Single-arm, Phase 2 Study of Valemetostat Tosylate Monotherapy in Subjects With Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
Phase: PHASE2
Conditions: Relapsed/Refractory Peripheral T-Cell Lymphoma, Adult T Cell Leukemia/Lymphoma
Sponsor: Daiichi Sankyo

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CLINICAL STUDY PROTOCOL 
Single-Arm, Phase 2 Study of Valemetostat Tosylate 
Monotherapy in Subjects with Relapsed/Refractory 
Peripheral T-Cell Lymphoma 
(Valemetostat tosylate [DS-3201b], an enhancer of zeste 
homolog [EZH] 1/2 dual inhibitor, for R/R PTCL) 
 
PROTOCOL NUMBER DS3201-A-U202 
IND NUMBER 132312 
EudraCT NUMBER 2020-004954-31 
 
VERSION 4.0, 09 Sep 2022 
 
DAIICHI SANKYO, INC. 
211 MOUNT AIRY ROAD 
BASKING RIDGE, NEW JERSEY 07920 
 
CONFIDENTIALITY STATEMENT 
Information contained in this document is proprietary to Daiichi Sankyo, Inc.  The information is 
provided to you in confidence which is requested under an agreed upon and signed 
Confidentiality and Disclosure Agreement.  Do not give this document or any copy of it or reveal 
any proprietary information contained in it to any third party (other than those in your 
organization who are assisting you in this work and are bound by the Confidentiality and 
Disclosure Agreement) without the prior written permission of an authorized representative of 
Daiichi Sankyo, Inc. 
 

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INVESTIGATOR AGREEMENT 
Single-arm, Phase 2 Study of Valemetostat Tosylate Monotherapy in Subjects with 
Relapsed/Refractory Peripheral T-Cell Lymphoma 
Sponsor Approval: 
This clinical study protocol has been reviewed and approved by the Daiichi Sankyo, Inc. 
representative listed below. 
 
 Print Name 
Signature 
 
 Title 
Date (DD MMM YYYY) 
Investigator’s Signature: 
I have fully discussed the objectives of this study and the contents of this protocol with the Sponsor’s 
representative. 
I understand that information contained in or pertaining to this protocol is confidential and should not 
be disclosed, other than to those directly involved in the execution or the ethical review of the study, 
without written authorization from the Sponsor.  It is, however, permissible to provide information to 
a subject in order to obtain consent. 
I agree to conduct this study according to this protocol and to comply with its requirements, subject 
to ethical and safety considerations and guidelines, and to conduct the study in accordance with 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human 
Use (ICH) Guideline for Good Clinical Practice (ICH E6[R2]), which has its foundations in the 
Declaration of Helsinki, and applicable regional regulatory requirements. 
I agree to make available to Sponsor personnel, their representatives and relevant regulatory 
authorities, my subjects’ study records in order to verify the data that I have entered into the case 
report forms.  I am aware of my responsibilities as a Principal Investigator as provided by the 
Sponsor. 
I understand that the Sponsor may decide to suspend or prematurely terminate the study at any time 
for whatever reason; such a decision will be communicated to me in writing. 
Conversely, should I decide to withdraw from execution of the study, I will communicate my 
intention immediately in writing to the Sponsor. 
  
 
 Print Name 
Signature 
  
 
 Title 
Date (DD MMM YYYY) 
                        12 SEP 2022
PPD
PPD
PPD

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DOCUMENT HISTORY 
Version Number 
Version Date 
4.0 
09 Sep 2022 
3.0 
20 May 2022 
2.0 
09 Mar 2021 
1.0 
12 Oct 2020 
 

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SUMMARY OF CHANGES 
Please refer to the comparison document for protocol Version 4.0 (dated 09 Sep 2022) versus 
protocol Version 3.0 (dated 20 May 2022) for actual changes in text.  The summary of changes 
below is a top-line summary of major changes in the current DS3201-A-U202 clinical study 
protocol (Version 4.0) by section. 
Amendment Rationale: 
The main purpose of this amendment is to reflect the Sponsor’s strategic decision not to pursue 
the adult T-cell leukemia/lymphoma indication and to therefore close enrollment into Cohort 2.  
The closure of Cohort 2 was not due to safety, and the safety profile remains consistent with that 
observed during the ongoing development program.  No new safety signals have been observed, 
and the benefit/risk profile continues to support further clinical development. 
CONVENTIONS USED IN THIS SUMMARY OF CHANGES 
All locations (section numbers and/or paragraph/bullet numbers) refer to the current protocol 
version, which incorporates the items specified in this Summary of Changes document. 
Minor edits, such as updates to language that does not alter the original meaning, updates to 
version numbering, formatting, change in font color, corrections of typographical errors, use of 
abbreviations, moving verbiage within a section or table, changes in style, or changes in case, 
are not noted in the table below. 
 
Section # and Title 
Description of Change 
Brief Rationale 
Protocol Synopsis (Study 
Objectives/Outcome Measures and 
Endpoints) 
Protocol Synopsis (Statistical 
Analysis) 
Section 1.2 (Study Schema) 
Section 2.2 (Study Rationale) 
Section 3 (Objectives, Outcome 
Measures, and Endpoints) 
Section 4 (Study Design) 
Section 8.3 (Efficacy Assessments) 
Section 9 (Statistical Considerations) 
Section 10.1.5 (Committees) 
Updated the efficacy objectives, outcome 
measures, endpoints, and analyses to 
align with the Sponsor’s strategic 
decision not to pursue adult T-cell 
leukemia/lymphoma (ATL) indication 
and to therefore close enrollment into 
Cohort 2 . 
Updated Cohort 2 efficacy endpoints to 
be assessed by the investigator, not by 
blinded independent central review, and 
removed reference to original ATL 
response criteria. 
 
Sponsor’s strategic decision 
not to pursue ATL. 
Protocol Synopsis (Study Design) 
Section 4 (Study Design) 
Updated the time frame for analyses to be 
based only on meeting the primary 
efficacy endpoint in Cohort 1. 
 
Protocol Synopsis (Key Eligibility 
Criteria) 
Section 5.1.1 (Inclusion Criteria) 
Section 8.2 (Enrollment) 
Updated eligibility language for both 
Cohorts 
Clarification 

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Section # and Title 
Description of Change 
Brief Rationale 
Protocol Synopsis (Study Design) 
Protocol Synopsis (Planned Sample 
Size) 
Section 1.2 (Study Schema) 
Section 4 (Study Design) 
Section 9.3 (Sample Size 
Determination) 
Updated the sample size for the overall 
study and Cohort 2 (including statistical 
rationale). 
Enrollment to be stopped for 
R/R ATL Cohort 2. 
Protocol Synopsis (Study 
Objectives/Outcome Measures and 
Endpoints) 
Protocol Synopsis (Study Design) 
Section 1.2 (Study Schema) 
Section 3 (Objectives, Outcome 
Measures, and Endpoints) 
Section 4.1 (Overall Design) 
Section 4.1.2 (End of Study) 
Section 10.6 (Appendix 7 Key Data 
Analysis Requirements) 
Removed the primary completion date 
for Cohort 2. 
Enrollment to be stopped for 
R/R ATL Cohort 2. 
Protocol Synopsis (Statistical 
Analysis) 
Protocol Synopsis (Planned Sample 
Size) 
Section 4.1 (Overall Design) 
Section 8.1 (Eligibility Assessment) 
Section 8.2 (Enrollment) 
Section 9 (Statistical Considerations) 
Removed the central pathology review 
for Cohort 2. 
Enrollment to be stopped for 
R/R ATL Cohort 2. 
Section 1.3 (Schedule of Events) 
Section 8.4.4 (Other Safety) 
Updated the time matching of 
electrocardiogram (ECG) and 
pharmacokinetic (PK) assessments. 
As it may not always be 
possible to perform ECG 
within 15 minutes prior to 
the PK blood draw, the 
requirement has been 
relaxed to allow the sites to 
perform ECG 30 minutes or 
more after the PK sample 
collection for Cycles 2 to 5. 
Section 1.3 (Schedule of Events) 
Updated footnote b to reflect the update 
in the visit schedule from Cycle 3 and 
Beyond. 
Operational update based on 
stopping of R/R ATL cohort 
enrollment. 
Section 8.3 (Efficacy Assessments: 
Figure 8.1, Figure 8.2, and Table 
8.1) 
Updated the schedules for efficacy 
assessments. 
Enrollment to be stopped for 
R/R ATL Cohort 2 and to 
align with the standard of 
care for the ATL cohort. 
Section 8.3.2 (Bone Marrow 
Biopsy/Assessment) 
Clarified text for local pathology report 
and bone marrow specimen submission 
Clarification 

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Section # and Title 
Description of Change 
Brief Rationale 
Section 8.3.3 (Cohort 2 Additional 
Efficacy Assessments) 
Skin Lesion Assessment – removed 
guidance on whole body skin 
photographs 
Central review is no longer 
required 
Section 8.6 (Biomarker 
Assessments) 
Update text for biomarker assessments 
Clarification 
Section 4.1 (Overall Design) 
Section 9.7 (Interim Analyses) 
Removed the interim analysis for 
Cohort 2. 
Enrollment to be stopped for 
R/R ATL Cohort 2. 
Section 10.1.6 (Study 
Documentation and Storage) 
Added the email address for Sponsor 
notification regarding records 
maintenance. 
Information update. 
Section 10.2 (Appendix 2: Central 
and/or Local Laboratory) 
Updated the list of laboratory tests to be 
performed. 
Enrollment to be stopped for 
R/R ATL Cohort 2. 
Section 10.3.8 (Prespecified 
Stopping Boundaries) 
Updated Tables 10.9 to 10.11 listing 
prespecified stopping boundaries for 
Cohort 2. 
Enrollment to be stopped for 
R/R ATL Cohort 2. 
Protocol Synopsis (Key Eligibility 
Criteria) 
Section 2.1 (Background) 
Section 5.1.1 (Inclusion Criteria) 
Section 10.4.4 (mSWAT Score 
Calculation: Cohort 2) 
Section 11 (References) 
Moved or removed references associated 
with these changes  
Corrections due to updates 
made to Cohort 2 efficacy 
endpoints 

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TABLE OF CONTENTS 
INVESTIGATOR AGREEMENT...................................................................................................2 
DOCUMENT HISTORY.................................................................................................................3 
SUMMARY OF CHANGES ...........................................................................................................4 
1. 
PROTOCOL SUMMARY ............................................................................................15 
1.1. 
Protocol Synopsis ..........................................................................................................15 
1.2. 
Study Schema ................................................................................................................23 
1.3. 
Schedule of Events ........................................................................................................25 
2. 
INTRODUCTION ........................................................................................................38 
2.1. 
Background ...................................................................................................................38 
2.2. 
Study Rationale .............................................................................................................40 
2.3. 
Benefit and Risk Assessment ........................................................................................41 
Nonclinical Data ............................................................................................................................41 
Clinical Data ..................................................................................................................................41 
3. 
OBJECTIVES, OUTCOME MEASURES, AND ENDPOINTS .................................44 
3.1. 
Rationale for Selection of Primary and Select Secondary Endpoints for Cohort 
1 .....................................................................................................................................48 
4. 
STUDY DESIGN ..........................................................................................................49 
4.1. 
Overall Design ..............................................................................................................49 
4.1.1. 
Design Overview ...........................................................................................................49 
4.1.2. 
End of Study ..................................................................................................................50 
4.1.3. 
Dose Regimen ...............................................................................................................51 
4.1.4. 
Duration.........................................................................................................................51 
4.2. 
Rationale for Study Design ...........................................................................................51 
4.3. 
Justification for Dose ....................................................................................................52 
5. 
STUDY POPULATION ...............................................................................................53 
5.1. 
Treatment Period ...........................................................................................................53 
5.1.1. 
Inclusion Criteria ...........................................................................................................53 
5.1.2. 
Exclusion Criteria..........................................................................................................55 
5.2. 
Screening Failures, Rescreening, and Subject Replacement ........................................57 
6. 
STUDY TREATMENT ................................................................................................58 
6.1. 
Study Drug Description ................................................................................................58 

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6.2. 
Preparation, Handling, Storage, and Accountability for Study Drug ...........................58 
6.3. 
Method of Treatment Allocation ...................................................................................59 
6.4. 
Treatment Compliance ..................................................................................................60 
6.5. 
Guidelines for Dose Modification .................................................................................60 
6.5.1. 
Dose Interruptions and Reductions for Hematological and Nonhematological 
Toxicity .........................................................................................................................60 
6.5.2. 
Dose Reductions for Valemetostat Tosylate .................................................................63 
6.5.3. 
Permanent Discontinuation of Study Drug ...................................................................64 
6.5.4. 
Dose Modifications with Concomitant Strong CYP3A Inhibitors and/or P-gp 
Inhibitors .......................................................................................................................64 
6.6. 
Prior and Concomitant Medications..............................................................................65 
7. 
STUDY DRUG DISCONTINUATION AND DISCONTINUATION FROM 
THE STUDY .................................................................................................................67 
7.1. 
Discontinuation of Study Drug .....................................................................................67 
7.2. 
Subject Withdrawal/Discontinuation from the Study ...................................................69 
7.3. 
Lost to Follow-up ..........................................................................................................70 
8. 
STUDY PROCEDURES ..............................................................................................71 
8.1. 
Eligibility Assessment ...................................................................................................71 
8.2. 
Enrollment .....................................................................................................................72 
8.3. 
Efficacy Assessments ....................................................................................................73 
8.3.1. 
Radiographic Assessments (CT/MRI and FDG-PET Scans) ........................................74 
8.3.2. 
Bone Marrow Biopsy/Assessment ................................................................................76 
8.3.3. 
Cohort 2 Additional Efficacy Assessments...................................................................77 
8.3.4. 
Subsequent Anti-Lymphoma Treatments .....................................................................78 
8.3.5. 
Subsequent Hematopoietic Cell Transplantation ..........................................................78 
8.3.6. 
Survival Follow-up .......................................................................................................78 
8.4. 
Safety Assessments .......................................................................................................78 
8.4.1. 
Adverse Event ...............................................................................................................78 
8.4.1.1. 
Serious Adverse Events Reporting................................................................................80 
8.4.1.2. 
Overdose .......................................................................................................................81 
8.4.1.3. 
Medication Error, Misuse, and Abuse...........................................................................81 
8.4.1.4. 
Adverse Events of Special Interest ...............................................................................82 
8.4.2. 
Pregnancy ......................................................................................................................83 

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8.4.3. 
Clinical Laboratory Evaluations ...................................................................................84 
8.4.4. 
Other Safety ..................................................................................................................84 
8.5. 
Pharmacokinetic Assessments ......................................................................................85 
8.5.1. 
Pharmacokinetic Sample Collection for Co-Administration with 
Strong/Moderate CYP3A Inhibitors or Inducers and/or P-gp Inhibitors ......................86 
8.6. 
Biomarker Assessments ................................................................................................87 
8.6.1. 
Analysis of Biopsied Tumor Tissue ..............................................................................87 
8.6.2. 
Minimal Residual Disease (MRD) Assessment Using Peripheral Blood 
Samples .........................................................................................................................88 
8.6.3. 
Profiling of T-cells in Freshly Collected Peripheral Blood Samples Using 
Flow Cytometry Assay ..................................................................................................88 
8.6.4. 
Pharmacogenomic (Inherited Genetic) Analysis ..........................................................88 
8.6.4.1. 
Banking of Specimens for Inherited Genetic Analysis .................................................88 
8.6.5. 
Storage of Specimens ....................................................................................................89 
9. 
STATISTICAL CONSIDERATIONS ..........................................................................90 
9.1. 
General Statistical Considerations ................................................................................90 
9.2. 
Statistical Hypothesis ....................................................................................................90 
9.3. 
Sample Size Determination ...........................................................................................90 
9.4. 
Population for Analysis Sets .........................................................................................90 
9.5. 
Statistical Analysis ........................................................................................................91 
9.5.1. 
Efficacy Analyses..........................................................................................................91 
9.5.1.1. 
Primary Efficacy Analysis – Cohort 1 Only .................................................................91 
9.5.1.2. 
Secondary Efficacy Analyses – Cohort 1 Only.............................................................91 
9.5.1.3. 
Exploratory Analyses ....................................................................................................92 
9.5.1.4. 
Subgroup Analysis ........................................................................................................92 
9.5.1.5. 
Multiplicity Adjustment ................................................................................................92 
9.5.2. 
Safety Analyses .............................................................................................................93 
9.5.3. 
Other Analyses ..............................................................................................................94 
9.6. 
Unacceptable Toxicities and Stopping Criteria.............................................................95 
9.7. 
Interim Analyses ...........................................................................................................95 
10. 
APPENDICES – SUPPORTING DOCUMENTATION AND 
OPERATIONAL CONSIDERATIONS .......................................................................96 
10.1. 
Appendix 1 Regulatory and Ethical Considerations .....................................................96 

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10.1.1. 
Regulatory Compliance .................................................................................................96 
10.1.2. 
Informed Consent ..........................................................................................................97 
10.1.3. 
Subject Confidentiality..................................................................................................98 
10.1.4. 
Data Integrity and Quality Assurance ...........................................................................98 
10.1.5. 
Committees .................................................................................................................100 
Blinded Independent Central Review Committee .......................................................................100 
Data Monitoring Committee ........................................................................................................101 
10.1.6. 
Study Documentation and Storage ..............................................................................101 
10.1.7. 
Finances.......................................................................................................................102 
10.1.8. 
Publication and Public Disclosure Policy ...................................................................102 
10.1.9. 
Protocol Deviations .....................................................................................................103 
10.1.10. Study and Site Closure ................................................................................................103 
10.1.11. Product Complaints .....................................................................................................104 
10.2. 
Appendix 2: Central and/or Local Laboratory ............................................................104 
10.3. 
Appendix 3: Reference Standards ...............................................................................105 
10.3.1. 
Cockcroft-Gault Equation ...........................................................................................105 
10.3.2. 
New York Heart Association ......................................................................................106 
10.3.3. 
Eastern Cooperative Oncology Group Performance Status ........................................106 
10.3.4. 
Karnofsky Performance Status Scale Definitions Rating (%) Criteria .......................107 
10.3.5. 
CYP3A/P-gp Inhibitors and Inducers .........................................................................107 
10.3.6. 
Highly Effective Contraception ..................................................................................109 
10.3.7. 
ATL Subtypes .............................................................................................................110 
10.3.8. 
Prespecified Stopping Boundaries ..............................................................................112 
10.3.9. 
GVHD Grading and Staging .......................................................................................115 
10.4. 
Appendix 4: Response Criteria ...................................................................................118 
10.4.1. 
Target Lesions .............................................................................................................118 
10.4.2. 
2014 Lugano Criteria: Cohort 1 ..................................................................................119 
10.4.3. 
Modified 2009 ATL Criteria: Cohort 2 .......................................................................122 
10.4.4. 
mSWAT Score Calculation: Cohort 2 ........................................................................124 
10.4.5. 
5-Point Scale: Cohort 1 and Cohort 2 .........................................................................125 
10.5. 
Appendix 6: General Information - Adverse Events...................................................125 
10.5.1. 
Definition of Adverse Event .......................................................................................125 

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10.5.2. 
Serious Adverse Event ................................................................................................127 
10.5.3. 
Grade Assessment .......................................................................................................128 
10.5.4. 
Causality Assessment ..................................................................................................128 
10.5.5. 
Action Taken Regarding Study Drug(s) .....................................................................129 
10.5.6. 
Other Action Taken for Event .....................................................................................129 
10.5.7. 
Adverse Event Outcome .............................................................................................129 
10.6. 
Appendix 7 Key Data Analysis Requirements............................................................129 
11. 
REFERENCES ............................................................................................................131 
12. 
LIST OF ABBREVIATIONS .....................................................................................137 
 

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LIST OF TABLES 
Table 1.1: Schedule of Events .....................................................................................................25 
Table 2.1: Study DS3201-A-J101 Overview of TEAEs, All R/R NHL Subjects, by 
Dose (Safety Analysis Set) .........................................................................................42 
Table 3.1: Description of Objectives, Outcome Measures, and Endpoints .................................44 
Table 6.1: Study Drug Dosing Information .................................................................................58 
Table 6.2: Dose Interruptions/Reductions for Hematological and Nonhematological 
Toxicity .......................................................................................................................60 
Table 6.3: Dose Reductions for Valemetostat Tosylate...............................................................64 
Table 6.4: Dose Reduction for Concomitant Use of Strong CYP3A Inhibitors and/or 
P-gp Inhibitors ............................................................................................................64 
Table 8.1: Schedule for Efficacy Assessment by CT (or MRI) Scan ..........................................75 
Table 8.2: Schedule for FDG-PET Scans ....................................................................................76 
Table 8.3: Schedule of PK/AAG Sample Collection ...................................................................86 
Table 9.1: 95% Confidence Interval at Various Observed ORRs (R/R PTCL Subjects) ............90 
Table 10.1: Clinical Laboratory Tests .........................................................................................104 
Table 10.2: New York Heart Association Classifications ...........................................................106 
Table 10.3: Eastern Cooperative Oncology Group Performance Status ......................................106 
Table 10.4: CYP3A/P-gp Inhibitors and CYP3A Inducers .........................................................108 
Table 10.5: Diagnostic Criteria for Clinical Subtype of ATL73 ...................................................110 
Table 10.6: Cohort 1: Probability of Grade 4 (hematologic or non-hematologic toxicity) 
= 30% (Sample Size = 128 & Desired probability of early stopping = 0.05) ..........112 
Table 10.7: Cohort 1: Probability of AE of Special Interest (thrombocytopenia, Grade 
≥3) = 35% (Sample Size = 128 & Desired probability of early stopping = 
0.05) ..........................................................................................................................113 
Table 10.8: Cohort 1: Probability of Grade 5 (hematologic or nonhematologic toxicity) = 
5% (Sample Size = 128 & Desired probability of early stopping = 0.05) ................114 
Table 10.9: Cohort 2: Probability of Grade 4 = 30% (hematologic or non-hematologic 
toxicity) (sample size = 20 and desired probability of early stopping = 0.05) .........115 
Table 10.10: Cohort 2: Probability of AE of Special Interest (thrombocytopenia, Grade 
≥3) = 35% (sample size = 20 and desired probability of early stopping = 
0.05) ..........................................................................................................................115 
Table 10.11: Cohort 2: Probability of Grade 5 (hematologic or non-hematologic 
toxicity) = 5% (sample size = 20 and desired probability of early stopping = 
0.05) ..........................................................................................................................115 

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Table 10.12: Acute GVHD Grading and Staging .....................................................................115 
Table 10.13: Percent Body Surfaces .........................................................................................116 
Table 10.14: Organ Scoring of Chronic GVHD .......................................................................116 
Table 10.15: Definition of Target Lesions (Cohorts 1 and 2: PTCL and ATL) .......................118 
Table 10.16: Additional Lesions/Disease for Response Assessment (Cohort 2: ATL) ............118 
Table 10.17: 2014 Lugano Criteria for Cohort 1 (PTCL) .........................................................119 
Table 10.18: Modified 2009 ATL Criteria ................................................................................123 
Table 10.19: Table for Calculation of Body Surface Area .......................................................124 
Table 10.20: Key Data Requirements .......................................................................................130 
 

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LIST OF FIGURES 
Figure 1.1: Study-level Flow Diagram ..........................................................................................23 
Figure 1.2: Flow Diagram .............................................................................................................24 
Figure 8.1: Cohort 1 Efficacy Assessment Schedule ....................................................................73 
Figure 8.2: Cohort 2 Efficacy Assessment Schedule ....................................................................74 
Figure 10.1: Regional Percent Body Surface Area ...................................................................125 
 

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To evaluate the pharmacokinetics (PK) of 
valemetostat and major metabolite 
(CALZ-1809a) 
Not applicable 
Total and unbound 
DS-3201a (free form of 
valemetostat tosylate) 
and total CALZ-1809a 
(major metabolite) 
concentration in plasma 
PK 
Cohort 1 Only 
To evaluate the duration of response (DoR) 
Title: Duration of 
response 
Description: Time 
from the first 
documented 
response (CR or 
PR) until 
documented disease 
progression 
(progressive or 
relapsed disease) 
based on BICR 
assessments or 
death from any 
cause 
DoR is defined as the 
time from the date of 
the first documentation 
of objective response 
(CR or PR) to the date 
of the first 
documentation of 
disease progression 
(progressive or relapsed 
disease) based on BICR 
assessments or to death 
due to any cause, 
whichever occurs first. 
Efficacy 
To assess the CR rate 
Title: Complete 
response rate 
Description: 
Percentage of 
subjects with no 
detectable evidence 
of PTCL 
CR rate is the 
percentage of subjects 
achieving CR as the 
BOR based on BICR 
assessments. 
Efficacy 
To evaluate the duration of CR (DoCR) 
Title: Duration of 
complete response 
Description: Time 
from the first 
documented CR 
until documented 
disease progression 
(progressive or 
relapsed disease) 
based on BICR 
assessments or 
death from any 
cause 
DoCR is defined as the 
time from the date of 
the first documentation 
of CR to the date of the 
first documentation of 
disease progression 
(progressive or relapsed 
disease) based on BICR 
assessments or to death 
due to any cause, 
whichever occurs first. 
Efficacy 
To assess the PR rate 
Title: Partial 
response rate 
Description: 
Percentage of 
subjects with 
regression of 
disease and no 
detectable evidence 
of new 
PR rate is the 
percentage of subjects 
achieving PR as the 
BOR based on BICR 
assessment. 
Efficacy 

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cancer/lesions in 
other parts of the 
body 
To assess the safety and tolerability of 
valemetostat tosylate monotherapy 
Title: Number of 
subjects with 
TEAEs during the 
study 
Description: Total 
number of Cohort 1 
subjects in the 
Safety Analysis Set 
with TEAE 
All safety assessments, 
including AE reporting 
(TEAEs; TEAESIs; 
TESAEs; TEAEs by 
severity CTCAE 
grading, including 
Grade 3 and Grade 4; 
fatal events; and TEAEs 
leading to treatment 
discontinuation, 
interruption, or 
reduction), laboratory 
assessments, vital signs, 
and ECG (including 
QTcF by central ECG 
reading) 
Safety 
Throughout this document, response is used in lieu of remission when discussing CR, and PR for R/R ATL.  

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 
Enteropathy-associated T-cell lymphoma 
 
Monomorphic epitheliotropic intestinal T-cell lymphoma 
 
Hepatosplenic T-cell lymphoma 
 
Primary cutaneous γδ T-cell lymphoma 
 
Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma 
 
PTCL, not otherwise specified  
 
Angioimmunoblastic T-cell lymphoma 
 
Follicular T-cell lymphoma 
 
Nodal PTCL with T-follicular helper (TFH) phenotype 
 
ALCL, ALK positive 
 
ALCL, ALK negative 
 
Cohort 2 (R/R ATL): acute, lymphoma, or unfavorable chronic type.  R/R ATL should be confirmed by the 
local pathologist; local diagnosis will be used for eligibility determination.  The positivity of anti-human T-
cell leukemia virus type 1 (HTLV-1) antibody will be locally determined for eligibility. 
 
