 
 
 
 
Xh 
 
 
 
Xh 
 
 
 
Xv 
X 
Immune Response 
Biomarker (ELISpot) 
 
Xh 
 
 
X 
X 
 
Xh 
 
 
X 
X 
 
Xh 
X 
X 
 
Xh 
X 
X 
 
Xv 
X 
Immune Response 
Biomarker (Tetramer)  
 
Xh 
 
 
 
X 
 
Xh 
 
 
 
X 
 
Xh 
 
X 
 
Xh 
 
X 
 
Xv 
X 
Immune Cell 
Phenotyping 
 
Xh 
 
 
X 
X 
 
Xh 
 
 
X 
X 
 
Xh 
X 
X 
 
Xh 
X 
X 
 
Xw 
X 
Cytokines 
 
Xh 
X 
X 
X 
X 
 
Xh 
X 
X 
X 
X 
 
Xh 
X 
X 
 
Xh 
X 
X 
 
Xw 
X 
Circulating Tumor DNA 
 
Xh 
 
 
 
 
 
Xh 
 
 
 
 
 
Xh 
 
 
 
Xh 
 
 
 
X 
Xx 
Archival Tumor Tissueq 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pulmonary function testz 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
Radiographic Disease 
Assessmentr 
X 
Every 56 ± 7 days 
 
IRT Transaction  
X 
Xs 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
ASP0739 Dosingt 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
Pembrolizumab Dosingu 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
Every 6 weeksu 
X 
 
Footnotes appear on next page 
 


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AE: adverse event; C: cycle; CR: complete response; CT: computed tomography; D: day; ECG: electrocardiogram; ECHO: echocardiogram; 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; MUGA: multiple gated acquisition scan; NY-ESO-1: New York esophageal 
squamous cell carcinoma 1; Pembro: pembrolizumab; 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 
a. 
Cycles 1 through 6 represent ASP0739 single agent or combination of ASP0739 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 ASP0739 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 ASP0739 in cycles 5 and 6. Participants who reach CR will not receive additional doses of 
ASP0739. 
d. Participants in combination therapy only will continue to receive pembrolizumab as monotherapy for doses 5 up to 17. If participant receives at least 1 dose of ASP0739 but 
discontinues combination treatment of ASP0739 at any time prior to C5D15, then the participant may continue pembrolizumab as monotherapy for up to 96 weeks for a total of 
17 doses of pembrolizumab total for the study. 
e. 
The EOT visit will occur within 7 days of the principal investigator decision to discontinue the participant for treatment or prior to the start of new anticancer treatment, whichever 
occurs first. If a participant is completing all visits in the last treatment cycle, the EOT visit will be within 7 days from the last planned visit. 
f. 
Height measurement performed at screening only. If height cannot be measured at the screening visit, it can be collected at any time during the course of the study, but should be 
recorded for the screening visit. Weight measurement performed at screening and day 1 of each cycle.  
g. The following vital sign assessments schedules apply: 
• 
At C1D1 and any visit when pembrolizumab and ASP0739 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 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 ASP0739 infusion, every 15 min (-5 to +10 min window) 
during ASP0739 infusion, at the end of ASP0739 infusion (-5 to +10 min window), and post dose (+30 min, +1, +2, +3 and +4 hours [± 10 min window each] from end of 
ASP0739 infusion).  
• 
ASP0739 dosing only: vital signs will be obtained within 15 min prior to start of ASP0739 infusion, every 15 min (-5 to +10 min window) during ASP0739 infusion, at the 
end of ASP0739 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 ASP0739 infusion. If 
participants are still available, additional optional vital sign assessments 3 hours (± 10 min) and 4 hours (± 10 min) after completion of the ASP0739 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 
pembrolizumab infusion; at the end of 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. 
h. Obtain predose.  
i. 
If performed within 2 weeks of screening (prior to ICF and performed as part of standard of care), then do not need to be repeated. If participants present positive troponin levels or 
new onset of cardiovascular symptoms, MUGA or ECHO should be performed.  
Footnotes continued on next page 


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j. 
12-lead ECGs will be recorded in triplicate (at least 2 min apart per time point) and transmitted electronically for central reading. On IP administration days, ECG will be obtained: 
• 
At C1D1 and any visit when pembrolizumab and ASP0739 are administered together, ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h 
post dose of ASP0739. 
• 
ASP0739 dosing only: ECGs are obtained predose (-1 h from start of ASP0739 infusion) and 1 to 2 h post dose of ASP0739. 
• 
Pembrolizumab dosing only: ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h post dose of pembrolizumab. 
k. Includes medications taken within 28 days prior to C1D1. Include all anticancer treatment received 28 days prior to IP administration. 
l. 
Urine or serum pregnancy test will be performed in women of childbearing potential. On treatment visit days, test must occur prior to IP administration.  
m. 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. For participants in combination therapy arm, troponin levels will be obtained at screening; thereafter, weekly for 6 weeks and subsequently every 
second week for 6 weeks. 
n. 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 (Screening, C2D15 then every 6 weeks). 
o. Whole blood for optional PGx study may be collected at C1D1 prior to IP administration. 
p. See Table 5 for collection schedule for ASP0739 single agent and ASP0739 and pembrolizumab combination therapy. 
q. 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. 
r. 
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. 
Imaging will occur every 56 ± 7 days until confirmed progression by iRECIST. 
s. 
Enrollment or randomization will be done via IRT system after confirmation of eligibility and prior to dosing. 
t. 
In both the monotherapy and combination cohorts, each participant must remain at the site facility for 4 hours following the participant’s first dose of ASP0739. For the next dose 
(second dose) or additional subsequent single agent with ASP0739, participants must remain at the site facility for at least 2 hours after ASP0739 dosing. 
u. In the combination therapy arm, pembrolizumab will be administered as an intravenous infusion over 30 min followed by ASP0739 administration at least 1 hour after 
pembrolizumab administration. For participants enrolled in Japanese safety lead-in, C1D8 assessments should be performed prior to discharge from hospital. 
v. Samples collected at pembrolizumab doses 5, 7, 9, 11 and 13 only. 
w. Samples collected at pembrolizumab doses 5 and 7 only. 
x. Sample collected at the time of discontinuation due to disease progression. 
y. If participant is completing all assessments within cycle 6, EOT assessment will be on C6D22 (± 3 days) or prior to the initiation of new anticancer therapy, whichever occurs first. 
z. 
Only participants in the combination therapy arm need to undergo pulmonary function tests at screening and at weeks 12 and 24 of study treatment. 


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Table 2 
Schedule of Assessments for Dose Expansion Monotherapy and Combination Therapy Cohort 
 
Scr 
Treatmenta 
Pembrolizumab 
Monotherapy 
EOTu,aa 
Cycle 1 
Cycle 2 
Cycles 3–4b 
Cycles 5–6c 
Doses 5-17d 
Visit Days 
(-28 
to -1) 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
15 
1 
15 
Every 6 weeks 
 
Window(days) 
 
0 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 3 
± 1 
± 3 
+ 7 
Signed ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and Disease 
History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examinatione 
Xe 
Xe 
X 
Xbb 
X 
X 
X 
Xe 
X 
Xbb 
X 
X 
X 
Xe 
X 
Xe 
X 
Xe 
Xe 
Vital Signsf 
X 
X 
X 
Xbb 
X 
X 
X 
X 
X 
Xbb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG Performance 
X 
Xg 
X 
 
X 
X 
X 
Xg 
X 
 
X 
Xh 
X 
Xg,h 
Xh 
Xg,h 
Xh 
Xg,h 
X 
MUGA or ECHO 
Xi 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-Lead ECGj 
X 
Xj 
 
 
 
 
 
Xj 
 
 
 
 
 
Xj 
 
Xj 
 
 
X 
Prior and Concomitant 
Medications 
Xk 
X 
X 
Xbb 
X 
X 
X 
X 
X 
Xbb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy Test for 
WOCBP 
X 
Xl 
 
 
 
 
 
Xl 
 
 
 
 
 
Xl 
 
Xl 
 
Xl 
X 
Clinical Laboratory 
Tests (chemistry, 
hematology, 
urinalysis)m 
X 
Xg 
X 
 
X 
X 
X 
Xg 
X 
 
X 
Xh 
X 
Xg,h 
Xh 
Xg,h 
Xh 
Xg,h 
X 
Coagulation Profile 
(PT/INR, fibrinogen)m 
X 
Xg 
X 
 
X 
X 
X 
Xg 
X 
 
X 
Xh 
X 
Xg,h 
Xh 
Xg,h 
Xh 
Xg,h 
X 
Thyroid Profile Panel 
m,n 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
Every 6 weeks after C2D15 dose 
 
 
X 
PGxo 
 
Xo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Buccal Swab for HLA 
Typing 
 
Xg 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE/SAE Assessment 
X 
X 
X 
Xbb 
X 
X 
X 
X 
X 
Xbb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Table continued on next page 


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Scr 
Treatmenta 
Pembrolizumab 
Monotherapy 
EOTu,aa 
Cycle 1 
Cycle 2 
Cycles 3–4b 
Cycles 5–6c 
Doses 5-17d 
Visit Days 
(-28 
to -1) 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
15 
1 
15 
Every 6 weeks 
 
Window(days) 
 
0 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 3 
± 1 
± 3 
+ 7 
Pharmacokinetic: 
ASP0739p 
See Table 5 for sample time points 
Pharmacokinetic: 
pembrolizumabp 
See Table 5 for sample time points 
Anti-NY-ESO-1 
antibody 
 
Xg 
 
 
 
 
 
Xg 
 
 
 
 
 
Xg 
 
Xg 
 
Xv 
X 
Immune Response 
Biomarker (ELISpot) 
 
Xg 
 
 
X 
X 
 
Xg 
 
 
X 
Xh 
 
Xg,h 
Xh 
Xg,h 
Xh 
Xh,v 
X 
Immune Response 
Biomarker (Tetramer) 
 
Xg 
 
 
 
X 
 
Xg 
 
 
 
Xh 
 
Xg,h 
Xh 
Xg,h 
Xh 
Xh,v 
X 
Immune Cell 
Phenotyping 
 
Xg 
 
 
X 
X 
 
Xg 
 
 
X 
Xh 
 
Xg,h 
Xh 
Xg,h 
Xh 
Xh,w 
X 
Cytokines 
 
Xg 
X 
X 
X 
X 
 
Xg 
X 
X 
X 
Xh 
 
Xg,h 
Xh 
Xg,h 
Xh 
Xh,w 
X 
Circulating tumor 
DNA 
 
Xg 
 
 
 
 
 
Xg 
 
 
 
 
 
Xg 
 
Xg 
 
X 
Xx 
Archival Tumor 
Tissueq 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor Tissue, Fresh 
Biopsy 
 
Xs 
 
 
 
 
 
 
 
 
 
Xt 
 
 
 
 
 
 
 
Pulmonary function 
test 
Xaa 
 
 
 
 
 
 
 
 
 
 
 
 
Xaa 
 
 
 
Xaa 
 
Radiographic Disease 
Assessmentr 
Xr 
Every 56 ± 7 days 
 
IRT Transaction  
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
ASP0739 Dosing  
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 
 
 
Pembrolizumab 
Dosingy 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
Every 6 weeks after C2D15 dose 
X 
 
Footnotes continued on next page 


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AE: adverse event; C: cycle; CR: complete response; CT: computed tomography; D: day; ECG: electrocardiogram; ECHO: echocardiogram; 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; iRECIST: immune response evaluation criteria in solid tumors; IRT: interactive response technology; MRI: magnetic resonance imaging; MUGA: multiple 
gated acquisition scan; NY-ESO-1: New York esophageal squamous cell carcinoma 1; 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  
a. 
Cycles 1 through 6 represent ASP0739 single agent or combination of ASP0739 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 ASP0739 as decided by the investigator. 
c. 
After the first 4 cycles, participants who achieve PR or SD may continue further treatment of ASP0739 in cycles 5 and 6. Participants who reach CR will not receive additional 
doses of ASP0739. 
d. Participants in combination therapy only will continue to receive pembrolizumab as monotherapy for doses 5 up to 17. If participant receives at least 1 dose of ASP0739 but 
discontinues combination treatment of ASP0739 at any time prior to C5D15, then the participant may continue pembrolizumab as monotherapy for up to 96 weeks for a total of 
17 doses of pembrolizumab total for the study. 
e. 
Height measurement performed at screening only. If height cannot be measured at the screening visit, it can be collected at any time during the course of the study, but should be 
recorded for the screening visit. Weight measurement performed at screening and day 1 of each cycle.  
f. 
The following vital sign assessments schedules apply: 
• 
At C1D1 and any visit when pembrolizumab and ASP0739 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 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 ASP0739 infusion, every 15 min (-5 to +10 min window) 
during ASP0739 infusion, at the end of ASP0739 infusion (-5 to +10 min window), and post dose (+30 min, +1, +2, +3 and +4 hours [± 10 min window each] from end of 
ASP0739 infusion). 
• 
ASP0739 dosing only: vital signs will be obtained within 15 min prior to start of ASP0739 infusion, every 15 min (-5 to +10 min window) during ASP0739 infusion, at the 
end of ASP0739 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 ASP0739 infusion. If 
participants are still available, additional optional vital sign assessments 3 hours (± 10 min) and 4 hours (± 10 min) after completion of the ASP0739 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 
pembrolizumab infusion; at the end of 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. 
g. Obtain predose. 
h. Obtain predose if participant receives pembrolizumab at the same visit. 
i. 
If performed within 2 weeks of screening (prior to ICF and performed as part of standard of care), then do not need to be repeated. If participants present positive troponin levels or 
new onset of cardiovascular symptoms, MUGA or ECHO should be performed. 
j. 
12-lead ECGs will be recorded in triplicate (at least 2 min apart per time point) and read locally. On IP administration days, ECG will be obtained: 
Footnotes continued on next page 
 


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• 
At C1D1 and any visit when pembrolizumab and ASP0739 are administered together: ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h 
post dose of ASP0739. 
• 
ASP0739 dosing only: ECGs are obtained predose (-1 h from start of ASP0739 infusion) and 1 to 2 h post dose of ASP0739. 
• 
Pembrolizumab dosing only: ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h post dose of pembrolizumab. 
k. Includes medications taken within 28 days prior to C1D1. Include all anticancer treatment received 28 days prior to IP administration. 
l. 
Urine or serum pregnancy test will be performed in women of childbearing potential. On treatment visit days, test must occur prior to IP administration.  
m. 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. For participants in combination therapy arm, troponin levels will be obtained at screening; thereafter, weekly for 6 weeks and subsequently every 
second week for 6 weeks. 
n. Thyroid panel including triiodothyronine or free triiodothyronine, free thyroxine and thyroid stimulating hormone will be measured prior to receiving pembrolizumab for 
participants in the combination cohort (Screening, C2D15 then every 6 weeks). 
o. Whole blood for optional PGx study may be collected at C1D1 prior to IP administration. 
p. See Table 5 for collection schedule for ASP0739 single agent and ASP0739 and pembrolizumab combination therapy. 
q. 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. 
r. 
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. 
Imaging will occur every 56 ± 7 days until confirmed progression by iRECIST. 
s. 
Participants in all expansion cohorts are required to provide a tumor specimen obtained within 56 days prior to first dose of IP. 
t. 
Participants in all expansion cohorts are required to provide an on-treatment tumor specimen collected ± 7 days of the C2D15 visit (or unscheduled). 
u. The EOT visit will occur within 7 days of the principal investigator decision to discontinue the participant for treatment or prior to the start of new anticancer treatment, whichever 
occurs first. If a participant is completing all visits in the last treatment cycle, the EOT visit will be within 7 days from the last planned visit. 
v. Samples collected at pembrolizumab doses 5, 7, 9, 11 and 13 only. 
w. Samples collected at pembrolizumab doses 5 and 7 only. 
x. Sample collected at the time of discontinuation due to disease progression. 
y. In the combination therapy arm, pembrolizumab will be administered as an intravenous infusion over 30 min followed by ASP0739 administration at least 1 hour after 
pembrolizumab administration. For participants enrolled in Japanese safety lead-in, C1D8 assessments should be performed prior to discharge from hospital. 
z. 
If participant is completing all assessments within cycle 6, EOT assessment will be on C6D22 (± 3 days) or prior to the initiation of new anticancer therapy, whichever occurs first.  
aa. Only participants in the combination therapy arm need to undergo pulmonary function tests at screening and at weeks 12 and 24 (before dose 3 and dose 5 of pembrolizumab, 
respectively) of study treatment. 
bb. These assessments only apply to the Japanese participants. 
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Table 3 
Schedule of Assessments for Follow-up Periods 
Visit 
Safety Follow-up 
Follow-up Period  
Year 1a 
Survival Follow-up 
 
30 dayb  
60 dayb 
90 dayb 
Every 8 weeksc 
Every 3 months 
Window (days) 
± 3 
± 3 
± 3 
± 7 
± 7 
Physical Examination 
X 
X 
X 
 
 
Vital Signs 
X 
X 
X 
 
 
ECOG Performance 
X 
X 
X 
 
 
Concomitant Medications 
X 
X 
X 
 
 
12-Lead ECG 
X 
X 
X 
 
 
Clinical Laboratory Tests (chemistry, hematology, coagulation, urinalysis) 
X 
X 
X 
 
 
Pregnancy Test for WOCBP 
X 
X 
X 
 
 
AE/SAE Assessment 
X 
X 
X 
 
 
Pharmacokinetic sample for cell kinetics (ASP0739) 
See Table 5 for sample time points 
Blood Sample for NY-ESO-1 antibody 
X 
X 
X 
Xd 
 
Blood Sample for Immune Response Biomarker (ELISpot)  
X 
X 
X 
Xe 
 
Blood Sample for Immune Response Biomarker (Tetramer)  
X 
X 
X 
Xd 
 
Blood Sample for Immune Cell Phenotyping 
X 
X 
X 
Xe 
 
Blood Sample for Cytokines 
X 
X 
X 
Xe 
 
Blood Sample for ctDNA 
X 
X 
X 
Xf 
 
Radiographic Disease Assessment 
 Every 56 ± 7 days 
 
Survival Follow-upg 
 
 
 
 
X 
AE: adverse event; ctDNA: circulating tumor DNA; ECG: electrocardiogram; ECOG: eastern cooperative oncology group; ELISpot: enzyme-linked immunospot; EOT: end of 
treatment; NY-ESO-1: New York esophageal squamous cell carcinoma 1; SAE: serious adverse event; WOCBP: woman of childbearing potential  
a. Follow-up visits every 2 months or until progression or start of a new anticancer therapy or death (whichever occurs first). 
b. From the last dose. 
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c. From EOT or the last planned assessment if EOT was not performed. 
d. Maximum of 5 samples collected during Follow-up Period Year 1. Samples will be collected at the time of the disease assessment visit.  
e. Maximum of 1 sample collected during Follow-up Period Year 1. Sample will be collected at the time of the disease assessment visit. 
f. Sample will be collected at the time of discontinuation due to disease progression or the start of a new anticancer therapy. 
g. Outcomes will be assessed by telephone calls every 3 months for up to 12 months. 
 


