Conditions: Non-Hodgkin's B-cell Lymphoma Leukemia, Lymphocytic, Chronic, B-Cell Small Lymphocytic Leukemia Diffuse Large B Cell Lymphoma Blood Cancer Hematological Malignancy
Keywords: CD20 immunotoxin NHL non-Hodgkin's lymphoma lymphoma cancer antibodies immunotherapy safety pharmacokinetics maximum tolerated dose MT-3724 relapsed refractory leukemia CLL SLL DLBCL efficacy
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 38
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the safety and tolerability of MT-3724 in subjects with relapsed or refractory B-Cell NHL or relapsed and refractory CLL (Part 1 only) and relapsed and refractory DLBCL (Part 2 and Part 3). Part 3 evaluates the efficacy of MT-3724.

Detailed description:
This is a three-part Phase 2 study

Part 1: (MT-3724 Dose Escalation) Define the maximum tolerated dose (MTD) of MT-3724 \[Completed\]

Part 2: (MTD Expansion Cohort) Confirm the safety and tolerability of the MTD of MT-3724 in the MTD Expansion Cohort.

Part 3: (Phase 2 MTD Expansion Cohort) Determine the efficacy of MT-3724 as monotherapy in subjects with relapsed or refractory DLBCL based on the overall response rate (ORR) by the revised Lugano Classification for Lymphoma adjusted according to LYRIC.

It is anticipated that up to 100 patients will be enrolled in Part 3. Treatment will continue for up to six 21 days cycles. If the subject exhibits SD, CR or PR after the end of Cycle 6 and the investigator determines that the benefit-risk ratio is favorable, then the treatment with MT-3724 may be continued after discussion with the sponsor.

Arms:
arm 1: Part 1: MT-3724 5 mcg/kg/dose IV for 6 doses over 12 days, followed by dose escalations (Part 1) until recommended phase 2 dose of MT-3724 is determined arm 2: Part 1: MT-3724 10 mcg/kg/dose IV for 6 doses over 12 days, followed by dose escalations (Part) until recommended phase 2 dose of MT-3724 is determined arm 3: Part 1: MT-3724 20 mcg/kg/dose IV for 6 doses over 12 days, followed by dose escalations (Part 1) until recommended phase 2 dose of MT-3724 is determined arm 4: Part 1: MT-3724 50 mcg/kg/dose IV for 6 doses over 12 days, followed by dose escalations (Part 1) until recommended phase 2 dose of MT-3724 is determined arm 5: Part 1: MT-3724 100 mcg/kg/dose IV for 6 doses over 12 days, followed by dose escalations (Phase 1) until recommended phase 2 dose of MT-3724 is determined arm 6: Part 1b: MT-3724 75 mcg/kg/dose IV for 6 doses over 12 days of 21-Day cycle for up to 4 additional cycles to explore safety, tolerability and tumor response to repeat doses of MT-3724 (subject will continue with dose that was tolerated in the Part 1 portion of the study) arm 7: Part 2: MT-3724 IV for 6 doses administered within 14 days of 21-Day cycle up to 6 Cycles. If the Subject exhibits stable disease or PR after end of Cycle 6 and investigator determines ratio is favorable, treatment with MT- 3724 may be continued for up to additional 6 cycles. arm 8: Part 3: MT-3724 IV 50 µg/kg/dose administered on Days 1, 3, 5, 8, 10, and 12 of each 21-day cycle. Treatment will continue until death, disease progression, unacceptable toxicity, withdrawal of consent, or another reason for withdrawal, or until study discontinuation arm 9: Part 4: In this arm, subjects were planned to receive all doses of MT-3724 as IV infusion as confirmed in Part 3.

Interventions: intervention 1: MT-3724 Phase 1 intervention 2: MT-3724 Phase 2
Intervention descriptions: intervention 1: Intravenous dosing Days 1, 3, 5, 8, 10 and 12; MT-3724 infusion over 2 hours on each dosing day over 28 day initial cycle and then 21 week repeat cycles for up to 5 total cycles. intervention 2: Intravenous dosing on Days 1, 3, 5, 8, 10 and 12; MT-3724 infusion over 1 hour on each dosing day over 21 day cycle up to 6 cycles and then can be continued for 6 additional cycles.

Protocol document:
Prot_000.pdf: 
Compound: MT-3724 
 
Protocol MT-3724_NHL_001 
Protocol Date and Version: 12 February 2021, v11.0 
 
CONFIDENTIAL 
 
Page 1 of 123 
TITLE PAGE 
Protocol Title: 
Safety, Pharmacodynamics and Efficacy of MT-3724 for the 
Treatment of Patients with Relapsed or Refractory DLBCL 
Protocol Number: 
MT-3724_NHL_001 
Compound: 
MT-3724 
Study Phase: 
1/2 
Sponsor  
Sponsor 
Name: 
Molecular Templates, Inc. 
Legal 
Registered 
Address: 
9301 Amberglen Boulevard 
Suite 100 
Austin, TX 78729 
Regulatory Agency 
Identifier Number(s) 
IND: 121918 
EudraCT: 2019-001073-86 
NCT: NCT02361346 
Protocol Version and 
Date: 
Document Version 
Date 
Original (version 1.0) 
30 JULY 2014 
Version 1.1 
18 AUGUST 2014 
Version 1.2 
05 SEPTEMBER 2014 
Version 2.0 
16 JANUARY 2015 
Version 3.0 
15 MAY 2015 
Version 4.0 
08 JULY 2015 
Version 5.0 
07 JANUARY 2016 
Version 6.0 
05 JANUARY 2017 
Version 7.0 
08 FEBRUARY 2018 
Version 7.1 
15 APRIL 2019 
Version 8.0 
15 FEBRUARY 2019 
Version 8.1 
02 APRIL 2019 
Version 8.2 
15 APRIL 2019 
Version 8.3 
24 OCTOBER 2019 
Version 8.4 
20 NOVEMBER 2019 
Version 9.0 
14 APRIL 2020 
Version 9.1 
29 JUNE 2020 
Version 10.0 
14 AUGUST 2020 
Version 11.0 
12 FEBRUARY 2021 
 
 


Compound: MT-3724 
 
Protocol MT-3724_NHL_001 
Protocol Date and Version: 12 February 2021, v11.0 
 
CONFIDENTIAL 
 
Page 2 of 123 
CONFIDENTIALITY NOTICE 
This confidential information in this document is provided to you as an investigator or consultant 
for review by you, your staff, and the applicable Institutional Review Board/Independent Ethics 
Committee. Your acceptance of this document constitutes agreement that you will not disclose 
the information contained herein to others without written authorization from the sponsor. 