Must have at least one of the following lesions which are measurable in 2 perpendicular dimensions on 
computed tomography (or magnetic resonance imaging) based on local radiological read: 
 
Longest diameter (LDi) ≥2.0 cm for a nodal lesion 
 
LDi >1.0 cm for an extranodal lesion 
 
For Cohort 2 (ATL), subjects who had disease only in peripheral blood or skin lesions are 
eligible as defined below.  
o 
An abnormal lymphocyte count (actual number) is ≥1.0 × 109/L and the abnormal 
lymphocyte-to-leucocyte ratio is ≥5%. 
o 
Skin lesion(s) measured by modified severity weighted assessment tool score.4 
 
Documented refractory, relapsed, or progressive disease after at least 1 prior line of systemic therapy. 
 
Refractory is defined as 
o 
Failure to achieve CR (or CRu for ATL) after first-line therapy  
o 
Failure to reach at least PR following second-line therapy or beyond 
 
Must have at least 1 prior line of systemic therapy for PTCL or ATL.   
 
Subjects must be considered hematopoietic cell transplantation (HCT) ineligible during 
Screening due to disease status (active disease), comorbidities, or other factors; the reason for 
HCT ineligibility must be clearly documented. 
 
In Cohort 1, subjects with ALCL must have prior brentuximab vedotin treatment. 
Key Exclusion Criteria: 
Subjects meeting any exclusion criteria for this study will be excluded from this study.  Below is a list limited to 
the key exclusion criteria: 
 
Diagnosis of mycosis fungoides, Sézary syndrome and primary cutaneous ALCL, and systemic 
dissemination of primary cutaneous ALCL 
 
Diagnosis of precursor T-cell leukemia and lymphoma (T-cell acute lymphoblastic leukemia and T-
cell lymphoblastic lymphoma), T-cell prolymphocytic leukemia, or T-cell large granular lymphocytic 
leukemia 
 
Prior malignancy active within the previous 2 years except for locally curable cancer that is currently 
considered as cured, such as cutaneous basal or squamous cell carcinoma, superficial bladder cancer, or 
cervical carcinoma in situ, or an incidental histological finding of prostate cancer. 
 
Presence of active central nervous system involvement of lymphoma 

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LTFU = Long-term Follow-up; ORR = objective response rate; OS = overall survival; PFS = progression-free 
survival; PR = partial response; PTCL = peripheral T-cell lymphoma; QD = once daily; US = United States 
a Prior brentuximab vedotin treatment is required for the ALCL subtype 
b The primary completion date is based on the initiation of study drug in Cohort 1 by the last subject to meet PTCL 
eligibility criteria as confirmed by central diagnosis.  The primary completion date will be at least 10 months after 
the first dose of study drug is taken by this subject. 
Note: The overall End of Study is defined as the last subject’s last visit. 
Figure 1.2: 
Flow Diagram 
Screening Period
(28 days Pre-dose)
Treatment Period
(28-day Continuous Cycles)
                     Follow-up Period
Subject 
signs ICF
Valemetostat Tosylate 200 mg/day
30D Safety 
Follow-up 
Visit 
(+ 7d)
LTFU Visits
(Q3M)
First Dose
Last Dose
EOT Visit 
(within 7d 
of last 
dose) 
 
EOT = End of Treatment; HCT = hematopoietic cell transplantation; ICF = informed consent form; LTFU = Long-term 
Follow-up; Q3M = every 3 months 
Subjects may discontinue the study drug at any time to undergo HCT.  If a subject undergoes HCT, HCT-relevant information 
and survival status will be collected during the Follow-up Period, starting at the 30-day Safety Follow-up Visit. 
 

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2. 
INTRODUCTION 
2.1. 
Background 
Peripheral T-Cell Lymphomas Background 
The term peripheral T-cell lymphoma (PTCL) comprises a heterogenous group of rare lymphoid 
malignancies, representing 10% to 15% of non-Hodgkin lymphomas (NHLs).8  The surveillance, 
epidemiology, and end-result (SEER) cancer registries in the United States (US) identified 
20,726 patients with PTCL 15 years or older between 2000 and 2012.9  Three major subtypes 
account for approximately 60% to 80% of PTCL: PTCL not otherwise specified (PTCL-NOS), 
angioimmunoblastic T-cell lymphoma (AITL), and anaplastic lymphoma kinase 
(ALK)-positive- or ALK-negative-systemic anaplastic large cell lymphoma (ALCL).  The 
remaining subtypes are extremely rare and include adult T-cell leukemia/lymphoma (ATL), 
enteropathy-associated T-cell lymphoma, and others.5  Subtypes differ by geographic 
distribution, disease and clinical characteristics, and prognoses8,10  The incidence of each subtype 
is influenced by age, gender, and ethnicity.11,12 
Patients with PTCL have a poor prognosis, with the 5-year overall survival (OS) and 5-year 
progression-free survival (PFS) being 34.1% and 25.7%, respectively, based on a Swedish 
registry study (n = 755).13  First-line standard of care therapy for most PTCL subtypes has not 
changed for decades.  Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP)-
based regimens, the current standard treatment for PTCL patients, were initially adopted from 
the regimen for B-cell NHL (B-NHL) without a strong scientific rationale specific to 
PTCL.14,15,16  National Comprehensive Cancer Network guidelines for most PTCL subtypes 
recommend CHOP as the preferred first-line treatment option.14  The only exception is the 
brentuximab vedotin-based regimen, which demonstrated superior PFS and OS in patients with 
previously untreated CD30-postive PTCL, including ALCL, when compared to CHOP in a Phase 
3 study.17  The benefits from brentuximab vedotin-based regimen is less pronounced in AITL 
and PTCL-NOS in the subgroup analysis, as the hazard ratio of PFS (95% confidence interval 
[CI]) was 1.40 (0.64 to 3.07) and 0.75 (0.41 to 1.37) for AITL and PTCL-NOS, respectively, 
both of which are not statistically significant.  Thus, other than ALCL, there have not been recent 
significant changes to the first-line treatment for PTCL other than ALCL, particularly in CD30-
negative PTCL. 
Furthermore, approximately 40% to 60% patients achieved a complete response (CR) from 
first-line therapy for PTCL, whereas the remaining subjects had refractory disease, having failed 
to attain a CR.18,19,20,21,22  Additionally, except for the patients with ALK-positive ALCL, the 
majority of the patients with PTCL treated with first-line therapy who achieved CR experienced 
a high relapse rate (eg, 43% in PTCL subjects compared to 29% in B-NHL subjects).22,23,24.  In a 
Swedish registry study, the median OS after relapse/progression in 211 patients initially 
responding to primary treatment was 6.0 months, whereas the median OS was only 2.5 months 
among 143 patients with primary refractory disease.13  The median OS was reported as 
6.5 months for patients who received conventional chemotherapy versus 3.7 months in patients 
who did not receive chemotherapy.25  Thus, survival outcome for patients with 
relapsed/refractory (R/R) PTCL still remains very poor. 

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For patients with R/R PTCL, the therapeutic options are currently limited.  Accelerated approval 
was granted for belinostat and pralatrexate for R/R PTCL in the US, which demonstrated 25.8% 
and 27% of objective response rate (ORR), respectively.6,26,27  No drug is approved for R/R 
PTCL in the European Union (EU).  Forodesine, a purine nucleoside phosphorylase inhibitor, 
was approved in Japan, with 22.5% of ORR28.  Brentuximab vedotin, an antibody-drug conjugate 
against CD30, showed 86% of ORR in ALCL, and is the only drug with full approval for 
R/R PTCL in the US.29,30  However, in the US and EU, its indication is limited to ALCL in 
which CD30 is universally expressed.  Although conventional chemotherapy can be used for 
patients with R/R PTCL, the durability of response is quite short; bendamustine monotherapy 
resulted in a median duration of response (DoR) of 3.5 months.31  Patients who are able to 
achieve a good response (typically CR) can undergo an allogeneic hematopoietic cell 
transplantation (HCT) for potential cure, but the modality is limited due to the lack of adequate 
donor and patients’ comorbidities.  Thus, there remains a compelling unmet need for improved 
salvage therapy for patients with R/R PTCL. 
Adult T-cell Leukemia/Lymphoma Background 
ATL, as a subtype of PTCL, is composed of highly atypical lymphocytes, which is caused by 
human T-cell leukemia virus type 1 (HTLV-1)2,7,32,33  HTLV-1 infection is endemic in the 
southwest region of Japan, Central and South America, and other regions.34 
ATL is sporadically reported in North America.34  Most of the cases are migrants from endemic 
areas, particularly in the New York metropolitan area and Florida in the US.  In Europe, most 
cases are reported in France and the United Kingdom.35  A recent epidemiology study indicated 
that the incidence of ATL is rising in nonendemic regions of the world.36 
Whereas favorable chronic and smoldering types are considered as indolent ATL, aggressive 
ATL consists of acute, lymphoma, and unfavorable chronic types, which usually require 
immediate systemic therapy.  The clinical course for subjects with aggressive ATL is poor.  For 
example, the median survival of newly diagnosed ATL was 6.2, 10.2, and 15 months for acute, 
lymphoma, and unfavorable chronic types, respectively.32  Unfortunately, there has been no 
significant progress in therapy, as the recent report by Katsuya et al indicated that the median 
survival of newly diagnosed ATL was 8.3 and 10.6 months for acute and lymphoma types, 
respectively.37 
The initial treatment for aggressive ATL varies depending on the available therapy by country or 
region.  The 2017 Consensus report recommends prospective clinical studies for all patients with 
initial diagnosis or R/R ATL.35  Outside of clinical studies, in Japan, the recommendation of the 
first-line therapy includes vincristine, cyclophosphamide, doxorubicin, and prednisone (VCAP); 
doxorubicin, ranimustine, and prednisone (AMP); and vindesine, etoposide, carboplatin, and 
prednisone (VECP) chemotherapy regimens (modified LSG15).38  However, outside of Japan, 
the recommended first-line therapy are other chemotherapy regimens (eg, CHOP), because 
certain components of the modified LSG15 is not available.  Regardless, the outcomes from the 
first line are miserable.  For instance, a randomized Phase 3 study showed that the median OS 
was 12.7 months and 10.9 months from the modified LSG15 regimen (an experimental arm) and 
from CHOP (a control arm), respectively.38  The median PFS was 7.0 months and 5.4 months 
from the modified LSG15 and from CHOP, respectively.  Therefore, most of the patients 
experience refractory or relapsed disease within 1 year from the initial diagnosis. 

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For refractory or relapsed ATL, no therapy clearly demonstrated survival benefits.  In Japan, 
mogamulizumab and lenalidomide are licensed for use in R/R aggressive ATL based on 
single-arm Phase 2 studies.  Mogamulizumab, an anti-chemokine receptor type 4 (CCR4) was 
tested in 27 subjects with relapsed CCR4-positive ATL after prior chemotherapy.39  The ORR 
was 50% (13/26) (95% CI: 30 to 70); the median PFS and OS were 5.2 months and 13.7 months, 
respectively.  In a Phase 2 study of lenalidomide, for 26 subjects with relapsed or recurrent 
aggressive ATL, including 11 subjects who were previously treated with mogamulizumab, the 
ORR was 42% (11/26) (95% CI: 23 to 63); the median PFS and OS were 3.8 months and 
20.3 months, respectively.40  Both studies showed short duration of PFS.  Outside Japan, no drug 
has been approved for relapsed or refractory ATL.  Bortezomib showed limited efficacy, with 
6.7% of ORR (95% CI 0.17% to 31.95%) in 15 R/R ATL subjects in Japan.41  The combination 
of arsenic trioxide and alpha interferon yielded some response in 2 small French and Japanese 
studies, although the treatment duration was very short.42,43  A Phase 2 study in the US for 
previously untreated ATL (n = 9) and R/R ATL (n = 20), alemtuzumab, an anti-CD52 antibody, 
yielded 15 responders (52% of 29 subjects), but the response was limited predominantly to acute 
or chronic subtypes; only 1 responder was reported among the 11 subjects with lymphoma-type 
ATL.44  Thus, a high unmet need exists for relapsed or refractory ATL patients. 
Valemetostat Tosylate 
Valemetostat tosylate is a potent and selective dual inhibitor of enhancer of zeste homolog 
(EZH)1 and EZH2, 2 epigenetic regulators with histone methyltransferase activity at lysine 27 of 
histone H3 (H3K27).45, 46  Valemetostat tosylate inhibits EZH1 and EZH2, preventing the 
tri-methylation of H3K27, and alters gene expression patterns which ultimately attenuate the 
proliferation of EZH1/2 dependent cancer cells.  Whereas selective inhibition of EZH2 caused 
compensation by EZH1, valemetostat tosylate has been proven to suppress both EZH1 and EZH2 
as a dual inhibitor.47  Valemetostat tosylate is currently the only dual EZH1 and EZH2 inhibitor 
in clinical development.   
2.2. 
Study Rationale 
Recent evidence suggests that PTCL, including ATL, can be driven by epigenetic 
dysregulation.48,49  EZH1 and EZH2, catalytic subunits of the polycomb repressive complex 2, 
specifically methylate H3K27.50  Hypertrimethylation of H3K27 is considered to silence tumor 
suppressor genes and has been associated with lymphoma progression, including PTCL and 
ATL.49,51,52 
Valemetostat tosylate may modify epigenetic changes, which plays an important role in the 
pathogenesis of PTCL.  In the ongoing open-label Phase 1 study (DS3201-A-J101, 25 Dec 2019 
data cut-off), valemetostat tosylate monotherapy demonstrated approximately 62% ORR 
(34% CR rate) from 21 evaluable R/R PTCL subjects and approximately 50% ORR (20% CR 
rate) from 10 evaluable R/R ATL subjects; details will be described in Section 2.3.  
This Phase 2 study will further characterize the safety and clinical activity of valemetostat 
tosylate and provide an estimate of the clinical benefit as measured by ORR in subjects with R/R 
PTCL.  Additionally, data from the R/R ATL cohort will be collected to supplement the overall 
safety and efficacy profile of valemetostat tosylate monotherapy. 

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Throughout the rest of this document, R/R PTCL will be used and refers to subjects who are 
R/R PTCL excluding ATL. 
2.3. 
Benefit and Risk Assessment 
The current benefit/risk assessment is based on available nonclinical data and clinical data from 
the Phase 1 studies. 
Nonclinical Data 
Valemetostat tosylate showed high potency as an inhibitor of the methyltransferase activities of 
EZH1 and EZH2 both in vitro and high efficacy in an in vivo mouse tumor model.  Safety 
pharmacology studies showed a low possibility for unexpected pharmacology-related adverse 
events (AEs) with valemetostat tosylate.  Completed studies showed no effects on the central 
nervous system or respiratory systems of rats.  In terms of cardiovascular effects, a potential for 
the prolongation of QT/ corrected QT interval (QTc) was observed both in the 4-week repeated 
dose toxicity study in dogs (where the QTc was extended in females) and in the dog telemetry 
study (where QT and QTc were increased).  However, there were no effects on QTc in the 
13-week dog study.  In addition, there were no effects on cardiac pathology in either rat or dog in 
the 4-week or 13-week repeated dose toxicity studies.  Based on the STD10 of 200 mg/kg in rats 
and the highest nonseverely toxic dose (HNSTD) of 30 mg/kg/day in dogs after 4 weeks of 
dosing, the first-in-human dose was set at 150 mg.  A 3-month toxicology study in rats 
administered valemetostat tosylate showed the potential risks of developing lymphoid 
malignancies.  A follow-up 3-month toxicity study in older rats (aged 55 weeks old at the time of 
initiation of dosing) was performed to further understand the pathogenic mechanism of this 
finding in younger rats showed administration of valemetostat tosylate to aged rats did not 
induce a lymphoma that had been previously observed with younger rats. 
Overall, based on nonclinical data, the potential risks associated with valemetostat tosylate 
exposure include bone marrow hypocellularity as demonstrated in clinical parameters of reduced 
platelets, white blood cells, and red blood cells (RBC); QT interval prolongation; and allergic-
like reactions due to elevated histamine levels. 
Please refer to the current valemetostat tosylate Investigator’s Brochure (IB) for additional 
details of nonclinical data supporting its use in clinical studies.53 
Clinical Data 
As of 18 Jan 2020, valemetostat tosylate has been investigated for malignant lymphoma in 
2 clinical studies; a Phase 1 study (DS3201-A-J101) and a Phase 2 study (DS3201-A-J201).  
Study DS3201-A-J101 is an ongoing open-label Phase 1 study with dose escalation, dose 
expansion, and drug-drug interaction (DDI) parts, evaluating the safety, pharmacokinetics (PK), 
and preliminary efficacy of valemetostat tosylate monotherapy in subjects with R/R NHL, 
specifically B-NHL, PTCL, and ATL. 
Study DS3201-A-J201 is an ongoing Phase 2, multicenter, open-label, single-arm study of 
valemetostat tosylate, 200 mg/day, in subjects with R/R ATL being conducted in Japan.  

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As of the data cut-off date of 18 Jan 2020, only 5 subjects have received treatment with 
valemetostat tosylate, and there is little available data from Study DS3201-A-J201.  Therefore, 
this benefit/risk assessment is based mainly on the data from dose escalation and dose expansion 
parts from Study DS3201-A-J101.   
Preliminary safety data from Study DS3201-A-J101 (data cut-off date: 25 Dec 2019) in 
56 subjects (Table 2.1) with R/R NHL, including B-cell NHL (N = 19), PTCL (N = 26), and 
ATL (N = 11), indicated that valemetostat tosylate appears manageable; 7, 40, 7, and 2 subjects 
received 150, 200, 250, and 300 mg of valemetostat tosylate once daily, respectively.  Grade ≥3 
treatment-emergent adverse events (TEAEs) occurred in 69.6% of subjects at all doses (150 mg 
to 300 mg) and in 100% of subjects who were treated at 250 mg or 300 mg. 
Table 2.1: 
Study DS3201-A-J101 Overview of TEAEs, All R/R NHL Subjects, by Dose 
(Safety Analysis Set) 
Valemetostat Tosylate 
 
150 mg/day 
N = 7 
n (%) 
200 mg/day 
N = 40 
n (%) 
250 mg/day 
N = 7 
n (%) 
300 mg/day 
N = 2 
n (%) 
Total 
N = 56 
n (%) 
Subjects with TEAEs, n (%) 
7 (100.0) 
40 (100.0) 
7 (100.0) 
2 (100.0) 
56 
(100.0) 
Grade ≥3  
4 (57.1) 
26 (65.0) 
7 (100.0) 
2 (100.0) 
39 (69.6) 
SAE 
3 (42.9) 
10 (25.0) 
0 (0.0) 
0 (0.0) 
13 (23.2) 
Associated with Dose Reduction 
0 (0.0) 
3 (7.5) 
2 (28.6) 
1 (50.0) 
6 (10.7) 
Associated with Dose Interruption 
1 (14.3) 
17 (42.5) 
4 (57.1) 
1 (50.0) 
23 (41.1) 
Associated with Study Drug 
Discontinuation 
1 (14.3) 
1 (2.5) 
0 (0.0) 
0 (0.0) 
2 (3.6) 
Associated with Fatal Outcome 
0 (0.0) 
1 (2.5) 
0 (0.0) 
0 (0.0) 
1 (1.8) 
SAE = serious adverse event; TEAE = treatment-emergent adverse event  
Source: Table 14.3.1.2, data-cut-off date: 25 Dec 2019 
Cytopenias (platelet count decreased, anemia, white blood cell count decreased, neutrophil count 
decreased, and lymphocyte count decreased) were the most common TEAEs (any grade) as well 
as the most common Grade ≥3 TEAEs.  In particular, platelet count decreased was reported as 
the most frequent TEAE of any grade in 40 (71.4%) subjects, including Grade 3 and Grade 4 
platelet count decreased in 6 (10.7%) and 4 (7.1%) subjects, respectively.  Additional 
information regarding thrombocytopenia can be found in Section 8.4.1.4.  No R/R NHL subjects 
discontinued study drug due to thrombocytopenia or platelet count decreased.  Opportunistic 
infections were also reported, including Pneumocystis jirovecii pneumonitis (n = 3) and 
cytomegalovirus (CMV) infection (n = 3).  Other common TEAEs included general 
symptomatology (alopecia, nasopharyngitis, dry skin, rash, fatigue, arthralgia, and pyrexia), 
gastrointestinal disorders (diarrhea, nausea, and decreased appetite), and central nervous system 
disorders (dysgeusia),which were primarily Grade 1 or Grade 2 in severity.  Electrocardiogram 

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(ECG) QT prolonged occurred in <10% of all R/R NHL subjects and all events were Grade 1 or 
Grade 2. 
The safety experience was generally similar in R/R PTCL and R/R ATL subjects compared to all 
R/R NHL subjects.  In the R/R PTCL group Grade ≥3 TEAEs occurred in 16 (61.5%) subjects.  
In R/R PTCL and R/R ATL subjects, platelet count decreased, anemia, white blood cell count 
decreased, neutrophil count decreased, and lymphocyte count decreased were the most common 
TEAEs as well as the most common Grade ≥3 TEAEs.  As with R/R NHL subjects, the other 
common TEAEs in these subjects included general symptomatology (alopecia, nasopharyngitis, 
fatigue, arthralgia, and pyrexia [only reported in R/R PTCL subjects]), gastrointestinal disorders 
(diarrhea, nausea, and decreased appetite), and central nervous system disorders (dysgeusia), 
which were primarily Grade 1 or Grade 2 in severity. 
In relation to safety data derived from animal studies, no cardiotoxicity, hepatotoxicity, 
hypersensitivity, or phototoxicity was observed in the Phase 1 clinical study, DS3201-A-J101.  
Overall, valemetostat tosylate appears manageable. 
Preliminary efficacy data from Study DS3201-A-J101 (data cut-off date: 25 Dec 2019) 
demonstrated that valemetostat tosylate treatment resulted in an objective response of 61.9% 
(95% CI: 38.4, 81.9) and 50.0 % (95% CI: 18.7, 81.3) in subjects with PTCL and ATL, 
respectively.  The median DoR (estimated using the Kaplan-Meier method) was 44.43 (95% CI: 
not estimable) weeks in subjects with PTCL but was not calculated for subjects with ATL due to 
the small number of subjects. 
On the basis of the nonclinical and clinical data available to date, the potential benefit from 
valemetostat tosylate exceeds the risks for a population of patients with late-stage disease with 
careful dosing and monitoring in clinical studies. 

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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a global, multicenter, open-label, single-arm, 2-cohort, Phase 2 study designed to evaluate 
the efficacy and safety of valemetostat tosylate monotherapy in approximately 148 subjects with 
R/R PTCL (128 subjects) and R/R ATL (20 subjects). 
The primary objectives are to evaluate the clinical benefit of valemetostat tosylate monotherapy 
as measured by BICR-assessed efficacy, that is, ORR in R/R PTCL (Cohort 1) and the safety and 
tolerability of valemetostat tosylate monotherapy in R/R ATL (Cohort 2).  A key secondary 
objective for the R/R PTCL (Cohort 1) is to evaluate other efficacy measures (eg, DoR) as well 
as the safety and tolerability of valemetostat tosylate monotherapy. 
This study is planned to be conducted in approximately 70 study sites in North America, Europe, 
Asia, and Oceania.  The study population is described in Section 5. 
The study start date is the date when the first subject has signed informed consent.  A subject is 
eligible to be enrolled into the interventional phase (divided into 3 periods: Screening, 
Treatment, and Follow-up) of the study when the investigator or designee has obtained written 
consent, all screening procedures have been completed, and the investigator has confirmed all 
eligibility criteria have been met by the subject at both Screening and Cycle 1 Day 1 prior to the 
first dose of study drug.  A subject is considered enrolled once they have taken their first dose of 
study drug. 
A non-binding futility interim analysis will be conducted for Cohort 1 when the first 
46 (40%) subjects with histologically confirmed PTCL, by central pathology review, complete a 
minimum of 4 months of follow-up from the first dose of valemetostat tosylate.  The futility 
criterion of BICR-assessed ORR is 23.9% or lower, that is, 11 or fewer responders from the first 
46 confirmed R/R PTCL subjects observed.  This boundary only provides the conditional power 
of 0.1% if the null hypothesis is true for the future coming patients. If the alternative hypothesis 
is true for the future coming patients, it provides the conditional power of 40%. This cohort may 
be terminated based on the totality of the evidence (response rate, safety, and benefit/risk), with 
consideration of the futility boundaries. 
An internal data monitoring committee (DMC) will evaluate the safety and/or efficacy data for 
these interim analyses, according to statistical procedures defined a priori and for periodic safety 
reviews and will recommend that the study be terminated early for safety and/or efficacy 
(futility) or continue as planned (Section 10.1.5).  The tasks performed by the DMC will be 
described in the DMC charter. 
The primary completion date is based on the initiation of study drug in Cohort 1 by the last 
subject to meet PTCL eligibility criteria as confirmed by central diagnosis.  The primary 
completion date will be at least 10 months after the first dose of study drug is taken by this 
subject.   
4.1.1. 
Design Overview 
Approximately 148 subjects will be enrolled (128 subjects with R/R PTCL and 20 subjects with 
R/R ATL).  This study will include 2 cohorts: 

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 Cohort 1 (R/R PTCL) 
 Prior treatment with brentuximab vedotin is required for ALCL, a subtype of 
PTCL. 
 Cohort 2 (R/R ATL) 
 Subjects with R/R ATL will be enrolled as a separate single-arm cohort because 
response criteria unique to ATL will be used. 
Enrollment into both cohorts will occur independent of each other and will run in parallel. 
At the beginning of the Screening Period, prior to undergoing any study procedures, subjects 
sign the informed consent form (ICF).  During the 28-day Screening Period, subjects’ eligibility 
will be confirmed.  They will undergo medical history evaluation, physical examination, vital 
sign determination, and radiographic assessments including computed tomography (CT) (or 
magnetic resonance imaging [MRI]) scans (neck, chest, abdomen, and pelvis) and 
fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET) scan (base of the skull to 
mid-thigh) (see Section 1.3 for a complete list of assessments).  Radiographic assessment for 
other lesions (eg, head) may be performed if clinically indicated.  Bone marrow biopsy is 
required in all subjects except for subjects who underwent bone marrow biopsy within 3 months 
of the first dose of study drug and when the bone marrow results are documented.  In Cohort 2 
subjects, upper gastrointestinal endoscopy is recommended for lesion evaluation during 
screening; if the presence of a clinical lesion is suspected, colonoscopy may be also performed 
during screening.  
During the Treatment Period, subjects will receive valemetostat tosylate 200 mg/day until 
disease progression or unacceptable toxicity (Section 7.1).  Each cycle will be 28 days in 
duration. 
Subjects may choose to discontinue the study drug at any time, during the Treatment Period, to 
undergo HCT.  Subjects who discontinue study drug for any reason other than disease 
progression will continue to have radiographic assessments at the intervals described in the 
Treatment Period until disease progression, start of a new anticancer therapy, lost to follow-up, 
or withdrawal of study consent. 
After study drug is discontinued, subjects will be followed for 30 days for safety (30-day Safety 
Follow-up).  All subjects will then enter Long-term Follow-up for collection of information on 
subsequent lymphoma treatment, response status, HCT and HCT-relevant information, and 
survival, including the cause and date of death. 
The subject population is described in Section 5.  Flow diagrams of study activities are presented 
in Figure 1.1 and Figure 1.2.  
4.1.2. 
End of Study 
The primary completion date is based on the initiation of study drug in Cohort 1 by the last 
subject to meet PTCL eligibility criteria as confirmed by central diagnosis.  The primary 
completion date will be at least 10 months after the first dose of study drug is taken by this 
subject. 