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Table 4 
Schedule of Replication Competent Lentivirus for Dose Escalation Cohort, Dose Expansion Cohort and Safety Lead-in Cohort 
Assessment 
C1D1 
3 Months after Treatment 
Initiation or End of 
Treatment, whichever is first 
6 Months after Treatment 
Initiation 
12 Months after Treatment 
Initiation 
18 Months after Treatment 
Initiation 
Window 
0 
± 7 day 
± 1 month 
± 1 month 
+1 month 
Blood Sample for RCLa 
Xb 
X 
X 
X 
X 
C1D1: cycle 1 day 1; RCL: replication competent lentivirus 
a. If there are positive results, additional follow-up assessments may be required. 
b. Obtained predose. 
 


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Table 5 
Sample Collection Schedule- Dose Escalation Cohort, Dose Expansion Cohort and Safety Lead-in Cohort 
Cycle 
Day 
Time Point 
Window 
Dose Escalation and  
Safety Lead-ing 
Dose Expansionh 
Pembrolizumab PKa 
ASP0739 PK 
Pembrolizumab 
PKa 
ASP0739 PK 
Cycle 1 
1 
Predose 
- 60 minb 
X 
X 
X 
X 
End of Pembrolizumab Infusion 
+ 10 minc 
X 
 
X 
 
End of ASP0739 Infusion 
+ 10 mind 
 
X 
 
X 
30-minute post ASP0739 Infusion 
± 10 min 
 
X 
 
X 
1-hour post ASP0739 Infusion 
± 10 min 
 
X 
 
X 
2-hour post ASP0739 Infusion 
± 15 min 
 
X 
 
X 
5-hour post ASP0739 Infusion 
± 15 min 
 
X 
 
X 
2 
24-hour post ASP0739 Infusion 
± 60 min 
 
X 
 
Xf 
4 
NA 
 
 
X 
 
 
Cycle 2 
1 
Predose 
- 60 mine 
 
X 
 
X 
End of ASP0739 Infusion 
+ 10 mind 
 
X 
 
Xf 
30-minute post ASP0739 Infusion 
± 10 min 
 
X 
 
Xf 
1-hour post ASP0739 Infusion 
± 10 min 
 
X 
 
Xf 
2-hour post ASP0739 Infusion 
± 15 min 
 
X 
 
Xf 
5-hour post ASP0739 Infusion 
± 15 min 
 
X 
 
Xf 
2 
24-hour post ASP0739 Infusion 
± 60 min 
 
X 
 
Xf 
4 
NA 
 
 
X 
 
 
15 
Predose 
- 60 minb 
X 
 
 
 
End of pembrolizumab Infusion 
+ 10 minc 
X 
 
 
 
Cycle 3 
1 
Predose 
- 60 mine 
 
X 
 
 
End of ASP0739 Infusion 
+ 10 mind 
 
X 
 
 
Table continued on next page 


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Cycle 
Day 
Time Point 
Window 
Dose Escalation and  
Safety Lead-ing 
Dose Expansionh 
Pembrolizumab PKa 
ASP0739 PK 
Pembrolizumab 
PKa 
ASP0739 PK 
Cycle 4 
1 
Predose 
- 60 minb 
X 
X 
Xf 
Xf 
End of pembrolizumab Infusion 
+ 10 minc 
X 
 
Xf 
 
End of ASP0739 Infusion 
+ 10 mind 
 
X 
 
Xf 
30-minute post ASP0739 Infusion 
± 10 min 
 
X 
 
 
1-hour post ASP0739 Infusion 
± 10 min 
 
X 
 
 
2-hour post ASP0739 Infusion 
± 15 min 
 
X 
 
 
5-hour post ASP0739 Infusion 
± 15 min 
 
X 
 
 
Cycle 5 
1 
Predose 
- 60 mine 
 
X 
 
 
End of ASP0739 Infusion 
+ 10 mind 
 
X 
 
 
15 
Predose 
- 60 minb 
X 
 
 
 
End of pembrolizumab Infusion 
+ 10 minc 
X 
 
 
 
Cycle 6 
1 
Predose 
- 60 mine 
 
X 
 
 
End of ASP0739 Infusion 
+ 10 mind 
 
X 
 
 
EOT 
EOT 
NA 
 
X 
X 
X 
X 
Safety Follow-up 
30 days 
NA 
 
 
X 
 
 
Pembrolizumab 
Single Agent: 
Doses 5 and 6 
1 
Predose 
- 60 minb 
X 
X 
X 
 
End of pembrolizumab Infusion 
+ 10 minc 
X 
 
X 
 
C: cycle; D: day; EOT: end of treatment; NA: not applicable; PK: pharmacokinetics. 
a. 
Pembrolizumab PK samples only applicable for participants in the combination therapy arm. 
b. Within 60 min prior to pembrolizumab infusion (combination arm) or prior to ASP0739 infusion (single agent arm). 
c. 
Within 10 min after the end of pembrolizumab infusion (before the infusion of ASP0739 on C1D1 and C4D1). 
d. Within 10 min after the end of ASP0739 infusion. 
e. 
Within 60 min prior to ASP0739 infusion. 
f. 
Sample not collected in Stage 2 of Dose Expansion. 
g. For the participants who enroll in the Japanese safety lead-in for monotherapy, PK sampling will be taken at the times indicated for dose escalation and safety lead-in. 
h. For Japanese participants who enroll after the Japanese safety lead-in is completed, PK sampling will be taken at the times indicated for dose expansion.     


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2 
INTRODUCTION 
In this study (0739-CL-0101), ASP0739 is indicated as a single agent and in combination 
with pembrolizumab in patients with advanced solid tumors known to express the 
tumor-associated antigen New York esophageal squamous cell carcinoma 1 (NY-ESO-1).  
Details about ASP0739 are provided in the Investigator’s Brochure. 
Details about pembrolizumab are provided in the locally approved summary of product 
characteristics/package insert of this product. 
2.1 
Study Rationale 
Cancer testis antigens (CTAs) have restricted expression in immune privileged organs (such 
as the testes and ovaries) and are silent in normal tissues. CTAs are stably expressed in many 
cancers and have high immunogenic potential [Gjerstorff et al, 2015]. In particular, NY-ESO-
1 has high and frequent expression in malignant cancers [Jungbluth et al, 2001] and is able to 
elicit potent integrated natural humoral and cellular responses [Gnjatic et al, 2006]. ASP0739 
has effects against NY-ESO-1 expressing tumors by inducing both natural killer cell activity 
(innate immunity) and NY-ESO-1-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 ASP0739 is active in NY-ESO-1 expressing tumors as 
described in Section 4.1.1.3 of the Investigator’s Brochure. A synergistic effect of ASP0739 
with anti-programmed cell death protein 1 (anti-PD-1) antibodies was observed in a 
nonclinical setting as detailed in Section 4.1.1.5 of the Investigator’s Brochure. Therefore, 
ASP0739 as monotherapy or in combination with anti-PD-1 antibodies may result in clinical 
benefit for solid tumors known to express NY-ESO-1.  
2.2 
Background 
ASP0739 is an aAVC product composed of human embryonic kidney 293 (HEK293) cells 
that can be transfected with a lentiviral vector to express the tumor-associated antigens, in 
this case NY-ESO-1, intracellularly and the antigen-presenting molecule, cluster of 
differentiation 1d, on the cell surface. These genetically engineered cells are then loaded with 
α Galactosylceramide (α-GalCer), followed by X-ray irradiation to inhibit ASP0739 cell 
proliferation. Another aAVC compound, ASP7517, which uses the same platform and only 
differs in the intracellularly expressed antigen (Wilms’ Tumor 1 [WT1] instead of NY-ESO-
1) is currently being evaluated in an ongoing clinical study (7517-CL-0101). ASP7517 and 
ASP0739 are similar in their ability to activate innate and adaptive immunity and have 
similar nonclinical toxicology profiles. 
NY-ESO-1 has been identified as a robust biomarker predicting clinical benefits with anti-
PD-1 monotherapy and is useful for decision making in clinical settings [Oka et al, 2020]. 
NY-ESO-1 is considered to be the most immunogenic CTA and is a target for cancer vaccine 
strategies that utilize the immune system [Esfandiary & Ghafouri-Fard, 2015]. It has been 
reported that about 75% of patients with cancer express NY-ESO-1 at some stage of their 


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illness [Barrow et al, 2006]. Several studies on the utility of NY-ESO-1 as a surrogate marker 
of clinical response in multiple myeloma [Leutkens et al, 2014], gastric cancer [Fujiwara et 
al, 2013] and other malignancies have been conducted. Antibodies against NY-ESO-1 were 
observed during disease progression in multiple myeloma [Leutkens et al, 2014], as well as in 
gastric cancer, with the frequency of antibody positivity increasing during disease 
progression for patients with gastric cancer [Fujiwara et al, 2013]. NY-ESO-1 protein 
expression has been detected in invasive melanomas [Giavina-Bianchi et al, 2015] with a 
positivity rate of 32% to 45% [Bolli et al, 2005; Vaughn et al, 2004], esophageal squamous 
cell carcinoma (ESCC) [Ueda et al, 2018] with a positivity rate of about 32% [Akcakanat et 
al, 2004] and non-small cell lung cancer (NSCLC) [Wang et al, 2019] with 12% to 25% of 
tumors testing positive [Bolli et al, 2005; Jungbluth et al, 2001]. Studies have confirmed the 
high frequencies of NY-ESO-1 expression in MRCL and synovial sarcoma (SS), [Endo et al, 
2015; Lai et al, 2012; Jungbluth et al, 2001]. NY-ESO-1 expression has also been noted as a 
sensitive and specific diagnostic biomarker in myxoid/round cell liposarcoma (MRCL) 
[Hemminger et al, 2013; Pollack et al, 2012]. Early data have shown that NY-ESO-1 is a 
valid target to generate clinical response via immunological activation.  
A detailed description of the chemistry, pharmacology, efficacy and safety of ASP0739 is 
provided in the Investigator’s Brochure. 
2.2.1 
Synovial Sarcoma and Myxoid/Round Cell Liposarcoma 
In the US, 13130 new patients (7470 males and 5660 females) are forecasted to be diagnosed 
with soft tissue sarcomas and 5350 patients are expected to die of the disease in 2020 
[American Cancer Society, 2020]. For patients diagnosed with soft tissue sarcomas between 
2009 and 2015, based on combined Surveillance, Epidemiology and End Results stages, the 
5-year survival rate was 65% [American Cancer Society, 2020]. SS is an uncommon 
malignant tumor of the tissue around the joints with the most common locations being the 
extremities with distant pulmonary metastases developing in most patients after primary 
tumor surgery [Zhang et al, 2014]. SS accounts for about 5% to 10% of soft tissue tumors 
[Fisher, 1998]. About 50% of patients die within 10 years of diagnosis even with treatment 
[Terry et al, 2005]. MRCL is typically found in the lower extremities [National Institutes of 
Health, 2016]. Prognosis is better for patients with a low grade MRCL with a small 
percentage of round cells (5-year survival rate of 92%) whereas a greater percentage of round 
cells (5% or higher) is associated with a much poorer prognosis and a 5-year survival rate of 
74% [Orphanet, 2013]. A systematic review of sarcoma survival rates indicated that 5-year 
survival rates for all patients with metastatic sarcoma were 20% to 25% for bone, and for soft 
tissue sarcoma 13% to 15% [Treasure et al, 2012]. About 88% of tumors in MRCL and 76% 
to 80% of tumors in SS express NY-ESO-1 [Endo et al, 2015; Lai et al, 2012; Jungbluth et al, 
2001]. 
2.2.2 
Ovarian Cancer 
It is estimated that 21750 women will be newly diagnosed with ovarian cancer in the US in 
2020 and 13940 will die of the disease in 2020 [American Cancer Society, 2020]. Ovarian 
cancer is predominantly diagnosed in postmenopausal women, and due to the lack of 


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symptoms in early stages, more than 75% of patients are diagnosed in advanced stages of the 
disease [Doubeni et al, 2016]. For patients with ovarian cancer, 5-year survival rates are 
below 45% [Webb & Jordan, 2017]. 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 (OS) is less than 15 months [Shimokawa et al, 2018]. About 43% of ovarian 
cancers express NY-ESO-1 [Odunsi et al, 2003]. 
2.3 
Risk/Benefit Assessment 
2.3.1 
Risk Assessment 
2.3.1.1 ASP0739 Risk Assessment 
As of 06 May 2022, 4 participants have received ASP0739; therefore, the safety profile, 
RP2D and possible contraindications of ASP0739 have not been established. However, 
preliminary data from 4 participants who have received at least 1 dose of ASP0739 
1 × 107 cells/dose in the dose escalation phase of Study 0739-CL-0101 have not identified 
any DLTs or safety concerns.  
ASP7517, another aAVC compound, uses the same platform as ASP0739 and only differs in 
the intracellularly expressed antigen (WT1 instead of NY-ESO-1). ASP7517 currently has 2 
ongoing clinical studies (7517-CL-0101 and 7517-CL-1101). As of 05 Oct 2021, 19 
participants have received at least 1 dose of ASP7517 at dose levels of 1 × 106 cells/dose, 1 × 
107 cells/dose and 1 × 108 cells/dose. The RP2D for ASP7517 in participants with R/R acute 
myeloid leukemia and R/R higher risk myelodysplastic syndromes was determined to be 1 × 
108 cells/dose. No DLTs in doses of up to 1 × 108 cells/dose have been identified.  
While different target antigens allow targeting different tumor types, no differences in the 
clinical safety profiles are expected between ASP0739 and ASP7517; this is supported by the 
very similar nonclinical safety profiles of both compounds. Target organs of toxicity for 
ASP7517 in nonclinical studies were primarily the liver, spleen and kidney, with minor 
non-toxicologically significant findings noted in pancreas, urinary bladder and epididymides. 
Table 6 
Summary of Potential Safety Concerns for ASP0739 
Target Organs/ 
Systems 
Potential Risks from Nonclinical Studies 
Risk Minimization and/or 
Characterization Action 
Liver 
Increased liver weight, elevated AST and ALT 
levels, emboli, hepatocyte focal necrosis, mixed 
inflammatory cell infiltration, microgranuloma, 
granulomatous inflammation, mononuclear cell 
aggregation, and pigment laden macrophage 
infiltration 
Close monitoring of liver function via 
laboratory assessments of liver 
function 
Hematology 
Decreased followed by increased platelet 
counts. Increased RBC parameters, decreased 
WBC and lymphocyte counts 
Standard laboratory assessment of 
hematology 
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Target Organs/ 
Systems 
Potential Risks from Nonclinical Studies 
Risk Minimization and/or 
Characterization Action 
Kidney 
Increased serum creatinine. Basophilic tubules 
and infiltration of mononuclear cells 
Standard monitoring of kidney 
function parameters (creatinine, blood 
urea nitrogen) and urinalysis 
Spleen  
Increased weight, apoptosis in lymphoid 
follicles, emboli, lymphoid follicular 
hyperplasia 
Standard laboratory assessment of 
hematology 
General 
Immune-Mediated Adverse Reaction, 
Cytokine-release syndrome – Not observed 
non-clinically 
Close monitoring of participant’s signs 
or symptoms; Chemokine/Cytokine 
panel and tryptase level. 
Infusion-Related Reaction – Not observed non-
clinically 
Close monitoring of participant’s signs 
or symptoms; Chemokine/Cytokine 
panel and tryptase level.  
Immunotoxicity directed against non-target 
toxicity (testis and placenta) - Risk cannot be 
ruled out based on nonclinical studies. 
However, as NY-ESO-1 is only expressed in 
immune privileged organs, the risk is 
considered low [Raza et al, 2020]. 
Close monitoring of participant’s signs 
or symptoms; Testosterone testing in 
male participants 
Allergic Reactions and Anaphylaxis – Not 
observed non-clinically 
Close monitoring of participant’s signs 
or symptoms; Chemokine/Cytokine 
panel and tryptase level. 
ALT: alanine aminotransferase; AST: aspartate aminotransferase; RBC: red blood cells; WBC: white blood cell 
● 
Liver Toxicity:  Close monitoring of liver function and toxicities is required during 
clinical studies. The liver is a target organ of toxicity for ASP0739, which is related to 
the activation of the innate immune system by α-GalCer. The hepatic findings in mice 
included increased liver weight, elevated aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT) levels, emboli, hepatocyte focal necrosis, mixed inflammatory 
cell infiltration, microgranuloma, granulomatous inflammation, mononuclear cell 
aggregation and pigment laden macrophage infiltration. The hepatic findings of 
increased AST and ALT 1 day after administration of ASP0739 were completely 
reversed following a 28-day recovery period. 
● 
Hematology:  The standard assessment of hematology is recommended in clinical 
studies. A dose-related decrease in platelet count was seen 1 day after the first and 
second dose. Platelet counts were increased above baseline 7 days after the first and 
second dose and recovered to normal physiological ranges by day 28. 
● 
Kidney:  The standard monitoring of kidney function parameters (creatinine, blood urea 
nitrogen) is recommended in clinical studies. Increased serum creatinine was noted 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 first and 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. 
● 
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 follicles of the spleen 1 day after the first or second dose. This 


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finding was completely resolved by 7 days following ASP0739 administration. Also, 
extramedullary hematopoiesis and lymphoid follicular hyperplasia occurred 7 days after 
the first and second dose and resolved by 28 days. Standard hematology testing is 
recommended in clinical trials. 
● 
Infusion-related Reactions:  In nonclinical studies with ASP0739, infusion-related 
reactions (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. 
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 (SOC). 
● 
Allergic Reactions and Anaphylaxis:  Based on the nonclinical data, no signs or 
symptoms of allergic reaction or anaphylaxis were seen following ASP0739 
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 SOC. 
Other 
Adverse events (AEs) reported from solid tumor early phase clinical studies using α-GalCer-
based immunotherapies include: fever, headache, fatigue, dizziness, chest pain, lymphopenia, 
hot flash, hyperkalemia, lactate dehydrogenase increase, creatinine increase, anemia, 
increased cancer pain and hyperbilirubinemia. In general, these therapies were shown to be 
safe and no severe adverse events (SAEs) were treatment related [Ishikawa et al, 2005; Kunii 
et al, 2009; Motohashi et al, 2009; Uchida et al, 2008]. 
The AEs reported in early phase NY-ESO-1-peptide vaccine clinical studies in patients with 
advanced solid tumors were mainly grade 1 or 2 events including injection site pain, fatigue, 
nausea, vomiting, pain, diarrhea and hyperkalemia [Mahipal et al, 2019; Odunsi et al, 2007]. 