Compound: MT-3724 
Protocol MT-3724_NHL_001 
Protocol Date and Version: 12 February 2021, v11.0 
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Page 3 of 123 
SPONSOR SIGNATORY 
MT-3724_NHL_001: Safety, Pharmacodynamics and Efficacy of MT-3724 for the Treatment of 
Patients with Relapsed or Refractory DLBCL 
I, the undersigned, have approved version 11.0 of the clinical trial protocol with the date of 
12 February 2021. 
Name and Title 
Signature and Date 
 MD 
Chief Medical Officer 
Molecular Templates, Inc. 
, PhD 
Senior Director, Clinical Development 
Molecular Templates, Inc. 
, MBA


Compound: MT-3724 
 
Protocol MT-3724_NHL_001 
Protocol Date and Version: 12 February 2021, v11.0 
 
CONFIDENTIAL 
 
Page 4 of 123 
INVESTIGATOR AGREEMENT 
MT-3724_NHL_001: Safety, Pharmacodynamics and Efficacy of MT-3724 for the Treatment of 
Patients with Relapsed or Refractory DLBCL 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details to conduct this study as described. I will conduct this study in compliance with all 
applicable regulations and guidelines as stated in the protocol and other information supplied to 
me. I will make a reasonable effort to complete the study within the time designated. 
I will provide all study personnel under my supervision with copies of the protocol and access to 
all information provided by Molecular Templates, Inc. I will discuss this material with them to 
ensure that they are fully informed about the drug(s) and the study.  
 
______________________________ 
 
__________________________ 
Principal Investigator Name (printed) 
 
Signature 
______________________________ 
Date 
 
 


Compound: MT-3724 
 
Protocol MT-3724_NHL_001 
Protocol Date and Version: 12 February 2021, v11.0 
 
CONFIDENTIAL 
 
Page 5 of 123 
LIST OF CONTACTS 
Function 
Contact Information 
Sponsor’s Medical Representative: 
 MD, MBA  
Chief Medical Officer 
Molecular Templates, Inc. 
Phone:
External Medical Monitor: 
Managed by CRO. Refer to the team contact list 
for the most up-to-date contact details. 
Pharmacovigilance and SAE Reporting: 
Managed by CRO. Refer to the team contact list 
for the most up-to-date contact details. 
Clinical Operations: 
, PharmD 
Director, Clinical Operations 
Molecular Templates, Inc. 
Phone: 
 
, CCRA 
Senior Clinical Trial Manager 
Molecular Templates, Inc. 
Phone: 
 
 
 
 


Compound: MT-3724 
 
Protocol MT-3724_NHL_001 
Protocol Date and Version: 12 February 2021, v11.0 
 
CONFIDENTIAL 
 
Page 6 of 123 
TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
SPONSOR SIGNATORY ...............................................................................................................3 
INVESTIGATOR AGREEMENT...................................................................................................4 
LIST OF CONTACTS .....................................................................................................................5 
TABLE OF CONTENTS .................................................................................................................6 
LIST OF TABLES .........................................................................................................................11 
1 
PROTOCOL SUMMARY ......................................................................................................12 
1.1 
Synopsis .............................................................................................................................12 
1.2 
Study Schema.....................................................................................................................23 
1.3 
Schedule of Activities (SoA) .............................................................................................24 
2 
INTRODUCTION ..................................................................................................................30 
2.1 
Background ........................................................................................................................30 
2.1.1 
Advanced Stage Cancer Patient Population .................................................................30 
2.1.2 
Epidemiology, Classification, and Treatment Standards .............................................30 
2.1.3 
Anti-CD20 mAb Therapy for Non-Hodgkin Lymphoma ............................................31 
2.2 
Molecular Templates Investigational Product Background: MT-3724 .............................32 
2.2.1 
Summary of Clinical Experience .................................................................................32 
2.2.2 
Guidance to the Investigator for Capillary Leak Syndrome ........................................33 
3 
OBJECTIVES AND ENDPOINTS ........................................................................................33 
3.1 
Part 3 Objectives and Endpoints ........................................................................................33 
3.2 
Part 4 Objectives and Endpoints ........................................................................................35 
4 
STUDY DESIGN ...................................................................................................................36 
4.1 
Overall Design ...................................................................................................................36 
4.1.1 
Part 3 ............................................................................................................................36 
4.1.1.1 
Subject Evaluable for Dose Decisions ...................................................................37 
4.1.2 
Part 4 ............................................................................................................................37 
4.1.3 
Parts 3 and 4 .................................................................................................................37 
4.2 
End of Study ......................................................................................................................38 
4.2.1 
End of Study Definition ...............................................................................................38 
5 
STUDY POPULATION .........................................................................................................38 
5.1 
Inclusion Criteria ...............................................................................................................39 
5.2 
Exclusion Criteria ..............................................................................................................40 
5.3 
Screen Failures ...................................................................................................................43 
6 
STUDY TREATMENT ..........................................................................................................43 
6.1 
Study Treatment(s) Administered ......................................................................................43 
6.1.1 
Investigational Product: MT-3724 ...............................................................................43 
6.1.1.1 
Dose Rationale .......................................................................................................44 
6.1.1.2 
Dose Selection .......................................................................................................44 


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6.1.1.3 
Dose Schedule ........................................................................................................46 
6.1.1.4 
Treatment Beyond Progression ..............................................................................47 
6.1.2 
Other Protocol-required Intervention ...........................................................................47 
6.1.3 
Excluded Treatments, Medical Devices, and/or Procedures During Study 
Period ..........................................................................................................................48 
6.2 
Dose Modification .............................................................................................................48 
6.2.1 
Dose Modification for Treatment-emergent Adverse Experiences .............................48 
6.3 
Measures to Minimize Bias: Randomization and Blinding ...............................................55 
6.3.1 
Randomization .............................................................................................................55 
6.3.2 
Blinding........................................................................................................................55 
6.4 
Study Treatment Compliance ............................................................................................55 
6.5 
Concomitant Therapy.........................................................................................................55 
6.6 
Treatment After the End of the Study ................................................................................56 
7 
SUBJECT WITHDRAWAL, REPLACEMENT AND STUDY 
DISCONTINUATION ...........................................................................................................56 
7.1 
Subject Withdrawal ............................................................................................................56 
7.2 
Subject Replacement ..........................................................................................................57 
7.3 
Study Discontinuation ........................................................................................................57 
7.4 
Lost to Follow-up ...............................................................................................................57 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................57 
8.1 
General Study Periods........................................................................................................57 
8.1.1 
Screening and Enrollment ............................................................................................57 
8.1.2 
Treatment Period ..........................................................................................................58 
8.1.3 
End of Treatment Visit.................................................................................................58 
8.1.4 
Short-term Follow-up Visit ..........................................................................................58 
8.1.5 
Long-term Follow-up ...................................................................................................58 
8.2 
General Assessments .........................................................................................................59 
8.2.1 
Demographics ..............................................................................................................59 
8.2.2 
Non-Hodgkin Lymphoma Assessment ........................................................................59 
8.2.3 
Prior Systemic Therapy ................................................................................................60 
8.2.4 
Prior Radiotherapy .......................................................................................................60 
8.3 
Efficacy Assessments .........................................................................................................60 
8.3.1 
Radiological Assessment of Tumor Response .............................................................60 
8.3.2 
Independent Centralized Review of Efficacy Results .................................................61 
8.3.3 
Quality of Life..............................................................................................................61 
8.4 
Safety Assessments ............................................................................................................61 
8.4.1 
Medical History ...........................................................................................................61 
8.4.2 
Prior and Concomitant Medications ............................................................................62 
8.4.3 
Physical Measurements ................................................................................................62 
8.4.4 
Physical Examinations .................................................................................................62 