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All subjects in either cohort who are still on treatment or who discontinued from study drug at 
the primary completion date will continue to follow the study Schedule of Events (Table 1.1) 
until the overall End of Study (EOS) is reached, or the subject is lost to follow-up, or the 
subject withdraws consent, or until death. 
Overall EOS will occur when the last subject’s last visit has occurred and is defined as the 
completion of survival follow-up of at least 3 years after the first dose of the last subject either 
from Cohort 1 or Cohort 2, whichever occurs later. 
The subject’s EOS is defined as the date of his/her last study visit/contact. 
4.1.3. 
Dose Regimen 
Subjects will be administered oral valemetostat tosylate at a dose of 200 mg once daily starting at 
Cycle 1 Day 1, until disease progression or unacceptable toxicity, according to the dosage 
regimens outlined in Table 6.1. 
4.1.4. 
Duration 
Study duration will include a Screening Period, a Treatment Period, and a Follow-up Period 
(which includes a 30-day safety follow-up and long-term survival follow-up), as shown in 
Figure 1.1.  
Duration of Treatment and Subject Participation 
After signing the ICF, subjects will be administered valemetostat tosylate at a dose of 200 mg 
once daily starting at Cycle 1 Day 1, until disease progression or unacceptable toxicity.  It is 
expected that a subject’s total duration of participation in the study will be up to 28 days in the 
Screening Period, more than 6 months in the Treatment Period, and 30 days (+7 days) in the 
Follow-up Period after the last study drug administration.  The Survival Follow-up Period will be 
at least 3 years after the first dose of the study drug in the last subject. 
Overall Study Duration 
The overall duration of enrollment for both cohorts is estimated to be approximately 20 months. 
The Survival Follow-up Period will be at least 3 years after the first dose of the study drug in the 
last subject. 
The anticipated total duration of the study from the first patient in through last patient out, which 
will include survival follow-up, will be approximately 56 months.  See Section 4.1 and 
Section 4.1.2 for the definition of study start and for the definition of the overall EOS, 
respectively. 
4.2. 
Rationale for Study Design 
The Phase 2 study is designed assuming that treatment with valemetostat tosylate monotherapy 
will produce a 95% CI, which would exclude the ORR of 27% in subjects with R/R PTCL 
(Cohort 1).  The ORR 27% was based on the ORR of 25.8, 26.2, and 27% from belinostat, 
romidepsin, and pralatrexate for R/R PTCL, respectively.6,26,27 
Conducting a single-arm study is generally acceptable for PTCL due to its rare incidence and the 
lack of a globally established standard of care for PTCL. 

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A parallel cohort approach was selected because the response criteria unique to ATL will be used 
in Cohort 2 for subjects with R/R ATL who may have disease in peripheral blood or skin 
lesion(s). 
4.3. 
Justification for Dose 
The 200-mg dose and once-daily dose regimen were selected based on the results of the ongoing 
study DS3201-A-J101 (NCT02732275). 
As of the data cut-off date (25 Dec 2019), the preliminary clinical data from 
Study DS3201-A-J101 suggests that 200 mg once daily valemetostat tosylate is expected to 
provide sufficient efficacy (an objective response of 57.9% and DoR 44.43 [95% CI: 5.86, 
56.00] weeks) in PTCL patients while keeping a manageable safety profile. 
The exposure-response (E-R) analysis showed that increased exposure did not provide increased 
efficacy; however, an area under the plasma concentration-time curve (AUC) at steady state can 
be achieved by most subjects receiving at least 200 mg/day valemetostat tosylate, implying that 
pharmacologic activity would be sufficient.  The E-R relationship for platelet count was also 
analyzed from Study DS3201-A-J101.  Platelet reduction was exposure dependent in the dose 
range tested (ie, 150 to 300 mg).  The frequency of dose reduction and study drug 
discontinuation at 200 mg/day, in Japan and the US was 7.5% and 2.5%, respectively, indicating 
that valemetostat tosylate at 200 mg/day was generally well tolerated and demonstrates an 
acceptable safety profile.  Thus, 200 mg/day valemetostat tosylate has been selected as the dose 
for this study.   
In a healthy subject study (Study DS3201-A-J103), food intake (high-fat meal) decreased the 
valemetostat (DS-3201a) AUC and maximum concentration (Cmax) by approximately 30% and 
50%, respectively, relative to a fasted condition.  Therefore, valemetostat tosylate tablets will be 
orally administered once daily to fasting subjects (at least 1 hour before or at least 2 hours after a 
meal) until additional data for the effect of different meal types become available. 
In the DDI study with cytochrome P4503A (CYP3A)/P-glycoprotein (P-gp) inhibitors 
(DS3201-A-J104), itraconazole (strong CYP3A inhibitor and P-gp inhibitor) increased AUC of 
valemetostat by 4.2-fold, and fluconazole (moderate CYP3A inhibitor) increased AUC by 
1.6-fold.  A physiologically based PK model has been developed to elucidate the contribution of 
CYP3A and P-gp; accordingly, a dosing adjustment guidance has been developed (Table 6.4).  
To further evaluate the effect of CYP3A/P-gp modulators on the PK of valemetostat to 
adequately inform DDI dose recommendations, additional PK samples will be collected after the 
initiation date of a strong/moderate CYP3A inhibitor or inducer, and/or P-gp inhibitor 
(Section 8.5.1).   

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5. 
STUDY POPULATION 
Adult subjects (aged ≥18 years or the minimum legal adult age [whichever is greater]) with a 
diagnosis of R/R PTCL or R/R ATL.  Prior brentuximab vedotin treatment is required for the 
ALCL subtype. 
5.1. 
Treatment Period 
5.1.1. 
Inclusion Criteria 
Subjects must meet all of the following criteria to be eligible for enrollment into the study: 
1. 
Sign and date the ICF, prior to the start of any study-specific qualification procedures. 
2. 
Subjects ≥18 years of age or the minimum legal adult age (whichever is greater) at the 
time the ICF is signed. 
3. 
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 
4. 
Cohort 1 (R/R PTCL): Diagnosis should be confirmed by the local pathologist; local 
histological diagnosis will be used for eligibility determination.  Subjects with the 
following subtypes of PTCL are eligible, according to 2016 World Health Organization 
classification prior to the initiation of study drug.5  Any T-cell lymphoid malignancies not 
listed below are excluded.  Below is the complete list of eligible subtypes: 
 Enteropathy-associated T-cell lymphoma 
 Monomorphic epitheliotropic intestinal T-cell lymphoma 
 Hepatosplenic T-cell lymphoma 
 Primary cutaneous γδ T-cell lymphoma 
 Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma 
 Peripheral T-cell lymphoma, NOS 
 Angioimmunoblastic T-cell lymphoma 
 Follicular T-cell lymphoma 
 Nodal PTCL with TFH phenotype 
 Anaplastic large cell lymphoma, ALK positive 
 Anaplastic large cell lymphoma, ALK negative 
5. 
Cohort 2 (R/R ATL): Acute, lymphoma, or unfavorable chronic type (Section 10.3.7).  
R/R ATL should be confirmed by the local pathologist; local diagnosis will be used for 
eligibility determination.  The positivity of anti-HTLV-1 antibody will be locally 
determined for eligibility (Section 10.3.7). 
6. 
Must have at least 1 of the following lesions which are measurable in 2 perpendicular 
dimensions on CT (or MRI) based on local radiological read: 
 Longest diameter (LDi) ≥2.0 cm for a nodal lesion 

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 LDi >1.0 cm for an extranodal lesion 
For Cohort 2 (ATL), subjects who had disease only in peripheral blood or skin 
lesions are eligible, as defined below.  
o An abnormal lymphocyte count (actual number) is ≥1.0 × 109/L and the 
abnormal lymphocyte-to-leucocyte ratio is ≥5%.   
o Skin lesion(s) measured by modified severity weighted assessment tool 
(mSWAT) score.4 
7. 
Documented refractory, relapsed, or progressive disease after at least 1 prior line of 
systemic therapy. 
Refractory is defined as 
 Failure to achieve CR (or uncertified CR [CRu] for ATL) after first-line therapy; or 
 Failure to reach at least PR following second-line therapy or beyond. 
8. 
Must have at least 1 prior line of systemic therapy for PTCL or ATL. 
 Subjects must also be considered as HCT-ineligible during Screening due to disease 
status (active disease), comorbidities, or other factors; the reason for HCT 
ineligibility must be clearly documented. 
 In Cohort 1, subjects with ALCL must have prior brentuximab vedotin treatment. 
9. 
Local laboratory data must meet the following criteria at both Screening and prior to 
dosing on the planned Cycle 1 Day 1 Visit to confirm relatively preserved organ 
function: 
a. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × upper 
limit of normal (ULN)  
b. Total bilirubin ≤1.5 × ULN, except for subjects with Gilbert’s syndrome (eg, a gene 
mutation in UGT1A1), who can have total bilirubin <3.0 mg/dL 
c. Absolute neutrophil count (ANC) ≥1.0 × 109/L 
d. Hemoglobin ≥8.0 g/dL 
e. Platelet count ≥75 × 109/L 
f. Creatinine clearance ≥30 mL/min (measured by the Cockcroft-Gault equation) 
(Section 10.3.1) 
10. 
Acute non-hematologic toxic effects (as evaluated by National Cancer Institute [NCI] 
Common Terminology Criteria for Adverse Events [CTCAE], Version 5.0) of any prior 
therapy (except alopecia) resolved as shown below: 
 Peripheral neuropathy: Grade ≤2 
 Fatigue: Grade ≤2 
 All others: Grade ≤1 
11. 
Is willing to provide tumor tissue (obtained during Screening or previously collected as 
a standard of care).  In Cohort 2, subjects with ATL disease should also be willing to 
submit peripheral blood samples. 

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12. 
If the subject is a female of childbearing potential, she must have a negative serum 
pregnancy test at Screening and must be willing to use highly effective birth control, as 
detailed in Section 10.3.6, upon enrollment, during the Treatment Period, and for 
3 months, following the last dose of study drug.  A female is considered of childbearing 
potential following menarche and until becoming postmenopausal (no menstrual period 
for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, 
bilateral salpingectomy or bilateral oophorectomy) with surgery at least 1 month before 
the first dose of study drug or confirmed by follicle-stimulating hormone (FSH) test 
>40 mIU/mL and estradiol <40 pg/mL (<140 pmol/L). 
13. 
If male with partner of childbearing potential, the subject must be surgically sterile or 
willing to use highly effective birth control (Section 10.3.6) upon enrollment, during the 
Treatment Period, and for 3 months following the last dose of study drug. 
14. 
Female subjects must not donate, or retrieve for their own use, ova from the time of 
screening and throughout the study treatment period, and for at least 3 months after the 
final study drug administration. 
15. 
Male subjects must not freeze or donate sperm starting at Screening and throughout the 
study period, and for at least 3 months after the final study drug administration. 
16. 
Is willing and able to comply with scheduled visits, drug administration plan, laboratory 
tests, other study procedures, and study restrictions. 
17. 
Estimated life expectancy >3 months based on investigator’s opinion. 
5.1.2. 
Exclusion Criteria 
Unless otherwise specified, the below criteria will be evaluated and subjects who meet any of the 
following criteria will be disqualified from entering the study: 
1. 
Diagnosis of mycosis fungoides, Sézary syndrome, and primary cutaneous ALCL and 
systemic dissemination of primary cutaneous ALCL  
2. 
Diagnosis of precursor T-cell leukemia and lymphoma (T-cell acute lymphoblastic 
leukemia and T-cell lymphoblastic lymphoma), T-cell prolymphocytic leukemia, or 
T-cell large granular lymphocytic leukemia  
3. 
Prior malignancy active within the previous 2 years except for locally curable cancer 
that is currently considered as cured, such as cutaneous basal or squamous cell 
carcinoma, superficial bladder cancer, or cervical carcinoma in situ, or an incidental 
histological finding of prostate cancer 
4. 
Presence of active central nervous system (CNS) involvement of lymphoma 
5. 
History of autologous HCT within 60 days prior to first dose of study drug 
6. 
History of allogeneic HCT within 90 days prior to the first dose of study drug 
7. 
Clinically significant graft-versus-host disease (GVHD) or GVHD requiring systemic 
immunosuppressive prophylaxis or treatment  
8. 
Inadequate washout period from prior lymphoma-directed therapy before enrollment, 
defined as follows: 

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 Prior systemic therapy (eg, chemotherapy, immunomodulatory therapy, or 
monoclonal antibody therapy) within 3 weeks or 5 half-lives of the drug, 
whichever is longer, prior to the first dose of study drug 
 Had curative radiation therapy or major surgery within 4 weeks or palliative 
radiation therapy within 2 weeks prior to the first dose of study drug 
9. 
Uncontrolled or significant cardiovascular disease, including the following: 
 Evidence of prolongation of QT/QTc interval (eg, repeated episodes of QT 
corrected for heart rate using Fridericia’s method [QTcF] >450 ms) (average of 
triplicate determinations) 
 Diagnosed or suspected long QT syndrome, or known family history of long 
QT syndrome 
 History of clinically relevant ventricular arrhythmias, such as ventricular 
tachycardia, ventricular fibrillation, or Torsade de Pointes 
 Uncontrolled arrhythmia (subjects with asymptomatic, controllable atrial 
fibrillation may be enrolled), or asymptomatic persistent ventricular tachycardia 
 Subject has clinically relevant bradycardia of <50 bpm unless the subject has a 
pacemaker 
 History of second- or third-degree heart block.  Candidates with a history of heart 
block may be eligible if they currently have pacemakers, and have no history of 
fainting or clinically relevant arrhythmia with pacemakers, within 6 months prior 
to Screening 
 Myocardial infarction within 6 months prior to Screening 
 Angioplasty or stent graft implantation within 6 months prior to Screening 
 Uncontrolled angina pectoris within 6 months prior to Screening 
 New York Heart Association (NYHA) Class 3 or 4 congestive heart failure 
(see Section 10.3.2) 
 Coronary/peripheral artery bypass graft within 6 months prior to Screening  
 Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or 
diastolic blood pressure >110 mmHg) 
 Complete left bundle branch block 
10. 
History of treatment with other EZH inhibitors 
11. 
Current use of moderate or strong cytochrome P450 (CYP)3A inducers (Table 10.4) 
12. 
Systemic treatment with corticosteroids (>10 mg daily prednisone equivalents).  Note: 
Short-course systemic corticosteroids (eg, prevention/treatment for transfusion reaction) 
or use for a non-cancer indication (eg, adrenal replacement) is permissible. 
13. 
Female who is pregnant or breast-feeding or intends to become pregnant during the study 

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14. 
Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic 
infection within 28 days prior to the first dose of study drug (hepatitis B surface antigen 
positive or have detectable HBV DNA or detectable HCV RNA). 
15. 
Known history of testing positive for human immunodeficiency virus (HIV) or known 
acquired immunodeficiency syndrome  
16. 
Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection requiring 
treatment with intravenous antibiotics, antivirals, or antifungals.  Note: Subjects with 
localized fungal infections of skin or nails are eligible. 
17. 
Any active uncontrolled systemic diseases or other medical conditions considered to be 
poorly controlled by the investigator, including, but not limited to, bleeding diatheses 
18. 
A medical history or complication considered inappropriate for participation in the study, 
or a serious physical or psychiatric disease, the risk of which may be increased by 
participation in the study in the investigator’s opinion 
19. 
Psychological, social, familial, or geographical factors or substance abuse that would 
prevent regular follow-up to be compliant with the protocol 
20. 
Known or suspected hypersensitivity to valemetostat tosylate or any of the excipients  
5.2. 
Screening Failures, Rescreening, and Subject Replacement 
Retesting of assessments, including laboratory parameters, within any single screening will be 
permitted.  Any new result prior to the first dose of study drug will override the previous result 
during screening.  
Rescreening is permitted in this study.  A new subject identification (SID) number should be 
assigned at the time of rescreening.  For any subject who failed to meet the eligibility criteria 
upon initial screening, the initial screening information and the reason why the subject is 
ineligible for the initial evaluation will be recorded on the Screening Log.   
If the subject successfully repeats the failed initial screening assessment(s) within the Screening 
Period, the subject may be enrolled.  Additionally, if a subject meets all eligibility criteria but 
cannot begin dosing with study drug within 28 days after signing the ICF, the subject must be 
rescreened.  Any assessments outside of the 28-day window from the first dose should be 
repeated, and the screening assessment data should be entered into the clinical database under the 
new SID.   
There is no limit on the number of times a subject may be rescreened, but subjects completing 
screening and enrolled into the study will not be replaced. 

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6. 
STUDY TREATMENT 
See Figure 1.1 for treatment sequence. 
6.1. 
Study Drug Description 
Table 6.1 describes the formulation, dose, regimen, duration, packaging, and labeling of 
valemetostat tosylate. 
Table 6.1: 
Study Drug Dosing Information 
Study Drug Name 
DS-3201b tablets 50 mg 
DS-3201b tablets 100 mg 
Dosage Formulation 
DS-3201b (valemetostat tosylate) tablets 50 mg are white, 
round-shaped, film-coated tablets, each of which contains 
50 mg of DS-3201a as the free form of valemetostat 
tosylate. 
DS-3201b (valemetostat tosylate) tablets 100 mg are 
grayish-red, oblong-shaped, film-coated tablets, each of 
which contains 100 mg of DS-3201a as the free form of 
valemetostat tosylate. 
Dosage Level(s) 
200 mg 
Route of Administration 
Oral 
Dosing Instructions 
200 mg, once daily.  Subjects are instructed to orally take 
valemetostat tosylate under fasting conditions (to be taken 
at least 1 hour before or at least 2 hours after a meal). 
Duration 
Until progression or unacceptable toxicity  
Packaging 
Bottles (32 tablets per bottle) 
High-density polyethylene plastic bottle with desiccants 
(with a child-resistant cap) 
Packaging will clearly display the name of product, storage 
condition, and other required information as applicable in 
accordance with local regulations 
Labeling 
Bottles will be labeled as required per local regulatory 
requirement 
6.2. 
Preparation, Handling, Storage, and Accountability for Study Drug 
Preparation, Handling, and Disposal 
The study drug will be supplied as tablets that need no further preparation at the study sites.   
The dispensation of study drug will be conducted in accordance with the Pharmacy Manual 
provided by the Sponsor.   
Procedures for proper handling and disposal should be followed in compliance with the standard 
operating procedures of the site. 
Administration 
The study drug will be orally administered once daily to fasting subjects (at least 1 hour before 
or at least 2 hours after a meal).  The study drug will be administered over continuous 28-day 

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cycles and will be continued until disease progression or unacceptable toxicity.  There will be no 
washout period between cycles.  When valemetostat tosylate cannot be administered as specified 
in the protocol, such as overdose or missed doses, then the investigator will promptly evaluate 
the situation and take the necessary measures.  On the following day, the study drug should be 
taken at least 12 hours after the last dose taken.  If a dose is forgotten or missed, the subject 
should continue to take the study drug at the same dose the next day; a subject should not take 
the study drug 2 times within a 12-hour period. 
If a subject vomits after taking a dose of the study drug, a replacement dose may not be given on 
the same day. 
In the event of overdose, the subject should immediately be examined for any symptoms or 
signs, and the necessary assessments will be performed, including laboratory tests and 12-lead 
ECG.  Furthermore, the event should be immediately reported to the Sponsor.  The Sponsor will 
give instructions about the dose of valemetostat tosylate on and after the following day. 
If a dose is forgotten or missed, or if a subject vomits after taking a dose of study drug, this will 
be recorded in the patient diary. 
Storage 
Valemetostat tosylate must be stored in a secure, limited access storage area under the 
recommended storage conditions noted on the label.  If storage conditions are not maintained per 
specified requirements, then the Sponsor or contract research organization (CRO) should be 
contacted. 
See the Pharmacy Manual for detailed information on storage conditions of study drug and 
management and collection.  
Drug Accountability 
When a drug shipment is received, the investigator or designee will check the amount and 
condition of the drug against the shipping documentation. 
The Receipt of Shipment Form should be faxed as instructed on the form, unless receipt is 
controlled by drug inventory management system (DIMs).  The original will be retained at the 
study site.  In Japan, the wet-ink signed “Receipt of Shipment Form” will be returned to the 
Sponsor, and a photocopy will be kept at the study site. 
In addition, the investigator or designee shall contact the Sponsor as soon as possible if there is a 
problem with the shipment. 
The investigator is responsible for study drug accountability, reconciliation, and record 
maintenance (ie, Receipt of Shipment Form, dispensation/return record, and certificate of 
destruction/return receipt). 
6.3. 
Method of Treatment Allocation 
This is a non-comparative, open-label, parallel-enrollment, single-arm study with 2 cohorts: 
 Cohort 1 (R/R PTCL) 

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Table 6.3: 
Dose Reductions for Valemetostat Tosylate 
Dose Level 
Study Drug Dose Administered 
1 
200 mg/day 
-1 
150 mg/day 
-2 
100 mg/day 
Once the dose of valemetostat tosylate has been reduced because of toxicity, all subsequent 
cycles should be administered at that lower dose level, unless further dose reduction is required.  
During the treatment periods, more than 2 dose reductions because of toxicity are not allowed.  If 
toxicity continues after 2 dose reductions, the subject will be withdrawn from the study drug.  
The dose reduction of valemetostat tosylate due to concomitant medication use will not be 
counted toward 2 times (see Section 6.5.4). 
6.5.3. 
Permanent Discontinuation of Study Drug  
Discontinue the study drug permanently if 
 Study drug interruption >28 days from the previous dose: 
 Except if, in the opinion of the investigator, the resuming of the study drug is 
considered to continue providing clinical benefits.  In such cases, the investigator 
may resume the study drug after consultation with the Sponsor Medical Monitor.  
 Study drug dose has been reduced more than 2 times. 
6.5.4. 
Dose Modifications with Concomitant Strong CYP3A Inhibitors and/or P-gp 
Inhibitors 
When drugs with strong CYP3A inhibitory effect and/or P-gp inhibitory effect are 
coadministered, the dose of the study drug should be reduced according to Table 6.4.  Refer to 
Table 10.4 for a list of strong CYP3A inhibitors and/or P-gp inhibitors.  The dose of the study 
drug should be returned to the previous dose level that the subject was given (or 200 mg once 
daily if the dose was reduced from the start of the study) after 3 days from the last dose of the 
concomitant strong CYP3A inhibitors and/or P-gp inhibitors. 
Table 6.4: 
Dose Reduction for Concomitant Use of Strong CYP3A Inhibitors and/or 
P-gp Inhibitors 
Inhibitor 
Study Drug Dose 
 
200 mg Once Daily 
150 mg or 100 mg Once Dailya 
Strong CYP3A inhibitors 
Reduce the dose of the study drug to 
100 mg once daily. 
Reduce the dose of the study drug to 
50 mg once daily. 
P-gp inhibitors 
Reduce the dose of the study drug to 
100 mg once daily. 
Reduce the dose of the study drug to 
50 mg once daily. 
Drugs having a strong CYP3A 
inhibitory effect and a P-gp inhibitory 
effect 
Reduce the dose of the study drug to 
50 mg once daily. 
Interrupt the study drug. 
CYP3A = cytochrome P4503A; P-gp = P-glycoprotein 
a When the dose of study drug is 150 mg or 100 mg once daily, the investigator should consult the Sponsor Medical Monitor 
before further reduction of the dose due to concomitant use of strong CYP3A or/and P-gp inhibitors. 

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6.6. 
Prior and Concomitant Medications 
Therapies used within 28 days prior to enrollment until 30 days after the last administration of 
valemetostat tosylate will be recorded in the electronic case report form (eCRF).  COVID-19 
vaccination within 12 weeks of the first dose of study drug will be recorded in the eCRF.  
Prophylactic therapies (including any required premedications), prior therapies, and all 
concomitant therapies will be recorded in the eCRF. 
All therapies received by subjects within 28 days prior to enrollment will be recorded as prior 
therapies.  Concomitant therapies include all prescription, over-the-counter, and herbal remedies. 
Prohibited Therapies/Products 
The following medications/therapies and products will be prohibited during the Treatment 
Period: 
 Any concurrent antineoplastic therapy (ie, chemotherapy, hormonal therapy, 
immunotherapy, radiation therapy except for local disease control, or standard or 
investigational agents for the treatment of cancer).  
 Other investigational therapeutic agents and investigational devices. 
 Donor lymphocyte infusion is prohibited after the first dose of valemetostat tosylate.  
If this is medically essential, investigators should contact the Sponsor Medical 
Monitor. 
 Food products (eg, grapefruit and Seville oranges) that are strong CYP3A inhibitors. 
 Consumption of herbs/fruits that may have an influence on the PK of valemetostat 
tosylate, such as star fruit, Seville orange or Seville orange-containing foods and 
beverages, and grapefruit or grapefruit-containing food or beverages, are 
prohibited from 3 days prior to the first dose of valemetostat tosylate up to the last 
dose of valemetostat tosylate. 
 Strong or moderate CYP3A inducers, including supplements with CYP3A-inducing 
properties (eg, foods and beverages containing St. John’s wort).  Refer to Table 10.4 
for a list of strong or moderate CYP3A inducers. 
 St. John’s wort (hypericin) is not permitted from 14 days prior to the first dose of 
valemetostat tosylate up to the last dose of valemetostat tosylate. 
 If strong or moderate CYP3A inducers are medically essential to use as 
supportive care, concomitant use of moderate and strong CYP3A inducers is 
permissible after the first dose of valemetostat tosylate.  In this case, dose 
interruption of valemetostat tosylate is not needed.  Avoid the concomitant use as 
much as possible because drugs having moderate or strong CYP3A-inducing 
properties may decrease the plasma concentration of valemetostat (the free form 
of valemetostat tosylate).  