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In addition, based on the above and the mechanism of action of ASP0739, immune-related 
AEs (irAEs) such as fever, headache, fatigue, hot flashes, diarrhea, muscular and joint pain 
should be considered and managed as required per SOC. 
2.3.1.2 Pembrolizumab Risk Assessment 
Refer to pembrolizumab package insert, summary of product characteristics monograph or 
local prescribing information for key safety information and potential toxicities. 
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 ASP0739 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 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 the study.  
Additionally, the following precautions mitigate risk and protect participant safety: 
● 
Enrollment within each dose escalation cohort will be staggered such that there will be a 
minimum of 28 calendar days between the treatment initiation of the first and second 
participants and 14 calendar days between the second and the third participants. In the 
absence of toxicity, additional participants may be treated at a dose level without any 
formal stagger. An interval of 28 calendar days will separate study treatment initiation of 
the last participant in a dose cohort from the first patient enrollment in sequential dose 
cohort.  
● 
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 [Liu & Yuan, 
2015] 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 


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the designated DLT observation period that meet DLT criteria (“delayed DLT”), will be 
considered by the committee. 
● 
A Tolerability Evaluation Meeting (TEM) consisting of sponsor representatives and 
investigators will convene once the number of Japanese participants [Section 10.1.5.1 
Tolerability Evaluation Meeting] completes the DLT observation period and data are 
available for review. 
● 
The safety in the expansion cohorts will be monitored using Bayesian logistic model 
based on all DLT data obtained up to that time from both escalation cohorts and 
expansion cohorts and drug-related 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 Statistical 
Considerations]. 
The potential risk of irAEs and 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 ASP0739 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]. The management of such toxicities should 
be based on institutional SOC and published guidelines, as appropriate based on investigator 
judgment, and on the protocol instructions regarding interruption or discontinuation of 
treatment.  
2.3.3 
Benefit Assessment 
No clinical studies have been completed; therefore, the antitumor activity of ASP0739 in 
humans is unknown. The nonclinical data suggest ASP0739 may have activity against 
NY-ESO-1 expressing tumors; therefore, participants with SS and MRCL as well as ovarian 
cancer and other NY-ESO-1 expressing tumors may receive clinical benefit from 
participation in this study. Based on the preclinical data, the clinical benefit of ASP0739 may 
be enhanced by combination with pembrolizumab. 
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 by the FDA to treat metastatic melanoma, NSCLC, 
SCLC, head and neck squamous cell cancer, classical Hodgkin lymphoma, primary 
mediastinal B-cell lymphoma, urothelial cancer, gastric cancer, esophageal cancer, cervical 
cancer, hepatocellular carcinoma, Merkel cell carcinoma, renal cell carcinoma, endometrial 
carcinoma, tumor mutational burden-high cancer, cutaneous squamous cell carcinoma and 
any unresectable or metastatic solid tumor with microsatellite instability and DNA mismatch 
repair deficiency. Pembrolizumab may improve the effect of ASP0739 since the inhibition of 


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the binding of PD-1 to its ligands prevents immune evasion by cancer cells. As such, aAVC 
would prime the immune system and make cancer cells more susceptible to effector T-cells 
that have been activated by ASP0739.  
Preclinical models suggest that ASP0739 treatment combinations with PD-1 pathway 
blockade may provide additive antitumor effect over treatment with either one alone. 
The majority of patients treated with the current SOC including with anti-PD-1 
monotherapies, when indicated, 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 
ASP0739 has effects against NY-ESO-1 expressing tumors and showed no significant safety 
findings in the preclinical pharmacology studies. In the mice repeated dose toxicity studies of 
ASP0739, all major findings were reversible and monitorable and will not interfere with 
human clinical studies considering its potential benefit against the risk. The clinical safety 
profile at identical doses of ASP7517 was acceptable and this is expected to be similar for 
ASP0739. 
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 ASP0739 and a PD-1 inhibitor, no overlapping toxicity is 
expected given that NY-ESO-1 is limited to the tumor. 
Overall, the risk associated with participation in this clinical study of ASP0739 as a single 
agent and in combination with pembrolizumab is considered to be acceptable for this 
population of participants with advanced/metastatic solid tumors who have received, declined 
or have a contraindication to all therapy with established clinical benefit for their malignancy. 
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. 


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3 
OBJECTIVES AND ENDPOINTS 
Table 7 
Study Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
● 
To evaluate the safety and tolerability of 
ASP0739 in participants with R/R solid tumors 
known to express NY-ESO-1 when 
administered as a single agent (phase 1 dose 
escalation), and in combination with 
pembrolizumab in participants with R/R SS, 
MRCL and ovarian cancer (safety lead-in) 
● 
Safety and tolerability as noted by: DLTs, AEs, 
SAEs, laboratory test results (serum chemistry, 
hematology, coagulation, urinalysis and 
pregnancy test), ECGs, vital signs, physical 
exams and ECOG performance status scores 
● 
To determine RP2D of ASP0739 when 
administered as a single agent 
● 
RP2D based on above 
● 
To evaluate the clinical response of ASP0739 
when administered as a single agent and in 
combination with pembrolizumab in 
participants with R/R SS, MRCL and ovarian 
cancer (phase 2) 
● 
Objective response rate per iRECIST (iORR) 
by Independent Central Review 
Secondary 
● 
To evaluate other measures of anticancer 
activity of ASP0739 when administered as a 
single agent and in combination with 
pembrolizumab based on central and local 
assessment in participants with R/R SS, MRCL 
or ovarian cancer (phase 2) 
● 
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) 
● 
To obtain preliminary efficacy based on central 
and local assessment in participants with R/R 
solid tumors known to express NY-ESO-1 
(melanoma, NSCLC-adenocarcinoma and 
squamous cell and ESCC) (phase 2) 
● 
Objective response rate per iRECIST (iORR) 
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Objectives 
Endpoints 
Exploratory 
● 
To evaluate potential genomic, proteomic 
and/or other biomarkers that may correlate with 
treatment outcome when ASP0739 is 
administered as a single agent and in 
combination with pembrolizumab 
● 
Exploratory biomarkers that may correlate with 
treatment outcome of ASP0739 as a single 
agent or in combination with pembrolizumab, 
including NY-ESO-1 expression 
● 
To evaluate pharmacodynamic activities of 
ASP0739 as a single agent and in combination 
with pembrolizumab  
• 
Pharmacodynamic effects of ASP0739, such as 
changes in: 
o 
Cytokine expression and secretion 
(e.g., IFNg) 
o 
NY-ESO-1-specific T lymphocytes 
(e.g., cytotoxic T lymphocytes) 
o 
Immune cell populations (NKT cells, 
Treg cells, etc.) 
o 
Anti-NY-ESO-1 antibodies 
o 
Tumor microenvironment (CD8, PD-
L1, etc.) 
● 
To evaluate pharmacokinetics of ASP0739 
when administered as a single agent and in 
combination with pembrolizumab 
• 
Cellular DNA load and kinetic parameter 
estimates (including AUC, Cmax, Ctrough and tmax) 
for ASP0739 as a single agent or in combination 
with pembrolizumab 
AE: adverse event; CD8: cluster of differentiation 8; DCR: disease control per RECIST v1.1; DLT: dose 
limiting toxicity; DOR: duration of response per RECIST v1.1; ECG: electrocardiogram; ECOG: Eastern 
Cooperative Oncology Group; ESCC: esophageal squamous cell carcinoma; iDCR: disease control per 
iRECIST; iDOR: duration of response per iRECIST; IFNg; interferon gamma; iORR: objective response rate 
per iRECIST; iPFS: progression-free survival per iRECIST; iRECIST: immune response evaluation criteria in 
solid tumors; MRCL: myxoid/round cell liposarcoma; NKT: natural killer T; NSCLC: non-small cell lung 
cancer; NY-ESO-1: New York Esophageal-1; ORR: objective response rate per RECIST v1.1; OS: overall 
survival; PD-L1: programmed death-ligand 1; PFS: progression-free survival per RECIST v1.1; R/R: 
relapsed/refractory; RECIST: response evaluation criteria in solid tumors; RP2D: recommended phase 2 dose; 
SAE: serious adverse event; SS: synovial sarcoma 
 
4 
STUDY DESIGN AND DOSE RATIONALE 
4.1 
Overall Study Design 
This is a phase 1, open-label study of ASP0739 in participants with R/R solid tumors known 
to express NY-ESO-1 and a phase 2 study of single agent and combination therapy with 
pembrolizumab in participants with R/R SS, MRCL or ovarian cancer. 
Phase 1 (dose escalation) in participants with solid tumors known to express NY-ESO-1 and 
phase 2 of ASP0739 single agent and combination therapy with pembrolizumab in R/R SS, 
MRCL and ovarian cancer who have not responded to SOC or are ineligible for standard 
therapy. Phase 2 single agent will also include a cohort of participants with select solid 


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tumors known to express NY-ESO-1 (melanoma, NSCLC-adenocarcinoma and squamous 
cell and ESCC). 
Both study phases consist of the following periods:   
● 
Screening (up to 28 days) 
● 
Treatment with ASP0739 (up to 6 doses every 28 days) and for participants in 
combination cohorts with pembrolizumab on cycle 1 day 1 (C1D1), and then every 
6 weeks, until disease progression, unacceptable toxicity or up to 17 doses  
● 
EOT visit after completion of IP: Within 7 days of EOT determination or prior to the 
initiation of new anticancer therapy, whichever occurs first 
● 
Safety follow-up visits at 30, 60 and 90 days from the last dose of treatment or prior to 
the initiation of new anticancer therapy 
● 
Follow-up visits every 2 months for up to 1 year or until progression or start of a new 
anticancer therapy or death (whichever occurs first) 
● 
Survival follow-up for up to 1 year by telephone calls every 3 months after the start of a 
new anticancer treatment or progression after ASP0739 and/or pembrolizumab treatment 
ASP0739 Single Agent 
Participants will receive an intravenous infusion of ASP0739 (HEK293 transfected with a 
lentiviral vector that is encoding the target antigen NY-ESO-1). Participants will receive 
1 dose every 28-day cycle for up to 4 doses; an additional 2 doses may be administered in 
participants with a partial response (PR) or stable disease (SD). Following the first 2 cycles, 
participants who have not met any individual treatment discontinuation criteria and are 
receiving clinical benefit may continue further treatment with ASP0739, as decided by the 
investigator.  
ASP0739 Combination with Pembrolizumab 
The recommended phase 2 dose (RP2D) of ASP0739 determined from the phase 1 dose 
escalation phase will be combined with pembrolizumab 400 mg for the safety lead-in with 
approximately 6 to 9 participants. If the RP2D is selected at the same dose level as the 
maximum tolerated dose (MTD) based on the phase 1 dose escalation portion, the 
combination safety lead-in will start at one dose level lower than the MTD. 
If DLTs occur in the safety lead-in cohort and the dose level is de-escalated to a lower dose 
level per BOIN design (either from 1 × 108 to 1 × 107 or from 1 × 107 to 1 × 106), the dose 
de-escalation cohort enrollment must be completed and determined to be safe by the DESC 
before enrollment in the ASP0739 and pembrolizumab combination expansion cohorts. 
Participants will receive 1 dose of ASP0739 every 28-day cycle for a total of 4 doses; an 
additional 2 doses may be administered for participants with PR or SD. Following the first 
2 cycles, participants who have not met any individual treatment discontinuation criteria and 
are receiving clinical benefit may continue further treatment with ASP0739 and 
pembrolizumab, as decided by the investigator. Participants will also receive pembrolizumab 
400 mg on C1D1, then every 6 weeks, until disease progression, unacceptable toxicity or for 
up to 17 doses or until one of the discontinuation criteria is met. For combination treatment, a 


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400 mg pembrolizumab infusion will be administered first, followed by an ASP0739 infusion 
at least 1 hour after the completion of the pembrolizumab infusion. 
Phase 1 Single Agent Dose Escalation: 
The single agent dose escalation phase will evaluate escalating dose levels of ASP0739 in 
approximately 3 to 12 DLT-evaluable participants.  
The starting dose is 1 × 107 cells/dose and the decision to dose escalate to the next dose level 
(1 × 108 cells/dose) or to dose reduce (1 × 106 cells/dose) to a lower dose level will be made 
based on the assessment of safety variables, including the occurrence of dose-limiting 
toxicities (DLTs).  
Table 8 
Dose Levels (Phase 1 Dose Escalation)  
Dose Level 
Dose 
0 
1 × 107 cells/dose 
+1 
1 × 108 cells/dose 
The dose escalation phase will assess safety and tolerability of ASP0739 during cycle 1. 
Participants will receive up to 6 doses of ASP0739 via intravenous infusion separated by 
28 days. Dosing will occur on day 1 of each cycle. After the first dose of ASP0739, 
participants must be observed for safety for a minimum of 4 hours. If new AEs are observed 
that are greater than grade 3 during this time, participants should continue to be observed 
until the AEs are less than grade 3.  
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 phase will 
enroll 3 to 4 evaluable participants for the initial assessment of each dose level. Refer to the 
Participant Replacement during Dose Escalation/Safety Lead-in section for definition of 
evaluable participants. Enrollment within each dose escalation cohort will be staggered such 
that there will be a minimum of 28 calendar days between the treatment initiation of the first 
and second participants and 14 calendar days between the second and third participants at the 
same dose level for all escalation cohorts. In the absence of toxicity, additional participants 
may be treated at a dose level without any formal stagger. An interval of 28 calendar days 
will separate study treatment initiation of the last participant in a dose cohort from the first 
patient enrollment in sequential dose cohort. If the decision is made to remain at the current 
dose level, an additional 3 or 4 evaluable participants may be enrolled in the current dose 
level. A minimum of 6 participants must be enrolled at the dose level used to determine the 
RP2D. 


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Dose evaluation rules based on the BOIN design with a 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 
NA 
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; NA; not applicable 
Definition of DLTs for ASP0739 Single Agent: 
A DLT is defined as any of the following events that occur within 28 days starting with the 
first dose on C1D1 in the dose escalation cohort and that is considered to be possibly, 
probably or definitely related to IP. Confirmation of DLTs will be made by the DESC. The 
severity of AEs will be assessed according to National Cancer Institute’s Common 
Terminology Criteria for Adverse Events (NCI-CTCAE), v5.0. Participants experiencing 
DLTs, who in the opinion of the investigator are deriving clinical benefit from the study 
treatment (e.g., marked reduction in tumor burden), may be allowed to continue study 
treatment with ASP0739 upon resolution of the event to ≤ grade 1 or baseline, upon 
discussion with the sponsor. Participants experiencing DLTs during the single agent dose 
escalation phase will not be replaced.  
DLTs are defined as follows:  
● 
Grade ≥ 2 autoimmune reaction 
● 
Grade 3 irAEs that do not resolve to grade ≤ 1 in 3 to 5 days 
● 
Grade 4 irAEs 
● 
Grade ≥ 3 non-hematological AE that does not resolve to grade ≤ 2 within 72 hours of 
onset 
● 
Grade 4 neutropenia 
● 
Grade 3 febrile neutropenia with or without infection 
● 
Grade 4 thrombocytopenia 
● 
Grade 3 thrombocytopenia accompanied by bleeding that requires any transfusion 
● 
Grade 4 anemia 
● 
Grade 3 anemia requiring transfusion 
● 
AST or ALT > 5 × upper limit of normal (ULN; grade ≥ 3) without liver metastases 
● 
AST or ALT > 8 × ULN in participants with liver metastases 
● 
AST or ALT > 3 × ULN and total bilirubin (TBL) > 2 × ULN (in participants with 
Gilbert syndrome: AST or ALT > 3 × ULN and direct bilirubin > 1.5) (confirmed Hy’s 
Law) 
● 
Grade ≥ 3 liver function test abnormality lasting ≥ 7 days 


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● 
Grade 5 toxicity 
● 
Prolonged delay (> 2 weeks) in initiating cycle 2 due to treatment-related toxicity 
The following AEs will not be considered DLTs: 
● 
Electrolyte abnormalities that are not associated with clinical sequelae or deemed not 
clinically significant and corrected with appropriate management or supplementation 
within 72 hours of onset 
● 
Grade 3 infusion site reaction if successfully managed and resolved within 72 hours of 
onset 
● 
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 within 72 hours of onset with standard antiemetic or antidiarrheal 
medications used at prescribed dose 
● 
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 ASP0739 will be considered to be a DLT 
● 
Grade 3 or lower irAEs that resolve to ≤ grade 1 within 72 hours of onset after starting 
treatment including corticosteroids 
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 be discontinued from treatment. 
● 
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 be discontinued from treatment. 
● 
If there is a delay in administration of the second cycle by > 4 weeks, it would result in 
discontinuation from treatment after discussion with the sponsor. 
ASP0739 in Combination with Pembrolizumab Safety Lead-in 
Enrollment in the combination therapy safety lead-in will start once phase 1 single agent dose 
escalation is completed and the RP2D is defined. 
The combination therapy safety lead-in portion will evaluate the RP2D of ASP0739 with a 
fixed dose of 400 mg pembrolizumab in 6 to 9 participants with at least 6 DLT-evaluable 
participants. If the RP2D is selected at the same dose level as the MTD based on the phase 1 
dose escalation portion, the combination safety lead-in will start at one dose level lower than 
the MTD.   