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8.4.4.1 
Complete Physical Examination ............................................................................63 
8.4.4.2 
Abbreviated Physical Examination ........................................................................63 
8.4.5 
New York Heart Association .......................................................................................64 
8.4.6 
Vital Signs ....................................................................................................................64 
8.4.7 
Left Ventricular Ejection Fraction ...............................................................................65 
8.4.8 
Electrocardiograms ......................................................................................................65 
8.4.9 
Clinical Safety Laboratory Assessments .....................................................................66 
8.4.10 
Safety Follow-up Phone Calls .....................................................................................66 
8.5 
Adverse Events and Serious Adverse Events ....................................................................66 
8.5.1 
Time Period and Frequency for Collecting Adverse Event Information .....................66 
8.5.2 
Method of Detecting Adverse Events and Serious Adverse Events ............................67 
8.5.3 
Regulatory Reporting Requirements for Serious Adverse Events ...............................67 
8.5.3.1 
SUSAR ...................................................................................................................68 
8.5.3.2 
Pregnancy Reporting Instructions ..........................................................................68 
8.6 
Pharmacokinetics ...............................................................................................................68 
8.7 
Pharmacodynamics ............................................................................................................69 
8.7.1 
Peripheral Blood ..........................................................................................................69 
8.7.2 
Optional Tumor Tissue Biopsy ....................................................................................69 
8.8 
Immunogenicity Assessments ............................................................................................69 
9 
STATISTICAL CONSIDERATIONS ...................................................................................70 
9.1 
Statistical Hypothesis and Sample Size Determination .....................................................70 
9.2 
Populations for Analyses ...................................................................................................71 
9.3 
Statistical Analyses ............................................................................................................71 
9.3.1 
General Considerations ................................................................................................71 
9.3.1.1 
Baseline Definition ................................................................................................71 
9.3.1.2 
Subject Disposition ................................................................................................72 
9.3.1.3 
Demographic and Baseline Characteristics ...........................................................72 
9.3.2 
Efficacy Analysis .........................................................................................................72 
9.3.2.1 
Primary Efficacy Variable (for Part 4) ...................................................................72 
9.3.2.2 
Secondary Efficacy Variables ................................................................................73 
9.3.2.3 
Quality of Life........................................................................................................74 
9.3.3 
Safety Analysis ............................................................................................................74 
9.3.3.1 
Adverse Events ......................................................................................................74 
9.3.3.2 
Laboratory Tests ....................................................................................................75 
9.3.3.3 
Vital Signs and Physical Examination Findings ....................................................75 
9.3.4 
Other Analyses .............................................................................................................75 
9.3.4.1 
Pharmacokinetic Analysis ......................................................................................75 
9.3.4.2 
Pharmacodynamic Analysis ...................................................................................76 
9.3.4.3 
Immunogenicity Analysis ......................................................................................76 
9.4 
Data Safety Monitoring Board ...........................................................................................76 


Compound: MT-3724 
 
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10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .........78 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ............................78 
10.1.1 
Investigators and Study Administrative Structure .......................................................78 
10.1.2 
Regulatory and Ethical Considerations ........................................................................79 
10.1.3 
Financial Disclosure .....................................................................................................80 
10.1.4 
Informed Consent Process ...........................................................................................80 
10.1.5 
Data Protection.............................................................................................................81 
10.1.6 
Study Monitoring .........................................................................................................81 
10.1.7 
Source Documents .......................................................................................................81 
10.1.7.1 
Case Report Forms and Study Records .................................................................81 
10.1.7.2 
Access to Source Documentation ..........................................................................83 
10.1.7.3 
Retention of Data ...................................................................................................83 
10.1.8 
Data Quality Assurance ...............................................................................................84 
10.1.9 
Publication and Disclosure Policy ...............................................................................84 
10.2 
Appendix 2: Clinical Laboratory Tests ..............................................................................86 
10.2.1 
General Guidance .........................................................................................................86 
10.2.2 
Analyte-specific Guidance ...........................................................................................87 
10.2.2.1 
Pregnancy Test .......................................................................................................87 
10.2.2.2 
Creatinine Clearance ..............................................................................................87 
10.2.2.3 
Complement, Histamine, and Cytokines ...............................................................88 
10.2.2.4 
Rituximab Concentration .......................................................................................88 
10.2.2.5 
Urinalysis ...............................................................................................................88 
10.3 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ............................................................................89 
10.3.1 
Definition of Adverse Event ........................................................................................89 
10.3.2 
Definition of Serious Adverse Event ...........................................................................90 
10.3.3 
Adverse Event Terminology ........................................................................................90 
10.3.4 
Severity ........................................................................................................................90 
10.3.5 
Causality / Relatedness ................................................................................................91 
10.3.6 
Expected and Unexpected Adverse Events and SUSARs ...........................................92 
10.3.7 
Action Taken with Study Treatment ............................................................................92 
10.3.8 
Outcome .......................................................................................................................93 
10.3.9 
Dose Limiting Toxicity (DLT) Criteria .......................................................................94 
10.4 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information .............96 
10.5 
Appendix 5: Staging of NHL .............................................................................................99 
10.6 
Appendix 6: Lugano Classification for Response Assessment in Lymphoma 
(Including the 5PS) ........................................................................................................101 
10.7 
Appendix 7: ECOG Performance Status ..........................................................................104 
10.8 
Appendix 8: New York Heart Association Functional Classification .............................105 
10.9 
Appendix 9: Abbreviations ..............................................................................................106 


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11 REFERENCES .....................................................................................................................110 
12 SUMMARY OF CHANGES ................................................................................................112 
12.1 
Version 11 ........................................................................................................................112 
12.2 
Version 10 ........................................................................................................................114 
12.3 
Version 9 ..........................................................................................................................117 
 
 


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Page 11 of 123 
LIST OF TABLES 
Table 1-1. 
Schedule of Activities ............................................................................................24 
Table 1-2. 
Schedule of Pharmacokinetic Samples ..................................................................29 
Table 6-1. 
Step-up Dosing Schedule for Cohorts 1 and 2 .......................................................45 
Table 6-2. 
Premedication ........................................................................................................47 
Table 6-3. 
Dose Reduction Steps ............................................................................................49 
Table 6-4. 
MT-3724 Dose Modification Guidance and Specific Management of Toxicities .50 
Table 10-1. 
 Protocol-Required Laboratory Assessments .........................................................86 
Table 10-2. 
 Classification of Adverse Events by Severity .......................................................91 
Table 10-3. 
 Classification of Adverse Events by Causality / Relationship to the Study Drug 92 
Table 10-4. 
 Ann Arbor Staging System With Cotswold Modification ....................................99 
Table 10-5. 
 Lugano Classification of Response Assessment in Lymphoma .........................101 
Table 10-6. 
 Modified Lugano 5-Point Scale (5PS) ................................................................103 
 
 
 