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Restricted Therapies/Products 
Subjects are permitted to receive the following only when absolutely necessary during the 
Treatment Period. 
Systemic use of corticosteroids is restricted, with the following exceptions: 
 Systemic corticosteroid (≤10 mg daily prednisone equivalents)  
 Short-course systemic corticosteroids (prevention/treatment for transfusion reaction) 
 Use for a non-cancer indication (eg, adrenal replacement) 
Topical corticosteroids (including cutaneous, ocular, intranasal, inhalational, or intra-articular 
use) are allowed.  Investigators should contact the Sponsor Medical Monitor when topical 
corticosteroids are used for cutaneous lesions that are used for response assessment in ATL 
subjects in Cohort 2. 
Avoid the use of sensitive P-gp substrates (digoxin, quinidine, paclitaxel, cyclosporine, 
sirolimus, tacrolimus, fentanyl, and phenytoin) with a narrow therapeutic index; alternative 
therapies that are not P-gp substrates should be considered.  If concomitant use of valemetostat 
tosylate and P-gp substrates is unavoidable, separate valemetostat tosylate administration by at 
least 6 hours before or after the administration of -narrow therapeutic index P-gp substrates to 
minimize the potential for interactions and monitor closely for adverse reactions, if feasible. 
Permitted Therapies/Products 
Subjects are permitted to receive prophylactic or supportive treatment (such as granulocyte 
colony-stimulating factor) as standard of care during the Treatment Period, per the investigator’s 
discretion and institutional guidelines. 
Subjects are permitted to receive strong/moderate CYP3A inhibitors or P-gp inhibitors.  
However, caution should be exercised with concomitant use of these drugs, as valemetostat is a 
substrate of P-gp and primarily metabolized by CYP3A.  Refer to Section 6.5.4 for dose 
modifications with concomitant use of strong CYP3A inhibitors or P-gp inhibitors.  Refer to 
Table 10.4 for a list of strong/moderate CYP3A inhibitors and/or P-gp inhibitors.   
The use of azole antifungal agents is permitted for prophylaxis or treatment for systemic fungal 
infections but should follow the dose modifications described in Section 6.5.4.   
Preventative Treatment 
Use of sulfamethoxazole-trimethoprim or drugs with equivalent indications is recommended for 
the prophylaxis of Pneumocystis jirovecii infection. 
The risk of tumor lysis syndrome is well described in patients with malignancies, including 
lymphoma. As a precautionary measure, subjects should be closely monitored and adequately 
hydrated. Per the institutional standards, additional management (eg, prophylactic use of 
anti-hyperuricemic agents) should be also considered in subjects with a higher risk of tumor lysis 
syndrome, including those with high tumor burden. 

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7. 
STUDY DRUG DISCONTINUATION AND DISCONTINUATION 
FROM THE STUDY 
7.1. 
Discontinuation of Study Drug 
The primary reason for the permanent discontinuation of valemetostat tosylate treatment 
administration must be recorded.  Reasons for treatment discontinuation include the following: 
 Death 
 Adverse event 
 Progressive or relapsed disease meeting the 2014 Lugano criteria for Cohort 1 
(Section 10.4.2) or meeting the modified 2009 ATL criteria for Cohort 2 
(Section 10.4.3) 
 Clinical progression 
 Withdrawal by Subject (to discontinue study drug).  NOTE: in this section this is 
only withdrawal for treatment with study drug and is NOT the same thing as a 
complete withdrawal from the study.  Discuss with the subject that he/she will remain 
in the study (ie, continue with study visits and assessments, including survival 
follow-up). 
 Lost to follow-up (see Section 7.3 for details on when a subject is considered lost to 
follow-up) 
 HCT 
 Pregnancy 
 Protocol deviation 
 Study termination by Sponsor 
 Other 
After study drug is permanently discontinued for any reason other than death or lost to 
follow-up, the subject will be treated as clinically indicated by the investigator or referring 
physician. 
Progressive or relapsed disease or clinical progression is considered a sufficient reason to 
discontinue the study drug; however, the investigator may continue the study drug until the 
investigator has alternative lymphoma therapies and considers the study drug to be no longer 
beneficial to the subject.  The decision to discontinue a subject from study drug remains the 
responsibility of the investigator. 
The investigator must discuss with the subject that his/her decision to permanently discontinue 
the study drug means the subject still agrees to continue into the Follow-up Period for onsite or 
modified follow-up visits.  Subjects will be followed for disease progression, if applicable, and 
survival at regularly scheduled intervals (see Table 1.1). 

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Procedures for Discontinuation from Study Drug 
The subject should be instructed to contact the investigator or study site staff before or at the 
time study drug is discontinued.   
If a subject is discontinued from the study drug 
 The reason(s) for discontinuation and the last dose date should be documented in the 
subject’s medical record and eCRF. 
 Due to an AE, the investigator will follow the subject until the AE has resolved or 
stabilized. 
 An End of Treatment (EOT) evaluation should be performed as described in the 
Schedule of Events (SoE) (Table 1.1). 
 A safety follow-up evaluation should be performed 30 days (+7 days) after the last 
dose of study drug as described in the SoE (Table 1.1). 
 If subject has not discontinued for “progressive or relapsed disease,” continue 
efficacy and survival assessments until disease progression or start of subsequent 
lymphoma therapy, if applicable, as described in the SoE (Table 1.1). 
 If subjects permanently discontinue the study drug with the intent to undergo HCT, 
valemetostat tosylate should be discontinued at least 7 days before starting 
preparative regimens.  After HCT, data collection of HCT-relevant information will 
be required (see details in Section 8.3.5). 
 Long-term Follow-up evaluations will be performed to assess survival, as described 
in the SoE (Table 1.1). 
The investigator will complete and report the observations as thoroughly as possible up to the 
date of discontinuation, including the date of the last dose.  All procedures and tumor 
assessments specified for the EOT Visit will be conducted.  See Table 1.1 for specific EOT 
procedures. 
If a subject does not agree to continue to come to the study site or is unable to come to the study 
site, then a modified follow-up must be arranged to ensure the continued collection of endpoints 
and safety information.  Options for modified follow-up are noted below. 
Modified Follow-up Options 
The following modified follow-up options can be offered to a subject who does not agree to 
study visits at the study site or is unable to come to the study site. 
 Study personnel contacting the subject by telephone (may be quarterly, bi-annually, 
annually, or only at the end of the study) 
 Study personnel contacting an alternative person (eg, family member, spouse, partner, 
legal representative, physician, or other healthcare provider) 
 Study personnel accessing and reviewing the subject’s medical information from 
alternative sources (eg, doctor’s notes and hospital records), including records from 
the transplant unit for subjects who have undergone HCT. 

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Dates of the modified follow-up contact(s) should be recorded.  See Section 7.2 for the definition 
of withdrawal by subject from the study (ie, withdrawal of consent). 
7.2. 
Subject Withdrawal/Discontinuation from the Study 
Subjects may discontinue from the study for any of the following reasons: 
 Death 
 Withdrawal by subject (from the study).  NOTE: this indicates that the subject 
withdraws consent and refuses to undergo any further study procedures or be 
followed for long-term survival 
 Lost to follow-up (see Section 7.3 for details on when a subject is considered lost to 
follow-up) 
 Study termination by the Sponsor 
 Other 
If the reason for study discontinuation is the death of the subject, the options for categorizing the 
primary cause of death are progressive disease or adverse event.  If reason of death is unknown 
every effort should be made to obtain the primary cause of death.  Only one AE will be 
recognized as the primary cause of death. 
Only subjects who refuse all of the following methods of follow-up will be considered to have 
withdrawn consent from study participation (ie, from the interventional portion and follow-up): 
 Attendance at study visits per protocol 
 Study personnel contacting the subject by telephone 
 Study personnel contacting an alternative person 
 Study personnel accessing and reviewing the subject’s medical information from 
alternative sources 
If the subject refuses all of the above methods of follow-up, the investigator should personally 
speak to the subject to ensure the subject understands all of the potential methods of follow-up.  
If the subject continues to refuse all potential methods of follow-up, the investigator will 
document this as a withdrawal of consent (from the interventional portion and follow-up). 
Withdrawal Procedures 
If a subject is withdrawn from both the interventional and follow-up portions of the study: 
 The investigator will complete and report the observations as thoroughly as possible 
up to the date of withdrawal including the date of last dose, date of last contact, and 
the reason for withdrawal 
 When disclosure of future information is also withdrawn, the Sponsor may retain and 
continue to use any data collected before such a withdrawal of consent 
 The subject may request destruction of any samples taken and not tested, and the 
investigator must document this in the site study records 

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 Study site personnel may use local, regional, and national public records (in 
accordance with local law) to monitor vital status. 
See SoE (Table 1.1) for data to be collected at the time of study discontinuation and follow-up 
and for any further evaluations that need to be completed. 
7.3. 
Lost to Follow-up 
Subjects will be considered lost to follow-up if he/she fails to return for scheduled visits and is 
unable to be contacted by the study site staff.  Before a subject is deemed lost to follow-up, the 
investigator or designee will make every effort to regain contact with the subject (where 
possible, telephone calls, texts, emails, and, if necessary, a certified letter to the subject’s last 
known mailing address or local equivalent methods).  These contact attempts should be 
documented. 
If direct contact with the subject is not possible, the site must make every effort to collect 
survival status from public records (eg, obituaries, death certificates, etc) in accordance with 
local laws. 

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8. 
STUDY PROCEDURES 
See the SoE, Table 1.1, for Screening, Treatment, EOT, and Follow-up study procedures.   
8.1. 
Eligibility Assessment 
The subject's demographics, medical and target disease history, vital signs, CT (or MRI) and 
FDG-PET scans, and results of tests done (eg, physical examination, ECG, ECOG PS, and 
laboratory assessments) should be reviewed and compared against the eligibility criteria 
(Section 5.1.1 and Section 5.1.2).  Retesting of laboratory parameters and/or other assessments 
within any single screening will be permitted.  A unique SID will be assigned after the subject 
has signed the ICF.  Any new result prior to the first dose of study drug during a single screening 
will override the previous result.  Subjects should continue to meet all study protocol eligibility 
criteria prior to the first dose of study drug, including laboratory results and ECOG PS.  
Non-clinically significant changes in ECG on Cycle 1 Day 1 Visit would be acceptable.  For 
rescreening information, refer to Section 5.2. 
Informed Consent  
Before a subject’s participation in the study, it is the investigator’s responsibility to obtain freely 
given consent, in writing, from the subject after adequate explanation of the aims, methods, 
anticipated benefits, and potential hazards of the study and before any protocol-specific 
procedures or any study drugs are administered.  Subjects should be given the opportunity to ask 
questions and receive responses to their inquiries and should have adequate time to decide 
whether or not to participate in the study.  The written ICF should be prepared in the local 
language(s) of the potential subject population.  See Section 10.1.2 for additional details. 
Demographics 
Review the subject’s demographics against the eligibility criteria.  Demographics include birth 
date, age at screening, sex, race, and ethnicity. 
General Medical History and Baseline Conditions 
Subject’s medical history will be obtained by the investigator or a qualified designee. 
Untoward medical occurrence (including clinically relevant laboratory values that are not 
symptoms of the primary disease/vital signs that are out of range) that were diagnosed or known 
to exist prior to the signing the ICF will be recorded on the General Medical History and 
Baseline Conditions eCRF, not the Adverse Event eCRF.  Record the start date of any medical 
occurrence that started before the ICF was signed and is ongoing at the time of the first dose of 
valemetostat tosylate on the General Medical History and Baseline Conditions eCRF. 
R/R PTCL or R/R ATL History 
Subject’s R/R PTCL or R/R ATL history will be obtained by the investigator or a qualified 
designee. 

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Qualifying Tumor Tissue Specimen 
 A fresh sample at baseline is mandatory for all subjects. 
 If a fresh sample is not obtainable during screening, it is acceptable to submit 
previously collected tumor tissue, including the samples at the initial diagnosis of 
lymphoma.  
 Along with the fresh sample, submission of previous tumor tissue samples from 
the initial diagnosis of lymphoma, if available, is strongly encouraged but is 
optional. 
 Samples should be from an excisional, incisional, or core needle biopsy. 
 Additional information on tumor tissue collection, processing, and immediate 
shipping procedures is included in the Study Laboratory Manual. 
 Specimens must be submitted to the central laboratory as soon as possible. 
 Central Pathology Review  
 After all eligibility criteria have been met, the central pathologist(s) will review 
tumor tissue (slides) to confirm PTCL.  Central pathologist(s)’ responsibilities 
and procedures of central review will be specified in the Central Pathology 
Review charter. 
Human Immunodeficiency Virus Antibody Test 
An HIV antibody test should be performed within 28 days prior to the first dose or as required by 
local regulations or independent institutional review boards (IRBs)/ethics committees (ECs).  For 
subjects enrolled in Japan and Germany, an HIV antibody test must be performed. 
Hepatitis Screening 
Hepatitis B and C testing should be performed during Screening (within 28 days prior to the first 
dose), which should include hepatitis B surface antigen, hepatitis B core antibody (anti-HBc), 
hepatitis B surface antibody, and hepatitis C antibody tests.  Hepatitis B virus DNA level or 
hepatitis C virus RNA testing may be performed if necessary. 
8.2. 
Enrollment 
Cohort 1 (R/R PTCL): Diagnosis should be confirmed by the local pathologist and shared with 
the investigators; local histological diagnosis will be used for eligibility determination.  After all 
eligibility criteria have been met, histology will be centrally confirmed.  Copies of de-identified 
local report for histological diagnosis and additional clinical information may be collected for 
central histology review.  Eligible T-cell lymphoma subtypes are provided in the inclusion 
criteria (Section 5). 
Cohort 2 (R/R ATL): Acute, lymphoma, or unfavorable chronic type.  R/R ATL should be 
confirmed by the local pathologist and shared with the investigators; local diagnosis will be used 
for eligibility determination.  The positivity of anti-HTLV-1 antibody will be locally confirmed 
for eligibility determination. 

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After all screening procedures are performed, results of screening tests are available (ie, between 
the Screening Visit and the Cycle 1 Day 1 Visit, as required in Section 5 and Section 5.1.2), and 
subjects are confirmed to continue to meet all eligibility criteria at the Cycle 1 Day 1 Visit, 
eligible subjects will be enrolled in study to receive valemetostat tosylate. 
8.3. 
Efficacy Assessments 
Efficacy assessments (radiographic assessments for all subjects and peripheral blood and skin 
lesion[s] assessments for Cohort 2 subjects) will be performed according to the schedule in 
Table 8.1, Figure 8.1, and Figure 8.2.  Radiological assessments performed for the evaluation of 
disease progression on the prior therapy will be acceptable as baseline if performed within 28 
days of the Cycle 1 Day 1 Visit. 
Efficacy assessment will be performed independently by BICR (Cohort 1) and investigators 
(Cohorts 1 and 2) using the following response criteria: 
 Cohort 1: CT-based response assessment per the 2014 Lugano criteria 
(Section 10.4.2). 
 The BICR and investigators will perform ancillary response evaluation based on 
PET-CT-based response assessment using 5-PS scores per the 2014 Lugano 
criteria in subjects with FDG-avid PET scans (5-PS score of 4 or 5 at baseline) 
 Cohort 2: Modified 2009 ATL criteria (Section 10.4.3), based on the response criteria 
from an International Consensus Meeting.2  The modification was made such that 
there is no requirement for each criterion to be present for a period of at least 
4 weeks. 
 mSWAT score will be used to evaluate skin lesions (Section 10.4.4). 
 Subjects’ body surface area (BSA) will be calculated using Table 10.19. 
All CT (or MRI) and FDG-PET scans that are performed until disease progression or prior to the 
initiation of a subsequent lymphoma therapy, whichever occurs earlier, should be submitted to 
the BICR. 
Figure 8.1: 
Cohort 1 Efficacy Assessment Schedule 
Pre-Dose
0 to 24 Weeks
24 to 156 Weeks
> 156 Weeks
-28 d 
(prior to 
C1D1)
Q8W (± 1  wk)
Q12W (± 2  wk)
Q24W (± 4  wk)
C1
C3
C5
C7
D1
D1
D1
D1
Scrn
C10
D1
D1
D1
D1
D1
D1
D1
D1
D1
D1
D1
C13
C16
C19
C22
C25
C28
C31
C34
C40
C37
D1
C46
D1
C52
D1
C58
Cx
EOT
D1
 
Legend: 
 = CT/MRI scan; 
 = FDG-PET scan  

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5-PS = 5-point scale; C = cycle; CT = computed tomography; D = day; EOT = End of Treatment; 
FDG = fluorodeoxyglucose; MRI = magnetic resonance imaging; PET = positron emission tomography; 
QxW = every x weeks; Scrn = Screening; wk = week 
Note: Post-baseline FDG-PET scan will be required only for the subjects who had FDG-avid tumor (4 or 5 on the 
5-PS score), per the investigator’s assessment at baseline.  If a FDG-PET scan was performed within 28 days 
prior to C5 D1, C13 D1 or EOT, then the FDG-PET scans on C5 D1, C13 D1, or EOT, respectively, do not 
need to be done.  Investigators can perform an FDG-PET scan at any time point during the study. 
Figure 8.2: 
Cohort 2 Efficacy Assessment Schedule 
Pre-Dose
0 to 24 Weeks
24 to > 156 Weeks
-28 d 
(prior to 
C1D1)
Q8W (± 1  wk)
Q24W (± 4  wk)
C1
C3
C5
C7
D1
D1
D1
D1
Scrn
C10
D1
D1
D1
D1
D1
D1
C16
C22
C28
C34
C40
D1
C52
D1
C58
Cx
EOT
D1
D1
C46
 
Legend: 
 = CT/MRI scan; 
 = peripheral blood and skin lesion(s) assessment 
C = cycle; CT = computed tomography; D = day; EOT = End of Treatment; MRI = magnetic resonance imaging; 
QxW = every x weeks; Scrn = Screening; wk = week 
8.3.1. 
Radiographic Assessments (CT/MRI and FDG-PET Scans) 
CT/MRI Scan 
A CT for neck, chest, abdomen, and pelvis and a FDG-PET scan from the base of the skull to the 
mid-thigh will be required at baseline and at the time points described in Table 8.1 and Table 8.2. 
 During the Treatment Period, CT, MRI, or FDG-PET scans should be performed with 
the same imaging parameters as those at Screening. 
 Radiographic assessments should be performed until disease progression 
(ie, progressive or relapsed disease) or until the subject initiates a subsequent 
lymphoma therapy, whichever occurs earlier.  If there is clinical suspicion of disease 
progression, a physical examination and radiographic assessment should be 
performed promptly, if feasible, rather than waiting for the next scheduled 
radiological assessment. 
CT scans of the neck to pelvis will be performed with a slice thickness of ≤5 mm for evaluation.  
Contrast media will be used for CT scans except for contraindications such as renal impairment 
or allergies to contrast media.  CT (or MRI) for other lesions (eg, head) may be performed if 
clinically indicated. 
 Combined hybrid PET-CT scanners may be used to acquire the CT images if CT 
images produced by the scanner are of diagnostic quality with intravenous contrast (if 
medically not contraindicated). 

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 An MRI can be used as an alternative to CT.  However, if used instead of a CT scan, 
then it should be used for all subsequent assessments. 
 Up to 6 target nodal or extranodal lesions will be selected at Screening.  See 
Section 10.4.1. 
Radiographic evaluations will be performed according to the schedule in Table 8.1. 
For Cohort 1 only, all CT (or MRI) scan images, including those at unscheduled visits, should be 
submitted to the BICR. 
Table 8.1: 
Schedule for Efficacy Assessment by CT (or MRI) Scan 
Time on Study 
Assessment Frequency 
Assessment Visit 
Assessment 
Window 
Predose  
Once 
Screening 
Within 28 
days prior 
to the first 
dose 
Cohort 1 Only 
For the first 24 weeks 
Every 8 weeks 
Day 1 of Cycles 3, 5, 
and 7 
±1 week 
After the first 24 weeks 
and up to the first 
156 weeks 
Every 12 weeks 
Day 1 of Cycles 10, 
13, 16, 19, 22, 25, 
28, 31, 34, 37, and 
40 
±2 weeks 
After the first 156 weeks 
and onward during the 
study 
Every 24 weeks 
Day 1 of Cycles 46, 
52, 58, and so on 
±4 weeks 
Cohort 2 Only 
For the first 24 weeks 
Every 8 weeks 
Day 1 of Cycles 3, 5, 
and 7 
±1 week 
After the first 24 weeks 
and onward during the 
study 
Every 24 weeks 
Day 1 of Cycles 10, 
16, 22, 28, 34, 40, 
46, 52, 58, and so on 
±4 weeks 
ATL = adult T-cell leukemia/lymphoma; CT = computed tomography; MRI = magnetic resonance imaging 
Note: In Cohort 2 (ATL), efficacy assessment in peripheral blood and skin lesion(s) will be performed at the same 
time as tumor assessment by CT (or MRI). 
FDG-PET Scans 
An FDG-PET scan from the base of the skull to mid-thigh will be performed for Cohort 1 
(PTCL) according to the schedule in Table 8.2. 
 Subjects who had FDG-avid tumor, per the investigator’s assessment (4 or 5 on the 
5-PS score) at baseline will have an FDG-PET scan at the time points noted in 
Table 8.2. 
 Subjects who had FDG non-avid tumor per the investigator’s assessment (1, 2, or 3 
on the 5-PS score) at baseline do not need an FDG-PET scan after Cycle 1 Day 1. 

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For Cohort 1 only, all FDG-PET scan images, including those at unscheduled visits, should be 
submitted to the BICR. 
An FDG-PET scan is optional for Cohort 2 (ATL). 
Table 8.2: 
Schedule for FDG-PET Scans 
Time on Study 
Assessment 
Frequency 
Assessment Visit 
Assessment Window 
Predose  
Once  
Screening 
Within 28 days prior to the 
first dose 
After the first dose 
 
Only for subjects who had 
FDG-avid tumor per the 
investigator’s assessment 
(4 or 5 on the 5-PS score) at 
baseline 
Once 
Cycle 5 Day 1a 
± 1 week 
Once 
Cycle 13 Day 1a 
± 2 weeks 
Once 
EOTb  
± 2 weeks 
As needed 
In addition, investigators can perform an FDG-PET scan at 
any time point during the study 
5-PS = 5-point scale; EOT = End of Treatment; FDG = fluorodeoxyglucose; HCT = hematopoietic cell 
transplantation; PET = positron emission tomography 
a FDG-PET scans on Cycle 5 Day 1 or Cycle 13 Day 1 are not mandated in subjects who underwent an FDG-PET 
scan within 28 days prior to Cycle 5 Day 1 or Cycle 13 Day 1. 
b This is unnecessary if a previous FDG-PET scan was performed within 28 days from the EOT. 
Note: Subjects who had FDG non-avid tumor per the investigator’s assessment (1, 2, or 3 on the 5-PS score) at 
baseline do not need an FDG-PET scan after Cycle 1 Day 1. 
8.3.2. 
Bone Marrow Biopsy/Assessment 
 Baseline bone marrow biopsy during the Screening Period is required in all subjects, 
except those who underwent bone marrow biopsy within 3 months of the first dose, 
with documented results. 
 The bone marrow sample will be sent to the local laboratory for assessment. 
 During treatment, bone marrow biopsy is required to confirm normal morphology to 
declare CR (or CRu for ATL) per CT-based response assessment in subjects with 
positive, indeterminate, or unknown lymphoma involvement in bone marrow at 
baseline.  Investigators may also perform bone marrow biopsy when an FDG-PET 
scan shows CR (or CRu for ATL) in subjects with positive, indeterminate, or 
unknown lymphoma involvement in bone marrow at baseline. 
 Bone marrow assessment will be performed by the local laboratory. 
 All results of bone marrow assessment until disease progression, until clinical 
progression, or prior to the initiation of a subsequent lymphoma therapy, 
whichever occurs earlier, should be reported. 
 A deidentified local pathology report should be collected and submitted to the 
Sponsor (for submission to the BICR upon request for Cohort 1 only). 

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 Submission of bone marrow specimen to the central laboratory at any time point 
(including baseline) is not required. 
8.3.3. 
Cohort 2 Additional Efficacy Assessments 
Assessment for disease in peripheral blood and skin lesion(s) will be performed at the same 
timing of tumor assessment by CT (or MRI) according to the schedule in Table 8.1. 
Disease assessment for peripheral blood and skin lesion(s) will be conducted during Screening 
and on Cycle 1 Day 1; whichever was assessed later prior to initiating the study drug will serve 
as the baseline values. 
Note that tumor assessment by CT (or MRI) and FDG-PET scan will be performed according to 
the schedule in Table 8.1, even for subjects who had disease only in peripheral blood, only in 
skin, or only in peripheral blood and in skin at baseline. 
Skin Lesion Assessment 
Disease in cutaneous lesions is evaluated by visual inspection based on the mSWAT score 
(Section 10.4.4). 
 In principle, the same physician should consistently assess cutaneous lesions in the 
same subject during the entire study to avoid inter-evaluator variability. 
 If it is difficult to determine whether it is an ATL lesion or not by visual inspection, a 
biopsy should be performed to make a histopathological diagnosis. 
Peripheral Blood Assessment 
Disease in peripheral blood, using the sample collected for the local hematology, will be 
evaluated based on white blood cell count, absolute lymphocyte count, and abnormal lymphocyte 
count (absolute count and abnormal lymphocyte-to-leukocyte percentage). 
 Peripheral blood must be assessed at every timepoint that a radiographic assessment 
is done (Table 8.1, Table 1.1, and Figure 8.2). 
 If there is clinical suspicion of disease progression, a physical examination and a 
peripheral blood assessment should be performed promptly, if feasible, rather than 
waiting for the next scheduled peripheral blood assessment. 
Evaluation of Gastrointestinal Lesions 
For subjects in Cohort 2, upper gastrointestinal endoscopy is recommended for lesion evaluation 
during screening.  If the presence of a clinical lesion is suspected, colonoscopy may also be 
performed during screening.  If the subject had gastrointestinal ATL lesions at baseline, an upper 
gastrointestinal endoscopy or/and colonoscopy will be performed when CR or CRu is declared.  
It is desirable to perform a biopsy for subjects when gastrointestinal endoscopy and/or 
colonoscopy is performed.  

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8.3.4. 
Subsequent Anti-Lymphoma Treatments 
Subsequent anti-lymphoma treatments taken after the last dose of the study drug and their 
outcomes must be monitored and recorded in the eCRF.  Monitoring will continue until death, 
withdrawal of consent, lost to follow-up, or study closure. 
8.3.5. 
Subsequent Hematopoietic Cell Transplantation  
HCT-relevant information will be reported from the subjects who underwent a subsequent HCT 
after permanent discontinuation of the study drug.  Subjects should complete the EOT, a 30-day 
Safety Follow-up Visit, and Long-term Follow-up. Additionally, HCT-related toxicities (eg, 
GVHD after a subsequent allogeneic HCT; Section 10.3.9) as of Day 100, 6 months from the 
date of HCT, and every 6 months thereafter will be collected and reported from these subjects.  
Submission of radiographic images to BICR will not be required after a subsequent HCT. 
Instead, the investigator will report disease status according to 2014 Lugano criteria (CT and/or 
PET-CT-based response assessment, if applicable) for subjects in Cohort 1 and to the modified 
2009 ATL criteria (CT-based response assessment) for subjects in Cohort 2, as follows:  
 The disease status (CR or non-CR) as of Day 100, 6 months from the date of HCT, 
and every 6 months thereafter will be collected and reported  
 The date of the first relapse/disease progression after HCT 
Alternatively, with the subject’s permission the investigator may make telephone contact with 
the subject’s referring hematologist, oncologist, and/or transplant physician to obtain and 
document this information if the subject is being followed by another physician. 
8.3.6. 
Survival Follow-up 
All subjects should be followed for survival at least every 3 months after discontinuing study 
drug.  Survival monitoring will continue until death, withdrawal of consent, lost to follow-up, or 
study closure. 
8.4. 
Safety Assessments 
8.4.1. 
Adverse Event 
Method to Detect Adverse Events 
The definitions of an AE or SAE can be found in Section 10.5.  Adverse events may be directly 
observed, reported spontaneously by the subject or by questioning the subject (or, when 
appropriate, by a caregiver, surrogate, or the subject's legally authorized representative) at each 
study visit.  Subjects should be questioned in a general way, without asking about the occurrence 
of any specific symptoms.  The investigator must assess all AEs to determine seriousness, 
severity, and causality.  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 AEs that are serious, considered related to the study drug or 
study procedures, or that caused the subject to discontinue valemetostat tosylate. 