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Safety lead-in will be guided according to the BOIN design [Liu & Yuan, 2015] to determine 
if the RP2D of ASP0739 with a fixed dose of 400 mg pembrolizumab is tolerable and based 
on DLT occurrence after 28 days. After the planned number of evaluable participants has 
completed the DLT observation period of 28 days for a given dose level, safety for that dose 
level will be assessed. Safety lead-in will enroll 3 to 4 evaluable participants for the initial 
assessment of RP2D. A minimum of 6 participants must be enrolled at the dose level used to 
determine the RP2D. Enrollment will be staggered such that there will be a minimum of 
28 calendar days between the treatment initiation of the first and second participants, as well 
as 14 calendar days between the second and third participants at the same dose level for the 
safety lead-in cohort. In the absence of toxicity, additional participants may be treated at a 
dose level without any formal stagger. An interval of 28 calendar days will separate study 
treatment initiation of the last patient in a dose cohort from the first participant treatment in 
sequential dose cohort.  
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 
NA 
2 
2 
2 
De-escalate if number of participants with  
DLT = a 
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; NA; not applicable 
a. Dose de-escalation will be implemented as a single dose level reduction to a lower dose of ASP0739 (either 
from 1 × 108 to 1 × 107 or from 1 × 107 to 1 × 106) in combination with pembrolizumab 400 mg. 
Definition of DLTs for ASP0739 and Pembrolizumab Combination Therapy 
A DLT is defined as any of the following events that occur within 28 days starting with the 
first dose on C1D1 in the safety lead-in cohort and that is considered to be possibly, probably 
or definitely related to ASP0739 and/or pembrolizumab. Confirmation of DLTs will be made 
by the DESC. The severity of AEs will be assessed according to NCI-CTCAE, v5.0. 
Participants experiencing DLTs, who in the opinion of the investigator are deriving clinical 
benefit from the study treatment (e.g., marked reduction in tumor burden), may be allowed to 
continue study treatment with ASP0739 upon resolution of the event to ≤ grade 1 or baseline, 
upon discussion with the sponsor. Participants experiencing DLTs during the combination 
safety lead-in portion will not be replaced. 
DLTs are defined as follows:  
● 
Grade ≥ 2 autoimmune reaction 
● 
Grade 3 irAEs that do not resolve to grade ≤ 1 in 3 to 5 days 
● 
Grade 4 irAE 
● 
Grade ≥ 3 non-hematological AE that does not resolve to grade ≤ 2 within 72 hours of 
onset 
● 
Grade 4 neutropenia 


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● 
Grade 3 febrile neutropenia with or without infection  
● 
Grade 4 thrombocytopenia 
● 
Grade 3 thrombocytopenia accompanied by bleeding that requires transfusion or 
hospitalization 
● 
Grade 4 anemia 
● 
Grade 3 anemia requiring transfusion 
● 
AST or ALT > 5 × ULN (grade ≥ 3) without liver metastases 
● 
AST or ALT > 8 × ULN in participants with liver metastases 
● 
AST or ALT > 3 × ULN and TBL > 2 × ULN (in participant with Gilbert syndrome: 
AST or ALT > 3 × ULN and direct bilirubin > 1.5) (confirmed Hy’s law) 
● 
TBL > 3 × ULN (grade ≥ 3) 
● 
Grade ≥ 3 liver function test abnormality lasting ≥ 7 days 
● 
Grade 5 toxicity 
● 
Prolonged delay (> 2 weeks) in initiating cycle 2 due to treatment-related toxicity 
● 
Grade ≥ 2 pneumonitis 
● 
Grade ≥ 2 encephalopathy, meningitis, or motor or sensory neuropathy 
● 
Guillain-Barré syndrome or myasthenic syndrome/myasthenia gravis 
● 
Infusion-related reaction that requires the infusion to be discontinued 
The following AEs will not be considered DLTs: 
● 
Electrolyte abnormalities that are not associated with clinical sequelae or deemed not 
clinically significant and corrected with appropriate management or supplementation 
within 72 hours of onset 
● 
Grade 3 infusion site reaction if successfully managed and resolved within 72 hours of 
onset 
● 
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 within 72 hours of onset with standard antiemetic or antidiarrheal 
medications used at prescribed dose 
● 
Grade 3 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 
ASP0739 and/or pembrolizumab will be considered to be a DLT 
● 
Grade 3 or lower irAEs that resolve to ≤ grade 1 within 72 hours of onset after starting 
treatment including corticosteroids 
Participants who are tolerating ASP0739 and/or pembrolizumab 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. Refer to the Participant 
Replacement during Dose Escalation/Safety Lead-in section for definition of evaluable 
participants. 


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DLTs Requiring Discontinuation of Treatment 
● 
If a study participant develops a grade 4 DLT after receiving cycle 1, then the study 
participant should be discontinued from treatment. 
● 
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 be discontinued from treatment. 
● 
If there is a delay in administration of the second cycle by > 4 weeks, it would result in 
discontinuation from treatment after discussion with the sponsor. 
Study Enrollment Interruption:  
Study enrollment will be temporarily interrupted pending review of the following: 
● 
Any death that is not related to disease progression occurring within 30 days of receiving 
ASP0739 and/or pembrolizumab 
● 
Occurrence of 2 grade ≥ 4 DLTs in 2 study participants 
● 
Any grade 4 hypersensitivity reaction/anaphylaxis 
Participant Replacement during Dose Escalation/Safety Lead-in:  
Participants may be replaced in the safety lead-in or dose escalation cohort if: 
● 
Participant is discovered to have enrolled without fully satisfying eligibility criteria. 
● 
Participant did not receive the planned dose in cycle 1 for reasons other than DLT. 
● 
Participant has no DLT and withdraws from the study before the end of the DLT 
evaluation period. 
The decision to replace participants will be made by the sponsor based on the above criteria. 
Recommended Phase 2 Dose 
The sponsor, in conjunction with the DESC, will determine the RP2D of ASP0739 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 ASP0739.  
The dose level determined to be the RP2D must have data from at least 6 participants. 
Dose Escalation 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 for the 
phase 1 dose escalation and safety lead-in. 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 
expansion and phase 2 expansion cohorts for single agent and combination therapy with 
pembrolizumab. 
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 


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considered by the DESC. The DESC will assess whether a longer DLT observation period is 
warranted based on emerging data. Additionally, only when determining the RP2D, the 
DESC may choose a more conservative dosing decision than the MTD selected by BOIN 
design, based on evaluation of the safety data and other available data. 
The decision on the dose level for the next cohort will be based on the BOIN design. In 
addition, MTD will be determined by BOIN from at least 6 participants. The RP2D dose for 
expansion will not be higher than the MTD. If the RP2D is selected at the same dose level as 
the MTD based on the phase 1 dose escalation portion, the combination safety lead-in will 
start at one dose level lower than the MTD. 
Phase 2 Single Agent 
Once RP2D is determined, the phase 2 single agent cohorts may be opened in R/R SS, 
MRCL, ovarian cancer and other solid tumors known to express NY-ESO-1 (melanoma, 
NSCLC-adenocarcinoma and squamous cell and ESCC). If a confirmed response (partial 
response based on iRECIST [iPR] or complete response based on iRECIST [iCR], per 
independent central review or local assessment) occurs in other solid tumors known to 
express NY-ESO-1, a tumor-specific dose expansion cohort may be opened in that tumor 
type.   
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]. For R/R 
SS, MRCL and ovarian cancer, initially 18 participants will be enrolled in each 
tumor-specific expansion cohort (stage 1). If the iORR does not meet the optimal stopping 
boundaries (see table below), then an additional 25 participants (stage 2) may be enrolled for 
a total maximum sample size of 43 participants. When the total number of participants 
reaches the maximum sample size of 43, it may be predicted that ASP0739 is effective if the 
number of responses is greater than or equal to 8.  
Optimized Stopping Boundaries for SS, MRCL and Ovarian Cancer 
Number of participants treated 
Stop if number of responses ≤  
18 
2 
MRCL: myxoid/round cell liposarcoma; SS: synovial sarcoma 
For the melanoma/NSCLC/ESCC cohort, after a minimum of 10 participants per tumor type 
are enrolled, if less than approximately 6 participants for each tumor type of melanoma, 
NSCLC-adenocarcinoma or squamous cell carcinoma or ESCC are NY-ESO-1 positive upon 
analysis of the most recent tissue sample, then additional participants may be enrolled into 
the tumor type with less than approximately 6 NY-ESO-1 positive participants. 
UNIQUE to Japan Sites: 
Japanese participants will only be enrolled into the monotherapy arm of the dose expansion 
cohort. 


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Phase 2 Single Agent Dose Expansion Cohort with Japanese Safety Lead-in 
After the phase 1 dose escalation cohort has been completed, the phase 2 single agent dose 
expansion cohort with Japanese safety lead-in will be opened. The Japanese safety lead-in 
will enroll 3 to 8 safety evaluable participants to confirm Japanese tolerability of the RP2D of 
ASP0739. Japanese participants must be managed under hospitalization for 7 days from 
C1D1 through C1D8 during the Japanese safety lead-in. Prior to hospital discharge, the 
investigator must ensure participant safety by performing medical tests and procedures listed 
on Day 8 of Cycle 1. During the Japanese safety lead-in, an interval of 7 days will separate 
study treatment initiation for the second participant from the first participant. In the absence 
of toxicity, additional participants may be treated without any formal stagger. 
The tolerability of ASP0739 single agent therapy RP2D will be assessed during the DLT 
observation period, which is from C1D1 to C1D28. Quantitative assessment of DLTs will be 
performed referring to the concept of a BOIN design with the target DLT rate of 30% and 
optimal interval of (0.236, 0.359) to determine if the ASP0739 single agent therapy RP2D is 
tolerable and is based on a DLT occurrence after 28 days. The tolerability evaluation rule is 
as follows:  
 
Number of Participants evaluable for DLT 
Assessment 
3 
4 
5 
6 
7 
8 
[Tolerable] 
If the number of participants with DLTs is 
equal or less than the number given in the 
corresponding cell, the ASP0739 single agent 
therapy RP2D can be determined to be 
tolerable. 
0 
0 
1 
1 
1 
1 
[Stay] 
If the number of participants with DLTs is 
equal to the number given in the 
corresponding cell, enrollment is continued 
until the maximum number of participants is 
reached. 
1 
1 
NA 
2* 
2* 
2* 
[Not tolerable] 
If the number of participants with DLTs is 
equal or greater than the number given in the 
corresponding cell, the ASP0739 single agent 
therapy RP2D is determined to be intolerable. 
2 
2 
2 
3 
3 
3 
DLT: dose limiting toxicity; NA: not applicable; RP2D: recommended phase 2 dose; TEM: tolerability 
evaluation meeting 
*When the number of participants for DLT assessment reaches the maximum number of participants and the 
recommended action is Stay, the tolerability of the dose will be assessed comprehensively at the TEM. 
A minimum of 3 evaluable participants must be enrolled at the dose level used to determine 
the tolerability of RP2D in Japanese participants. Three to four safety evaluable participants 
are enrolled as initial assessment. If the evaluation is to be continued based on DLT 


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occurrence, additional 3 to 4 safety evaluable participants are enrolled. After the tolerability 
of RP2D is confirmed in Japanese participants, additional Japanese participants will be 
enrolled into dose expansion part continuously. 
Tolerability Evaluation Meeting 
A TEM consisting of sponsor representatives and investigators will convene once the number 
of Japanese participants [Section 10.1.5.1 Tolerability Evaluation Meeting] completes the 
DLT observation period and data are available for review. TEM members should consider all 
available safety findings when making their evaluations and decisions. Additional details 
regarding responsibilities, membership requirements and safety review time points are 
included in the TEM Charter. 
Replacement of Participants in Japanese Safety Lead-in 
Participants may be replaced in the safety lead-in if: 
● 
The participant is discovered to have enrolled without fully satisfying the eligibility 
criteria. 
● 
The participant received less than the planned dose in C1 for reasons other than a DLT. 
● 
The participant has experienced 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 
safety lead-in will not be replaced. 
The 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 ASP0739 upon resolution of the DLT event to ≤ grade 1 or 
baseline. 
A participant who meets the stopping criteria will not be receive study drug at C2. 
Additionally, at the TEM, the aggregate safety data are reviewed if any study stopping rules 
below have been met: 
● 
If a study participant develops a grade 4 DLT after receiving C1 
● 
If a study participant develops a grade ≥ 3 non-hematological AE that does not resolve to 
≤ grade 2 within 72 hours of onset 
● 
Note: This event should be considered a DLT. 
● 
If there is a delay in administration of C2 by > 4 weeks, it may result in discontinuation 
of treatment after discussion with the sponsor. 
Study enrollment and study treatment of the Japanese safety lead-in will be temporarily 
interrupted if any of the following events occur in a participant: 
● 
Any death that is not related to disease progression occurring within 30 days of receiving 
ASP0739 


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● 
Occurrence of 2 grade ≥ 4 DLTs in 2 participants 
● 
Any grade 4 hypersensitivity reaction/anaphylaxis 
Phase 2 Combination of ASP0739 + Pembrolizumab  
Once safety lead-in is completed and 2 radiographic responses (iCR or iPR) are observed in 
the phase 2 dose expansion monotherapy cohort by local or central review, the phase 2 
combination cohorts may be opened in the respective tumor type where the responses were 
observed. 
For R/R SS, initially 22 participants will be enrolled in an expansion cohort (stage 1). If the 
iORR does not meet the optimal stopping boundaries (see table below) for R/R SS, then an 
additional 38 participants (stage 2) may be enrolled for a total maximum sample size of 60. 
When the total number of participants reaches the maximum sample size of 60, it may be 
predicted that ASP0739 in combination with pembrolizumab is effective if the number of 
responses is greater than or equal to 18.  
Optimized Stopping Boundaries for SS 
Number of participants treated 
Stop if number of responses ≤  
22 
3 
SS: synovial sarcoma 
For R/R MRCL, initially, 22 participants will be enrolled in an expansion cohort (stage 1). If 
the iORR does not meet the optimal stopping boundaries (see table below) for R/R MRCL, 
then an additional 38 participants (stage 2) may be enrolled for a total maximum sample size 
of 60. When the total number of participants reaches the maximum sample size of 60, it may 
be predicted that ASP0739 in combination with pembrolizumab is effective if the number of 
responses is greater than or equal to 18. 
Optimized Stopping Boundaries for MRCL 
Number of participants treated 
Stop if number of responses ≤  
22 
3 
MRCL: myxoid/round cell liposarcoma 
For R/R ovarian cancer, initially, 10 participants will be enrolled in an expansion cohort 
(stage 1). If the iORR does not meet the optimal stopping boundaries (see table below) for 
R/R ovarian cancer, then an additional 19 participants (stage 2) may be enrolled for a total 
maximum sample size of 29. When the total number of participants reaches the maximum 
sample size of 29, it may be predicted that ASP0739 in combination with pembrolizumab is 
effective if the number of responses is greater than or equal to 4.  
Optimized Stopping Boundaries for Ovarian Cancer 
Number of participants treated 
Stop if number of responses ≤  
10 
0 
If both single agent and combination therapy expansion cohorts are open for the same tumor 
type, participants will be randomized to either single agent or combination therapy cohorts 


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and the randomization ratio will be based on the number of open slots still available at each 
cohort.  
Replacement of Participants in Phase 2 Dose Expansion  
If a participant in phase 2 is not response evaluable (defined as the response analysis set 
[RAS]), then an additional participant may be enrolled in that cohort based on sponsor 
discretion.  
4.2 
Scientific Rationale for Study Design 
This study was designed to evaluate ASP0739 as monotherapy and in combination with 
pembrolizumab in selected participants with advanced solid tumors known to express the 
NY-ESO-1 antigen. Antitumor efficacy of ASP0739 was demonstrated in preclinical studies. 
In a murine metastatic cancer model, a suppression of lung metastases in mice was observed, 
and in a murine melanoma model, a suppression of tumor growth. 
The rationale for evaluating the combination of ASP0739 and pembrolizumab is supported 
by preclinical data obtained from a murine melanoma model that shows superior antitumor 
activity of combination therapy over monotherapy. ASP0739 is an aAVC expressing 
NY-ESO-1. Tumor volume was suppressed in animals receiving aAVC-NY-ESO-1 treatment 
in combination with anti-PD1 antibody relative to aAVC-NY-ESO-1 or anti-PD1 antibody 
alone. This suggests additive activity of ASP0739 with checkpoint inhibitors like 
pembrolizumab, which are known to restore immune system tumor surveillance, while 
ASP0739 functions by priming and activating the immune system against NY-ESO-1 tumor 
cells. 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 confirm 
safety for this combination.  
In this study, each participant will receive ASP0739 as single agent or in combination with 
pembrolizumab every 28 days. To ensure participant safety, each escalation cohort will 
stagger treatment initiation to 28 calendar days between the treatment initiation of the first 
and second participants and 14 calendar days between the second and third participants at the 
same dose level for all escalation cohorts (as a single agent) or the safety lead-in cohort (for 
combination with pembrolizumab). In the absence of toxicity, additional participants may be 
treated at a dose level without any formal stagger. 
The design will closely monitor safety while efficiently assessing efficacy of ASP0739 dose 
levels of 1 × 107 cells/dose and 1 × 108 cells/dose as monotherapy and in combination at the 
single agent RP2D with pembrolizumab fixed dose of 400 mg every 6 weeks, until disease 
progression, unacceptable toxicity or up to 17 doses. To ensure that a starting dose of 
ASP0739 in combination with pembrolizumab is safe, the combination cohort will only start 
once the RP2D of ASP0739 single agent dose escalation is completed and determined to be 
safe by the DESC. The combination therapy will start with a safety lead-in cohort with RP2D 
determined from single agent dose escalation. If the RP2D is selected at the same dose level 