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Page 12 of 123 
1 PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title: Safety, Pharmacodynamics and Efficacy of MT-3724 for the Treatment of 
Patients with Relapsed or Refractory DLBCL 
Study Phase: 1-2 
Objectives and Endpoints (Part 3) 
OBJECTIVES 
ENDPOINTS 
Primary 
• 
To evaluate the safety of MT-3724 as 
monotherapy in subjects with relapsed or 
refractory diffuse large B-cell lymphoma 
(DLBCL) 
• 
adverse events (AE) 
• 
laboratory abnormalities 
• 
vital signs 
Secondary 
• 
To evaluate the efficacy of MT-3724 as 
monotherapy in subjects with relapsed or 
refractory DLBCL based on the overall response 
rate (ORR) by the Lugano Classification for 
Lymphoma (Cheson, 2014) 
• 
Overall response rate is defined as the proportion 
of subjects with either a complete response (CR) 
or a partial response (PR) as determined by 
independent, blinded central review 
• 
To evaluate additional measures of efficacy of 
MT-3724 as monotherapy in subjects with 
relapsed or refractory DLBCL 
• 
Overall response rate, defined as the proportion of 
subjects with either a CR or a PR as determined by 
investigator assessment 
• 
duration of tumor response (DOR), defined as time 
from initial documentation of tumor response (CR 
or PR) to disease progression  
• 
disease control rate (DCR), defined as proportion 
of subjects who have achieved CR, PR and stable 
disease (SD; defined as SD for 6 months or longer) 
• 
To evaluate the pharmacokinetics (PK) of 
MT-3724 as monotherapy in subjects with 
relapsed or refractory DLBCL 
• 
Pharmacokinetics parameters, where calculable, 
include: maximum observed plasma concentration 
(Cmax), time to achieve Cmax (tmax), and area under 
the plasma concentration time curve from 0 to 4 
hours (AUC0-4), AUC from 0 to infinity (AUC0-inf), 
AUC from dosing to last measurable concentration 
(AUClast), half-life (t1/2), volume of distribution 
(Vz), and clearance (CL) 
• 
To evaluate the pharmacodynamics of MT-3724 as 
monotherapy in subjects with relapsed or 
refractory DLBCL 
• 
B-cell count 
• 
Immunophenotyping 
• 
Circulating immunoglobulins (IgA, IgG, IgM) 
• 
To evaluate the immunogenicity of MT-3724 as 
monotherapy in subjects with relapsed or 
refractory DLBCL 
• 
incidence of anti-drug antibodies (ADA) 


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Page 13 of 123 
OBJECTIVES 
ENDPOINTS 
Exploratory 
Objectives and Endpoints (Part 4) 
OBJECTIVES 
ENDPOINTS 
Primary 
x
To determine the efficacy of MT-3724 as
monotherapy in subjects with relapsed or
refractory DLBCL based on the ORR by the
Lugano Classification for Lymphoma (Cheson,
2014)
x
overall response rate is defined as the proportion
of subjects with either a CR or a PR as determined
by independent, blinded central review
Key Secondary 
x
To determine additional measures of efficacy of
MT-3724 as monotherapy in subjects with
relapsed or refractory DLBCL
x
Duration of tumor response, defined as time from
initial documentation of tumor response (complete
response [CR] or partial response [PR]) to disease
progression
Secondary 
x
To determine the safety of MT-3724 as
monotherapy in subjects with relapsed or
refractory DLBCL
x
adverse events
x
laboratory abnormalities
x
vital signs
x
To evaluate the effect of MT-3724 on the QT/QTc
interval in subjects with relapsed or refractory
DLBCL
x
electrocardiograms (ECGs)
x
adverse events suggestive of cardiotoxicity
x
To determine additional measures of efficacy of
MT-3724 as monotherapy in subjects with
relapsed or refractory DLBCL
x
overall response rate (ORR), defined as the
proportion of subjects with either a CR or a PR as
determined by investigator assessment
x
disease control rate (DCR), defined as proportion
of subjects who have achieved CR, PR and SD
(defined as SD for 6 months or longer)
PPD


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OBJECTIVES 
ENDPOINTS 
x
progression-free survival (PFS), defined as the
time from study enrollment to the earliest date of
disease progression or death from any cause
x
overall survival (OS), defined as the time from
study enrollment to death from any cause
x
To determine the pharmacokinetics (PK) of
MT-3724 as monotherapy in subjects with
relapsed or refractory DLBCL
x
Pharmacokinetics parameters, where calculable,
include: Cmax, tmax, AUC0-4, AUC0-inf, AUClast, t1/2,
Vz and CL
x
To determine the pharmacodynamics of MT-3724
as monotherapy in subjects with relapsed or
refractory DLBCL
x
B-cell count
x
Immunophenotyping
x
Circulating immunoglobulins (IgA, IgG, IgM)
x
To determine the immunogenicity of MT-3724 as
monotherapy in subjects with relapsed or
refractory DLBCL
x
incidence of ADA
Exploratory 
Overall Design: 
This is an open-label, Phase 1/2, study of MT-3724. 
Part 1 of the protocol included evaluating escalating doses of MT-3724 in subjects with relapsed, 
refractory B-cell non-Hodgkin Lymphoma (NHL) or chronic lymphocytic leukemia to determine 
the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).  
Part 2 (implemented in version 6.0 of the protocol) included an expansion of the MTD cohort to 
evaluate safety, tolerability, and potential efficacy at the MTD or RP2D. Implemented in version 
7.0 of the protocol, up to 40 additional subjects with diffuse large B-cell lymphoma (DLBCL) 
were to be treated with MT-3724 at the MTD/ RP2D (50 μg/kg/dose). 
Parts 3 and 4 will be a multi-center, multinational, open-label, single-arm evaluation of MT-3724 
given as monotherapy in repeat doses in subjects with relapsed or refractory DLBCL who have 
received 2 or more lines of prior therapy. 
Part 3 will be a continuation of the expansion of the MTD cohort with the intention to verify the 
safety, dose and dosing schedule in up to 25 subjects. 
PPD