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All clinical laboratory results, vital signs, and ECG results or findings should be appraised by the 
investigator to determine their clinical significance.  Isolated abnormal laboratory results, vital 
sign findings, or ECG findings (ie, not part of a reported diagnosis) should be reported as AEs if 
they are symptomatic, lead to study drug discontinuation, lead to dose reduction, require 
corrective treatment, or constitute an AE in the investigator’s clinical judgment. 
Time Period for Collecting Adverse Events, Including Adverse Events of Special Interest 
and Serious Adverse Events 
All AEs, including SAEs, occurring after the subject signs the ICF and up to 30 days after the 
last dose of study drug (ie, the Follow-up Period), whether observed by the investigator or 
reported by the subject, will be recorded on the Adverse Event eCRF.  All SAEs will be followed 
until resolution, stabilization, the event is otherwise explained, or the subject is lost to follow-up.  
After 30 days from the last dose of study drug, only SAEs considered to be related to study drug 
by the investigators and secondary malignancies (regardless of seriousness or causality) should 
be reported. 
All non-serious AEs occurring after the subject signs the ICF until 30 days after the last dose of 
study drug will be recorded on the Adverse Event eCRF. 
Exacerbation of a pre-existing medical condition and symptom after the subject signs the ICF 
including increase in severity of the symptom will be recorded as an AE on the Adverse Event 
eCRF, unless it is a condition of PTCL/ATL. 
Reporting Procedure for Investigators 
All AEs (including AEs of special interest [AESIs] and SAEs) will be reported in the Adverse 
Event eCRF.  Procedure-related events must be reported as a non-serious or serious AEs.  All 
AEs (serious and non-serious) must be reported with the investigator’s assessment of 
seriousness, severity, and causality to valemetostat tosylate.  Additionally, the action taken with 
regard to the study drug and for the event must be reported.  See Section 10.5 for additional 
details. 
Always report the diagnosis as the AE or SAE term.  When a diagnosis is unavailable, report the 
primary sign or symptom as the AE or SAE term with additional details included in the narrative 
until the diagnosis becomes available.  If the signs and symptoms are distinct and do not suggest 
a common diagnosis, report them as individual entries of AE or SAE. 
Disease-Specific AEs and SAEs 
Disease progression/worsening of R/R PTCL or R/R ATL will not be recorded as an AE on the 
Adverse Event eCRF.  However, events associated with disease progression, such as intestinal 
perforation of malignant lymphoma, may be recorded as AEs.  As an exception, if no other 
immediate cause of death is identified, then Grade 5 disease progression should be reported as an 
SAE. 
Death due to disease progression should be recorded on the Death eCRF; in this case, disease 
progression should be reported as the primary cause of death.  If a subject died due to disease 
progression as the primary cause of death within 30 days from the last dose of study drug, the 

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Grade 5 AE, which was the underlying or immediate cause of death should be also reported as an 
SAE. 
Example 
If a subject died due to intestinal perforation of malignant lymphoma, disease progression 
should be reported as the primary cause of death.  Additionally, if death occurred within 
30 days from the last dose of study drug, intestinal perforation of malignant lymphoma 
should be reported as a Grade 5 SAE. 
8.4.1.1. 
Serious Adverse Events Reporting 
The following types of events should be reported by the investigator in the electronic data 
capture (EDC) within 24 hours of awareness: 
If death is due to progressive disease, it should be reported within 24 hours even though it is 
NOT an SAE. 
 SAEs (Section 10.5.2) 
 Hepatic events (both serious and non-serious) meeting the laboratory criteria of a 
potential Hy’s Law criteria (as defined in Section 8.4.1.4). 
 Overdose (as defined in Section 8.4.1.2) 
 Secondary malignancy (both serious and non-serious, Section 8.4.1.4) 
 Pregnancy (as defined in Section 8.4.2) 
Details summarizing the course of the SAE, including its evaluation, treatment, and outcome 
should be provided.  Specific or estimated dates of AE onset, treatment, and resolution should be 
included.  Medical history, concomitant medications, and laboratory data that are relevant to the 
event should also be summarized in the SAE report.  For fatal events, the SAE report should 
state whether an autopsy was or will be performed and should include the results if available.  
Source documents (including medical reports) will be retained at the study site and should not be 
submitted to the Sponsor for SAE reporting purposes. 
If using EDC for SAE reporting: Complete the eCRF within 24 hours of awareness.  In the event 
that the eCRF is unavailable, report SAEs by faxing or emailing the SAVER (Serious Adverse 
Event Report) form to the CRO using the provided fax transmittal form and the appropriate fax 
number provided for your country or email address.  Once EDC becomes available, please enter 
SAEs reported on the SAVER form into the eCRF as soon as possible.  Please refer to the eCRF 
Completion Guide for additional instructions. 
See Section 8.4.1 for details on the time period for collecting SAEs. 
Reporting Requirement to Sites and Regulatory Authorities 
The Sponsor/CRO will inform investigators and regulatory authorities of any suspected 
unexpected serious adverse reactions (SUSARs) occurring in study sites or other studies of the 
study drug, as appropriate per institutional and/or local reporting requirements. 

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Sponsor and/or CRO will comply with any additional local safety reporting requirements.  The 
investigator will assess if an AE is to be considered “unexpected” based on the “Reference 
Safety Information” section in the current IB.53 
Follow-up for AEs and SAEs 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated 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 healthcare 
professionals. 
Urgent safety queries and follow-up information such as those upgraded to fatal/life-threatening 
cases must be followed up and addressed promptly.  The investigator will submit any updated 
SAE data to the CRO/Sponsor within 24 hours of receipt of the information.  Follow-up 
information and response to non-urgent safety queries should be combined for reporting to 
provide the most complete data possible within each follow-up report. 
8.4.1.2. 
Overdose 
An overdose is defined as the accidental or intentional administration of any dose of a product 
that is considered both excessive and medically important.  All occurrences of overdose 
(regardless of whether an AE occurs) must be reported to (CRO or Sponsor) within 24 hours of 
awareness.  Overdose will be reported via eCRF.  The Sponsor will give instructions about the 
dose of valemetostat tosylate on and after the following day. 
In the event of overdose, the subject should immediately be examined for any symptoms or 
signs, and the necessary assessments will be performed, including laboratory tests and 12-lead 
ECG.  It is advised to frequently monitor complete blood count for thrombocytopenia for the 
subsequent 3 weeks after the overdose incident.  Supportive care should be provided per the local 
standard of care that is in the best interest of the subject.   
An “excessive and medically important” overdose includes any overdose in which either an 
SAE, a non-serious AE, or no AE occurs and is considered by the investigator as clinically 
relevant, ie, poses an actual or potential risk to the subject. 
Occupational exposures must be reported via the SAVER form. 
8.4.1.3. 
Medication Error, Misuse, and Abuse 
Medication errors and uses outside what is foreseen in the protocol, including misuse and abuse 
of the product, shall be subject to the same reporting obligations as AEs. 
 Medication error: This is an unintended failure in the drug treatment process that 
leads to, or has the potential to lead to harm to the subject 
 Misuse: This refers to situations in which the medicinal product is intentionally and 
inappropriately used in a manner inconsistent with the protocol or the product 
labeling 

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 Abuse: This corresponds to the persistent or sporadic, intentional excessive use of a 
medicinal product, which is accompanied by harmful physical or psychological 
effects to the user 
8.4.1.4. 
Adverse Events of Special Interest 
An AESI will include hepatic events that meet the potential Hy’s Law criteria (defined as an 
elevated ALT and/or AST ≥3 × ULN and an elevated TBL >2 × ULN, regardless if it is due to 
disease progression per investigator assessment, which may occur at different time points during 
the study conduct), thrombocytopenia, and secondary malignancy, including lymphoid 
malignancy. 
Combined Elevations of Aminotransferases and Bilirubin 
Hepatic events (both serious and non-serious) that meet the potential Hy’s Law criteria defined 
as an elevated (ALT and/or AST) ≥3 × ULN and an elevated TBL >2 × ULN, regardless if it is 
due to disease progression per investigator assessment, that may occur at different time points 
during the study conduct, should always be reported to the Sponsor.76  These events must be 
reported by eCRF, with the investigator’s assessment of seriousness, severity, causality, and a 
detailed narrative.  These events should be reported within 24 hours of investigator’s awareness 
of the event regardless of seriousness.  A targeted questionnaire will be available as an eCRF to 
collect relevant additional information for these potential cases. 
If the subject discontinues study drug due to liver enzyme abnormalities, the subject will have 
additional clinical and laboratory evaluations as described in Section 10.2 in order to determine 
the nature and severity of the potential liver injury. 
Secondary Malignancy 
A 3-month nonclinical toxicology study in rats administered valemetostat tosylate showed the 
potential risks of developing lymphoid malignancies.  A follow-up 3-month study in older rats 
performed to further understand the pathogenic mechanisms of this above finding in younger rats 
showed administration of valemetostat tosylate to aged rats did not induce a lymphoma that had 
been previously observed with younger rats.  In addition, no similar findings were noted in other 
3-month animal toxicity studies of valemetostat tosylate (see Section 2.3 for details).  In the 
ongoing clinical program, cases of secondary malignancies have been reported (see current 
valemetostat IB for additional details). 
The treatment of subjects with an EZH2 inhibitor may increase the risk of developing a 
secondary T-cell malignancy.  T-cell lymphomas have been observed in animals treated with 
valemetostat tosylate and other agents that inhibit EZH2 in repeat-dose toxicology studies.  A 
pediatric patient treated with an EZH2 inhibitor (tazemetostat) developed a secondary T-cell 
lymphoblastic lymphoma after approximately 15 months of therapy.  A dose or duration of 
therapy at which agents that inhibit EZH2 would not increase the risk of a secondary T-cell 
malignancy is currently unknown. 
Subjects receiving valemetostat tosylate should further be monitored for signs and symptoms of 
toxicities suggestive of secondary malignancy.  Any confirmed new diagnosis of secondary 
malignancy should be reported as AESIs and reported to the Sponsor in an expedited manner.  

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Generally, these events should be reported as SAEs (Section 8.4.1.1) (with at least a seriousness 
criterion of important medical event, unless other criteria are met); however, if the events do not 
meet the seriousness criteria, the events should be reported as non-serious AESIs.  These events 
should be reported within 24 hours of investigator’s awareness of the event regardless of 
seriousness. 
Thrombocytopenia 
A nonclinical toxicology study in rats and dogs showed the potential risks of hematopoietic 
changes (including changes in RBC parameters and platelets).  Clinical data from the ongoing 
Phase 1 study (DS3201-A-J101) in R/R NHL, including R/R PTCL subjects support this.  The 
most commonly reported TEAE overall was platelet count decreased, occurring in 
40 (71.4%) R/R NHL subjects and 15 (57.7%) R/R PTCL subjects, as of the data cut-off date of 
25 Dec 2019. 
Based on laboratory data in R/R NHL subjects, among 56 subjects who had a baseline and 
post-baseline platelet count recorded, 29 (51.8%) subjects had a platelet count decrease of 
maximum Grade ≤1, 12 (21.4%) subjects had Grade 2, and 13 (23.2%) subjects had Grade 3 or 
Grade 4 across all dose levels. 
In Study DS3201-A-J101, there were 13 subjects who experienced ≥Grade 3 thrombocytopenia 
based on laboratory data.  The overall median time to onset was 50.0 days (range: 10 days to 
457 days) across all dose cohorts.  Among these 13 subjects, 10 subjects had platelet recovery to 
≥50 × 109/L. The overall median time to onset of recovery of platelet count (defined as the first 
date of platelet increase ≥50 × 109/L from the first date of platelet reduction <50 × 109/L) was 
13.8 days (range: 2 days to 31 days). 
Subjects should be monitored for signs and symptoms of platelet count decreased (see Table 6.2 
for dose modifications guidelines to be followed for thrombocytopenia).  The usual AE/SAE 
reporting conventions should be applied. 
8.4.2. 
Pregnancy 
Sponsor must be notified of any female subject or partner of a male subject who becomes 
pregnant while receiving or within 90 days of discontinuing valemetostat tosylate. 
Although pregnancy is not technically an AE, all pregnancies must be followed to conclusion to 
determine their outcome.  If a pregnancy is reported, the investigator should inform the Sponsor 
within 24 hours of learning of the pregnancy. 
This information is important for both drug safety and public health concerns.  It is the 
responsibility of the investigator, or designee, to report any pregnancy in a female subject or 
partner of a male subject using the Exposure In Utero (EIU) Reporting form.  Please contact your 
study monitor to receive the EIU Reporting form upon learning of a pregnancy.  The investigator 
should make every effort to follow the female subject or partner of a male subject (upon 
obtaining written consent from partner) until completion of the pregnancy and complete the EIU 
Reporting form with complete pregnancy outcome information, including normal delivery and 
induced abortion.  Any adverse pregnancy outcome, either serious or non-serious, should be 
reported in accordance with study procedures.  If the outcome of the pregnancy meets the criteria 
for immediate classification as an SAE (ie, post-partum complications, spontaneous or induced 

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abortion, stillbirth, neonatal death, or congenital anomaly, including that in an aborted fetus), the 
investigator should follow the procedures for reporting SAEs. 
Pregnancy Test 
For women of childbearing potential (as defined in Section 5), document the results of a negative 
serum pregnancy test at Screening.  For eligibility, if not performed as a part of routine care 
within 14 days of Cycle 1 Day 1, a serum pregnancy test must be performed, with the results 
available prior to Cycle 1 Day 1.  A serum or urine pregnancy should also be performed per the 
SoE (Table 1.1).   
8.4.3. 
Clinical Laboratory Evaluations 
The clinical laboratory tests, including hematology, coagulation, serology, blood chemistry, lipid 
profile, and urinalysis, will be locally performed.  Refer to Section 10.2 for the complete list of 
laboratory parameters. 
Abnormal laboratory values (NCI-CTCAE Grade 3 or Grade 4) occurring during the clinical 
study will be followed until repeat test results return to normal (or baseline), stabilize, or are no 
longer clinically relevant.  Routine scheduled local laboratory tests and relevant unscheduled 
local laboratory test results should be recorded into the Lab eCRF.  New or worsened clinically 
relevant abnormalities should be recorded as AEs on the Adverse Event eCRF. 
As described in Section 2.3, platelet count decreased was reported as the most frequent TEAE of 
any grade from the ongoing, open-label, Phase 1 study (DS3201-A-J101, 25 Dec 2019 data 
cut-off).  Nonetheless, the reason and kinetics of thrombocytopenia associated with valemetostat 
tosylate are not well known.  Therefore, thrombopoietin and immature platelet fraction will be 
centrally assessed to elucidate the mechanism of thrombocytopenia.77,78,79,80,81 
Markers of Platelet Production 
Thrombopoietin and immature platelet fraction (IPF) will be assessed. 
Blood samples from Cycle 1 Day 1 through Cycle 3 Day 1 will be collected and sent to the 
central laboratory.  At other visits when platelet count is <75 × 109/L, the investigator may 
submit samples after consultation with the Sponsor Medical Monitor. 
Cytomegalovirus Tests 
In the ongoing open-label Phase 1 study (DS3201-A-J101, 25 Dec 2019 data cut-off), CMV 
infection as an AE was reported from 3 subjects.  The etiology of this opportunistic infection was 
unclear.  To characterize the CMV infection, blood samples will be collected and sent to the 
central laboratory for CMV viral load by quantitative polymerase chain reaction (PCR). 
8.4.4. 
Other Safety 
Physical Examinations 
A complete physical examination should include a weight measurement and an evaluation of the 
head, eyes, ears, nose, and throat and the cardiovascular, dermatological, musculoskeletal, 
respiratory, gastrointestinal, genitourinary, and neurological systems.  Any abnormality 

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identified at baseline should be recorded on the General Medical History and Baseline 
Conditions eCRF.  At subsequent visits (or as clinically indicated), limited symptom-directed 
physical examinations should be performed.  Changes from baseline abnormalities should be 
collected in the subject’s study record.  New or worsened clinically relevant abnormalities should 
be recorded as AEs on the Adverse Event eCRF. 
Vital Signs 
Vital signs will include the measurements of heart rate, systolic and diastolic blood pressures, 
temperature, height (obtained once, prior to dosing), body weight, and BSA (calculated in the 
eCRF using the Du Bois formula).55 
Blood pressure and pulse rate will be measured after the subject has rested for 5 minutes or more. 
Electrocardiograms 
Triplicate 12-lead ECGs will be performed and recorded for every subject per the SoE 
(Table 1.1). 
The ECG will be measured after the subject has rested for 5 minutes or more. 
At each time point, triplicate ECGs are required.  The 3 individual ECG tracings should be 
obtained as closely as possible in succession, but no more than 2 minutes apart.  The full set of 
triplicates should be completed in less than 4 minutes.  All ECGs must be performed within 
15 minutes (Cycle 1 only) or within 30 minutes (Cycles 2 to 5) prior to the collection of all PK 
samples collected up to Cycle 5 Day 1.  If it is not possible, then ECG should be performed 
30 minutes or more after the PK sample collection.  For ECG assessments without time-matched 
PK samples, ECG should be performed before any blood collection. 
At any visit during which a subject exhibits a heart rate ≤50 bpm or other clinical indications for 
ECG, the ECG will be repeated.  Abnormal, clinically relevant findings occurring post-baseline 
will be reported as AEs.  Whether or not the measurement is performed, the date the ECG is to 
be performed, heart rate, PR interval, RR interval, QRS amplitude, QT interval, QTcF interval, 
and results will be transmitted electronically to a central ECG laboratory. 
ECOG Performance Status 
The subject’s ECOG PS should be assessed and recorded (Table 10.3). 
Karnofsky Performance Status 
For subjects who permanently discontinue the study drug with the intent to undergo HCT, the 
subject’s Karnofsky PS should be assessed and recorded at the EOT visit, prior to the date of the 
planned HCT (Section 10.3.4). 
8.5. 
Pharmacokinetic Assessments 
Blood samples for PK and α-1-acid glycoprotein (AAG) analyses will be obtained at the time 
points shown in Table 8.3.  Cycle 1 Day 8, Day 15, and Day 1 of Cycle 2 to Cycle 5 predose 
blood samples should be collected as close as possible to 24 hours after the prior dose.  Subjects 
must be instructed not to take the day’s dose of valemetostat tosylate until after the predose 
sample is collected.  The actual time of study drug administration and the exact time of blood 

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sampling collection for PK of valemetostat, its major metabolite (CALZ-1809a), and AAG 
analysis must be recorded on the eCRF. 
Plasma concentrations of valemetostat and major metabolite (CALZ-1809a) will be measured 
using a validated assay method.  Plasma protein binding for valemetostat will be determined as a 
free fraction (fu) by equilibrium dialysis.  The fu will be used to derive unbound plasma 
concentration of valemetostat. 
Alpha-1 Acid Glycoprotein Measurement 
Valemetostat binds to AAG in plasma and the level of AAG varies among subjects.  Measuring 
levels of AAG may help in understanding the intersubject variability in the PK of valemetostat. 
In order to measure AAG, blood will be collected from each subject. 
Details for blood sampling, processing, storage, and shipment for PK and AAG samples will be 
provided in the Study Laboratory Manual. 
Table 8.3: 
Schedule of PK/AAG Sample Collection 
Cycle 
1 
2 to 5 
Day 
1 
8 
15 
1 
 
Predose 
Postdose (Time Relative to Dose) 
Predosea 
Predosea 
Predosea 
Hours 
 
1 
2 
4 
5 
 
 
 
Window 
-24 h 
±15 min 
±15 min 
±20 min 
±20 min 
 
 
 
Sample 
Collected 
 
 
 
 
 
 
 
 
PK 
X 
X 
X 
X 
X 
X 
X 
X 
AAG 
X 
 
 
 
 
X 
X 
X 
AAG = α-1-acid glycoprotein; h = hour; min = minutes; PK = pharmacokinetics 
a The predose sample should be collected as close as possible to 24 hours after the prior dose. 
8.5.1. 
Pharmacokinetic Sample Collection for Co-Administration with 
Strong/Moderate CYP3A Inhibitors or Inducers and/or P-gp Inhibitors 
When drugs with a strong/moderate CYP3A inhibitory or inducing effect and/or P-gp inhibitory 
effect are coadministered with the study drug, additional PK and AAG samples are required to be 
collected 10 days (or up to 14 days) after the initiation date of the inhibitor or inducer.  Three PK 
samples (1 predose and 2 postdose samples) and 1 AAG sample (predose) will be collected.  
Specifically, for the PK postdose samples, 1 sample between 0.5 hour and 4 hours postdose and 
1 sample between 4 hours and 8 hours postdose of valemetostat tosylate will be collected.  If 
collecting 3 PK samples is difficult, at least 2 PK samples (1 predose and 1 postdose sample) will 
be collected.  In this case, it is ideal to collect the sample closer to 4 hours postdose, but 1 PK 
sample at 0.5 hour to 8 hours will be acceptable.  Note: More than 2 postdose PK samples will be 
acceptable as multiple postdose samples could increase the predictability of PK parameters and 
1 blood sample collection for AAG measurement at predose on the same day of PK blood 
sampling back in the procedure.  AAG data will be used for population PK (PopPK) modeling. 

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Refer to Table 10.4 for a list of strong/moderate CYP3A inhibitors or inducers and P-gp 
inhibitors. 
The actual dose, actual date, and time of dosing for the comedications mentioned above must be 
recorded on the eCRF. 
An example for 3 PK samples and 1 AAG sample: 
 Fluconazole, a moderate CYP3A inhibitor, initiated on 01 Aug. 
 Collect 1 AAG sample (predose prior to valemetostat tosylate administration) on 
11 Aug.  
 Collect 3 PK samples (predose and 2 postdose samples) on 11 Aug: 
 1 predose PK sample prior to valemetostat tosylate administration  
 1 postdose PK sample between 0.5 hour and 4 hours (eg, 3 hours) after 
valemetostat tosylate administration 
 Additional 1 postdose PK sample between 4 hours and 8 hours (eg, 6 hours) after 
valemetostat tosylate administration 
An example for 2 PK samples and 1 AAG sample: 
 Fluconazole, a moderate CYP3A inhibitor, initiated on 01 Aug. 
 Collect 1 AAG sample (predose prior to valemetostat tosylate administration) on 
11 Aug. 
 Collect 2 PK samples on 11 Aug: 
 1 predose prior to valemetostat tosylate administration  
 1 postdose PK sample between 0.5 and 8 hours (eg, 4 hours) after valemetostat 
tosylate administration.  When only 1 postdose PK sample is collected, it is ideal 
to collect the sample closer to 4 hours postdose. 
8.6. 
Biomarker Assessments 
8.6.1. 
Analysis of Biopsied Tumor Tissue 
Fresh samples obtained during Screening and/or previously collected archival tumor tissue will 
be used.  On Cycle 1 Day 1, oral mucosa swabs will also be collected for subjects who have 
provided informed consent for oral mucosa collection.  Oral mucosa will be used as reference 
specimens to identify tumor-specific somatic mutations.  The analyses can be conducted using 
fresh tumor samples from biopsies, which are performed at unscheduled time points after the 
first dose of valemetostat tosylate and optionally submitted. 
The analyses of biopsied tumor tissue will include the following assays depending on the 
availability of the tumor tissue.  First, comprehensive gene alteration profiling with 
next-generation sequencing (NGS) or other assay at baseline and at unscheduled points will be 
performed to analyze the mechanism of action and mechanism of resistance to valemetostat 
tosylate.  This will include EZH1 and EZH2 mutational status at baseline to investigate its 

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potential impact on the activity of valemetostat tosylate.  In the analysis of gene mutations, oral 
mucosa will be used as reference specimens to identify tumor-specific somatic mutations. 
Second, CD30 and other molecules will be evaluated using immunohistochemistry (IHC).  Last, 
H3K27me3 status in biopsied tumor tissue with IHC will be performed in order to assess 
correlation between any methylation levels and clinical response.  The remaining biopsied tumor 
samples will be used for further analysis to address scientific questions related to the efficacy 
and/or safety of valemetostat tosylate. 
8.6.2. 
Minimal Residual Disease (MRD) Assessment Using Peripheral Blood Samples 
Peripheral blood samples will be collected to evaluate the depth of response.  Peripheral blood 
samples will be analyzed by PhasED Sequence, PCR, and flow cytometry to detect 
tumor-derived cell-free DNA and residual tumor cells. 
A sample will be collected at these time points: Day 1 of Cycle 1, Cycle 2, Cycle 5, Cycle 13, 
and every 6 cycles onward starting Day 1 of Cycle 19 (ie, Day 1 of Cycle 19, Cycle 25, Cycle 
31, and so on).  In addition, peripheral blood samples will be collected at the time of the first CR 
or, if not obtainable, at the subsequent visit after the first CR when the first CR is determined by 
investigator per CT-based assessment (for primary efficacy analysis) or FDG-PET 
based-assessment (for primary exploratory analysis; see Table 1.1).   
8.6.3. 
Profiling of T-cells in Freshly Collected Peripheral Blood Samples Using Flow 
Cytometry Assay 
Fresh peripheral blood samples will be collected for flow cytometry assay to evaluate the impact 
of valemetostat tosylate on immune cells on Day 1 of Cycle 1, Cycle 2, Cycle 3, Cycle 5, and 
Cycle 7.  If further evaluation is required for immune cells, sample collection at additional time 
points is allowed (see Table 1.1). 
8.6.4. 
Pharmacogenomic (Inherited Genetic) Analysis 
An oral mucosa swab for optional future pharmacogenetic analysis will be collected predose on 
Cycle 1 Day 1 from each subject who consented to this analysis.  Detailed instructions for the 
collection, handling, and shipping of samples are outlined in the Study Laboratory Manual.  
Participation in this part of the study is optional for all subjects.  Subjects who do not wish to 
participate in this part may still participate in the study. 
If subjects agree, the remaining DNA will be stored, as outlined in Section 8.6.4.1, for 
performing pharmacogenetic analysis in the future; otherwise, all remaining DNA samples will 
be destroyed. 
8.6.4.1. 
Banking of Specimens for Inherited Genetic Analysis 
Subjects’ samples will be banked for future biomarker analyses, which may include 
comprehensive gene mutation and expression profiling with NGS and RNA sequencing. 
Procedures for the long-term preservation (banking) of blood and/or DNA specimens extracted 
from subjects’ blood samples for each subject who consented are described in the Study 
Laboratory Manual. 