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as the MTD based on the phase 1 dose escalation portion, the combination safety lead-in will 
start at one dose level lower than the MTD. 
Tumor-specific expansion cohorts for ASP0739 monotherapy will begin following the 
determination of RP2D. The types of cancer for the expansion cohorts were selected based on 
expression of NY-ESO-1 in the tumor. Combination therapy in respective cancer cohort 
groups may begin once 2 local or central radiographic responses have been observed. 
Participants with human immunodeficiency virus will be excluded since a compromised 
immune system may affect the immune response induced by ASP0739.  
Objective response rate (ORR) is selected as a suitable primary efficacy endpoint in such an 
early phase study because it can be generally assessed early and with a smaller sample size 
compared with survival studies. In addition, ORR 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 
ASP0739 as monotherapy and in combination with pembrolizumab in the selected 
participants. 
4.3 
Dose Rationale 
4.3.1 
ASP0739 
The starting dose of ASP0739 is set at 1 × 107 cells/dose by intravenous infusion. This dose 
for the FIH study is anticipated to be safe with some pharmacological activity, as supported 
by the nonclinical studies and the ongoing FIH study for ASP7517 (7517-CL-0101) in which 
no DLTs were observed during the dose escalation phase, which includes 3 dose levels: 
1 × 106 cells/dose, 1 × 107 cells/dose and 1 × 108 cells/dose (highest dose determined to be 
tolerable by DESC; currently enrolling additional patients for confirmation of safety). The 
only difference between ASP0739 and ASP7517 is the antigen, NY-ESO-1 instead of WT1. 
Different antigens allow for targeting different tumor types without expected changes to the 
safety profile. 
Nonclinical pharmacology data suggest that the minimum biologically-active dose of 
ASP0739-surrogate or ASP0739 is 5 × 103 cells/mouse, since natural killer T (NKT) cell 
activation with anti-tumor effect was observed at this dose level or higher. The dose of 
5 × 103 cells/mouse is calculated as 1.7 × 105 cells/kg (5 × 103 cells/30 g) and estimated to be 
1 × 107 cells/dose/human (1.7 × 105 cells/kg × 60 kg). The starting dose for the FIH study 
was also assessed based on the results of the nonclinical toxicology studies. Toxicities (e.g., 
liver findings, changes in platelet count) were observed after ASP0739 intravenous 
administration at the lowest dose used in nonclinical studies (1 × 105 cells/kg: equivalent to 
6 × 106 cells/dose, administered per 60 kg human), and the no-observed-adverse-effect level 
was not established in those studies. However, the observed toxicity profile is similar to that 
of ASP7517 and it was noted that the toxicities are reversible and monitorable in the 
nonclinical studies. While ASP7517 expresses WT1, ASP0739 expresses NY-ESO-1; 


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however, the primary mode of toxicity is considered to be related to α-GalCer, which is part 
of the construct in both ASP7517 and ASP0739 in similar amounts. The difference in antigen 
targeting is not expected to increase toxicity, and may be decreased for ASP0739, because 
WT1 is reported to be expressed in several tissues including testis, kidney and mesothelium 
[Maki et al, 2017], whereas NY-ESO-1 is reported to be selectively expressed in the testis 
only [Raza et al, 2020; Jungbluth et al, 2001].  
From these nonclinical results and the observed safety data in Study 7517-CL-0101 using the 
same aAVC platform, the recommended starting dose for the FIH study for ASP0739 is 
1 × 107 cells/dose. The dose level will be escalated to 1 × 108 cells/dose (highest dose in 
study 0739-CL-0101), since nonclinical data showed reversible and monitorable toxicities 
across the proposed investigational doses.  
The dosing regimen for the FIH study consists of repeated dosing in 28-day intervals. Since 
nonclinical pharmacology data suggest immune cells are further stimulated by repeated doses 
of aAVC with 4-week interval, an additive pharmacology effect could occur with this 
extended treatment regimen. Repeated doses (2 doses 28 days apart) resulted in a similar 
safety profile in mouse toxicity studies, including severity and frequency of findings, when 
compared with single dose administration. Also, there were no safety findings specific to the 
second dosing period, i.e., no cumulative toxicities were observed. Therefore, the currently 
available data support repeat dosing in the clinical setting. Following the first 2 cycles, 
participants who have not met any individual treatment discontinuation criteria and are 
receiving clinical benefit, may continue further treatment with ASP0739 (up to a total of 
6 doses) and pembrolizumab, as decided by the investigator. 
4.3.2 
Pembrolizumab 
The planned dose of pembrolizumab for this study is 400 mg every 6 weeks, until disease 
progression, unacceptable toxicity or for a total of 17 doses or until one of the discontinuation 
criteria is met. For combination treatment, a 400 mg pembrolizumab infusion will be 
administered first, followed by an ASP0739 infusion at least 1 hour after the completion of 
the pembrolizumab infusion. 
Recently, the manufacturer of pembrolizumab (Merck) has gained regulatory approval for a 
more convenient dosage in adult patients 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 patients whose weights are higher than 
average, with occupancy of 97% for patients weighing 100 kg and 96% for those weighing 
150 kg [Canadian Agency for Drugs and Technologies in Health, CADTH technology 
review, 2019]. 


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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.  
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., Health 
Insurance Portability and Accountability Act authorization for US study sites) must be 
obtained from the participant or legally authorized representative prior to any study-
related procedures (including withdrawal of prohibited medication, if applicable). 
2. Participant is at least 18 years of age and legally an adult according to local regulation at 
the time of signing the ICF.  
3. Phase 1 Dose Escalation only: 
● 
Participant has R/R solid tumor known to express NY-ESO-1 (examples are, but not 
limited to, gastric cancer, melanoma, ESCC, NSCLC, MRCL, SS, hepatic, SCCHN 
or ovarian cancer) after completing available SOC therapy or is not a candidate for 
SOC therapy. NY-ESO-1 expression status is not required for participant entry. 
4. Safety lead-in, Phase 2 Single agent and Combination Therapy only: 
● 
Participant has R/R SS or MRCL disease after undergoing available SOC treatment 
or is not a candidate for SOC therapy (must have previously received either an 
anthracycline or ifosfamide containing regimen or another systemic regimen, if not a 
candidate for either agent). 
o Participant has not received prior checkpoint inhibitor therapy (i.e., 
PD-1/PD-L1 treatment naïve) 
o SS: confirmation by the presence of a translocation between SYT on the X 
chromosome and SSX1, SSX2 or, SSX4 on chromosome 18 (may be 
presented in the pathology report as t [X; 18]). If unconfirmed, enrollment into 
the study should be discussed with the medical monitor. 


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o MRCL: confirmation by the presence of the reciprocal chromosomal 
translocation t (12;16) (q13;p11) or t(12; 22) (q13;q12). If unconfirmed, 
enrollment into the study should be discussed with the medical monitor. 
● 
Participant has R/R ovarian cancer that is: 
o platinum resistant 
OR 
platinum-sensitive, but the participant is not a candidate for platinum or other 
SOC therapy.  
o Participant has not received prior checkpoint inhibitor therapy (i.e., naïve PD-
1/PD-L1 treatment patients). 
● 
Participant has R/R solid tumor (melanoma, NSCLC-adenocarcinoma and squamous 
cell or ESCC) after available SOC treatment or is not a candidate for SOC therapy 
(single-agent only).  
5. Participant consents to provide an archival tumor specimen in a tissue block or unstained 
serial slides prior to IP administration. If an archival tissue sample is not available, 
enrollment into the study should be discussed with the medical monitor. 
6. Participant in phase 2 consents to provide tumor specimen obtained within 56 days prior 
to first dose of study treatment, as tissue block or unstained serial slides. 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.  
7. Participant in phase 2 consents to undergoing a tumor biopsy (core needle biopsy or 
excision) during the treatment period as indicated in the schedule of assessments.  
8. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 
≤ 2.  
9. Participant with life expectancy of ≥ 12 weeks at the time of screening. 
10. Participant must meet the following criteria as indicated on the clinical laboratory tests 
during screening period: 
● 
Serum AST and ALT ≤ 2.5 × ULN (or < 5 × ULN if known liver metastases) 
● 
Serum TBL ≤ 1.5 × ULN (or < 3 × ULN if known liver metastases) 
● 
Serum creatinine ≤ 1.5 × ULN or an estimated glomerular filtration rate of 
> 50 mL/min as calculated by the Modification of Diet in Renal Disease equation. 
● 
Platelets ≥ 100000/μL  
● 
ANC ≥ 1500/μL 
● 
Hemoglobin ≥ 9 g/dL 
● 
Prothrombin time/international normalized ratio (PT/INR) < 1.5 × ULN unless on 
warfarin.  
● 
PTT < 1.5 × institutional normal limits. 
11. A female participant is eligible to participate if she is not pregnant [Section 10.2 
Appendix 2: Contraception Requirements] and at least one of the following conditions 
apply: 
● 
Not a woman of childbearing potential (WOCBP) as defined in [Section 10.2 
Appendix 2: Contraception Requirements] 
OR 


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● 
WOCBP who agrees to follow the contraceptive guidance as defined in [Section 10.2 
Appendix 2: Contraception Requirements] throughout the treatment period and for at 
least 6 months after the final IP administration. 
12. Female participant must not be breastfeeding at screening or during the study period and 
for 6 months after the final IP administration. 
13. Female participant must not donate ova at screening and throughout the study period and 
for 6 months after the final IP administration. 
14. A male participant with female partner(s) of childbearing potential must agree to use 
contraception as detailed in [Section 10.2 Appendix 2 Contraception Requirements] 
during the treatment period and for at least 6 months after the final IP administration. 
15. Male participant must not donate sperm starting at screening and throughout the study 
period and for 6 months after the final IP administration. 
16. Participant agrees not to participate in another interventional study while on treatment. 
17. Participant has measurable disease according to RECIST 1.1. For participant with only 1 
measurable lesion and prior radiotherapy, the lesion must be outside the field of prior 
radiotherapy or must have documented progression following radiation therapy. 
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 has persistent non-hematological toxicities of ≥ grade 2 (NCI-CTCAE v5.0), 
with symptoms and objective findings from treatment (including chemotherapy, kinase 
inhibitors, immunotherapy, experimental agents, radiation or surgery). 
2. Participant has received any of the following therapies (for inclusion in the study, all 
abnormalities must have returned to ≤ grade 1):  
● 
Systemic immunomodulators (checkpoint inhibitors) - except the dose escalation 
phase and the NY-ESO-1 solid tumor (melanoma, NSCLC-adenocarcinoma and 
squamous cell and ESCC) cohorts in the dose expansion phase of monotherapy, 
which may have received prior checkpoint inhibitor therapy 
● 
Immunosuppressive drugs including steroids ≤ 14 days prior to treatment 
● 
Cytotoxic agents ≤ 14 days prior to treatment 
● 
Investigational agent ≤ 21 days prior to treatment or 5 half-lives, whichever is 
shorter 
● 
Radiation therapy ≤ 21 days prior to treatment 
3. Participant has clinically active or untreated nervous system metastases. Participants with 
previously treated central nervous system (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 study treatment 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. 


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4. Participant has an active autoimmune disease. Participant 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. 
5. 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.  
6. Participant has known history of serious hypersensitivity reaction to a known ingredient 
of ASP0739 or pembrolizumab or severe hypersensitivity reaction to treatment with 
another monoclonal antibody. 
7. Participant has a prior malignancy active (i.e., requiring treatment or intervention) within 
the previous 2 years prior to 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. 
8. Participant has received a prior allogeneic bone marrow or solid organ transplant. 
9. Participant has an active uncontrolled infection within 14 days of treatment. 
10. Participant is known to have human immunodeficiency virus infection. 
11. Participant has active hepatitis B or C or other active hepatic disorder or participant is on 
hepatitis treatment. Hepatitis C RNA testing is not required in participants with negative 
hepatitis C antibody testing. 
12. Participant has any condition which, in the investigator’s opinion, makes the participant 
unsuitable for study participation. 
13. Participant has had a major surgical procedure and has not completely recovered within 
28 days prior to the start of study treatment. 
14. Participant has had a myocardial infarction or unstable angina within 6 months prior to 
the start of study treatment 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. 
15. Participant is expected to require another form of anti-cancer therapy while on study 
treatment. 
16. This criterion has been removed.  
17. Participant has a known or suspected hypersensitivity to bovine-derived protein or has 
suspected hypersensitivity to any ingredients of ASP0739. 
Additional Exclusion Criteria for Participants in Combination Therapy Cohorts 
1. Participants with a history of myocarditis or congestive heart failure (as defined by New 
York Heart Association Functional Classification III or IV), as well as unstable angina, 
serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 
6 months prior to study entry. 
2. Participants with active interstitial lung disease (ILD)/pneumonitis or a history of 
ILD/pneumonitis requiring treatment with systemic steroids. 
3. Participants with baseline pulse oximetry < 92% “on Room air.” 


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4. Participants must not have known microsatellite instability-high or deficient MisMatch 
Repair. 
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 be resolved 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 must be 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) 
6.1 
Investigational Product(s) Administered 
Table 9 
Investigational Product(s) 
Name 
ASP0739 
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 
The solution is clear to slightly 
opalescent, colorless to slightly yellow 
Unit Dose Strength 
 
 
 
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 or obtained 
locally 
IMP: Investigational Medicinal Product 
Refer to the pharmacy manual for detailed information regarding preparation, handling and 
storage of ASP0739. 
Refer to the approved pembrolizumab package insert, summary of product characteristics, 
monograph or local product information supplied by the manufacturer for additional 
instructions for drug preparation and dilution.  
6.1.1 
Investigational Product Administration 
ASP0739 will be diluted with Lactated Ringer’s injection to approximately 50 mL and 
administered by intravenous infusion at 4 to 6 mL/min infusion rate through a dedicated 
intravenous line every 28 days during treatment beginning on C1D1. 
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 
the ASP0739 injection for participants in the ASP0739 and pembrolizumab combination 
therapy arms.   
6.2 
Preparation/Handling/Storage/Accountability 
6.2.1 
Packaging and Labeling 
Sponsor-provided IP used in this study will be prepared, packaged and labeled under the 
responsibility of qualified personnel at Astellas Pharma Global Development, Inc. (APGD) or 
CCI


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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 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 safety lead-in portion of the ASP0739 and 
pembrolizumab combination arm when both phase 2 single agent dose expansion and 
combination therapy safety lead-in are open. 
If both single agent and combination therapy expansion cohorts are open for the same tumor 
type, participants will be randomized to either single agent or combination therapy cohorts 
and the randomization ratio will be based on the number of open slots still available at each 
cohort. 


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UNIQUE to Japan Sites:  
Japanese participants will be only enrolled into the monotherapy arm of the dose expansion 
cohort. 
6.4 
Investigational Product Compliance 
Dosing will take place in the clinical unit. The administration of IP will be supervised to 
ensure treatment compliance. The exact day and time of IP administration will be 
documented. 
6.5 
Dose Modification 
Dose modifications of ASP0739 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 AE after receiving a dose of ASP0739 may receive 
the subsequently scheduled dose of ASP0739 only after the observed grade 3 AE has 
resolved to grade 1; the subsequent dose of ASP0739 may be reduced by one dose level, 
either from 1 × 108 to 1 × 107 cells/dose or from 1 × 107 to 1 × 106 cells/dose.  
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 [Sections 10.8 Appendix 8: Infusion Reaction Dose Modification and Treatment 
(Guidelines for ASP0739 and Pembrolizumab); 10.10 Appendix 10: Dose Modification and 
Toxicity Management for Immune-related Adverse Events; and 10.11 Appendix 11: Dose 
Modification and Toxicity Management of Infusion Reactions Related to Pembrolizumab] 
and the 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  
ASP0739 will be given up to a maximum of 6 cycles. ASP0739 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 ASP0739 does not have 
authorization to be administered after the study is complete.  
6.7 
Treatment of Overdose  
In the event of suspected ASP0739 overdose, the participant should receive supportive care 
and monitoring. The medical monitor/expert should be contacted as applicable. 


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For this study, an overdose of pembrolizumab will be defined as any dose of 1000 mg or 
≥ 2.5 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. 
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:  
● 
The use of systemic steroids (> 30 mg per day of hydrocortisone or > 10 mg per day of 
prednisone or equivalent) is not allowed during study treatment unless needed to manage 
AEs related to study treatment. 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 
study treatment (e.g., delayed-type hypersensitivity reaction caused by a contact 
allergen) is also allowed. Corticosteroids to manage irAEs are permitted.  
● 
Immunosuppressive agents including but not limited to, high dose steroids, mammalian 
target of rapamycin inhibitors (e.g., rapamycin) or mycophenolate mofetil. 
● 
Investigational agents other than ASP0739 and pembrolizumab. 
● 
Any other cancer directed therapies are prohibited during the study with ASP0739 and 
ASP0739 and pembrolizumab, including chemotherapy, biologic therapy, radiation 
therapy or surgery. 
o Palliative (limited field) radiation therapy: for bone metastases is allowed. Study 
treatment 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 prior to screening. 
● 
Vaccines: Live vaccines are prohibited while the participant is receiving study treatment 
and for 30 days after last dose of study treatment. 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-Guérin and typhoid vaccine. 
o COVID-19 prevention is allowed if non-live vaccines are to be used. In cases where 
a live vaccine is needed for COVID-19 prevention, please contact the medical 
monitor for discussion. 


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Refer to [Section 10.5 Appendix 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 3]. 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 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. 
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 


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consent as SOC 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 complete response (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 progressive 
disease (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 3] 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. 
● 
Laboratory assessments must be submitted for centralized data entry. 
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 3]. 
● 
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 of rest and will include 
temperature, systolic and diastolic blood pressure and pulse. 
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 3]. 
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. If height cannot be measured at the 
screening visit, it can be collected at any time during the course of the study but should be 
recorded for the screening visit. 