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Part 4: The goal of Part 4 is to provide sufficient evidence to test the null hypothesis that the true 
response rate with MT-3724 ≤ 17% vs the alternative hypothesis that the true response rate with 
MT-3724 ≥ 32% at the 1-sided alpha level of 0.025 with high statistical power. At least 
88 evaluable subjects will be required to test the null hypothesis vs the alternative hypothesis in 
Part 4. If at least 23 of 88 subjects respond at the end of Part 4, then the null hypothesis is 
rejected in favor of the alternative hypothesis and the effectiveness of MT-3724 as monotherapy 
will have been proven. Under the stated null and alternative hypotheses, Part 4 carries 90.4% 
power at the 1-sided alpha level of < 0.025. 
Eligible subjects will be identified and treated through competitive enrollment across multiple 
global sites. 
All study procedures will be the same for Parts 3 and 4. After eligibility is assessed in the 
screening period (up to 35 days), subjects enter the treatment period. Each treatment cycle will 
be 21 days in length. Treatment will continue until death, disease progression, unacceptable 
toxicity, withdrawal of consent, or another reason for withdrawal, or until study discontinuation. 
Treatment Beyond Progression 
For subjects who have radiological, but not clinical, evidence of disease progression within 
3 months of Cycle 1 Day 1 (C1D1), in lieu of discontinuation, the investigator may continue 
treatment at the dose they are given at the time progression is identified if s/he believes the 
benefit outweighs the risk and provided the conditions identified below are met. 
Conditions for continued treatment: 
•
absence of symptoms and signs, including worsening of laboratory values, indicating
unequivocal progressive disease (PD),
•
no decline in Eastern Cooperative Oncology Group performance status (ECOG PS) due to
PD,
•
absence of tumor progression at critical anatomical sites (eg, leptomeningeal disease),
•
subject’s written consent to defer any standard treatment options that may exist in favor of
continuing MT-3724 treatment at the time of initial progression.
Radiological assessments should be repeated in 4 to 6 weeks from the time of initial progression. 
End of Treatment: upon discontinuation from treatment, all subjects should undergo the End of 
Treatment (EoT) Visit as soon as possible (up to 14 days) after the last dose of MT-3724 and 
before start of new therapy. 
Short-term Safety Follow-up: The Short-term Follow-up (STFU) Visit for safety assessment 
should occur 30 days (± 3 days) after the last dose of MT-3724, except for subjects who 


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withdrew consent and objected to further data collection, started new therapy for DLBCL or 
started another investigational drug. 
Long-Term Follow-up: Long-term Follow-up (LTFU) Visits should occur every 3 months 
(± 14 days) after the last dose of MT-3724 for up to 18 months from the last dose. Subjects who 
discontinue the study for disease progression will be followed only for OS. Subjects who 
discontinue the study for toxicity, or reasons other than disease progression, will be followed for 
progression-free survival (PFS; as reported by investigators) and OS. Subjects with complete 
response (CR), partial response (PR), or stable disease (SD) should also be followed for 
radiology assessment until PD, death, or start of new anticancer treatment. Visits may occur by 
telephone contact when radiology data can be obtained from medical records. 
Study Treatment: 
All subjects will receive a single course of study drug via a 1 hour (54 to 75 minute window) 
intravenous (IV) infusion of MT-3724. Following a single AE of grade 5 capillary leak 
syndrome (CLS), a revised Part 3 will include 2 cohorts. For Cohort 1, the starting MT-3724 
dose for each subject will be 10 µg/kg/dose for the first 2 doses and then increased to 25 µg/kg 
for the remaining doses of the first 21-day cycle and all doses of Cycle 2. Dosing will then 
continue at 25 µg/kg weekly beginning with Cycle 3. If fewer than 2/6 subjects have a 
dose-limiting toxicity (DLT) in Cohort 1, then the study will proceed to Cohort 2. If 2 or more 
subjects have a DLT in Cohort 1, the study will be stopped. 
For Cohort 2, the starting MT-3724 dose in each subject will be 10 µg/kg for the first 2 doses. 
The dose will then be increased to 25 µg/kg for 2 doses and then the dose will be increased to 
50 µg/kg for the remaining doses of the first 21-day cycle and all doses of Cycle 2. Dosing will 
then continue at 50 µg/kg weekly beginning with Cycle 3. 
If fewer than 2/6 subjects have a DLT in Cohort 2, then the study will continue to Part 4 using 
the Cohort 2 dose and schedule. If 2 / 6 subjects experience a DLT in Cohort 2, the study will 
continue to Part 4 using the Cohort 1 dose and schedule. 
For Cycle 1 and 2 doses are preferably administered on Days 1, 3, 5, 8, 10, and 12 (± 1 d). For 
Cycle 3 and later doses are preferably administered on Days 1, 8, and 15. All subsequent doses 
should be at least 20 hours apart (more than 5 half-lives of MT-3724 in serum) and must not be 
administered on more than 2 consecutive days; however the first 3 doses of Cycle 1 must be 
administered 2 days (approximately 48 hours) apart. Each subject will receive 1 dose of 
MT-3724 on Day 1.  
The first dose of the first cycle will require approximately 5 hours in the clinic which include 
approximately 4 hours of post-dose safety assessments. Subsequent doses will require 
approximately 3 hours in the clinic which include approximately 2 hours of safety assessments 
post-dose (see also Section 1.3, Schedule of Activities (SoA)). All subjects will be evaluated for 
AEs prior to each infusion during all cycles of MT-3724 treatment. See Section 6.2 for guidance 
on treatment modifications. 


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Treatment will continue until death, disease progression, unacceptable toxicity, withdrawal of 
consent, or another reason for withdrawal, or until study discontinuation. 
Number of Subjects: 
Approximately 113 subjects with histologically confirmed, relapsed or refractory DLBCL: 
approximately 25 in Part 3 and approximately 88 evaluable subjects in Part 4. Additional 
subjects may be enrolled to ensure an adequate number of evaluable subjects in Part 4. 
Inclusion criteria: 
Subjects meeting ALL the following inclusion criteria will be eligible for participation in the 
study.  
1. Subjects must be informed about the study and fully consent to participation as demonstrated
by signing the written informed consent form (ICF) before any screening procedure.
2. Male and female subjects ≥ 18 years of age at the time of informed consent.
3. Subjects must have relapsed or refractory DLBCL according to the Revised European
American Lymphoma/World Health Organization classification (Swerdlow, 2016). Subjects
must have proof of CD20+ DLBCL, based on either:
a.
historical biopsies (obtained with diagnosis of relapsed or refractory disease), or
b. fresh biopsies
c.
bone marrow biopsy, excisional lymph node biopsy, and core biopsy of any involved
organ are all acceptable methods; Fine Needle Aspirate is not acceptable.
NOTE: Composite lymphoma (DLBCL and indolent histology in the same specimen) is also 
acceptable. 
4. Subjects must have received at least 2 standard of care (SoC) regimens (including anti-CD20
antibody therapy) appropriate for DLBCL treatment.
a.
Subjects whose prior therapy includes CAR-T therapy are eligible.
b. Subjects who underwent stem cell transplant (SCT) > 100 days for autologous SCT or
> 180 days for allogeneic SCT before study drug administration.
c.
Subjects who have been ineligible for SoC DLBCL treatment(s) may be eligible at the
investigator’s discretion, upon sponsor approval.
5. Subjects must have at least 1 bi-dimensional tumor lesion at screening that is measurable by
CT and/or magnetic resonance imaging (MRI) according to the Lugano criteria (Cheson,
2014). Bi-dimensionally measurable tumor lesion by CT and/or MRI is defined as longest
diameter of > 1.5 cm for lymph nodes and > 1.0 cm for extranodal disease.
6. Subjects must have life expectancy of > 3 months from the start of treatment.
7. Subjects must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
8. Subjects must have met ALL the following laboratory criteria:
a.
Absolute neutrophil count ≥ 1.0 × 109/L with no myeloid growth factors (granulocyte
colony-stimulating factor [G-CSF] or granulocyte‐macrophage colony-stimulating factor
preparations) administered within 2 weeks of C1D1