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The banked samples may be analyzed for genes involved in the absorption, distribution, 
metabolism, elimination, safety, and efficacy of valemetostat tosylate.  Additionally, samples 
may be analyzed for genes involved in valemetostat tosylate-related signaling pathways or to 
examine diseases or physiologic processes related to valemetostat tosylate.  DNA samples will 
not be immortalized or sold to anyone.  This information may be useful in increasing the 
knowledge of differences among individuals in the way they respond to the study drug, as well 
as helping in the development of new drugs or improvement of existing drugs. 
Storage and Disposal of Specimens 
Banked DNA samples will be stored for a maximum of 15 years after the finalization of the 
clinical study report for this protocol.  These specimens will be kept for pharmacogenetic 
analysis in case new genomic or genetic information is obtained in the future regarding the 
response (PK or pharmacodynamic) to valemetostat tosylate or in case serious adverse drug 
reactions are noted in a clinical study and pharmacogenetic analysis is to be conducted for 
investigation into the cause. 
During the storage period, the samples will be coded with labels having no personal information 
and will not be immortalized or sold to anyone.  Subjects will have the right to withdraw consent 
and have their sample destroyed at any time.  However, the data will not be discarded if analysis 
has been completed before the subject withdraws consent. 
Disclosure of the Results of Future Pharmacogenetic Analysis 
Because the nature and value of future pharmacogenetic analysis cannot be known at this time, 
any results obtained from research involving pharmacogenetic samples will not be disclosed to 
the subject or investigators now or in the future. 
8.6.5. 
Storage of Specimens 
In consideration of the possibility that the relationship between the biomarker and the efficacy or 
safety of valemetostat tosylate may be additionally analyzed based on newly obtained 
knowledge, the submitted specimens may be stored in the central laboratory or sample storage 
facility for a maximum of up to 15 years after the start of the clinical study (ie, the time of 
submission of the clinical trial plan notification). 

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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
General Statistical Considerations 
The statistical analysis plan (SAP) will be developed and finalized before the first subject is 
enrolled and will describe the subject populations to be included in the analyses and procedures 
for accounting for missing, unused, and spurious data. 
9.2. 
Statistical Hypothesis 
Valemetostat tosylate is efficacious in subjects with R/R PTCL. 
9.3. 
Sample Size Determination 
Cohort 1 
The total number of Cohort 1 is approximately 128 R/R PTCL subjects.  Assuming 90% of 
enrolled R/R PTCL subjects will have PTCL histology confirmed by central pathology review, 
the sample size of 115 R/R PTCL subjects will provide sufficient statistical precision for the 
inference of the ORR.  With a sample size of 115 subjects, the probability of observing the lower 
bound of the 95% CI >27% (historical ORR rate) is at least 90%, if the expected ORR with 
valemetostat tosylate is 42%. 
Table 9.1 shows the 95% exact CI (based on the Clopper-Pearson method) at different observed 
ORRs.  The maximum half width of 95% CI for ORR will be approximately 9.5%. 
Table 9.1: 
95% Confidence Interval at Various Observed ORRs (R/R PTCL Subjects) 
Responders 
Total Sample Size 
Observed ORR 
95% Exact CI 
42 
115 
36.5% 
27.7% 
46.0% 
47 
115 
40.9% 
31.8% 
50.4% 
52 
115 
45.2% 
35.9% 
54.8% 
CI = confidence interval; ORR = objective response rate 
Cohort 2 
A total sample size of approximately 20 R/R ATL subjects is expected at the time of enrollment 
closing.  This sample size is not based on statistical considerations. 
9.4. 
Population for Analysis Sets 
Analysis Sets 
 The Safety Analysis Set will include all subjects who received at least 1 dose of 
study drug.   

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Efficacy Population: 
Cohort 1: Defined as all subjects who received at least 1 dose of valemetostat tosylate 
and had an eligible PTCL subtype that was confirmed by central hematopathology 
review. 
Cohort 2: Defined as all subjects who received at least 1 dose of valemetostat tosylate 
and had an eligible ATL subtype. 
 The PK Analysis Set will include all subjects in the Safety Analysis Set who had 
measurable plasma concentrations of valemetostat. 
 The Biomarker Analysis Set will include all subjects who received at least 1 dose of 
the study drug, who provided specimens for the biomarker study, and whose 
measurement data obtained for the specimens are usable. 
9.5. 
Statistical Analysis 
The SAP will be developed and finalized before the first subject is enrolled and will describe the 
subject populations to be included in the analyses, and procedures for accounting for missing, 
unused, and spurious data.  This section is a summary of the planned statistical analyses of the 
primary and secondary endpoints. 
9.5.1. 
Efficacy Analyses 
Table 3.1 lists the primary and secondary endpoints and their corresponding definitions of all 
endpoints.  Additional details for the analysis and censoring rules are noted in the following 
sections.  Detailed censoring rules for the primary and applicable secondary efficacy endpoints 
will be specified in the SAP. 
Analysis will be conducted separately for PTCL and ATL cohorts. 
9.5.1.1. 
Primary Efficacy Analysis – Cohort 1 Only 
The primary efficacy analysis will be based on the data from the Cohort 1 efficacy population. 
 ORR (CR + PR) based on CT-based BICR assessment 
The primary efficacy analysis will be performed on the ORR in R/R PTCL subjects with 
centrally confirmed eligible PTCL subtype.  The exact 95% CIs for the ORR will be calculated 
using the Clopper-Pearson method.  Any response assessment after initiating a subsequent 
lymphoma therapy or a preparative regimen for a HCT will not be included into the primary 
efficacy analysis. 
Sensitivity and supportive analyses of the primary efficacy analysis may be performed based on 
a subset of subjects from the efficacy population. 
9.5.1.2. 
Secondary Efficacy Analyses – Cohort 1 Only 
 DoR based on CT-based BICR assessment 
 CR rate based on CT-based BICR assessment 
 PR rate based on CT-based BICR assessment 

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 Duration of CR (DoCR) based on CT-based BICR assessment 
 ORR, DoR, CR/PR rate, and DoCR based on investigator assessment 
Summary statistics will be provided for DoR/DoCR based on BICR and investigator assessments 
as well as ORR based on investigator assessments.  Kaplan-Meier curves will be provided, and 
the median survival and 95% CI will be calculated for DoR/DoCR assessed by both BICR and 
investigator.  For the primary analysis of DoR/DoCR based on the BICR assessment, subjects 
who start subsequent therapy or HCT before BICR-assessed disease progression will be censored 
at the last evaluable tumor assessments prior to or on the date of initiation of the subsequent 
anticancer therapy or HCT.  There will be a sensitivity analysis of DoR/DoCR based on the 
BICR and investigator assessment performed without censoring HCT.  The censoring rules for 
the primary and sensitivity analyses for DoR/DoCR will be the same with the rules of PFS 
analysis. 
 PFS based on BICR and investigator assessments 
 OS 
 DoCR, CR, and PR rates by BICR and investigator assessments. 
9.5.1.3. 
Exploratory Analyses 
An EZH2 inhibitor has different clinical activity in EZH2 wildtype and mutated follicular 
lymphoma.56  The potential impact of EZH1 and EZH2 mutational status on the activity of 
valemetostat tosylate in PTCL is unknown.  Therefore, EZH1 and EZH2 mutational status at 
baseline will be evaluated and its impact on the activity of valemetostat tosylate treatment will be 
analyzed based on mutational status. 
Although the primary efficacy analysis for Cohort 1 will be performed according to CT-based 
response assessment of the 2014 Lugano criteria1, the BICR and investigators will also conduct 
PET-CT-based response assessment for exploratory efficacy analysis.  Unlike classical Hodgkin 
lymphoma or diffuse large B cell lymphoma, the role of FDG-PET scans in PTCL has not been 
fully established yet due to limited data.57,58,59,60,61  PTCLs can be variably FDG avid, but the 
higher uptake was in aggressive subtypes.60,62,63  Thus, FDG-PET scan-based response 
assessment may be informative to the utility of FDG-PET scans for measuring the therapeutic 
outcome in PTCL including ATL. 
Exploratory analyses of efficacy for Cohort 2 subjects will be summarized in a descriptive 
manner. 
9.5.1.4. 
Subgroup Analysis 
Subgroup analyses will be performed for ORR based on age categories, gender, race, geographic 
region, PTCL subgroup, and number of prior regimens.   
9.5.1.5. 
Multiplicity Adjustment 
Not applicable. 

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9.5.2. 
Safety Analyses 
Safety analyses will be performed using the Safety Analysis Set, and subjects will be analyzed 
according to their actual treatment received. 
Safety will be measured by the incidence of all clinical and laboratory safety assessments, 
including TEAEs; TESAEs; severe events (Grades 3 and Grade 4); fatal events; TEAEs 
associated with treatment discontinuation, interruption, or reduction; and AESIs (as noted above 
in common toxicities/AEs of special interest). 
Adverse Events 
TEAEs are defined as new AEs or pre-existing conditions that worsen in NCI-CTCAE grade 
after the first dose of study drug and up to 30 days after the last dose of study drug.  AEs 
collected after 30 days after the last dose of study drug will not be considered TEAEs unless they 
are treatment-related.  TEAEs will be tabulated.  TEAEs will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA) terminology and tabulated by body organ group 
using the MedDRA system organ class and by AE term using preferred terms. 
All AEs will be coded using the MedDRA dictionary.  An AE will be assigned to the study 
period in which it started, even if it resolved in a subsequent period.  The number and percentage 
of subjects reporting TEAEs will be calculated overall, by system organ class, by preferred term, 
and by treatment group. 
Treatment-emergent adverse events will be further summarized by NCI-CTCAE Version 5.0 
grade and relationship to study drug.  Similarly, the number and percentage of subjects reporting 
treatment-emergent SAEs and related treatment-emergent SAEs, treatment-emergent AESIs, and 
TEAEs leading to discontinuation of study drug will be tabulated. 
A by-subject AE (including treatment-emergent) data listing, including, but not limited to 
verbatim term, preferred term, system organ class, NCI-CTCAE grade, and relationship to study 
drug will be provided.  Deaths, all SAEs, AESIs, and AEs associated with study drug 
discontinuation will be listed. 
Clinical Laboratory Evaluation 
Descriptive statistics will be provided for the clinical laboratory results by scheduled time of 
evaluation and by treatment group, as well as for the change from baseline.  The baseline value is 
defined as the last non-missing value before the initial administration of study drug, that is, the 
most current result prior to the first dose of the study drug will serve as the baseline values.  In 
addition, mean change from baseline will be presented by treatment group for the maximum and 
minimum post-treatment values and the values at the EOT Visit. 
Abnormal clinical laboratory results will be graded according to NCI-CTCAE Version 5.0, if 
applicable, and the grade will be presented in a by-subject data listing.  A shift table, presenting 
by treatment group the 2-way frequency tabulation for baseline and the worst post-treatment 
value according to the NCI-CTCAE grade, will be provided for clinical laboratory tests.  A 
listing of abnormal clinical laboratory test results deemed of clinical significance or of Grade 3 
or Grade 4 will be generated. 

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Electrocardiogram 
Descriptive statistics will be provided for the ECG measurements by scheduled time of 
evaluation and by treatment group, as well as for the change from baseline.  The baseline value is 
defined as the last non-missing value before the initial administration of study drug.  In addition, 
the number and percentage of subjects with ECG interval values meeting the criteria will be 
tabulated (eg, QTc ≤450 ms, >450 ms to ≤480 ms, >480 ms to ≤500 ms, and >500 ms, increase 
from baseline >30 ms to 60 ms, and increase from baseline >60 ms). 
A listing of ECG data will be generated. 
Vital Signs 
Descriptive statistics will be provided for the vital signs measurements by scheduled time of 
evaluation and by treatment group, as well as for the change from baseline.  The baseline value is 
defined as the last non-missing value before the initial administration of study drug.  A listing of 
vital sign data will be generated. 
Other 
Listings of all other safety endpoints (eg, physical examination findings, including ECOG PS, 
echocardiogram/multigated acquisition, and ophthalmologic findings) will be generated. 
9.5.3. 
Other Analyses 
The following other analyses are planned in this study. 
Pharmacokinetics 
Pharmacokinetics analyses will be performed using the PK Analysis Set. 
Total and unbound concentrations for valemetostat in plasma and total concentration of 
CALZ-1809a in plasma will be listed and summarized using descriptive statistics at each time 
point. 
Population PK analysis and exposure-response analyses for key efficacy and safety endpoints 
will be performed.  Results from the PopPK analysis and exposure-response will be reported 
separately. 
Biomarker 
Peripheral blood and tumor biopsies will be collected at various time points including at 
baseline, on treatment and/or at the EOT, and/or at the time of relapse in order to characterize 
associated biomarkers in peripheral blood and tumor biopsies that may predict the effect of 
valemetostat on safety and efficacy measures.  Those exploratory biomarkers will be used to 
evaluate any potential relationship between clinical outcome and biomarkers, including CD 
markers, changes in H3K27me3 status, immune cell population, gene mutation, and expression 
profiles.  Other specimens aside from peripheral blood and tumor biopsies at several time points 
will also be collected and banked for future exploratory biomarker research. 

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9.6. 
Unacceptable Toxicities and Stopping Criteria 
Unacceptable toxicities are defined as excessive toxicities in any of the following: 
 Rate of Grade 4 (hematologic or non-hematologic toxicity) ≥30% or 
 Rate of AESI (thrombocytopenia Grade ≥3) ≥35% or 
 Rate of Grade 5 (hematologic or non-hematologic toxicity) ≥5%, when the primary 
cause of death is not reported as disease progression. 
The stopping rules for the unacceptable toxicities are derived using the Pocock-type boundary.64  
The Pocock boundary allows stopping as early as possible for use in the stopping rule for 
excessive toxicity.  These stopping boundaries for unacceptable toxicity will be applied 
separately to both Cohort 1 (see prespecified stopping boundaries in Appendix 3, Section 10.3.8, 
Table 10.6 through Table 10.8) and Cohort 2 (see prespecified stopping boundaries in Appendix 
3, Section 10.3.8, Table 10.9 through Table 10.11). 
Patient accrual will be halted, and the DMC meeting will be immediately triggered to make a 
recommendation based upon their comprehensive evaluation if excessive numbers of toxicities 
are observed (per each category above), that is, if the number of toxicities is equal to or exceeds 
stopping boundary out of the number of subjects with full follow-up. 
See Section 10.1.4 for the frequency of assessments by the DMC. 
9.7. 
Interim Analyses 
Futility interim analysis will be conducted for both cohorts based on the primary endpoint, ORR. 
Cohort 1: A non-binding futility interim analysis will be conducted when the first 46 (40%) 
subjects with histology-confirmed PTCL, by central pathology review, complete a minimum of 
4 months of follow-up from the first dose of valemetostat tosylate.  The futility criterion of 
BICR-assessed ORR is 23.9% or lower, that is, 11 or fewer responders from the first 46 subjects 
with R/R PTCL.  The futility boundary is calculated using the spending function of Lan-DeMets 
with a parameter of O'Brien-Fleming, assuming an ORR rate of 27% (historical rate) and 42% 
(expected treatment effect rate) for valemetostat.  This boundary only provides the conditional 
power of 0.1% if the null hypothesis is true for the future coming patients.  If the alternative 
hypothesis is true for the future coming patients, it provides the conditional power of 40%.  This 
cohort may be terminated based on the totality of the evidence (response rate, safety, and 
benefit/risk), with consideration of the futility boundaries.  Additional interim analyses may be 
conducted if it is necessary to make decisions regarding further development. 
An internal DMC, independent of the study team, will evaluate the safety and efficacy data for 
these interim analyses according to statistical procedures defined a priori and for periodic safety 
reviews.  Based on the results of the interim analysis, the DMC will recommend that the study be 
terminated early for safety and/or efficacy (futility) or continue as planned. 

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10. 
APPENDICES – SUPPORTING DOCUMENTATION AND 
OPERATIONAL CONSIDERATIONS 
10.1. 
Appendix 1 Regulatory and Ethical Considerations 
10.1.1. 
Regulatory Compliance 
The study protocol, the IB, available safety information, recruitment procedures 
(eg, advertisements), subject information and consent form, any subject written instructions to be 
given to the subject, information about payments and compensation available to the subjects, and 
documentation evidencing the investigator’s qualifications should be submitted to the 
independent IRB or EC for ethical review and approval according to local regulations, prior to 
the study start.  The written approval should identify all documents reviewed by name and 
version. 
Changes in the conduct of the study or planned analysis will be documented in a protocol 
amendment and/or the SAP.  Written approval of all protocol amendments and changes to any of 
the above listed documents must be obtained from the IRB or EC. 
The investigator should notify the IRB or EC of deviations from the protocol or SAEs occurring 
at the study site and other AE reports received from the Sponsor/CRO, in accordance with local 
procedures. 
The Sponsor will appoint a coordinating investigator.  Among other possible duties, the 
coordinating investigator will be responsible for reviewing the final clinical study report and 
testifying to the accuracy of the description of the study conduct.  Because the coordinating 
investigator should have personal knowledge of the conduct of the study, he/she will normally be 
chosen from among those investigators who have enrolled and treated at least 1 subject.  
However, where an investigator has special knowledge of the field or of the study, the 
coordinating investigator can be chosen prior to the enrollment of the first subject.  In all cases, 
the coordinating investigator must be chosen prior to locking the database. 
Compliance Statement, Ethics, and Regulatory Compliance 
This study will be conducted in compliance with the protocol, the ethical principles that have 
their origin in the Declaration of Helsinki, the International Conference for Harmonisation (ICH) 
consolidated Guideline E6 for Good Clinical Practice (GCP) (CPMP/ICH/135/95), and 
applicable regulatory requirement(s) including the following: 
 Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 
Apr 2014 on clinical trials on medicinal products for human use, and repealing 
Directive 2001/20/EC and/or; 
 European Commission Directive (2001/20/EC Apr 2001) and/or; 
 European Commission Directive (2005/28/EC Apr 2005) and/or; 
 US Food and Drug Administration (FDA) GCP Regulations: Code of Federal 
Regulations (CFR) Title 21, parts 11, 50, 54, 56 and 312 as appropriate and/or; 

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 Japanese Ministry of Health, Labor and Welfare Ordinance No. 28 (27 Mar 1997) 
and/or; 
 The Act on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical 
Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and 
Cosmetics No. 1 (25 Nov 2014); 
 Other applicable local regulations. 
In addition, the investigator will inform the Sponsor in writing within 24 hours of any urgent 
safety measures taken by the investigator to protect the study subjects against any immediate 
hazard, and of any suspected/actual serious GCP non-compliance that the investigator becomes 
aware of. 
Supply of New Information Affecting the Conduct of the Study 
When new information becomes available that may adversely affect the safety of subjects or the 
conduct of the study, the Sponsor will inform all investigators involved in the clinical study, 
IECs/IRBs, and regulatory authorities of such information, and when needed, will amend the 
protocol and/or subject information. 
The Investigator should immediately inform the subject whenever new information becomes 
available that may be relevant to the subject’s consent or may influence the subject’s willingness 
to continue participation in the study.  The communication should be documented on medical 
records, for example, and it should be confirmed whether the subject is willing to remain in the 
study. 
If the subject information is revised, it must be re-approved by the independent ethics 
committee/institutional review board (IEC/IRB).  The investigator should obtain written 
informed consent to continue participation with the revised written information even if subjects 
were already informed of the relevant information.  The investigator or other responsible 
personnel who provided explanations and the subject should sign and date the revised ICF. 
10.1.2. 
Informed Consent 
In obtaining and documenting informed consent, the investigator should comply with the 
applicable regulatory requirements, and should adhere to GCP and to the ethical principles that 
have their origin in the Declaration of Helsinki.  The ICF and any revision(s) should be approved 
by the IEC/IRB prior to being provided to potential subjects. 
The subject’s written informed consent should be documented in the subject’s medical records.  
The ICF should be signed and personally dated by the subject and by the person who conducted 
the informed consent discussion (not necessarily the investigator).  The original signed ICF 
should be retained in accordance with institutional policy, and a copy of the signed ICF should 
be provided to the subject.  The date and time (if applicable) that informed consent was given 
must be recorded in the eCRF. 
If the subject cannot read, then according to ICH GCP Guideline, Section 4.8.9, an impartial 
witness should be present during the entire informed consent discussion.  This witness should 
sign the ICF after the subject has consented to their participation.  By signing the ICF, the 
witness attests that the information in the ICF and any other written information was adequately 

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explained to and apparently understood by the subject and that informed consent was freely 
given by the subject. 
A separate special consent for inherited genetic analysis will be obtained from subjects in 
accordance with health authorities in their particular region/country. 
Suggested model text for the ICF for the study and any applicable subparts (PK, 
pharmacodynamic, etc) is provided in the Sponsor’s ICF template for the investigator to prepare 
the documents to be used at his or her study site.  Updates to applicable forms will be 
communicated via letter from the Sponsor. 
For study sites in the US, included with the ICF, an additional consent is required for the Health 
Insurance Portability and Accountability Act. 
10.1.3. 
Subject Confidentiality 
The investigators and the Sponsor will preserve the confidentiality of all subjects taking part in 
the study, in accordance with GCP and local regulations. 
For EU study sites, the Sponsor will observe the rules laid down in the European Data Protection 
Directive 95/46/EC on the protection of individuals with regard to the processing of personal 
data and the free movement of such data. 
The Investigator must ensure that the subject’s anonymity is maintained.  On the eCRFs or other 
documents submitted to the Sponsor or the CRO, subjects should be identified by a unique SID 
as designated by the Sponsor.  Documents that are not for submission to the Sponsor or the CRO 
(eg, signed ICF) should be kept in strict confidence by the investigator. 
In compliance with ICH GCP Guidelines, it is required that the investigator and institution 
permit authorized representatives of the company, of the regulatory agency(s), and the 
independent IRB/EC direct access to review the subject’s original medical records for 
verification of study-related procedures and data.  The investigator is obligated to inform the 
subject that his/her study-related records will be reviewed by the above named representatives 
without violating the confidentiality of the subject. 
10.1.4. 
Data Integrity and Quality Assurance 
Monitoring and Inspections 
The Sponsor/CRO monitor and regulatory authority inspectors are responsible for contacting and 
visiting the investigator for the purpose of inspecting the facilities and, upon request, inspecting 
the various records of the study (eg, eCRFs, source data, and other pertinent documents). 
The verification of adherence to the protocol; completeness, accuracy, and consistency of the 
data; and adherence to ICH GCP and local regulations on the conduct of clinical research will be 
accomplished through a combination of onsite visits by the monitor and review and verification 
of study data remotely.  The Sponsor intends to implement remote source data verification 
(SDV) of medical records in the study conduct if in compliance with national and local 
regulations.  The investigator or study site, in consultation with their data protection officer, if 
applicable, must confirm their agreement to remote SDV, which should be compliant with all 
applicable local guidance documents and national regulations.  Investigators and study sites that 

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must comply with “EMA Guidance on Conduct of Clinical Trials of Medical Products During 
the COVID-19” should inform each study subject that their study records may be reviewed 
remotely and document their agreement or disagreement.66 
The frequency of the monitoring visit and remote SDV will vary based on the activity at each 
study site.  The monitor is responsible for inspecting the eCRFs and ensuring completeness of 
the study essential documents.  The monitor should have access to subject medical records and 
other study-related records needed to verify the entries on the eCRFs.  Detailed information is 
provided in the monitoring plan. 
The Sponsor/designee will monitor for study drug accountability, reconciliation, and record 
maintenance (ie, Receipt of Shipment Form, dispensation/return record, and certificate of 
destruction/return receipt). 
The monitor will communicate deviations from the protocol, SOPs, GCP and applicable 
regulations to the investigator and will ensure that appropriate action (s) designed to prevent 
recurrence of the detected deviations is taken and documented. 
The investigator agrees to cooperate with the monitor to ensure that any problems detected in the 
course of these monitoring visits are addressed to the satisfaction of the Sponsor and 
documented. 
In accordance with ICH GCP and the Sponsor’s audit plans, this study may be selected for audit 
by representatives from the Sponsor.  Audit of study site facilities (eg, pharmacy, drug storage 
areas, laboratories) and review of study-related records will occur in order to evaluate the study 
conduct and compliance with the protocol, ICH GCP, and applicable regulatory requirements.  
The Investigator should respond to audit findings. 
In the event that a regulatory authority informs the investigator that it intends to conduct an 
inspection, the Sponsor shall be notified immediately. 
Data Collection 
An eCRF must be completed for each subject who signs an ICF and undergoes any screening 
procedure.  If a subject is not treated, the reason must be recorded on the eCRF.  All data 
collected during the study will be recorded in this individual, subject-specific eCRF.  Instructions 
will be provided for the completion of the eCRF and any corrections made will be automatically 
documented via an “audit trail.” 
The eCRF should be kept current to enable the study monitor to review the subject’s status 
throughout the course of the study.  Upon completion of the subject’s eCRF, it will be reviewed 
and signed off by the investigator via the EDC system’s electronic signature.  Throughout the 
study, the investigator may also be required to confirm ongoing review of the subject’s eCRF. 
This signature will indicate that the investigator inspected or reviewed the data in the subject-
specific eCRF, the data queries, and the site notifications and agrees with the eCRF content. 
Data Management 
Each subject will be identified in the database by a unique SID. 

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To ensure the quality of clinical data across all subjects and study sites, a Sponsor/CRO Clinical 
and Data Management review will be performed on subject data according to specifications 
developed by the Sponsor.  Data will be vetted both electronically by programmed data rules 
within the application and manually.  Queries generated by rules and raised by reviewers will be 
generated within the EDC application.  During this review, subject data will be checked for 
consistency, completeness and any apparent discrepancies. 
Data received from external sources such as central laboratories will be reconciled to the clinical 
database. 
All AEs will be coded using MedDRA.  Serious adverse events in the clinical database will be 
reconciled with the safety database. 
All concomitant medications and prior cancer therapies will be coded using the World Health 
Organization Drug Reference (WHODRUG) Dictionary. 
Safety Monitoring 
The Sponsor will monitor the subjects’ safety on an ongoing basis during this study. 
 The safety of subjects on this study are reviewed, on a systematic and continuous 
basis, by the study physicians (medical monitor and safety lead).  This includes a 
review of serious and non-serious adverse events, including hematological and 
nonhematological events.   
 The safety data across the entire valemetostat tosylate program is reviewed at regular 
intervals throughout the study by the Safety Management Team (SMT).  The SMT is 
responsible for reviewing data from all sources, including nonclinical and clinical 
studies, which include but are not limited to this study. 
 In addition, study-wide accrual stopping criteria will be based upon excess 
occurrences of “unacceptable toxicities” and will be performed every 3 months.  If 
any of the unacceptable toxicities occur in excess of the predefined stopping 
boundaries, this will prompt enrollment of new subjects into the study to be paused 
and a comprehensive review of the safety data by the adhoc DMC.  See Section 9.6 
for the definition of unacceptable toxicities details on the study-wide stopping 
boundaries. 
10.1.5. 
Committees 
Blinded Independent Central Review Committee 
A BICR will be utilized in this study for Cohort 1 for the determination of BICR-assessed 
endpoints such as ORR, CR rate, PR rate, and associated durations of response.  The BICR will 
review all available tumor assessment scans for all Cohort 1 treated subjects and, when 
applicable, relevant clinical data (at minimum, bone marrow results and tumor biopsy results).  
Copies of de-identified local pathology report for bone marrow or tumor biopsies performed in 
the study (with SID noted) may be collected, upon request by the BICR.  Details of BICR 
responsibilities and procedures will be specified in the BICR charter.  