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7.2.4 
Electrocardiogram  
12-lead ECGs will be recorded in triplicate (at least 2 min apart per time point) and 
transmitted electronically for central reading. On IP administration days, ECGs will be 
obtained: 
● 
At C1D1 and any visit when pembrolizumab and ASP0739 are administered together, 
ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h post 
dose of ASP0739. 
● 
ASP0739 dosing only: ECGs are obtained predose (-1 h from start of ASP0739 infusion) 
and 1 to 2 h post dose of ASP0739. 
● 
Pembrolizumab dosing only: ECGs are obtained predose (-1 h from start of 
pembrolizumab infusion) and 1 to 2 h post dose of pembrolizumab.  
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  
Radiographic disease assessment is to be performed at screening and throughout the study 
every 56 ± 7 days. The 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 SOC are acceptable as screening scans, if done within 28 days prior to C1D1.  
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 3].  
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 
 


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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 and other procedures, or 
that caused the participant to discontinue the IP and other procedures and/or study [see 
Section 10.3 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 3] 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 3] 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 of an SAE/AE 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 pre-dose 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. 


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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 
Section 10.3.7 Reporting Procedures for Special Situations]) 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 an 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 an SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the sponsor will 


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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 
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]. 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 IRRs are 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.  


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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 ASP0739 cells via 
determination of genomic DNA in the cell by a quantitative polymerase chain reaction 
method for the dose escalation cohort, expansion cohort and safety lead-in cohort. Sampling 
time points are as shown in the schedule of assessments [Table 5].  
Serum concentrations of pembrolizumab will be evaluated in the combination therapy arm, 
including safety lead-in, as outlined in the schedule of assessments [Table 5]. 
Refer to the laboratory manual for detailed information regarding sampling, processing, 
shipping and storage instructions. 
7.5 
Pharmacodynamics/Biomarker  
Samples for exploratory pharmacodynamics and biomarker analyses of ASP0739 will be 
collected according to the schedules of assessments [Table 1 and Table 2].  
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 ASP0739.  
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 


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as described in [Section 9.4.5.1 Analysis of Exploratory Biomarker(s)]. Examples of these 
biomarkers include, but are not limited to, anti-NY-ESO-1 antibodies, cytokine expression 
and secretion (e.g., IFNg), NY-ESO-1-specific T lymphocytes (e.g., cytotoxic 
T lymphocytes), immune cell populations (e.g., NKT cells, NK cells, etc.), expression levels 
of NY-ESO-1 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 NY-ESO-1, 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 (5 microns thick) is necessary. 
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). 


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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 4]. 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 of treatment and local laboratory requirements. At any time during the 
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 will be from participants on C1D1 
and will not exceed 80 mL; the maximum amount of blood collected in one cycle will be 
during C1 and will not exceed 130 mL. 
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 that, in the opinion of the 
investigator, indicates continued treatment is not in the best interest of the participant. 


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● 
In the combination therapy arm only, treatment will be permanently discontinued 
following occurrence of grade 3 to 4 myocarditis. 
● 
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/or the participant is no longer 
deriving clinical benefit, in the opinion of the investigator. 
● 
Participant begins other anti-cancer therapies. 
● 
Participant experiences disease relapse/progression. 
● 
Investigator/subinvestigator determines that the continuation of the study treatment will 
be detrimental to the participant. 
● 
Participant is in need of receiving prohibited concomitant treatment(s) based on 
Investigator’s clinical opinion. 
● 
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 schedule of 
assessments [Table 3]. 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 schedule of 
assessments [Table 3]. 
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 hypothesis for the primary efficacy endpoint for each indication and dose level are given 
as follows: 
Phase 2 Single Agent (SS, MRCL, Ovarian) 
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. 


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Solid tumors known to express NY-ESO-1 (melanoma, NSCLC-adenocarcinoma and 
squamous cell as well as ESSC) 
There is no formal statistical hypothesis for this cohort. 
Phase 2 Combination Therapy 
SS 
H0:  iORR is 20%, at which the treatment is deemed as unacceptable. 
H1:  iORR is at least 35%, at which the treatment is deemed as acceptable. 
MRCL 
H0:  iORR is 20%, at which the treatment is deemed as unacceptable. 
H1:  iORR is at least 35%, at which the treatment is deemed as acceptable. 
Ovarian 
H0:  iORR is 5%, at which the treatment is deemed as unacceptable.  
H1:  iORR is at least 20%, at which the treatment is deemed as acceptable. 
9.2 
Sample Size Determination 
ASP0739 Single Agent 
A total of approximately 181 participants may be enrolled in single agent treatment. 
Phase 1 Single Agent Dose Escalation:  
The sample size of approximately 12 participants for the dose escalation phase 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, a minimum of 6 evaluable and up 
to 12, should provide adequate information for the dose escalation and safety objectives of 
the study.  
Phase 2 Single Agent:  
It is estimated that up to approximately 169 participants may be enrolled in the single agent 
arms. The iORR is monitored using the BOP2 design.  
For each indication (SS, MRCL or ovarian), with assumptions mentioned in the statistical 
hypotheses section, the statistical power would be approximately at least 0.80 while 
controlling the type I error rate at 0.05 (1-sided).  
The sample size of approximately 40 participants for other solid tumors known to express 
NY-ESO-1 is not based on statistical power calculation. A minimum of 10 participants per 
tumor type will be enrolled. If less than approximately 6 participants within each tumor type 
of melanoma, NSLCC-adenocarcinoma or squamous cell and ESCC are NY-ESO-1 positive 
based on analysis of the most recent tissue sample, additional participants may be added so 
that there are approximately 6 NY-ESO-1 positive participants. 
ASP0739 Combination with Pembrolizumab:  
A total of approximately 158 participants may be enrolled in combination therapy.  


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Combination Therapy Safety Lead-in 
The sample size of approximately 6 to 9 participants for safety lead-in 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 safety objectives of the study.  
Phase 2 Combination Therapy:  
It is estimated that up to approximately 149 participants may be enrolled in the combination 
therapy arms. The iORR is monitored using the BOP2 design.  
For each indication, with assumptions mentioned in the statistical hypotheses section, the 
statistical power would be approximately at least 0.80 while controlling the type I error rate 
at 0.05 (1-sided). 
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 1 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 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 the 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 the DLT evaluation period. 
The DEAS will be used for the analysis of DLT data. 
DLT: dose limiting toxicity 
 


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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 nonmissing observation prior to the first administration of 
IP, unless otherwise specified. 
In general, dose escalation and safety lead-in data will be summarized by dose level. Phase 2 
data will be summarized by monotherapy and combination therapy arms and by tumor types, 
unless specified otherwise. 
Demographics and baseline characteristics will be summarized for all treated participants. 
The number and percentage of participants who completed and discontinued treatment and 
reasons for treatment discontinuation will be presented for all enrolled participants, for 
participants in the safety analysis set (SAF). Similar tables for screening disposition, 
follow-up period disposition and survival follow-up disposition will also be presented for all 
treated participants. 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. IP exposure will be 
summarized using descriptive statistics and will be listed. 
9.4.2 
Analysis of Efficacy  
Binary efficacy endpoint analysis will be conducted on the response analysis set (RAS), 
while time to event endpoints will be conducted on the full analysis set (FAS). The 
interpretation of results of the primary efficacy endpoint will be based on the RAS. 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 
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. 


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9.4.2.2 Sensitivity Analysis 
The same analysis used for 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 used for 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 
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 by 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. 


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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. 
9.4.3.1 Adverse Events  
AEs will be coded using MedDRA and graded using NCI-CTCAE v5.0. 
A treatment-emergent adverse event (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 single agent and 
combination therapy arms, by dose level, and overall and by time point. Shifts from baseline 
to the worst grade based on NCI-CTCAE v5.0 in laboratory tests will also be tabulated.  
Laboratory data will be listed. 


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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 single agent and combination therapy arms, 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 single agent and combination 
therapy arms, by dose level and by time point. 
Interpretations of routine 12-lead ECG results will be summarized by single agent and 
combination therapy arms, by dose level and by 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. 
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 ASP0739 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 ASP0739 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 
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. 


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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 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 a 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 
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 during which 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 International Ethical Guidelines 
o Applicable ICH 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 or their legally authorized representative and answer all questions regarding 
the study. 
● 
Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed consent 
that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health 


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Insurance Portability and Accountability Act requirements, where applicable, and the 
IRB/IEC or study center. 
● 
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 or their legally authorized 
representative. 
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. A copy of the signed 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 


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representative(s), the IRB/IEC and when necessary, representatives of the regulatory health 
authorities to review and/or to copy any medical records relevant to the study. 
The sponsor agrees to comply and process personal data in accordance with all applicable 
privacy laws and regulations, including, without limitation, the Personal Information 
Protection Law in Japan and privacy laws in the US. If the services will involve the collection 
or processing of personal data (as defined by applicable data protection legislation) within the 
European Economic Area (EEA), then the sponsor shall serve as the controller of such data, 
as defined by the EU Data Protection Directive (DPD), and investigator and/or third party 
shall act only under the instructions of the sponsor in regard to personal data. If the sponsor is 
not based in the EEA, the sponsor must appoint a third party to act as its local data protection 
representative or arrange for a co-controller established in the EU for data protection 
purposes in order to comply with the DPD. 
10.1.5 Committee(s) Structure 
10.1.5.1 Tolerability Evaluation Meeting 
UNIQUE to Japan Sites: 
A TEM consisting of sponsor representatives and investigators will convene once the number 
of Japanese participants (defined in the protocol) completes the DLT observation period and 
data are available for review. TEM members should consider all available safety findings 
when making their evaluations and decisions. Additional details regarding responsibilities, 
membership requirements and safety review time points are included in the TEM Charter. 
10.1.5.2 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. 
While safety data from the DLT observation period in the escalation cohorts and the safety 
lead-in are the minimum safety data needed for the DESC meeting, all available safety 
findings will be considered by the DESC. The DESC will assess whether a longer DLT 
observation period is warranted based on emerging data. Additionally, only when 
determining the RP2D, the DESC may choose a more conservative dosing decision than the 
MTD selected by BOIN design, based on evaluation of the safety data and other available 
data. 
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 


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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 
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., 
CROs). 
● 
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 in the CRF. 
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, archived, 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 


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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 CRF 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. 
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 


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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. 
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 CRO(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. 


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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.  
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, CRFs and source 
documents. Direct access to these documents will be required by the auditors. 
• QTLs will be predefined in the applicable plan(s) to identify systematic issues that 
can impact participant safety and/or reliability of study results. These predefined 
parameters will be monitored during the study, and important deviations from the 
QTLs and remedial actions taken will be summarized in the CSR. 
 


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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 months 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. 
aLocal laws and regulations may require use of alternative and/or additional contraception 
methods. 
bTypical 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 
aLocal 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], 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. 
● 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment. 


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● 
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 
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 


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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 NCI-CTCAE 
guidelines, v5.0. The items that are not stipulated in the NCI-CTCAE, v5.0 will be assessed 
according to the criteria below and entered into the eCRF:  
Table 11 
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. 
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 


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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. 
Specific to Japan Sites: 
In the case of an 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 
OYOBIFUGUAI HOUKOKUSHO or JUTOKUNA YUUGAIJISHOU HOUKOKUSHO 
containing all information that is required by the appropriate regulatory authorities to the 
sponsor by fax or email immediately (within 24 hours of awareness) and to the head of the 
hospital.  
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 
 


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UNIQUE to Japan Sites: 
For contact details, see [Contact Details of Sponsor's Key Personnel]. Fax or email the 
JUTOKUNA YUUGAIJISHOU HOUKOKUSHO or JUTOKUNA YUUGAIJISHOU 
OYOBI FUGUAI HOUKOKUSHO and special situations worksheet to: 
Astellas Pharma Inc. – Japan 
Pharmacovigilance 
Fax number +3-3243-5747  
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 6 months 
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 
an 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. 
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 IPs, 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).  
Provision of information from the PV department to the quality assurance 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. 


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10.3.9 Urgent Safety Measures 
An urgent safety measure (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 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 12 
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 an 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 are prohibited, with the exception of immune-related AEs. 
10.5.2 Other Investigational Agents 
Treatment with investigational agents other than ASP0739 or pembrolizumab 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 13 
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, 
Fibrinogen) 
Activated partial thromboplastin time (aPTT) 
International normalized ratio (INR) 
Prothrombin time (sec) (PT) 
Fibrinogen  
Thyroid Panel (combination 
cohort only) 
Triiodothyronine or free triiodothyronine 
Free thyroxine 
Thyroid stimulating hormone 
eCRF: electronic case report form; hCG: human chorionic gonadotrophin; PT/INR: prothrombin 
time/international normalized ratio. 
†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 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 ASP0739 and Pembrolizumab) 
Table 14 
Infusion Reaction Dose Modification and Treatment (Guidelines for ASP0739 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 hours. 
• 
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 hr of stopping drug infusion, the infusion may be 
restarted at 50% of the original infusion rate (e.g., from 100 mL/hr. to 50 mL/hr.). 
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 treatment (pembrolizumab only) 
Pembrolizumab only: Participant may be 
premedicated 1.5 hours  
(± 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 
ASP0739 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 hours 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. 
hr: hour; NCI: National Cancer Institute; NSAID: non-steroidal anti-inflammatory drug; po: by mouth 
 


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10.9 
Appendix 9: Monitoring of Pembrolizumab Potential Immune-related Adverse Events 
Table 15 
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 Adverse Events 
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 16. 
Based on the mechanism of action of ASP0739, 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]) and managed as required per SOC. 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 16 
Dose Modification and Toxicity Management Guidelines for Immune-related Adverse Events Associated with Pembrolizumab 
General instructions: 
1. Severe and life-threatening 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 
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 
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irAEs 
Toxicity grade (CTCAE 
v5.0) 
Action with pembrolizumab 
Corticosteroid and/or other 
therapies  
Monitoring and follow-up  
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 
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 
AE: adverse event; ALT: alanine aminotransferase; AST: aspartate aminotransferase; CTCAE: common terminology criteria for adverse events; GI: gastrointestinal; irAE: immune-
related adverse event; IV: intravenous; T1DM: Type 1 diabetes mellitus; ULN: upper limit of normal 
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aAST/ALT: > 3.0 to 5.0 × ULN if baseline normal; > 3.0 to 5.0 × baseline, if baseline abnormal; bilirubin: > 1.5 to 3.0 × ULN if baseline normal; > 1.5 to 3.0 × baseline if baseline 
abnormal 
bAST/ALT: > 5.0 to 20.0 × ULN, if baseline normal; > 5.0 to 20.0 × baseline, if baseline abnormal; bilirubin: > 3.0 to 10.0 × ULN if baseline normal; > 3.0 to 10.0 × baseline if 
baseline abnormal 
cAST/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 
dThe 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. 
eEvents that require discontinuation include but are not limited to: Guillain-Barre Syndrome, encephalitis, Stevens-Johnson Syndrome and toxic epidermal necrolysis. 


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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 17.  
Table 17 
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 hours. 
• 
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 hr of stopping drug infusion, the infusion may be 
restarted at 50% of the original infusion rate (e.g., from 100 mL/hr. to 50 mL/hr.). 
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 hours 
(± 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). 
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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 
hr: hour; 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 4] unless the site principal 
investigator discusses the need with the Astellas medical monitor to implement the alternate 
measures.  
The approach outlined within this appendix defines which assessments are required to 
maintain a favorable benefit/risk to the 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 Study 
Design and Dose Rationale] 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 principal investigator 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 patients 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 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 poses an additional risk to the 
participant’s health and safety 
Adherence to the original protocol as reflected in the schedule of assessment Table 1 to 
Table 4 is expected, where plausible, in the case of a crisis. The alternate measures as noted 
in Table 18 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 IP and maintaining critical safety and efficacy assessments for 
patients 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). 
Alternative Schedule of Assessments in Response to a Crisis 
No alternative measures are permissible for C1D1 and ASP0739 and/or pembrolizumab 
dosing days during combination therapy.  
 