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b. Platelet count ≥ 50 × 109/L with no Thrombopoietin-receptor agonists agents or platelet 
transfusions given within 2 weeks of C1D1 
c. Hemoglobin ≥ 8.0 g/dL with no erythropoietin stimulating agents or peripheral red blood 
cell (PRBC) transfusions within 2 weeks of C1D1 
d. Creatinine clearance (CLcr) to be ≥ 50 ml/min either measured or estimated using the 
Cockcroft-Gault formula (Section 10.2.2.2).  
e. Total bilirubin (or direct bilirubin for patients with Gilbert’s disease) < 1.5 × upper limit 
of normal (ULN) 
f. Alanine transaminase (ALT) ≤ 3.0 × ULN (or ≤ 5.0 x ULN if liver involvement). 
g. Aspartate aminotransferase (AST) ≤ 3.0 × ULN (or ≤ 5.0 x ULN if liver involvement). 
h. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN (unless on 
therapeutic anticoagulants) 
i. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (unless on therapeutic 
anticoagulants) 
9. Have adequate serum albumin, as determined by: 
a. Albumin ≥ 3.0 g/dL  
10. QT interval correction for heart rate using Fridericia’s formula (QTcF) ≤ 480 ms determined 
as the average of 3 QTcF values from the triplicate ECG obtained at screening. 
11. Women of reproductive potential must have a negative highly sensitive pregnancy test within 
72 hours before the start of treatment. Women who are postmenopausal or permanently 
sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy) may be considered as 
not of reproductive potential.  
12. Subjects of reproductive potential must agree either to abstain continuously from 
heterosexual intercourse or to use a highly effective birth control method from signing the 
informed consent until the STFU visit for females and until 90 days after the last dose of 
MT-3724 for males. Refer to Section 10.4 for guidance on contraception.  
13. Subject must be able to comply with all study-related procedures and medication use. 
Exclusion criteria: 
Subjects who meet ANY of the following criteria must be excluded: 
Prior or current therapies 
1. Received any amount of anti-CD20 monoclonal antibodies (mAbs) within the following 
periods before the start of treatment:  
a. Rituximab (Rituxan®/MabThera® or rituximab biosimilar): within 84 days (12 weeks); if 
a subject has received rituximab within 37 weeks before the start of treatment, then serum 
rituximab level must be negative (< 500 ng/mL) at screening. 
b. Obinutuzumab (Gazyva®): 184 days 
c. Ofatumumab (Arzerra®): 88 days 


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d. Any other anti-CD20 agents (eg, investigational agents), the washout period is 
5 half-lives. The investigator must contact the medical monitor to discuss the most 
appropriate washout for non-approved CD20-targeting agents, where the half-life is not 
known. 
2. Received approved or investigational treatment for DLBCL (except anti-CD20 agents where 
exclusion criterion 1 applies and radioimmunoconjugates) within 4 weeks before the start of 
treatment. For small molecules (MW < 0.9 kiloDaltons [kDa]), the washout is 5 half-lives or 
at least 2 weeks. Radioimmunoconjugates are excluded within 12 weeks before the start of 
treatment.  
3. Received radiation therapy to tumor lesions that would serve as target lesions (measurable 
disease) within 4 weeks before the start of treatment, unless the lesion exhibited objective 
progression between radiation therapy and screening according to the Lugano Classification 
(Cheson, 2014).  
a. Palliative radiation therapy to non-target lesions may be permitted at the investigator’s 
discretion after consultation with the medical monitor and sponsor. See Section 6.5 for 
more information on permissible use of palliative radiotherapy. 
4. Require the use of systemic immune modulators during study treatment: 
a. Systemic immune modulators include, but are not limited to, systemic corticosteroids at 
doses > 20 mg/day of prednisone equivalent, cyclosporine and tacrolimus. Please see 
Section 6.1.3 for more details and exceptions. 
b. The use of non-steroidal anti-inflammatory drugs (NSAIDS) is permitted. 
5. Received any live vaccines within 4 weeks before the start of treatment. 
6. Prior treatment with MT-3724. 
Medical history 
7. Current evidence of Common Terminology Criteria for Adverse Events (CTCAE) Grade > 1 
toxicity (due to prior anticancer therapy) before the start of treatment, except for hair loss and 
those Grade 2 toxicities listed as permitted in other eligibility criteria. 
8. Current evidence of significant (CTCAE Grade ≥ 2) infection or wound within 4 weeks 
before the start of treatment. 
a. Subjects with Grade 2 infection that has stabilized or improved with oral anti-infectives 
before the start of treatment may be eligible at the sponsor’s discretion.  
9. Known or suspected hypersensitivity to the study drug or excipients contained in the study 
drug formulation. 
10. Current evidence of hypersensitivity or other underlying illness requiring systemic 
corticosteroids at doses > 20 mg/day prednisone equivalent. 
11. Current evidence of uncontrolled human immunodeficiency virus (HIV), hepatitis B virus 
(HBV) or hepatitis C virus (HCV) at screening. Serology testing is not required if 
seronegativity is documented in the medical history, and if there are no clinical signs 
suggestive of HIV or hepatitis infections, or suspected exposure. The following exceptions 
apply for subjects with positive viral serology:  


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a. Subjects with HIV and an undetectable viral load and CD4+ T-cell (CD4+) counts 
≥ 350 cells/mL may be enrolled, but must be taking appropriate opportunistic infection 
prophylaxis, if clinically relevant. 
b. Subjects with positive HBV serology are eligible if they have an undetectable viral load 
and the subject will receive antiviral prophylaxis for potential HBV reactivation per 
institutional guidelines. 
c. Subjects with positive HCV serology are eligible if quantitative PCR for plasma HCV 
RNA is below the lower limit of detection. Concurrent antiviral HCV treatment per 
institutional guidelines is allowed. 
12. Current evidence of incomplete recovery from surgery or radiotherapy before start of 
treatment, or planned surgery or radiotherapy from the start of treatment until the EoT visit, 
except minor elective surgery deemed acceptable by the investigator or palliative radiation 
therapy to non-target lesions, as described in Section 6.5. 
13. History of cardiovascular, renal, hepatic or any other disease within 3 months before the start 
of treatment that in the investigator’s opinion, may increase the risks associated with study 
participation or require treatments that may interfere with the conduct of the study or the 
interpretation of study results. 
14. History or current evidence of neoplastic disease that is histologically distinct from NHL, 
except cervical carcinoma in situ, superficial noninvasive bladder tumors, curatively treated 
Stage I-II non-melanoma skin cancer. Subjects with prior, curatively treated cancer > 2 years 
ago before the start of treatment can be enrolled. 
15. Current evidence of new or growing brain or spinal metastases during screening. Subjects 
with known brain or spinal metastases may be eligible if they:  
a. Had radiotherapy or another appropriate therapy for the brain or spinal metastases; 
concurrent prophylactic treatment is allowed  
b. Neurologic symptoms must be stable and no worse than Grade 2 
c. Have evidence of stable brain or spinal disease on CT or MRI scan obtained within 
4 weeks before signing the informed consent and compared with prior imaging results 
d. Do not require steroid therapy (or, if applicable, have been stable on dose of no more than 
prednisone 20 mg/day or equivalent by C1D1) 
16. Women who are pregnant or breastfeeding. 
17. History of non-adherence to the schedule of procedures or medication use. 
18. Current evidence of Graft vs Host Disease 
19. History or current evidence of significant cardiovascular disease including, but not limited to, 
the following conditions: 
a. Unstable angina (symptoms of angina at rest) or new-onset angina within 3 months 
before the start of treatment. 
b. Arterial thrombosis or pulmonary embolism within 3 months before the start of 
treatment. 
c. Myocardial infarction or stroke within 3 months before the start of treatment. 