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Data Monitoring Committee 
An internal DMC, independent of the study team, will evaluate the safety and efficacy data for 
this interim analysis according to statistical procedures defined a priori, and for periodic safety 
reviews, which includes the review of unacceptable toxicities (Section 9.6 and Section 10.1.4).  
Members of the DMC are independent of the study and will consist of both internal Sponsor 
experts (including safety physician, hematologist(s)/oncologist(s), and biostatistician) and 
external experts (including hematologist(s)/oncologist(s) with expertise in malignant lymphoma).  
Other external experts may be included if additional expertise is needed.   
Based on the review of the data, the DMC will recommend that the study be terminated early for 
safety and/or efficacy (futility) or continue as planned.  Details of DMC responsibilities and 
procedures will be specified in the DMC charter. 
10.1.6. 
Study Documentation and Storage 
The investigator will maintain a Signature List of appropriately qualified persons to whom 
he/she has delegated study duties.  All persons authorized to obtain informed consent and make 
entries and/or corrections on eCRFs will be included on the Signature List. 
Investigators will maintain a confidential Screening Log of all potential study candidates that 
includes limited information of the subjects, date and outcome of the screening process. 
Investigators will be expected to maintain an Enrollment Log of all subjects enrolled in the study 
indicating their assigned study number. 
Investigators will maintain a confidential SID code list.  This confidential list of names of all 
subjects allocated to study numbers on enrolling in the study allows the investigator to reveal the 
identity of any subject when necessary. 
Source documents are original documents, data, and records from which the subject’s eCRF data 
are obtained.  These include but are not limited to hospital records, clinical and office charts, 
laboratory and pharmacy records, diaries, microfiches, X-rays, and correspondence. 
Records of subjects, source documents, monitoring visit logs, data correction forms, eCRFs, 
inventory of study drug, regulatory documents (eg, protocol and amendments, IEC/IRB 
correspondence and approvals, approved and signed ICFs, Investigator’s Agreement, clinical 
supplies receipts, distribution and return records), and other Sponsor correspondence pertaining 
to the study must be kept in appropriate study files at the study site (site specific Trial Master 
File).  Source documents include all recordings and observations or notations of clinical 
activities and all reports and records necessary for the evaluation and reconstruction of the 
clinical study.  These records will be retained in a secure file for the period required by local 
laws or regulations or study site policy.  Prior to transfer or destruction of these records, the 
Sponsor must be notified in writing via email to DSPDRecords@dsi.com and be given the 
opportunity to provide further instruction. 
Record Keeping 
The investigator and study staff are responsible for maintaining a comprehensive and centralized 
filing system (site specific Trial Master File) of all study-related (essential) documentation, 

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suitable for inspection at any time by representatives from the Sponsor and/or applicable 
regulatory authorities.  Essential documents include: 
 Subject files containing completed eCRFs, ICFs, and supporting source 
documentation (if kept). 
 Study files containing the protocol with all amendments, IB, copies of relevant 
essential documents required prior to commencing a clinical study, and all 
correspondence to and from the independent IRB/EC and the Sponsor. 
 Records related to the study drug(s) including acknowledgment of receipt at study 
site, accountability records and final reconciliation and applicable correspondence. 
In addition, all original source documents supporting entries in the eCRFs must be maintained 
and be readily available. 
All essential documentation will be retained by the investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least 2 years have lapsed since the 
formal discontinuation of clinical development of the investigational drug.  These documents 
should be retained for a longer period, however, if required by the applicable laws or regulatory 
requirements or by an agreement with the Sponsor.  It is the responsibility of the Sponsor to 
inform the Investigator/Institution as to when these documents no longer need to be retained. 
Subjects’ medical files should be retained in accordance with applicable legislation and in 
accordance with the maximum period of time permitted by the hospital, institution or private 
practice.  
No study document should be destroyed without prior written agreement between the Sponsor 
and the investigator.  Should the investigator wish to assign the study records to another party or 
move them to another location, he/she must notify the Sponsor in writing via email to 
DSPDRecords@dsi.com of the new responsible person and/or the new location. 
10.1.7. 
Finances 
Prior to starting the study, the Principal Investigator and/or Institution will sign a clinical study 
agreement with Sponsor or designee.  This agreement will include the financial information 
agreed upon by the parties. 
Reimbursement, Indemnity, and Insurance 
The Sponsor provides insurance for study subjects to make available compensation in case of 
study-related injury. 
Reimbursement, indemnity and insurance shall be addressed in a separate agreement on terms 
agreed upon by the parties. 
10.1.8. 
Publication and Public Disclosure Policy 
The Sponsor is committed to meeting the highest standards of publication and public disclosure 
of information arising from clinical studies sponsored by the company.  The Sponsor will 
comply with US, EU, and Japanese policies for public disclosure of the clinical study protocol 
and clinical study results, and for sharing of clinical study data.  The Sponsor will follow the 
principles set forward in “Good Publication Practice for Communicating Company-Sponsored 

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Medical Research (GPP3)”, and publications will adhere to the “Recommendations for the 
Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals” 
established by the International Council of Medical Journal Editors (ICMJE). 
In order to ensure compliance with the public disclosure policies and the ICMJE 
recommendations, and to protect proprietary information generated during the study, all 
publications (manuscripts, abstracts, or other public disclosure) based on data generated in this 
study must be reviewed and approved in writing by the Sponsor prior to submission. 
10.1.9. 
Protocol Deviations 
The investigator should conduct the study in compliance with the protocol agreed to by the 
Sponsor and, if required, by the regulatory authority(ies), and which was given 
approval/favorable opinion by the IECs/IRBs. 
A deviation to any protocol procedure or waiver to any stated criteria will not be allowed in this 
study except where necessary to eliminate immediate hazard(s) to the subject. 
The Sponsor must be notified in writing of all intended or unintended deviations to the protocol 
(eg, inclusion/exclusion criteria, dosing, missed study visits) within 24 hours and in accordance 
with the clinical study agreement between the parties. 
The investigator, or person designated by the investigator, should document and explain any 
deviation from the approved protocol. 
If a subject was ineligible or received the incorrect dose or study treatment, and had at least one 
administration of study drug, data should be collected for safety purposes. 
If applicable, the investigator should notify the IEC/IRB of deviations from the protocol in 
accordance with local procedures. 
10.1.10. 
Study and Site Closure 
The Sponsor 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: 
 Failure of the investigator to comply with the protocol, the requirements of the 
IEC/IRB or local health authorities, the Sponsor's procedures, or GCP guidelines 
 Inadequate recruitment of subjects by the investigator 
 Discontinuation of further study intervention development 
The internal DMC will determine if potential early termination of the study, based on 
pre-specified criteria noted in the DMC charter, is warranted. 
Study termination may also be requested by (a) competent authority/ies. 

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10.1.11. 
Product Complaints 
A product complaint is any dissatisfaction with a product that may be attributed to the identity, 
quality, durability, reliability, or safety of the product.  Individuals who identify a potential 
product complaint situation should immediately report the event.  Whenever possible, the 
associated product should be maintained in accordance with the label instructions pending 
further guidance from a quality representative from the Sponsor. 
For product complaints, refer to the Pharmacy Manual for instructions and details. 
10.2. 
Appendix 2: Central and/or Local Laboratory 
The clinical laboratory tests listed in Table 10.1 are to be performed in this study. 
Table 10.1: 
Clinical Laboratory Tests 
Local Laboratory Used Unless Otherwise Indicated 
Test 
Analytes 
 
Blood Chemistry 
Albumin 
Alanine aminotransferase (ALT) 
Alkaline phosphatase (ALP) 
Aspartate aminotransferase (AST) 
Bilirubin (total) 
Bilirubin (direct) 
Blood urea nitrogen (BUN) (Urea if BUN 
cannot be performed) 
Calcium (Ca) 
Chloride (Cl) 
Creatinine 
Gamma-glutamyl transaminase (GGT) 
Glucose, random 
Lactate dehydrogenase (LDH) 
Magnesium (Mg) 
Phosphorus 
Potassium (K) 
Protein (total) 
Sodium (Na) 
Uric acid 
 
Serology 
C-reactive protein (CRP) 
Immunoglobulin (Ig) G 
IgA 
IgM 
β2 microglobulin 
Hematology 
Hemoglobin 
Hematocrit 
Platelet count 
Red blood cell (RBC) count 
White blood cell (WBC) count 
Reticulocyte  
Differential WBC count: 
Basophils  
Eosinophils  
Lymphocytes  
Monocytes  
Neutrophils  
Abnormal lymphocytes [tumor cells] 
(optional for Cohort 1) 
Lipid Profile 
Cholesterol (total) 
Lipoprotein, high density (HDL) 
Lipoprotein, low density (LDL) 
Triglycerides 

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Local Laboratory Used Unless Otherwise Indicated 
Test 
Analytes 
 
Coagulation 
Prothrombin time (PT) or PT ratio 
Activated partial thromboplastin time (aPTT) or APTT ratio 
International normalized ratio (INR) 
Urinalysis  
Glucose 
Occult blood 
Protein 
Urobilinogen 
Hepatitis B and C 
Hepatitis B surface antigen 
Hepatitis B core antibody 
hepatitis B surface antibody 
(Hepatitis B virus DNA level may be performed 
if necessary) 
Hepatitis C antibody   
(Hepatitis C virus RNA testing may be 
performed if necessary) 
Central Laboratory Tests 
Markers of 
Platelet 
Production 
Markers of Platelet Production (thrombopoietin 
and immature platelet fraction) 
 
 
HTLV-1 antibody 
HTLV-1 antibody (Cohort 2 only) 
 
Cytomegalovirus 
CMV viral load by quantitative polymerase 
chain reaction (PCR) 
 
10.3. 
Appendix 3: Reference Standards 
10.3.1. 
Cockcroft-Gault Equation 
The estimated creatinine clearance (CrCl; mL/min) will be calculated using the Cockcroft-Gault 
equation based on actual weight in kilograms (1 kilogram = 2.2 pounds):67 
Conventional – serum creatinine in mg/dL 
Male: 
CrCl (mL/min) =  
Female: 
CrCl (mL/min) = 
× 0.85 
International System of Units – serum creatinine in μmol/L 
Male: 
CrCl (mL/min) =  
Female: 
CrCl (mL/min) = 
× 0.85 
[140 - age (in years)] × weight (in kg) 
serum creatinine (in mg/dL) × 72 
[140 - age (in years)] × weight (in kg) 
serum creatinine (in mg/dL) × 72 
[140 - age (in years)] × weight (in kg) 
serum creatinine (in µmol/L) × 72 × 0.0113 
[140 - age (in years)] × weight (in kg) 
serum creatinine (in µmol/L) × 72 × 0.01 

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10.3.2. 
New York Heart Association 
The NYHA classifications are summarized in Table 10.2.68  
Table 10.2: 
New York Heart Association Classifications 
Class 
Functional Capacity 
Objective Assessment 
I 
Subjects with cardiac disease but without resulting 
limitation of physical activity.  Ordinary physical activity 
does not cause undue fatigue, palpitation, dyspnea, or 
anginal pain. 
A.  No objective evidence of 
cardiovascular disease. 
II 
Subjects with cardiac disease resulting in slight limitation of 
physical activity.  They are comfortable at rest.  Ordinary 
physical activity results in fatigue, palpitation, dyspnea, or 
anginal pain. 
B.  Objective evidence of minimal 
cardiovascular disease. 
III 
Subjects with cardiac disease resulting in marked limitation 
of physical activity.  They are comfortable at rest.  Less 
than ordinary activity causes fatigue, palpitation, dyspnea, 
or anginal pain. 
C.  Objective evidence of moderately 
severe cardiovascular disease. 
IV 
Subjects with cardiac disease resulting in inability to carry 
on any physical activity without discomfort.  Symptoms of 
heart failure or anginal syndrome may be present even at 
rest.  If any physical activity is undertaken, discomfort is 
increased. 
D.  Objective evidence of severe 
cardiovascular disease. 
Source: American Heart Association. Classification of Functional Capacity and Objective Assessment, Ninth edition 
14 Mar 1994. 
http://my.americanheart.org/professional/StatementsGuidelines/ByPublicationDate/PreviousYears/Classification-of- 
Functional-Capacity-and-Objective-Assessment_UCM_423811_Article.jsp 
10.3.3. 
Eastern Cooperative Oncology Group Performance Status 
The ECOG PS scale scores are summarized in Table 10.3.69 
Table 10.3: 
Eastern Cooperative Oncology Group Performance Status 
Score 
Performance Status 
0 
Fully active, able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or 
sedentary nature (eg, light housework, office work). 
2 
Ambulatory and capable of all self-care, but unable to carry out any work activities.  Up and about 
more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or chair. 
5 
Dead. 
Source: Oken MM, Creech RH, Tormey DC, et al. Toxicity and Response Criteria of the Eastern Cooperative 
Oncology Group. Am J Clin Oncol. 1982;5:649-55 

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10.3.4. 
Karnofsky Performance Status Scale Definitions Rating (%) Criteria 
The Karnofsky PS scale scores are summarized below.70 
 
Rating  Description  
Able to carry on normal activity and to work; no 
special care needed. 
100 
Normal; no complaints; no evidence of 
disease. 
90 
Able to carry on normal activity; minor 
signs or symptoms of disease. 
80 
Normal activity with effort; some signs 
or symptoms of disease.  
Unable to work; able to live at home and care for 
most personal needs; varying amount of assistance 
needed. 
70 
Cares for self; unable to carry on 
normal activity or to do active work. 
60 
Requires occasional assistance but is 
able to care for most of his personal 
needs. 
50 
Requires considerable assistance and 
frequent medical care.  
Unable to care for self; requires equivalent of 
institutional or hospital care; disease may be 
progressing rapidly. 
40 
Disabled; requires special care and 
assistance. 
30 
Severely disabled; hospital admission 
is indicated although death not 
imminent. 
20 
Very sick; hospital admission 
necessary; active supportive treatment 
necessary. 
10 
Moribund; fatal processes progressing 
rapidly. 
0 
Dead 
Source: Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: reliability, validity, and 
guidelines. J Clin Oncol. 1984 Mar;2(3):187-93 
10.3.5. 
CYP3A/P-gp Inhibitors and Inducers 
Please note that the following list (Table 10.4) of CYP3A inhibitors/inducers and P-gp inhibitors 
is not all inclusive.71 

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Table 10.4: 
CYP3A/P-gp Inhibitors and CYP3A Inducers 
CYP3A/P-gp Inhibitors 
CYP3A Inducersa 
Drugs having a strong CYP3A inhibitory effect and a 
P-gp inhibitory effect 
Clarithromycin 
Itraconazole 
Ritonavir 
Lopinavir and ritonavir 
Saquinavir and ritonavir 
Telaprevir 
Tipranavir and ritonavir 
 
Strong CYP3A inhibitors 
Boceprevir 
Cobicistat 
Danoprevir and ritonavir 
Elvitegravir and ritonavir 
Grapefruit juice 
Idelalisib 
Indinavir and ritonavir 
Ketoconazole 
Nefazodone 
Nelfinavir 
Paritaprevir and ritonavir and (ombitasvir and/or 
dasabuvir) 
Posaconazole 
Troleandomycin 
Voriconazole 
Mibefradil 
Telithromycin 
 
Moderate CYP3A inhibitors 
Aprepitant 
Ciprofloxacin 
Crizotinib 
Cyclosporine 
Conivaptan 
Diltiazem 
Dronedarone 
Erythromycin 
Fluconazole 
Fluvoxamine 
Imatinib 
Isavuconazole  
Tofisopam 
Verapamil 
 
Strong CYP3A inducers 
Apalutamide 
Carbamazepine 
Enzalutamide 
Mitotane 
Phenytoin 
Rifampicin 
St. John’s wort 
Avasimibe 
Rifapentine 
 
Moderate CYP3A inducers 
Bosentan 
Efavirenz 
Etravirine 
Phenobarbital 
Primidone  
Rifabutin  
 
Weak CYP3A inducers 
Armodafinil 
Rufinamide 
Modafinil 

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CYP3A/P-gp Inhibitors 
CYP3A Inducersa 
Weak CYP3A Inhibitors 
Chlorzoxazone 
Cilostazol 
Cimetidine 
Clotrimazole 
Fosaprepitant 
Istradefylline 
Ivacaftor 
Lomitapide 
Ranitidine 
Ranolazine 
Ticagrelor 
 
P-gp inhibitors (no strong CYP3A inhibition) 
Amiodarone 
Carvedilol 
Dronedarone 
Lapatinib 
Propafenone 
Quinidine 
Ranolazine 
Verapamil 
 
Topical medicine is excluded. 
CYP3A = cytochrome P450 3A; P-gp = P-glycoprotein 
a If currently used, these medications need to be discontinued at least 14 days prior to valemetostat tosylate 
administration (substitution by alternative medications should be considered). 
Sources:  
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm0
93664.htm#table2-2,table3-3,table5-2 
https://www.druginteractionsolutions.org 
10.3.6. 
Highly Effective Contraception 
Methods considered to be highly effective contraception include the following:72 
 Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation: 
 Oral 
 Intravaginal 
 Transdermal 
 Progestogen-only hormonal contraception associated with inhibition of ovulation: 
 Oral 
 Injectable 
 Implantable 
 Intrauterine device 
 Intrauterine hormone-releasing system 

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 Bilateral tubal occlusion 
 Vasectomized partner 
 Complete sexual abstinence 
 Note: 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 study treatments.  The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the clinical study and the preferred and 
usual lifestyle of the subject. 
Periodic abstinence (calendar, symptothermal, post-ovulation methods), 
withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea 
method (LAM) are not acceptable methods of contraception and therefore must 
not be used in this clinical study. 
10.3.7. 
ATL Subtypes 
Criteria for ATL subtypes are provided in Table 10.5. 
Table 10.5: 
Diagnostic Criteria for Clinical Subtype of ATL73 
 
Smoldering 
Chronic 
Lymphoma 
Acute 
Anti-HTLV-1 antibody 
+ 
+ 
+ 
+ 
Lymphocyte ( × 10 y/L) 
<4 
≥4a 
<4 
* 
Abnormal T-lymphocytes 
≥5% 
+b 
≤1% 
+b 
Flower cells of T-cell marker 
Occasionally 
Occasionally 
No 
+ 
LDH 
≤1.5 N 
≤2 N 
* 
* 
Corrected Ca (mmol/L) 
<2.74 
<2.74 
* 
* 
Histology-proven lymphadenopathy 
No 
* 
+ 
* 
Tumor lesion 
 
 
 
 
Skin 
** 
* 
* 
* 
Lung 
** 
* 
* 
* 
Lymph node 
No 
* 
Yes 
* 
Liver 
No 
* 
* 
* 
Spleen 
No 
* 
* 
* 
CNS 
No 
No 
* 
* 
Bone 
No 
No 
* 
* 
Ascites 
No 
No 
* 
* 
Pleural effusion 
No 
No 
* 
* 
GI tract 
No 
No 
* 
* 
Ca = calcium; CNS = central nervous system; GI = gastrointestinal; LDH = lactate dehydrogenase; N = normal 
upper limit  
* No essential qualification, except for terms required for other subtype(s).  
** No essential qualification if other terms are fulfilled, but histology-proven malignant lesion is required in case 
abnormal T-lymphocytes are <5% in the peripheral blood. 
a Accompanied by T-lymphocytosis (3.5 × 10 y/L or more).  
b In case abnormal T-lymphocytes are <5% in the peripheral blood, histology-proven tumor lesion is required. 

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Eligibility criteria of clinical types for enrollment into Cohort 2 in this study are indicated 
below. 
Smoldering Type (Ineligible) 
 ≥5% or more abnormal lymphocytes of T-cell nature in the peripheral blood. 
 Normal lymphocyte level (<4 × 109/L). 
 No hypercalcemia (corrected calcium level <2.74 mmol/L). 
 Lactate dehydrogenase (LDH) value of up to 1.5 × the normal upper limit.  
 No lymphadenopathy; no involvement of the liver, spleen, CNS, bone and 
gastrointestinal tract; and neither ascites nor pleural effusion.  Skin and pulmonary 
lesion(s) may be present.  
 In case of <5% abnormal T-lymphocytes in the peripheral blood, at least 1 of the 
histologically-proven skin and pulmonary lesions should be present. 
Chronic Type (Ineligible Other Than Unfavorable) 
 Absolute lymphocytosis (≥4 × 109/L) with T-lymphocytosis >3.5 × 109/L. 
 LDH value up to twice the normal upper limit. 
 No hypercalcemia. 
 No involvement of CNS, bone and gastrointestinal tract, and neither ascites nor 
pleural effusion.  Lymphadenopathy and involvement of the liver, spleen, skin, and 
lung may be present. 
 In case of <5% abnormal T-lymphocytes in the peripheral blood, at least 1 of the 
histologically-proven tumor lesions should be present. 
a. Favorable (ineligible) 
 Absence of any 3 unfavorable prognostic factors 
b. Unfavorable (eligible) 
Presence of at least 1 of the 3 unfavorable prognostic factors:   
 Serum blood urea nitrogen level > normal upper limit 
 Serum LDH level > normal upper limit 
 Serum albumin levels < normal lower limit 
Lymphoma Type (Eligible) 
 No lymphocytosis (<4 × 109/L), 1% or less abnormal T-lymphocytes, and 
histologically proven lymphadenopathy with or without extranodal lesions.  
Acute Type (Eligible) 
 Remaining ATL subjects who have usually leukemic manifestation and tumor 
lesions, but are not classified as any of the 3 other types.65  

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10.3.8. 
Prespecified Stopping Boundaries 
Table 10.6: 
Cohort 1: Probability of Grade 4 (hematologic or non-hematologic toxicity) = 
30% (Sample Size = 128 & Desired probability of early stopping = 0.05) 
No. of 
subject 
enrolled 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
Stopping 
boundary 
- 
- 
- 
- 
5 
6 
6 
7 
7 
8 
8 
9 
9 
10 
10 
10 
No. of 
subject 
enrolled 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
Stopping 
boundary 
11 
11 
12 
12 
13 
13 
13 
14 
14 
15 
15 
15 
16 
16 
17 
17 
No. of 
subject 
enrolled 
33 
34 
35 
36 
37 
38 
39 
40 
41 
42 
43 
44 
45 
46 
47 
48 
Stopping 
boundary 
17 
18 
18 
19 
19 
19 
20 
20 
21 
21 
21 
22 
22 
23 
23 
23 
No. of 
subject 
enrolled 
49 
50 
51 
52 
53 
54 
55 
56 
57 
58 
59 
60 
61 
62 
63 
64 
Stopping 
boundary 
24 
24 
24 
25 
25 
26 
26 
26 
27 
27 
27 
28 
28 
29 
29 
29 
No. of 
subject 
enrolled 
65 
66 
67 
68 
69 
70 
71 
72 
73 
74 
75 
76 
77 
78 
79 
80 
Stopping 
boundary 
30 
30 
30 
31 
31 
31 
32 
32 
33 
33 
33 
34 
34 
34 
35 
35 
No. of 
subject 
enrolled 
81 
82 
83 
84 
85 
86 
87 
88 
89 
90 
91 
92 
93 
94 
95 
96 
Stopping 
boundary 
35 
36 
36 
37 
37 
37 
38 
38 
38 
39 
39 
39 
40 
40 
41 
41 
No. of 
subject 
enrolled 
97 
98 
99 
100 
101 
102 
103 
104 
105 
106 
107 
108 
109 
110 
111 
112 
Stopping 
boundary 
41 
42 
42 
42 
43 
43 
43 
44 
44 
44 
45 
45 
45 
46 
46 
47 
No. of 
subject 
enrolled 
113 
114 
115 
116 
117 
118 
119 
120 
121 
122 
123 
124 
125 
126 
127 
128 
Stopping 
boundary 
47 
47 
48 
48 
48 
49 
49 
49 
50 
50 
50 
51 
51 
51 
52 
52 
 

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Table 10.7: 
Cohort 1: Probability of AE of Special Interest (thrombocytopenia, Grade 
≥3) = 35% (Sample Size = 128 & Desired probability of early stopping = 0.05) 
No. of 
subject 
enrolled 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
Stopping 
boundary 
- 
- 
- 
- 
5 
6 
7 
7 
8 
8 
9 
9 
10 
10 
11 
11 
No. of 
subject 
enrolled 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
Stopping 
boundary 
12 
12 
13 
13 
14 
14 
15 
15 
16 
16 
17 
17 
17 
18 
18 
19 
No. of 
subject 
enrolled 
33 
34 
35 
36 
37 
38 
39 
40 
41 
42 
43 
44 
45 
46 
47 
48 
Stopping 
boundary 
19 
20 
20 
21 
21 
22 
22 
22 
23 
23 
24 
24 
25 
25 
25 
26 
No. of 
subject 
enrolled 
49 
50 
51 
52 
53 
54 
55 
56 
57 
58 
59 
60 
61 
62 
63 
64 
Stopping 
boundary 
26 
27 
27 
28 
28 
28 
29 
29 
30 
30 
31 
31 
31 
32 
32 
33 
No. of 
subject 
enrolled 
65 
66 
67 
68 
69 
70 
71 
72 
73 
74 
75 
76 
77 
78 
79 
80 
Stopping 
boundary 
33 
34 
34 
34 
35 
35 
36 
36 
36 
37 
37 
38 
38 
39 
39 
39 
No. of 
subject 
enrolled 
81 
82 
83 
84 
85 
86 
87 
88 
89 
90 
91 
92 
93 
94 
95 
96 
Stopping 
boundary 
40 
40 
41 
41 
41 
42 
42 
43 
43 
44 
44 
44 
45 
45 
46 
46 
No. of 
subject 
enrolled 
97 
98 
99 
100 
101 
102 
103 
104 
105 
106 
107 
108 
109 
110 
111 
112 
Stopping 
boundary 
46 
47 
47 
48 
48 
48 
49 
49 
50 
50 
50 
51 
51 
52 
52 
52 
No. of 
subject 
enrolled 
113 
114 
115 
116 
117 
118 
119 
120 
121 
122 
123 
124 
125 
126 
127 
128 
Stopping 
boundary 
53 
53 
54 
54 
54 
55 
55 
56 
56 
57 
57 
57 
58 
58 
59 
59 
 