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Table 18 
Study Interruption: Schedule of Assessments – Dose Escalation Cohort and Safety Lead-in Combination Cohort 
 
Alternate 
Approach(es) 
Treatmenta 
Pembro-
lizumab 
Mono-
therapy 
EOTe,w 
Cycle 1 
Cycle 2 
Cycles 3 to 4b 
Cycles 5 to 6c 
Doses  
5 to 17d 
Visit Days 
 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
8 
15 
22 
1 
8 
15 
22w 
Every 6 
weeks 
 
Window (days) 
 
 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
+ 7 
Physical 
Examinationf 
Except for ASP0739 
and/or Pembrolizumab 
administration days at 
study site, may be 
obtained at local 
facility and results 
submitted to PI  
Xf 
X 
 
X 
X 
X 
Xf 
X 
 
X 
X 
X 
Xf 
X 
X 
X 
Xf 
X 
X 
X 
Xf 
Xf 
Vital Signsg 
Except for ASP0739 
and/or Pembrolizumab 
administration days at 
study site, may be 
obtained at local 
facility and results 
submitted to PI 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG 
Performance 
Except for ASP0739 
and/or Pembrolizumab 
administration days at 
study site, may be 
obtained remotely via 
telemedicine visit or at 
local facility and 
results submitted to PI 
Xh 
X 
 
X 
X 
X 
Xh 
X 
 
X 
Xh 
X 
Xh 
X 
X 
X 
Xh 
X 
X 
X 
Xh 
X 
Table continued on next page 


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Alternate 
Approach(es) 
Treatmenta 
Pembro-
lizumab 
Mono-
therapy 
EOTe,w 
Cycle 1 
Cycle 2 
Cycles 3 to 4b 
Cycles 5 to 6c 
Doses  
5 to 17d 
Visit Days 
 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
8 
15 
22 
1 
8 
15 
22w 
Every 6 
weeks 
 
Window (days) 
 
 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
+ 7 
12-Lead ECGi 
Except for ASP0739 
and/or Pembrolizumab 
administration days at 
study site, may be 
obtained at local 
facility and results 
submitted to PI. If 
cannot be performed, 
Astellas medical 
monitor to assess for 
study continuation. 
Xi 
 
 
X 
X 
 
Xi 
 
 
X 
Xi 
 
Xi 
 
 
 
Xi 
 
 
 
 
X 
Prior and 
Concomitant 
Medications 
Except for ASP0739 
and/or Pembrolizumab 
administration days at 
study site, may be 
obtained remotely via 
telemedicine visit 
X 
X 
 
X 
X 
X 
X 
X 
 
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 clinic and 
result submitted to PI 
Xj 
 
 
 
 
 
Xj 
 
 
 
 
 
Xj 
 
 
 
Xj 
 
 
 
Xj 
Xj 
Clinical 
Laboratory Tests 
(chemistry, 
hematology, 
urinalysis)k 
Except for ASP0739 
and/or Pembrolizumab 
administration days at 
study site, may be 
obtained at local 
facility and results 
submitted to PI 
Xh 
X 
 
X 
X 
X 
Xh 
X 
 
X 
X 
X 
Xh 
X 
X 
X 
Xh 
X 
X 
X 
Xh 
X 
Table continued on next page 


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Alternate 
Approach(es) 
Treatmenta 
Pembro-
lizumab 
Mono-
therapy 
EOTe,w 
Cycle 1 
Cycle 2 
Cycles 3 to 4b 
Cycles 5 to 6c 
Doses  
5 to 17d 
Visit Days 
 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
8 
15 
22 
1 
8 
15 
22w 
Every 6 
weeks 
 
Window (days) 
 
 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
+ 7 
Coagulation 
Profile (PT/INR, 
fibrinogen)k 
Except for ASP0739 
and/or Pembrolizumab 
administration days at 
study site, may be 
obtained at local 
facility and results 
submitted to PI 
Xh 
X 
 
X 
X 
X 
Xh 
X 
 
X 
X 
X 
Xh 
 
 
 
Xh 
 
 
 
Xh 
X 
Thyroid Profile 
Panelk,l 
Except for ASP0739 
and/or Pembrolizumab 
administration days at 
study site, may be 
obtained at local 
facility and results 
submitted to PI 
 
 
 
 
 
 
 
 
 
 
X 
 
Every 6 weeks after C2D15 dose 
 
 
 
PGxm 
None 
Xm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Buccal Swab for 
HLA Typing 
None 
Xh 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE/SAE 
Assessment 
Except for ASP0739 
and/or Pembrolizumab 
administration days at 
study site, may be 
obtained remotely via 
telemedicine visit 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetic: 
ASP0739n 
None 
See Table 5 for detailed sample time points 
Table continued on next page 


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Alternate 
Approach(es) 
Treatmenta 
Pembro-
lizumab 
Mono-
therapy 
EOTe,w 
Cycle 1 
Cycle 2 
Cycles 3 to 4b 
Cycles 5 to 6c 
Doses  
5 to 17d 
Visit Days 
 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
8 
15 
22 
1 
8 
15 
22w 
Every 6 
weeks 
 
Window (days) 
 
 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
+ 7 
Pharmacokinetic: 
Pembrolizumabn 
None 
See Table 5 for detailed sample time points 
Anti-NY-ESO-1 
antibody 
None 
Xh 
 
 
 
 
 
Xh 
 
 
 
 
 
Xh 
 
 
 
Xh 
 
 
 
Xt 
X 
Immune 
Response 
Biomarker 
(ELISpot) 
None 
Xh 
 
 
X 
X 
 
Xh 
 
 
X 
X 
 
Xh 
X 
X 
 
Xh 
X 
X 
 
Xt 
X 
Immune 
Response 
Biomarker 
(Tetramer)  
None 
Xh 
 
 
 
X 
 
Xh 
 
 
 
X 
 
Xh 
 
X 
 
Xh 
 
X 
 
Xt 
X 
Immune Cell 
Phenotyping 
None 
Xh 
 
 
X 
X 
 
Xh 
 
 
X 
X 
 
Xh 
X 
X 
 
Xh 
X 
X 
 
Xu 
X 
Cytokines 
None 
Xh 
X 
X 
X 
X 
 
Xh 
X 
X 
X 
X 
 
Xh 
X 
X 
 
Xh 
X 
X 
 
Xu 
X 
Circulating 
Tumor DNA 
None 
Xh 
 
 
 
 
 
Xh 
 
 
 
 
 
Xh 
 
 
 
Xh 
 
 
 
X 
Xv 
Archival Tumor 
Tissueo 
None 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pulmonary 
function testx 
May be obtained at 
local facility and 
results submitted to PI 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
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Alternate 
Approach(es) 
Treatmenta 
Pembro-
lizumab 
Mono-
therapy 
EOTe,w 
Cycle 1 
Cycle 2 
Cycles 3 to 4b 
Cycles 5 to 6c 
Doses  
5 to 17d 
Visit Days 
 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
8 
15 
22 
1 
8 
15 
22w 
Every 6 
weeks 
 
Window (days) 
 
 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
± 1 
± 1 
± 1 
± 3 
+ 7 
Radiographic 
Disease 
Assessmentp 
May be collected 
locally and submitted 
to PI. Assessment to be 
done per protocol 
requirements. Outside 
of the window, 
assessments need to be 
escalated to Astellas 
medical monitor 
Every 56 ± 7 days 
 
ASP0739 
Dosingr 
None 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
Pembrolizumab 
Dosings 
Every other dose may 
be administered locally 
during Pembrolizumab 
monotherapy only, 
otherwise must be 
administered at study 
site. 
X 
 
 
 
 
 
 
 
 
 
X 
 
Every 6 weekss 
X 
 
AE: adverse event; C: cycle; CR: complete response; CT: computed tomography; D: day; ECG: electrocardiogram; ECHO: echocardiogram; 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; MUGA: multiple gated acquisition scan; NY-ESO-1: New York esophageal 
squamous cell carcinoma 1; 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  
a. 
Cycles 1 through 6 represent ASP0739 single agent or combination of ASP0739 and pembrolizumab therapy; each ASP0739 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 ASP0739 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 ASP0739 in cycles 5 and 6. Participants who reach CR will not receive additional doses of 
ASP0739. 
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d. Participants in combination therapy only will continue to receive pembrolizumab as monotherapy for doses 5 up to 17. If participant receives at least 1 dose of ASP0739 but 
discontinues combination treatment of ASP0739 at any time prior to C5D15, then the participant may continue pembrolizumab as monotherapy for up to 96 weeks for a total of 17 
doses of pembrolizumab total for the study. 
e. 
The EOT visit will occur within 7 days of the PI decision to discontinue the participant for treatment or prior to the start of new anticancer treatment, whichever occurs first. If a 
participant is completing all visits in the last treatment cycle, the EOT visit will be within 7 days from the last planned visit. 
f. 
Height measurement performed at screening only. If height cannot be measured at the screening visit, it can be collected at any time during the course of the study, but should be 
recorded for the screening visit. Weight measurement performed at screening and day 1 of each cycle.  
g. The following vital sign assessments schedules apply: 
• 
At C1D1 and any visit when pembrolizumab and ASP0739 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 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 ASP0739 infusion, every 15 min (-5 to +10 min window) 
during ASP0739 infusion, at the end of ASP0739 infusion (-5 to +10 min window), and post dose (+30 min, +1, +2, +3 and +4 hours [± 10 min window each] from end of 
ASP0739 infusion). 
• 
ASP0739 dosing only: vital signs will be obtained within 15 min prior to start of ASP0739 infusion, every 15 min (-5 to +10 min window) during ASP0739 infusion, at the 
end of ASP0739 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 ASP0739 infusion. If 
participants are still available, additional optional vital sign assessments 3 hours (± 10 min) and 4 hours (± 10 min) after completion of the ASP0739 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 
pembrolizumab infusion; at the end of 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. 
h. Obtain predose. 
i. 
12-lead ECGs will be recorded in triplicate (at least 2 min apart per time point) and transmitted electronically for central reading. On IP administration days, ECG will be obtained:  
• 
At C1D1 and any visit when pembrolizumab and ASP0739 are administered together, ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h 
post dose of ASP0739. 
• 
ASP0739 dosing only: ECGs are obtained predose (-1 h from start of ASP0739 infusion) and 1 to 2 h post dose of ASP0739. 
• 
Pembrolizumab dosing only: ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h post dose of pembrolizumab. 
j. 
Urine or serum pregnancy test will be performed in women of childbearing potential. 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. For participants in combination therapy arm, troponin levels will be obtained at screening; thereafter, weekly for 6 weeks and subsequently every 
second week for 6 weeks. 
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 (Screening, C2D15 then every 6 weeks).  
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m. Whole blood for optional PGx study may be collected at C1D1 prior to IP administration. 
n. See Table 5 for collection schedule for ASP0739 single agent and ASP0739 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. 
Imaging will occur every 56 ± 7 days until confirmed progression by iRECIST. 
q. Enrollment or randomization will be done via IRT system after confirmation of eligibility and prior to dosing. 
r. 
In both the monotherapy and combination cohorts, each participant must remain at the site facility for 4 hours following the participant’s first dose of ASP0739. For the next dose 
(second dose) or additional subsequent single agent with ASP0739, participants must remain at the site facility for at least 2 hours after ASP0739 dosing. 
s. 
In the combination therapy arm, pembrolizumab will be administered as an intravenous infusion over 30 min followed by ASP0739 administration at least 1 hour after 
pembrolizumab administration. For participants enrolled in Japanese safety lead-in, C1D8 assessments should be performed prior to discharge from hospital. 
t. 
Samples collected at pembrolizumab doses 5, 7, 9, 11 and 13 only. 
u. Samples collected at pembrolizumab doses 5 and 7 only. 
v. Sample collected at the time of discontinuation due to disease progression. 
w. If participant is completing all assessments within cycle 6, EOT assessment will be on C6D22 (± 3 days) or prior to the initiation of new anticancer therapy, whichever occurs first. 
x. Only participants in the combination therapy arm need to undergo pulmonary function tests at screening and at Weeks 12 and 24 of study treatment. 
 


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Table 19 
Study Interruption: Schedule of Assessments – Dose Expansion Monotherapy and Combination Therapy Cohort 
 
Alternate 
Approach(es) 
Treatmenta 
Pembrolizumab 
Monotherapy 
EOTs 
 
Cycle 1 
Cycle 2 
Cycles 3 to 4b 
Cycles 5 to 6c 
Doses 5 to 17d 
 
Visit Days 
 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
15 
1 
15 
Every 6 weeks 
 
Window(days) 
 
0 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 3 
± 1 
± 3 
+ 7 
Physical 
Examinatione 
Except for 
ASP0739 and/or 
Pembrolizumab 
administration days 
at study site, may be 
obtained at local 
facility and results 
submitted to PI 
Xe 
X 
Xz 
X 
X 
X 
Xe 
X 
Xz 
X 
X 
X 
Xe 
X 
Xe 
X 
Xe 
Xe 
Vital Signsf 
Except for 
ASP0739 and/or 
Pembrolizumab 
administration days 
at study site, may be 
obtained at local 
facility and results 
submitted to PI 
X 
X 
Xz 
X 
X 
X 
X 
X 
Xz 
X 
X 
X 
X 
X 
X 
X 
Xf 
X 
ECOG 
Performance 
Except for 
ASP0739 and/or 
Pembrolizumab 
administration days 
at study site, may be 
obtained remotely 
via telemedicine 
visit or at local 
facility and results 
submitted to PI 
Xg 
X 
 
X 
X 
X 
Xg 
X 
 
X 
Xh 
X 
Xg,h 
Xh 
Xg,h 
Xh 
Xg,h 
X 
Table continued on next page  


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Alternate 
Approach(es) 
Treatmenta 
Pembrolizumab 
Monotherapy 
EOTs 
 
Cycle 1 
Cycle 2 
Cycles 3 to 4b 
Cycles 5 to 6c 
Doses 5 to 17d 
 
Visit Days 
 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
15 
1 
15 
Every 6 weeks 
 
Window(days) 
 
0 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 3 
± 1 
± 3 
+ 7 
12-Lead ECGi 
Except for 
ASP0739 and/or 
Pembrolizumab 
administration days 
at study site, may be 
obtained at local 
facility and results 
submitted to PI. If 
cannot be 
performed, Astellas 
medical monitor to 
assess for study 
continuation. 
Xi 
 
 
 
 
 
Xi 
 
 
 
 
 
Xi 
 
Xi 
 
 
X 
Prior and 
Concomitant 
Medications 
Except for 
ASP0739 and/or 
Pembrolizumab 
administration days 
at study site, may be 
obtained remotely 
via telemedicine 
visit 
X 
X 
Xz 
X 
X 
X 
X 
X 
Xz 
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 
clinic and result 
submitted to PI 
Xj 
 
 
 
 
 
Xj 
 
 
 
 
 
Xj 
 
Xj 
 
Xj 
X 
Table continued on next page 


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Alternate 
Approach(es) 
Treatmenta 
Pembrolizumab 
Monotherapy 
EOTs 
 
Cycle 1 
Cycle 2 
Cycles 3 to 4b 
Cycles 5 to 6c 
Doses 5 to 17d 
 
Visit Days 
 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
15 
1 
15 
Every 6 weeks 
 
Window(days) 
 
0 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 3 
± 1 
± 3 
+ 7 
Clinical 
Laboratory Tests 
(chemistry, 
hematology, 
urinalysis)j,k 
Except for 
ASP0739 and/or 
Pembrolizumab 
administration days 
at study site, may be 
obtained at local 
facility and results 
submitted to PI 
Xg 
X 
 
X 
X 
X 
Xg 
X 
 
X 
Xh 
X 
Xg,h 
Xh 
Xg,h 
Xh 
Xg,h 
X 
Coagulation 
Profile (PT/INR, 
fibrinogen)k 
Except for 
ASP0739 and/or 
Pembrolizumab 
administration days 
at study site, may be 
obtained at local 
facility and results 
submitted to PI 
Xg 
X 
 
X 
X 
X 
Xg 
X 
 
X 
Xh 
X 
Xg,h 
Xh 
Xg,h 
Xh 
Xg,h 
X 
Thyroid Profile 
Panelk,l 
Except for 
ASP0739 and/or 
Pembrolizumab 
administration days 
at study site, may be 
obtained at local 
facility and results 
submitted to PI 
 
 
 
 
 
 
 
 
 
 
X 
 
Every 6 weeks after C2D15 dose 
X 
PGxm 
None 
Xm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Buccal Swab for 
HLA Typing 
None 
Xg 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table continued on next page 


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Alternate 
Approach(es) 
Treatmenta 
Pembrolizumab 
Monotherapy 
EOTs 
 
Cycle 1 
Cycle 2 
Cycles 3 to 4b 
Cycles 5 to 6c 
Doses 5 to 17d 
 
Visit Days 
 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
15 
1 
15 
Every 6 weeks 
 
Window(days) 
 
0 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 3 
± 1 
± 3 
+ 7 
AE/SAE 
Assessment 
Except for 
ASP0739 and/or 
Pembrolizumab 
administration days 
at study site, may be 
obtained remotely 
via telemedicine 
visit 
X 
X 
Xz 
X 
X 
X 
X 
X 
Xz 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetic: 
ASP0739n 
None 
 
See Table 5 for sample time points 
 
Pharmacokinetic: 
Pembrolizumabn 
None 
 
See Table 5 for sample time points 
 
 
Anti-NY-ESO-1 
antibody 
None 
Xg 
 
 
 
 
 
Xg 
 
 
 
 
 
Xg 
 
Xg 
 
Xt 
X 
Immune 
Response 
Biomarker 
(ELISpot) 
None 
Xg 
 
 
X 
X 
 
Xg 
 
 
X 
Xh 
 
Xg,h 
Xh 
Xg,h 
Xh 
Xh,t 
X 
Immune 
Response 
Biomarker 
(Tetramer) 
None 
Xg 
 
 
 
X 
 
Xg 
 
 
 
Xh 
 
Xg,h 
Xh 
Xg,h 
Xh 
Xh,t 
X 
Immune Cell 
Phenotyping 
None 
Xg 
 
 
X 
X 
 
Xg 
 
 
X 
Xh 
 
Xg,h 
Xh 
Xg,h 
Xh 
Xh,u 
X 
Cytokines 
None 
Xg 
X 
X 
X 
X 
 
Xg 
X 
X 
X 
Xh 
 
Xg,h 
Xh 
Xg,h 
Xh 
Xh,u 
X 
Table continued on next page 


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Alternate 
Approach(es) 
Treatmenta 
Pembrolizumab 
Monotherapy 
EOTs 
 
Cycle 1 
Cycle 2 
Cycles 3 to 4b 
Cycles 5 to 6c 
Doses 5 to 17d 
 
Visit Days 
 
1 
2 
4 
8 
15 
22 
1 
2 
4 
8 
15 
22 
1 
15 
1 
15 
Every 6 weeks 
 
Window(days) 
 
0 
0 
± 1 
± 1 
± 1 
± 1 
± 1 
0 
± 1 
± 1 
± 1 
± 1 
± 3 
± 1 
± 3 
± 1 
± 3 
+ 7 
Circulating tumor 
DNA 
None 
Xg 
 
 
 
 
 
Xg 
 
 
 
 
 
Xg 
 
Xg 
 
X 
Xv 
Archival Tumor 
Tissueo 
None 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor Tissue, 
Fresh Biopsy 
None 
Xq 
 
 
 
 
 
 
 
 
 
Xr 
 
 
 
 
 
 
 
Pulmonary 
function test 
May be obtained at 
local facility and 
results submitted to 
PI 
 
 
 
 
 
 
 
 
 
 
 
 
Xy 
 
 
 
Xy 
 
Radiographic 
Disease 
Assessmentp 
May be collected 
locally and send to 
PI. Assessment to 
be done per protocol 
requirements. 
Outside of the 
window 
assessments need to 
be escalated to 
Astellas medical 
monitor 
Every 56 ± 7 days 
 