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d. Pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade ≥ 2), non-malignant 
pleural effusion (CTCAE Grade ≥ 2) or malignant pleural effusion (CTCAE Grade ≥ 3) 
within 3 months before the start of treatment with MT-3724.  
e. Congestive heart failure (New York Heart Association [NYHA] Class III or IV) at 
screening or left ventricular ejection fraction (LVEF) ≤ 45%, assessed by echocardiogram 
(ECHO) or multigated acquisition (MUGA) scan within 1 month before starting study 
treatment (inclusion of subjects with LVEF between 40% to 45% should be discussed 
with the medical monitor and approved by the sponsor). (ECHO or MUGA performed 
within 6 months before screening and at least 28 days after the last cancer therapy is 
acceptable provided the subject has not received any potentially cardiotoxic agents since 
then). 
f. Cardiac arrhythmia requiring anti-arrhythmic therapy at screening. Subjects receiving 
digoxin, calcium channel blockers, or beta-adrenergic blockers are eligible at the 
investigator’s discretion after consultation with medical monitor and sponsor if the dose 
has been stable for ≥ 2 weeks before the start of treatment with MT-3724. Subjects with 
sinus arrhythmia and infrequent premature ventricular contractions are eligible at the 
investigator’s discretion. 
 
Statistical Methods: 
Detailed methodology for summary and statistical analyses of the data collected in Parts 3 and 4 
this study will be documented in a statistical analysis plan, which will be maintained by the 
sponsor. This document may modify the plans outlined in the protocol; however, any major 
modifications will also be reflected in a protocol amendment and documented in the clinical 
study report. 
Clinical Endpoints  
Categorical variables will be summarized using counts and percentages, while continuous 
variables will be summarized using the mean, median, standard deviation, minimum, maximum, 
and number of observations. The frequency of AEs will be tabulated. Baseline, end-of-study, and 
change from baseline clinical laboratories, vital signs, ECG and imaging data will be 
summarized. Descriptive statistics will be computed for safety parameters as appropriate. Further 
statistical evaluations may be applied for select endpoints, if warranted. 
Efficacy Endpoints  
Tumor response and disease progression will be evaluated by the independent central review 
(ICR) for the Part 4 primary endpoint and the Part 3 secondary endpoint; and by the investigator 
for secondary efficacy endpoints (Parts 3 and 4) according to the Lugano Classification for 
Lymphoma (Cheson, 2014). 
All subjects who receive at least 1 dose of study medication will be included in the full analysis 
set (FAS) for the efficacy analysis.  


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The efficacy analysis will include the ORR, DOR, and DCR at the Final Study Assessment Visit. 
Subjects who have not progressed at the time of analysis will be censored at the date of their last 
tumor assessment. Progression-free survival and OS will also be presented using Kaplan-Meier 
techniques. 
The overall response rate (ORR) and DOR will be descriptively summarized; exact 95% 
confidence intervals (CI) will be produced. 
 


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1.2 
Study Schema 
 


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1.3 
Schedule of Activities (SoA) 
Table 1-1. Schedule of Activities 
 
SCRa 
Treatment Period (21-day Cycles)b 
EoTd 
STFUe 
LTFUf 
Notes 
D1 D3 D5 D8 D10 D12 D15c D16-21 
General and Safety Assessments 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
  
Eligibility criteria 
X 
 
 
 
 
 
 
 
 
 
 
  
Demography 
X 
 
 
 
 
 
 
 
 
 
 
  
Physical exam 
X 
X 
 
 
 
 
 
 
 
X 
 
 Complete physical exam at screening and EoT. Abbreviated exam D1 of 
every cycle. See Section 8.4.4 for details. 
Height 
X 
 
 
 
 
 
 
 
 
 
 
  
Weight  
X 
X 
X 
X 
X 
X 
X 
(X) 
 
X X 
 
Body weight measured before the start of treatment on C1D1 will be used to 
calculate the MT-3724 dose in all subsequent cycles. The dose must be 
re-calculated when the body weight has changed by ≥ 10% from the baseline 
value; or according to institutional policies should they require adjustment 
for any change in body weight. 
(X): Collected only if weekly dosing is implemented. 
BMI 
X 
 
 
 
 
 
 
 
 
 
 
  
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
Illnesses that occurred at any time before the start of screening that, in the 
investigator’s opinion, could increase the risk to subject and/or influence the 
study endpoints should be captured in the medical history as prior illnesses. 
Illnesses that are active at the time of informed consent should be captured in 
the medical history as concomitant illnesses. 
NHL assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
Initial diagnosis: include the type, histology, staging (Ann Arbor 
Classification-Cotswold Modification) and grading according to International 
Prognostic Index (IPI) for NHL 
At time of relapse: IPI and time to progression after first line of therapy 
(captured as date of first relapse/progression) 
Current status: additionally collect the genetic mutational status (eg, MYC, 
BCL2, and BCL6 rearrangement / overexpression) and molecular subtype 
(GCB vs ABC) (if available). 


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Table 1-1. Schedule of Activities 
SCRa 
Treatment Period (21-day Cycles)b 
EoTd 
STFUe 
LTFUf 
Notes 
D1 D3 D5 D8 D10 D12 D15c D16-21 
Prior medication 
X 
Any medication (prescription, OTC, and supplements) used within 4 weeks 
prior to the start of treatment. 
Prior systemic NHL 
therapy (including SCT 
and CAR-T) 
X 
The start and stop date of each individual agent / regimen and outcome 
should be recorded. The date of the last CD20-based therapy should also be 
documented in the eCRF. 
Prior NHL radiotherapy 
X 
NYHA 
X (X) 
X 
Only applicable to subjects with heart failure. 
(X): Only collected D1 every 7th cycle 
ECOG 
X 
X 
X 
Triplicate 12-lead ECGg X (X) 
(X) 
X 
Should be obtained as 3 standard ECGs recorded in close succession and not 
more than 2 minutes apart. The subject must rest quietly in supine or 
semi-recumbent position for at least 5 minutes before the first ECG and 
during the assessment. 
(X): Collected: 
•
C1D1: predose, within 10 min before EOI, and 2.0 (± 10 min) after EOI
•
C1D12: predose and 2.0 h (± 10 min) after EOI
Vital signs (BP, HR,
RR, body temperature)g 
X
X 
X 
X 
X 
X 
X 
(X) 
X X 
Should be measured after at least 5 minutes of quiet rest in a sitting or 
semi-recumbent position. 
Collect VS at the following times on dosing days (± 10 min): 
•
predose (any time before start of infusion)
•
0.5, 1, 2 hours after start of infusion
•
C1D1: also collect 3 and 4 hours after start of infusion
(X): Collected only if weekly dosing is implemented.
LVEF 
X 
ECHO or MUGA performed within 6 months before screening and at least 28 
days after the last cancer therapy is acceptable provided the subject has not 
received any potentially cardiotoxic agents since then.  
AE review 
(X) X 
X 
X 
X 
X 
X 
X 
X 
X X 
(X): Events which occur during screening that are related to a protocol 
screening procedure should be reported as AEs. 
Concomitant medication 
review 
X 
X 
X 
X 
X 
X 
X 
X 
X X 