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Table 10.8: 
Cohort 1: Probability of Grade 5 (hematologic or nonhematologic toxicity) = 
5% (Sample Size = 128 & Desired probability of early stopping = 0.05) 
No. of 
subject 
enrolled 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
Stopping 
boundary 
- 
2 
2 
3 
3 
3 
3 
3 
3 
4 
4 
4 
4 
4 
4 
4 
No. of 
subject 
enrolled 
17 
18 
19 
20 
21 
22 
23 
24 
25 
26 
27 
28 
29 
30 
31 
32 
Stopping 
boundary 
4 
4 
5 
5 
5 
5 
5 
5 
5 
5 
5 
6 
6 
6 
6 
6 
No. of 
subject 
enrolled 
33 
34 
35 
36 
37 
38 
39 
40 
41 
42 
43 
44 
45 
46 
47 
48 
Stopping 
boundary 
6 
6 
6 
6 
6 
6 
7 
7 
7 
7 
7 
7 
7 
7 
7 
7 
No. of 
subject 
enrolled 
49 
50 
51 
52 
53 
54 
55 
56 
57 
58 
59 
60 
61 
62 
63 
64 
Stopping 
boundary 
7 
8 
8 
8 
8 
8 
8 
8 
8 
8 
8 
8 
8 
9 
9 
9 
No. of 
subject 
enrolled 
65 
66 
67 
68 
69 
70 
71 
72 
73 
74 
75 
76 
77 
78 
79 
80 
Stopping 
boundary 
9 
9 
9 
9 
9 
9 
9 
9 
9 
9 
10 
10 
10 
10 
10 
10 
No. of 
subject 
enrolled 
81 
82 
83 
84 
85 
86 
87 
88 
89 
90 
91 
92 
93 
94 
95 
96 
Stopping 
boundary 
10 
10 
10 
10 
10 
10 
11 
11 
11 
11 
11 
11 
11 
11 
11 
11 
No. of 
subject 
enrolled 
97 
98 
99 
100 
101 
102 
103 
104 
105 
106 
107 
108 
109 
110 
111 
112 
Stopping 
boundary 
11 
11 
11 
11 
12 
12 
12 
12 
12 
12 
12 
12 
12 
12 
12 
12 
No. of 
subject 
enrolled 
113 
114 
115 
116 
117 
118 
119 
120 
121 
122 
123 
124 
125 
126 
127 
128 
Stopping 
boundary 
12 
13 
13 
13 
13 
13 
13 
13 
13 
13 
13 
13 
13 
13 
13 
14 
 

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Table 10.9: 
Cohort 2: Probability of Grade 4 = 30% (hematologic or non-hematologic 
toxicity) (sample size = 20 and desired probability of early stopping = 0.05) 
No. of Subjects Enrolled 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Stopping boundary 
- 
- 
- 
4 
5 
5 
6 
6 
7 
7 
No. of subject enrolled 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
Stopping boundary 
7 
8 
8 
9 
9 
10 
10 
10 
11 
11 
Table 10.10: Cohort 2: Probability of AE of Special Interest (thrombocytopenia, Grade 
≥3) = 35% (sample size = 20 and desired probability of early stopping = 0.05) 
No. of Subjects 
Enrolled 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Stopping boundary 
- 
- 
- 
4 
5 
6 
6 
7 
7 
8 
No. of subject enrolled 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
Stopping boundary 
8 
9 
9 
10 
10 
11 
11 
11 
12 
12 
Table 10.11: 
Cohort 2: Probability of Grade 5 (hematologic or non-hematologic toxicity) 
= 5% (sample size = 20 and desired probability of early stopping = 0.05) 
No. of Subjects Enrolled 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Stopping boundary 
- 
2 
2 
2 
2 
3 
3 
3 
3 
3 
No. of subject enrolled 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
Stopping boundary 
3 
3 
3 
3 
4 
4 
4 
4 
4 
4 
The method generates a Pocock-type boundary for repeated testing for toxicity.74 
10.3.9. 
GVHD Grading and Staging 
Table 10.12: Acute GVHD Grading and Staging 
Stage 
Skin 
Liver 
Gut 
1 
Rash on <25% of skina 
Bilirubin 
2-3 mg/dLb 
Diarrhea >500 mL/dayc or persistent nausead 
Pediatric: 280-555 mL/m2/day or 
10-19.9 mL/kg/day 
2 
Rash on 25-50% of skin 
Bilirubin 
3-6 mg/dL 
Diarrhea >1000 mL/day 
Pediatric: 556-833 ml/m2/day or 
20-30 mL/kg/day 
3 
Rash on >50% of skin 
Bilirubin 
6-15 mg/dL 
Diarrhea >1500 mL/day 
Pediatric: >833 mL/m2/day or >30 mL/kg/day 
4 
Generalized erythroderma with 
bullous formation 
Bilirubin 
>15 mg/dL 
Severe abdominal pain, with or without ileus, 
and/or grossly bloody stool 

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Stage 
Skin 
Liver 
Gut 
Gradee 
I 
Stage 1-2 
None 
None 
II 
Stage 3 
Stage 1 
Stage 1 
III 
— 
Stage 2-3 
Stages 2-4 
IVf 
Stage 4 
Stage 4 
— 
GVHD = graft-versus-host disease 
a Use “Rule of Nines” (see Table 10.13 below) or burn chart to determine extent of rash. 
b Range given as total bilirubin. Downgrade one stage if an additional cause of elevated bilirubin has been documented. 
c Volume of diarrhea applies to adults. For pediatric patients, the volume of diarrhea should be based on body surface area. 
Downgrade one stage if an additional cause of diarrhea has been documented. 
d Persistent nausea with or without histologic evidence of GVHD in the stomach or duodenum. 
e Criteria for grading given as minimum degree of organ involvement required to confer that grade. 
f Grade IV may also include lesser organ involvement with an extreme decrease in performance status. 
 
Table 10.13: Percent Body Surfaces 
Body Area 
Percentage 
Total Percentage 
Each Arm 
9% 
18% 
Each Leg 
18% 
36% 
Chest & Abdomen 
18% 
18% 
Back 
18% 
18% 
Head 
9% 
9% 
Pubis 
1% 
1% 
 
Table 10.14: Organ Scoring of Chronic GVHD 
Organ 
Score 0 
Score 1 
Score 2 
Score 3 
Skin % BSAa 
No BSA involved 
1%-18% BSA 
19%-50% BSA 
>50% BSA 
Skin Features 
No sclerotic 
features 
N/A 
Superficial sclerotic 
features but not 
“hidebound” 
Deep sclerotic features; 
“hidebound;” impaired 
mobility; ulceration 
Mouth 
No symptoms 
Mild symptoms with 
disease signs but not 
limiting oral intake 
significantly 
Moderate symptoms 
with disease signs 
with partial limitation 
of oral intake 
Severe symptoms with 
disease signs with major 
limitation of oral intake 
Eyes 
No symptoms 
Mild dry eye 
symptoms not 
affecting ADL 
(requirement of 
lubricant drops 
≤3×/day) 
Moderate dry eye 
symptoms partially 
affecting ADL 
(requiring lubricant 
drops >3×/day or 
punctal plugs) 
WITHOUT new 
vision impairment 
due to 
Severe dry eye symptoms 
significantly affecting 
ADL (special eyewear to 
relieve pain) OR unable 
to work because of ocular 
symptoms OR loss of 
vision due to KCS 

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Organ 
Score 0 
Score 1 
Score 2 
Score 3 
keratoconjunctivitis 
sicca (KCS) 
GI Tract 
No symptoms 
Symptoms without 
significant weight 
loss (<5%) 
Symptoms associated 
with mild to moderate 
weight loss (5-15%) 
within 3 months OR 
moderate diarrhea 
without significant 
interference with 
daily living 
Symptoms associated 
with significant weight 
loss (>15%) within 
3 months, requires 
nutritional supplement for 
most calorie needs OR 
esophageal dilation OR 
severe diarrhea with 
significant interference 
with daily living 
Liver 
Normal total 
bilirubin and ALT 
or AP <3 × ULN 
Normal total 
bilirubin with ALT 
≥3 to 5 × ULN or AP 
≥3 × ULN 
Elevated total 
bilirubin but 
≤3 mg/dL or ALT 
>5 × ULN 
Elevated total bilirubin 
>3 mg/dL 
Lungs 
Symptom 
Score: 
No symptoms 
Mild symptoms 
(SOB after climbing 
one flight of steps) 
Moderate symptoms 
(SOB after walking 
on flat ground) 
Severe symptoms (SOB at 
rests; requires O2) 
Lungs Lung 
Score: 
FEV1 ≥80% 
FEV1 60-79% 
FEV1 40-59% 
FEV1 ≤39% 
Joints and 
Fascia 
No symptoms 
Mild tightness of 
arms or legs, normal 
or mild decreased 
range of motion 
AND not affecting 
ADL 
Tightness of arms or 
legs OR joint 
contractures, 
erythema thought to 
be due to fasciitis, 
moderate decrease of 
range of motion AND 
mild to moderate 
limitation of ADL 
Contractures WITH 
significant decrease of 
range of motion AND 
significant limitation of 
ADL (unable to tie shoes, 
button shirts, dress self, 
etc) 
Genital Tractb 
No signs 
Mild signs and 
females with or 
without discomfort 
on exam 
Moderate signs and 
may have signs of 
discomfort on exam 
Severe signs with or 
without symptoms 
Other 
Featuresc 
No GVHD 
Mild 
Moderate 
Severe 
ADL = activities of daily living; ALT = alanine aminotransferase; AP = alkaline phosphatase; BSA = body surface 
area; FEV1 = forced expiratory volume in the first second; GVHD = graft versus host disease; N/A = not applicable; 
O2 = oxygen;  SOB = shortness of breath; ULN = upper limit of normal 
a Features to be scored by BSA: Maculopapular rash, lichen planus-like features, sclerotic features, papulosquamous 
lesions or ichthyosis, keratosis pilaris-like GVHD. 
b Scoring is based on severity of the signs instead of symptoms, based on limited available data and the opinions of 
experts. Female or male genital GVHD is not scored if a practitioner is unable to examine the patient. 
c May include ascites, pericardial effusion, pleural effusion(s), nephrotic syndrome, myasthenia gravis, peripheral 
neuropathy, polymyositis, weight loss without GI symptoms, eosinophilia >500/μL, platelets <100,000/μL, others. 
Source: NIH Consensus Criteria, 201475 

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10.4. 
Appendix 4: Response Criteria 
10.4.1. 
Target Lesions 
Definition of Target Lesions 
Selection of Target Nodal and Extranodal Lesions (up to 6 in total) for Cohort 1 (PTCL) and 
Cohort 2 (ATL) 
Definition of target lesions is provided in Table 10.15 for Cohort 1 (PTCL) and Cohort 2 (ATL), 
and additional lesions/disease for response assessment is provided in Table 10.16 for 
Cohort 2 (ATL). 
Up to 6 of the largest target nodal lesions that are measurable in 2 diameters (longest diameter 
[LDi] and shortest diameter [SDi]) should be identified from different body regions 
representative of the subject’s overall disease burden and include mediastinal and retroperitoneal 
disease, if involved.  Extranodal disease (eg, hepatic nodules) may be included in the 
6 representative, measured lesions.  
All other lesions (including nodal and extranodal lesions that were not selected as target lesions) 
should be followed as non-target lesions (eg, GI, bone, spleen, liver, kidneys, pleural or 
pericardial effusions, and ascites).  Splenomegaly, hepatomegaly, and bone marrow involvement 
are not considered as target lesions.  Tumor lesions situated in a previously irradiated area are 
not considered target lesions unless there is an apparent exacerbation of the lesion after 
radiotherapy. 
Table 10.15: Definition of Target Lesions (Cohorts 1 and 2: PTCL and ATL) 
Lesion 
Definition of Target Lesions Based on Cross-Sectional CT (or MRI) Scan 
Nodal Lesions 
Meeting all of the following conditions:  
 
Enlarged lymph nodes (nodal lesions)  
 
Measurable in 2 perpendicular dimensions  
 
LDi >1.5 cm (15 mm) 
Extranodal Lesions 
Meeting all of the following conditions:  
 
Nodular lesions in extranodal organs  
 
Measurable in 2 perpendicular dimensions  
 
LDi >1.0 cm (10 mm) 
CT = computed tomography; LDi = longest diameter; MRI = magnetic resonance imaging 
Table 10.16: Additional Lesions/Disease for Response Assessment (Cohort 2: ATL) 
Lesion 
Definition  
Skin Lesions 
Cutaneous lesion(s) confirmed by visual inspection.   
If it is difficult to determine whether it is an ATL lesion or not by visual inspection, a 
biopsy should be performed to make a histopathological diagnosis. 
Disease in 
Peripheral Blood 
 
Abnormal lymphocyte count (actual number) is ≥1 × 109/L (1000/μL) and  
 
The abnormal lymphocyte-to-leukocyte ratio is ≥5% 
ATL = adult T-cell leukemia/lymphoma 

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10.4.3. 
Modified 2009 ATL Criteria: Cohort 2 
Modified ATL criteria are provided in Table 10.18.  The modification was made such that there 
is no requirement for each criterion to be present for a period of at least 4 weeks. 

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Table 10.18: Modified 2009 ATL Criteria 
Antitumor 
Response 
Definition 
Target Lesion 
Non-target Lesion 
Spleen, 
Liver 
Skine 
Peripheral 
Blood 
Bone 
Marrow 
Lymph 
Node 
Extranodal 
Lesion 
Lymph Node 
Extranodal Lesion 
CR 
Disappearance of 
disease 
Normal 
Disappearance 
Normal 
Disappearance 
Normal 
Normal 
Normala 
Normal 
CRu 
Stable residual mass 
in bulky lesion 
≥75% decreaseb 
Normal 
Disappearance 
Normal 
Normal 
Normala 
Normal 
PR 
Regression of disease 
≥50% decreaseb 
Normal or no 
increase 
Disappearance or 
no increase 
No 
increase 
≥50% 
decrease 
≥50% 
decrease 
Irrelevant 
SD 
Failure to attain 
complete/ 
partial remission and 
no progressive disease 
No change in size 
Not qualifying as 
CR, PR, or PD 
Not qualifying as 
CR, PR, or PD 
No change 
in size 
No change 
in size 
No change 
No change 
RD/PD 
New or increased 
lesions 
New or ≥50% increasec 
Increase or re-
enlargement 
Increase or re-
appearance 
≥50% 
increasef 
≥50% 
increase 
New or ≥50% 
increased 
New or re-
appearance 
NA 
― 
― 
― 
― 
― 
― 
― 
― 
― 
CR = complete response; CRu = uncertified complete response; mSWAT = modified severity-weighted assessment tool; NA = not applicable; PD = progressive disease; 
PR = partial response; RD = relapsed disease; SD = stable disease 
a Provided that <5% of flower cells remains, complete remission is judged to have been attained if the absolute lymphocyte count, including flower cells, is <4 × 109/L. 
b Calculated by the sum of the products of the greatest diameters of target lesions. 
c Defined by ≥50% increase from nadir in the sum of the products of target lesions. 
d Defined by ≥50% increase from nadir in the count of flower cells and an absolute lymphocyte count, including flower cells, of >4 × 109/L. 
e Calculated by the mSWAT score for skin lesions. 
f In the setting of splenomegaly, the splenic length must increase by >50% of the extent of its prior increase beyond baseline or nadir, whichever was smaller (eg, a 15-cm spleen 
must increase to >16 cm).  If no prior splenomegaly, the splenic length must increase by at least 2 cm from baseline. 
Source:  Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on 
Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014 Sep 20;32(27):3048-58. doi: 10.1200/JCO.2013.53.5229. Erratum in: J Clin Oncol. 2016 Jul 20;34(21):2562. 
PMID: 25113771; PMCID: PMC5015423. 

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10.4.4. 
mSWAT Score Calculation: Cohort 2 
The total body surface area (TBSA) of humans is regarded as 100, and a sum of the percentage 
of body surface area (%BSA) of each site is defined in Table 10.19 and Figure 10.1 (eg, head: 7, 
neck: 2, and anterior trunk: 13).3,4  By site, lesion type (patch [flat erythema], plaque [elevated 
area], tumor [dome-shaped nodular lesion with >10-mm elevation], or ulcer [lesion with 
significant loss of superficial skin, including loss of the entire epidermis or some portion of the 
upper dermis]), and %BSA of normal skin will be assessed; the percentage total body surface 
area (%TBSA) will then be calculated by summing the %BSA of each site by lesion type.  
Furthermore, mSWAT score will be derived by multiplying the %TBSA by weighting factor, 
and all individual numbers will then be added to produce a total score (0 to 400). 
mSWAT score = (patch %TBSA × 1) + (plaque %TBSA × 2) + (tumor and ulcer %TBSA × 4) 
Table 10.19: Table for Calculation of Body Surface Area 
Body Lesion 
%BSA 
Patch 
%BSA 
Plaque 
Tumor or Ulcer 
%BSA 
Normal 
%BSA 
Total %BSA 
of Each Lesion 
Head 
 
 
 
 
7 
Neck 
 
 
 
 
2 
Anterior trunk 
 
 
 
 
13 
Posterior trunk 
 
 
 
 
13 
Buttocks 
 
 
 
 
5 
Groin 
 
 
 
 
1 
Arms 
 
 
 
 
8 
Forearms 
 
 
 
 
6 
Hands 
 
 
 
 
5 
Thighs 
 
 
 
 
19 
Legs 
 
 
 
 
14 
Feet 
 
 
 
 
7 
%TBSA of 
each lesion 
 
 
 
 
100 
BSA = body surface area; TBSA = total body surface area 

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Figure 10.1: Regional Percent Body Surface Area 
 
10.4.5. 
5-Point Scale: Cohort 1 and Cohort 2 
The most intense uptake in a site of initial disease: 
1. 
No uptake 
2. 
Uptake ≤ mediastinum 
3. 
Uptake > mediastinum but ≤ liver 
4. 
Uptake moderately higher than liver 
5. 
Uptake markedly higher than liver and/or new lesions 
6. 
X. New areas of uptake unlikely to be related to lymphoma 
10.5. 
Appendix 6: General Information - Adverse Events 
10.5.1. 
Definition of Adverse Event 
An AE is any untoward medical occurrence in a subject administered a pharmaceutical product 
and that does not necessarily have to have a causal relationship with this treatment.  An AE can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for 
example), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product.  

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It is the responsibility of investigators, based on their knowledge and experience, to determine 
those circumstances or abnormal laboratory findings which should be considered AEs. 
Events Meeting the AE Definition 
 Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, and vital signs measurements), 
including those that worsen from baseline, considered clinically relevant in the 
medical and scientific judgment of the investigator (ie, 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 intervention administration even 
though it may have been present before the start of the study. 
 Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent.  Such overdoses should be reported regardless of sequelae. 
Events NOT Meeting the AE Definition 
 Any clinically relevant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the subject’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 subject’s 
condition. 
 Medical or surgical procedure (eg, 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). 
 “Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an AE or SAE.  Such instances will be captured in the efficacy 
assessments.  However, the signs, symptoms, and/or clinical sequelae resulting from 
lack of efficacy will be reported as an AE or SAE if they fulfill the definition of an 
AE or SAE. 
 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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10.5.2. 
Serious Adverse Event 
A serious adverse event is 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 subject 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 
 In general, hospitalization signifies that the subject 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. 
 Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline or for administration of anticancer therapy after 
discontinuation of study drug is not considered an AE. 
 Results in persistent or significant disability/incapacity 
 The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
 This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
 Is a congenital anomaly/birth defect 
 Is an important medical event 
 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 subject 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. 
 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. 

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10.5.3. 
Grade Assessment 
The severity of AEs will be graded using the latest NCI-CTCAE (version 5.0).  For each episode, 
the highest severity grade attained should be reported. 
The NCI-CTCAE guidelines do not allow certain grades for certain AEs.  For example, pain can 
be Grade 1 to 3 only (ie, cannot be life-threatening or fatal), whereas sepsis can only be Grade 4 
or 5 (ie, can only be life-threatening or fatal).  In addition, alopecia can only be Grade 1 or 2.  
The NCI-CTCAE guidelines should be followed closely. 
 Grade 1: Mild AE 
 Grade 2: Moderate AE 
 Grade 3: Severe AE 
 Grade 4: Life-threatening consequences; urgent intervention indicated 
 Grade 5: Death related to AE 
Difference between Severity and Seriousness 
The term “severe” is often used to describe the intensity (severity) of a specific event (as in mild, 
moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor 
medical significance (such as severe headache).  This is not the same as “serious,” which is 
based on subject/event outcome or action criteria usually associated with events that pose a threat 
to a subject's life or functioning.  Seriousness (not severity) serves as a guide for defining 
regulatory reporting obligations. 
10.5.4. 
Causality Assessment 
The investigator should assess causal relationship between an adverse event and the study drug 
based on his/her clinical judgment and the following definitions.  The causality assessment must 
be made based on the available information and can be updated as new information becomes 
available. 
 Related: 
 The AE follows a reasonable temporal sequence from study drug administration 
and cannot be reasonably explained by the subject’s clinical state or other factors 
(eg, disease under study, concurrent diseases, and concomitant medications). 
or 
 The AE follows a reasonable temporal sequence from study drug administration 
and is a known reaction to the drug under study (or its chemical group) or is 
predicted by known pharmacology. 
 Not Related: 
 The AE does not follow a reasonable sequence from study drug administration or 
can be reasonably explained by the subject’s clinical state or other factors 
(eg, disease under study, concurrent diseases, and concomitant medications). 

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10.5.5. 
Action Taken Regarding Study Drug(s) 
 Dose Not Changed: No change in study drug dosage was made. 
 Drug Withdrawn: The study drug was permanently stopped. 
 Dose Reduced: The dosage of study drug was reduced. 
 Drug Interrupted: The study drug was temporarily stopped. 
 Not Applicable: Subject died, study drug completed/permanently discontinued prior 
to reaction/event, or reaction/event occurred prior to the first dose. 
 Unknown: Subject is lost to follow-up. 
10.5.6. 
Other Action Taken for Event 
 None. 
 No treatment was required. 
 Medication required. 
 Prescription and/or over-the-counter medication was required to treat the AE. 
 Hospitalization or prolongation of hospitalization was required. 
 Hospitalization was required or prolonged due to the AE, whether or not 
medication was required. 
 Other. 
10.5.7. 
Adverse Event Outcome 
 Recovered/Resolved 
 The subject fully recovered from the AE, with no sequelae observed. 
 Recovered/Resolved with Sequelae 
 The subject fully recovered from the AE, but with sequelae. 
 Recovering/Resolving 
 The AE is improving but not recovered. 
 Not Recovered/Not Resolved 
 The AE continues without improving. 
 Fatal 
 Fatal should be used when death is a direct outcome of the AE. 
 Unknown 
10.6. 
Appendix 7 Key Data Analysis Requirements 
Key data analysis requirements are provided in Table 10.20. 

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Table 10.20: Key Data Requirements 
Endpoint/Analysis 
Key Data Requirements (assessed both by BICR and investigators) 
ORR 
The numerator will be the number of subjects who have at least 
1 response. 
The denominator will be the number of the subjects who were dosed with 
at least 1 dose (regardless whether subjects had 1 assessment). 
Primary analysis will be performed at least 10 months after the first dose 
of the last subject in Cohort 1. 
DoR/DoCR 
The numerator will be the number of subjects who have at least 
1 response (CR/CRu only).  
The denominator will be the number of the subjects who were dosed with 
at least 1 dose (regardless of whether subjects had 1 assessment). 
Primary analysis will be performed at least 10 months after the first dose 
of the last subject in Cohort 1. 
CR/PR rate 
The numerator will be the number of subjects who have at least 1 CR/PR.  
The denominator will be the number of the subjects who were dosed with 
at least 1 dose (regardless of whether subjects had 1 assessment). 
Primary analysis will be performed at least 10 months after the first dose 
of the last subject in Cohort 1. 
ATL = adult T-cell leukemia/lymphoma; BICR = blinded independent central review; CR = complete response; 
CRu = uncertified complete remission (response); DoCR = duration of complete response; DoR = duration of 
response; ORR = objective response rate; PR = partial response 
CRu for ATL will be included into ORR or CR rate and DoR/DoCR analysis in Cohort 2. 

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11. 
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12. 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AAG 
α-1-acid glycoprotein 
AE 
adverse event 
AESI 
adverse event of special interest 
AITL 
angioimmunoblastic T-cell lymphoma 
ALCL 
anaplastic large cell lymphoma 
ALK 
anaplastic lymphoma kinase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
ATL 
adult T-cell leukemia/lymphoma 
AUC 
area under the plasma concentration-time curve 
BICR 
blinded independent central review 
BSA 
Body surface area 
CCR4 
Chemokine receptor type 4 
CFR 
code of federal regulations 
CHOP 
Cyclophosphamide, Doxorubicin, Vincristine and Prednisone 
CI 
confidence interval 
Cmax 
maximum concentration 
CMV 
cytomegalovirus 
CNS 
Central nervous system 
CR 
complete response  
CrCl 
creatinine clearance 
CRO 
contract research organization 
CRu 
uncertified complete remission (response) 
CT 
computed tomography 
CTCAE 
common terminology criteria for adverse events 
CYP 
cytochrome P450 
DIMS 
drug inventory management system 
DLT 
dose-limiting toxicity 
DMC 
data monitoring committee 
DoCR 
duration of complete response 
DoR 
duration of response 
DS-3201a 
Free form of DS-3201b 
EC 
ethics committee 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 

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Abbreviation 
Definition 
EDC 
electronic data capture 
EIU 
exposure in utero 
EOS 
End of Study 
EOT 
End of Treatment 
EU 
European Union 
EZH 
enhancer of zeste homolog 
FDA 
Food and Drug Administration 
FDG 
fluorodeoxyglucose 
GCP 
Good Clinical Practice 
GVHD 
graft-versus-host disease  
H3K27 
lysine 27 of histone H3 
HCT 
hematopoietic cell transplantation 
HIV 
human immunodeficiency virus 
HNSTD 
highest nonseverely toxic dose 
HTLV-1 
human T-cell leukemia virus type 1 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation  
ICMJE 
International Council of Medical Journal Editors 
IEC 
independent ethics committee 
IHC 
immunohistochemistry 
INN 
international non-proprietary name 
IPF 
immature platelet fraction 
IRB 
institutional review board 
LAM 
lactational amenorrhoea method 
LDH 
lactate dehydrogenase 
LDi 
longest diameter  
LTFU 
Long-term Follow-up 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
mSWAT 
modified severity weighted assessment tool  
NCI 
National Cancer Institute 
NGS 
next-generation sequencing 
NHL 
non-Hodgkin lymphoma 
NOS 
not otherwise specified  
NYHA 
New York Heart Association  
ORR 
objective response rate 
OS 
overall survival 

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Abbreviation 
Definition 
P-gp 
P-glycoprotein 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PET 
positron emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic 
PopPK 
population pharmacokinetic 
PPD 
product of the perpendicular diameter 
PR 
partial response  
PS 
performance status 
PT 
post-transplant 
PTCL 
peripheral T-cell lymphoma 
QTc 
corrected QT interval 
QTcF 
QT interval corrected with Fridericia’s formula 
RBC 
red blood cell 
R/R  
relapsed/refractory  
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SDi 
shortest diameter 
SDV 
source data verification 
SID 
subject identification 
SMT 
safety management team 
SoE 
Schedule of Events 
SUSAR 
suspected unexpected serious adverse reaction 
TBSA 
total body surface area 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
TFH 
T-follicular helper 
ULN 
upper limit of normal 
US 
United States 
 

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