ASP0739 Dosing  None 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 
 
 
Pembrolizumab 
Dosingw 
Every other dose 
may be 
administered locally 
during 
Pembrolizumab 
monotherapy only, 
otherwise must be 
administered at 
study site. 
X 
 
 
 
 
 
 
 
 
 
X 
 
Every 6 weeks after C2D15 dose 
X 
 
Footnotes appear on next page 


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AE: adverse event; C: cycle; CR: complete response: CT: computed tomography; D: day; ECG: electrocardiogram; ECHO: echocardiogram; 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; MUGA: multiple gated acquisition scan; NY-ESO-1: New York esophageal 
squamous cell carcinoma 1; 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  
a. 
Cycles 1 through 6 represent ASP0739 single agent or combination of ASP0739 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 ASP0739 as decided by the investigator. 
c. 
After the first 4 cycles, participants who achieve PR or SD may continue further treatment of ASP0739 in cycles 5 and 6. Participants who reach CR will not receive additional 
doses of ASP0739. 
d. Participants in combination therapy only will continue to receive pembrolizumab as monotherapy for doses 5 up to 17. If participant receives at least one dose of ASP0739 but 
discontinues combination treatment of ASP0739 at any time prior to C5D15, then the participant may continue pembrolizumab as monotherapy for up to 96 weeks for a total of 17 
doses of pembrolizumab total for the study. 
e. 
Height measurement performed at screening only. If height cannot be measured at the screening visit, it can be collected at any time during the course of the study, but should be 
recorded for the screening visit. Weight measurement performed at screening and day 1 of each cycle.  
f. 
The following vital sign assessments schedules apply: 
• 
At C1D1 and any visit when pembrolizumab and ASP0739 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 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 ASP0739 infusion, every 15 min (-5 to +10 min window) 
during ASP0739 infusion, at the end of ASP0739 infusion (-5 to +10 min window), and post dose (+30 min, +1, +2, +3 and +4 hours [± 10 min window each] from end of 
ASP0739 infusion).  
• 
ASP0739 dosing only: vital signs will be obtained within 15 min prior to start of ASP0739 infusion, every 15 min (-5 to +10 min window) during ASP0739 infusion, at the 
end of ASP0739 infusion (-5 to +10 min window) and 30 min (± 10 min) after completion of the ASP0739 infusion. If participants are still available, additional optional vital 
sign assessments 3 hours (± 10 min) and 4 hours (± 10 min) after completion of the ASP0739 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 
pembrolizumab infusion; at the end of pembrolizumab infusion (-5 to +10 min window), as well as, at 30 min (± 5 min), 1 hour (± 10 min) and 2 hours (± 10 min) after 
completion of the pembrolizumab infusion for participants in the combination therapy.  
g. Obtain predose. 
h. Obtain predose if participant receives pembrolizumab at the same visit.  
i. 
12-lead ECGs will be recorded in triplicate (at least 2 min apart per time point) and read locally. On IP administration days, ECG will be obtained: 
• 
At C1D1 and any visit when pembrolizumab and ASP0739 are administered together: ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h 
post dose of ASP0739. 
• 
ASP0739 dosing only: ECGs are obtained predose (-1 h from start of ASP0739 infusion) and 1 to 2 h post dose of ASP0739. 
• 
Pembrolizumab dosing only: ECGs are obtained predose (-1 h from start of pembrolizumab infusion) and 1 to 2 h post dose of pembrolizumab. 
Footnotes continued on next page 


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j. 
Urine or serum pregnancy test will be performed in women of childbearing potential. 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. For participants in combination therapy arm, troponin levels will be obtained at screening; thereafter, weekly for 6 weeks and subsequently every 
second week for 6 weeks. 
l. 
Thyroid panel including triiodothyronine or free triiodothyronine, free thyroxine and thyroid stimulating hormone will be measured prior to receiving pembrolizumab for 
participants in the combination cohort (Screening, C2D15 then every 6 weeks). 
m. Whole blood for optional PGx study may be collected at C1D1 prior to IP administration. 
n. See Table 5 for collection schedule for ASP0739 single agent and ASP0739 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. 
Imaging will occur every 56 ± 7 days until confirmed progression by iRECIST. 
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). 
s. 
The EOT visit will occur within 7 days of the PI decision to discontinue the participant for treatment or at the start of new anticancer treatment, whichever occurs first. 
t. 
Samples collected at pembrolizumab doses 5, 7, 9, 11 and 13 only. 
u. Samples collected at pembrolizumab doses 5 and 7 only. 
v. Sample collected at the time of discontinuation due to disease progression. 
w. In the combination therapy arm, pembrolizumab will be administered as an intravenous infusion over 30 min followed by ASP0739 administration at least 1 hour after 
pembrolizumab administration. For participants enrolled in Japanese safety lead-in, C1D8 assessments should be performed prior to discharge from hospital. 
x. If participant is completing all assessments within cycle 6, EOT assessment will be on C6D22 (± 3 days) or prior to the initiation of new anticancer therapy, whichever occurs first.  
y. Only participants in the combination therapy arm need to undergo pulmonary function tests at screening and at weeks 12 and 24 of study treatment. 
z. 
These assessments only apply to the Japanese participants. 
 


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Table 20 
Study Interruption: Schedule of Assessments – Schedule of Assessments for Follow-up Periods 
Visit 
Alternate Approach(es) 
Safety Follow-up 
Follow-up Period  
Year 1a 
Survival 
Follow-up 
 
 
30 dayb  
60 dayb 
90 dayb 
Every 8 weeksc 
Every 3 months 
Window (days) 
 
± 3 
± 3 
± 3 
± 7 
± 7 
Physical Examination 
May be obtained at local facility and results 
submitted to PI 
X 
X 
X 
 
 
Vital Signs 
May be obtained at local facility and results 
submitted to PI 
X 
X 
X 
 
 
ECOG Performance 
May be obtained remotely via telemedicine 
visit or at local facility and results submitted 
to PI 
X 
X 
X 
 
 
Concomitant Medications 
May be obtained remotely via telemedicine 
visit 
X 
X 
X 
 
 
12-Lead ECG 
May be obtained at local facility and results 
submitted to PI 
X 
X 
X 
 
 
Clinical Laboratory Tests (chemistry, hematology, 
coagulation, urinalysis) 
May be obtained at local facility and results 
submitted to PI 
X 
X 
X 
 
 
Pregnancy Test for WOCBP 
May be obtained at local facility and results 
submitted to PI 
X 
X 
X 
 
 
AE/SAE Assessment 
May be obtained remotely via telemedicine 
visit 
X 
X 
X 
 
 
Pharmacokinetic sample for cell kinetics (ASP0739) 
None 
 See Table 5 for sample time points 
Blood Sample for NY-ESO-1 antibody 
None 
X 
X 
X 
Xd 
 
Blood Sample for Immune Response Biomarker (ELISpot)  
None 
X 
X 
X 
Xe 
 
Blood Sample for Immune Response Biomarker (Tetramer)  
None 
X 
X 
X 
Xd 
 
Blood Sample for Immune Cell Phenotyping 
None 
X 
X 
X 
Xe 
 
Blood Sample for Cytokines 
None 
X 
X 
X 
Xe 
 
Blood Sample for ctDNA 
None 
X 
X 
X 
Xf 
 
Table continued on next page 


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Visit 
Alternate Approach(es) 
Safety Follow-up 
Follow-up Period  
Year 1a 
Survival 
Follow-up 
 
 
30 dayb  
60 dayb 
90 dayb 
Every 8 weeksc 
Every 3 months 
Window (days) 
 
± 3 
± 3 
± 3 
± 7 
± 7 
Radiographic Disease Assessment 
Assessment to be done per protocol 
requirements and submitted to PI. Outside of 
the window assessments need to be escalated 
to Astellas medical monitor 
 Every 56 ± 7 days 
 
Survival Follow-upg 
May be obtained remotely via telemedicine 
visit 
 
 
 
 
X 
AE: adverse event; ctDNA: circulating tumor DNA; ECG: electrocardiogram; ECOG: eastern cooperative oncology group; ELISpot: enzyme-linked immunospot; EOT: end of 
treatment; NY-ESO-1: New York esophageal squamous cell carcinoma 1; PI: principal investigator; SAE: serious adverse event; WOCBP: woman of childbearing potential  
a. 
Follow-up visits every 2 months or until progression or start of a new anticancer therapy or death (whichever occurs first). 
b. From the last dose. 
c. 
From EOT or the last planned assessment if EOT was not performed. 
d. Maximum of 5 samples collected during Follow-up Period Year 1. Samples will be collected at the time of the disease assessment visit.  
e. 
Maximum of 1 sample collected during Follow-up Period Year 1. Sample will be collected at the time of the disease assessment visit. 
f. 
Sample will be collected at the time of discontinuation due to disease progression or the start of a new anticancer therapy. 
g. Outcomes will be assessed by telephone calls every 3 months for up to 12 months. 
 


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Table 21 
Study Interruption: Schedule of Assessments – Schedule of Replication Competent Lentivirus for Dose Escalation Cohort, Dose 
Expansion Cohort and Safety Lead-in Cohort 
Assessment 
Alternate Approach(es) 
C1D1 
3 Months after Treatment 
Initiation or End of 
Treatment, whichever is first 
6 Months after 
Treatment Initiation 
12 Months after 
Treatment Initiation 
18 Months after 
Treatment Initiation 
Window 
 
0 
± 7 day 
± 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. 
b. Obtained predose. 
 


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INVESTIGATIONAL PRODUCT SUPPLY 
If any of the conditions outlined above in the Participants Procedures Assessment are met, 
one or all of the following mitigating strategies will be employed, as needed, to ensure 
continuity of IP supply to the participants:   
• Increase stock of IP on site to reduce number of shipments required, if site space will 
allow.  
DATA COLLECTION REQUIREMENTS 
Additional data may be collected in order to indicate how participation in the study may have 
been affected by a crisis and to accommodate data collection resulting from alternate 
measures implemented to manage the conduct of the study and 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 
α-GalCer 
α Galactosylceramide 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
anti-PD-1 
anti-programmed cell death protein 1 
APGD 
Astellas Pharma Global Development, Inc. 
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 
C 
cycle 
Cmax 
maximum concentration 
CNS 
central nervous system 
CPI 
checkpoint inhibitor 
CR 
complete response 
CRO 
contract research organization 
CRS 
cytokine-release syndrome 
CSR 
clinical study report 
CT 
computed tomography 
CTA 
cancer testis antigens 
CTCAE 
common terminology criteria for adverse events 
ctDNA 
circulating tumor DNA 
Ctrough 
concentration immediately prior to dosing at multiple dosing 
CV 
coefficient of variation 
DCR 
disease control rate per RECIST v1.1 
DEAS 
DLT evaluation analysis set 
DESC 
Dose Escalation and Safety Committee 
DLT 
dose limiting toxicity 
DOR 
duration of response per RECIST v1.1 
DPD 
Data Protection Directive 
ECG 
electrocardiogram 


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Abbreviations 
Description of abbreviations 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EEA 
European Economic Area 
ELISpot 
enzyme-linked immunospot 
EOT 
end of treatment 
ESCC 
esophageal squamous cell carcinoma 
FAS 
full analysis set 
FFPE 
formalin-fixed, paraffin embedded 
FIH 
first-in-human 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practices 
HEK293 
human embryonic kidney cell 
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 
confirmed disease progression by iRECIST 
iCR 
complete response based on iRECIST 
iDCR 
disease control rate per iRECIST 
iDOR 
duration of response per iRECIST 
IEC 
Independent Ethics Committee 
IFNg 
interferon gamma 
ILD 
interstitial lung disease 
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 
LA-CRF 
liver abnormality case report form 
LFT 
liver function test 
MRCL 
myxoid/round cell liposarcoma 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 


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Abbreviations 
Description of abbreviations 
NCI-CTCAE 
National Cancer Institute’s Common Terminology Criteria for Adverse Events 
NK 
natural killer 
NKT 
natural killer T 
NSCLC 
non-small cell lung cancer 
NY-ESO-1 
New York esophageal squamous cell carcinoma 1 
ORR 
objective response rate per RECIST v1.1 
OS 
overall survival 
PD 
progressive disease 
PDAS 
pharmacodynamic analysis set 
PFS 
progression-free survival per RECIST v1.1 
PGx 
pharmacogenomic 
PKAS 
pharmacokinetic analysis set 
PMDA 
Pharmaceutical and Medical Devices Agency 
PR 
partial response 
PT/INR 
prothrombin time/international normalized ratio 
PV 
pharmacovigilance 
QA 
quality assurance 
QC 
quality control 
QTL 
quality tolerance limits 
R/R 
relapsed/refractory 
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 
SAP 
statistical analysis plan 
SD 
stable disease 
SOC 
standard of care 
SOP 
standard operating procedure 
SS 
synovial sarcoma 
SUSAR 
suspected unexpected serious adverse reactions 
TBL 
total bilirubin 
TEAE 
treatment-emergent adverse event 
TEM 
Tolerability Evaluation Meeting 
tmax 
time of maximum concentration  
ULN 
upper limit of normal 
USM 
urgent safety measure 
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 pharmacogenomics).  
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 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Protocol 0739-CL-0101 A Phase 1/2 Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP0739 as a Single Agent and in 
Combination with Pembrolizumab in Patients with Advanced Solid Tumors known to Express NY-ESO-1 
Amendment 4 [Substantial] 24 Aug 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 
This amendment is to update the protocol for accuracy, to provide clarification and to add responses to requests from the PMDA. 
Summary of Changes 
Table 1 
Substantial Changes 
Section Number 
Description of Change 
Brief Rationale 
1.1, 1.2, 2.3.2, 4.1, 6.3.1, 
10.1.5.1 
Add phase 2 single agent dose expansion cohort with Japanese safety 
lead-in and a TEM 
To update the protocol to reflect the decision to 
include the Japanese safety lead-in cohort 
1.3 (Table 2), 10.12 (Table 
19) 
Footnote “i", which specified which participants should undergo 
ECHO or MUGA assessment, is removed 
ECHO (or MUGA) assessments will now be 
conducted for all participants in combination 
therapy arms as part of screening 
1.3 (Table 5) 
Table headers are updated and footnotes added 
To reflect inclusion of the Japanese safety lead-
in participants 
5.1 
Revised inclusion criterion 17 to read “Participant has measurable 
disease according to RECIST 1.1. For participant with only 
1 measurable lesion and prior radiotherapy, the lesion must be 
outside the field of prior radiotherapy or must have documented 
progression following radiation therapy.” 
To clarify inclusion criterion 17 regarding 
history of prior radiotherapy 
5.2 
Allow participants who have received systemic immunomodulators 
in the dose escalation phase and systemic immunomodulators for 
NY-ESO-1 solid tumor cohorts in the dose expansion phase in 
exclusion criterion 2 
To clarify exclusion criterion 2 regarding prior 
use of systemic immunomodulators in both the 
dose escalation and dose expansion phases 


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Section Number 
Description of Change 
Brief Rationale 
5.2 
Add suspected hypersensitivity to bovine-derived protein or any 
ingredients of ASP0739 as a new exclusion criterion 
Added as a safety precaution 
 
Table 2 
Nonsubstantial Changes 
Section Number 
Description of Change 
Brief Rationale 
Contact Details of 
Sponsor’s Key Personnel 
and 13 
Update identity of medical monitor to 
 and 
correct contact information 
To align with updated personnel 
1.1 and 4.1 
Clarify that participant replacement includes participants in the 
safety lead-in 
To provide clarification 
1.1, 4.1 and Table 8 
Remove “Part 1” 
To correct an error 
1.1, 4.1, 4.4, 10.5.2 
Clarify IP includes ASP0739 and pembrolizumab 
To provide clarification 
1.2 (Figure 2) 
Provide clarity for study design in footnotes 
To provide clarification 
1.3 (Table 1), 10.12 
(Table 18) 
An “X” was added to C2D2 for ECOG performance 
To correct an error 
1.3 (Table 1 and Table 
2), 10.12 (Table 18 and 
Table 19) 
Timing of sampling for thyroid function assessments is modified 
To align with sampling schedules from other 
programs 
1.3 (Table 2), 10.12 
(Table 19) 
Clarify pulmonary function testing during C1 and clarify ECOG, 
clinical laboratory, coagulation and thyroid panel, immune 
response biomarker, immune cell phenotyping and cytokine 
assessment times relative to dosing 
To provide clarification 
1.3 (Table 3), 10.12 
(Table 20) 
Clarify the timing of the last planned assessment 
To provide clarification 
2.3.1.1, 4.3.1 
Update risk assessment and dose rationale for ASP0739 
To provide more current information 
PPD


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Section Number 
Description of Change 
Brief Rationale 
4.1 
Remove “at least possibly related to study drug” from grade ≥ 3 
liver function test abnormality and “treatment-related” from the 
description of grade 5 toxicity 
To provide clarification 
4.1 
The far-right column is removed from 2 tables describing “Number 
of Participants Treated at Current Dose Level” 
Columns are removed because the number of 
participants noted, 9, will not be enrolled 
5.2 
Criterion 16 is removed and placed as criterion 4 in the subsequent 
section entitled “Additional Exclusion Criteria for Participants in 
Combination Therapy Cohorts” 
Criterion was placed in the incorrect location; to 
correct an error 
Table 1, Table 2, 7.2.4 
Update timing of ECG assessments relative to IP dosing 
To provide clarification 
7.5.2 
Add that participants who have an FFPE block and a frozen tissue 
specimen taken within 56 days prior to the first dose of study 
treatment do not require a new biopsy 
To improve the participant experience 
7.8 
Modify text related to total amount of blood collected 
To clarify the maximum amount of blood collected 
at any one visit and over the course of any cycle 
10.1.12 
Replace QTL text in Quality Assurance section with bullet point 
from current template 
To reflect the current protocol template version 
10.6 (Table 13) 
Include CO2 as an option for chemistry testing in clinical laboratory 
tests and make the test not mandatory if testing is not available 
To provide clarification 
10.6 (Table 13) 
Add that the thyroid panel is for the combination cohort only 
To provide clarification 
Throughout 
Minor administrative-type changes, e.g., typos, format, numbering, 
consistency throughout the protocol.   
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
PPD
PPD