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Table 1-1. Schedule of Activities 
 
SCRa 
Treatment Period (21-day Cycles)b 
EoTd 
STFUe 
LTFUf 
Notes 
D1 D3 D5 D8 D10 D12 D15c D16-21 
Safety follow-up call 
 
 
 
 
 
 
 
X 
 
 
 Not applicable for weekly dosing 
LTFU call 
 
 
 
 
 
 
 
 
 
 
 
X  
Local Laboratory Assessments 
Albumin 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Albumin will be collected within 24 h before infusion and reviewed prior to 
each dose in Cycle 1. Additional assessments of serum albumin should be 
made in subjects with hypoalbuminemia or other signs and symptoms of CLS 
as clinically indicated. See Section 6.2 for dose modification guidance for 
CLS. 
CK 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 CK must be collected within 24 h before infusion in Cycle 1.  
Viral serology 
X 
 
 
 
 
 
 
 
 
 
 
 
Serology for HIV, HBV, and HCV is not required if seronegativity is 
documented in the medical history and there are no clinical signs suggestive 
of HIV or hepatitis infections, or suspected exposure. Refer to Table 10-1 for 
specific analytes. 
Urinalysis (dipstick) 
X 
X 
 
 
X 
 
 
 
 
X X 
 Analysis of urine microsediment may be performed at the investigator’s 
discretion by the local lab. 
Pregnancy test  
 
(X) 
 
 
 
 
 
 
 
X X 
 (X): performed within 72 h before dosing on D1 
Central Laboratory Assessments 
Serum rituximab level 
(if applicable) 
X 
 
 
 
 
 
 
 
 
 
 
 
Only applicable to subjects that have received the last dose of prior RTX 
(Rituxan® or biosimilar) > 84 days before the start of treatment. See 
Section 10.2.2.4 for further details. 
Hematology  
X 
X 
 
 
X 
 
 
 
 
X X 
  
Chemistry 
X 
X 
 
 
X 
 
 
 
 
X X 
 Includes eCrCl (see Section 10.2.2.2).  
Coagulation 
X (X) 
 
 
 
 
 
 
 
X 
 
 
(X): Assessed D1 of every odd cycle. 
Thyroid function 
X (X) 
 
 
 
 
 
 
 
X 
 
 
HbA1c 
X (X) 
 
 
 
 
 
 
 
X 
 
 
PKg 
 
X 
X 
 
 
 
X 
 
 
 
 
 Refer to Table 1-2 for detailed time point collection. 
Beta-2 microglobulin 
X 
 
 
 
 
 
 
 
 
 
 
  
MT-3724 ADA/NAb 
X 
X 
 
 
 
 
(X) 
 
 
X X 
 (X): Day 12 of Cycle 1 only 


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Table 1-1. Schedule of Activities 
 
SCRa 
Treatment Period (21-day Cycles)b 
EoTd 
STFUe 
LTFUf 
Notes 
D1 D3 D5 D8 D10 D12 D15c D16-21 
B-cells and 
immunophenotype 
X 
X 
 
 
 
 
(X) 
 
 
X X 
 (X): Day 12 of Cycle 1 only 
Complement 
X 
X 
 
 
 
 
 
 
 
X 
 
 Should be assessed before the start of infusion and 3 hours after the start of 
infusion (± 10 min), or if a subject experiences a Grade ≥ 2 IRR/CLS/CRS or 
other hypersensitivity reaction. See Section 10.2.2.3 for details. 
Histamine 
X 
X 
 
 
 
 
 
 
 
X 
 
 
Cytokines 
X 
X 
 
 
 
 
 
 
 
X 
 
 
Immunoglobulins 
X 
X 
 
 
 
 
 
 
 
X 
 
 Should be assessed before the start of infusion and 3 hours after the start of 
infusion (± 10 min). 
Optional tumor tissue 
biopsy 
 
 
 
 
 
 
 
 
 
X 
 
 Applicable to subjects who had consented for this procedure, exhibit PD, and 
have accessible peripheral lymph node(s). 
Efficacy Assessments 
Radiological assessment X 
Every 6 weeks (± 1 week) starting from C1D1, 
until disease progression, death, or lost to follow-up 
AND 
For subjects without response or SD at EoT: within 
7 days of the EoT Visit (only if the previous tumor 
scan has been performed > 4 weeks before the EoT 
Visit) 
The investigator is encouraged to obtain the screening tumor scan as close as 
possible to the start of treatment. The original schedule needs to be 
maintained even if there is a delay is dosing. Subjects who continue to 
receive treatment beyond progression should also have repeat scans. 
EQ-5D 
X (X) 
 
 
 
 
 
 
 
X X 
 (X): Collected D1 of every even cycle (C2, C4, C6, etc) 
Study Treatment 
Premedication 
 
X 
X 
X 
X 
X 
X 
(X) 
 
 
 
 
Administered within 60 minutes prior to MT-3724 infusion. Refer to 
Section 6.1.2 for guidance. 
(X): Only when weekly dosing is implemented. 
MT-3724 infusion 
(TIW) 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
The first 3 doses of Cycle 1 must be administered at least 2 days (approx. 
48 hours) apart. 
All subsequent doses must be given within ± 1 day of scheduled visit. All 
6 doses must be given within the first 16 days, the doses should be at least 
20 hours apart, and should not be administered on more than 2 consecutive 
days. 
MT-3724 infusion 
(weekly schedule)h 
 
X 
 
 
X 
 
 
X 
 
 
 
 Starting with Cycle 3, doses will be administered weekly. Doses must be 
given within ± 2 day of scheduled visit. 


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ABC = activated B-cell; ADA = anti-drug antibodies; AE = adverse event; BMI = body-mass index; BP = blood pressure; C = cycle; CAR-T = chimeric antigen 
receptor T-cell therapy; CLS = capillary leak syndrome; CK = creatine phosphokinase; CRS = cytokine release syndrome; CT = computerized tomography; D = 
day; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; eCrCl = estimated creatinine clearance; eCRF = 
electronic case report form; EOI = end of infusion; EoT = end of treatment; EQ-5D = EuroQol Group Quality of Life – 5-dimensions; GCB = germinal center B 
cell; HbA1c = glycated hemoglobin; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency syndrome; LTFU = long-term 
follow-up; NHL = non-Hodgkin's lymphoma; HR = heart rate; IRR = infusion-related reaction; LVEF = left ventricular ejection fraction; MRI = magnetic 
resonance imaging; MUGA = multigated acquisition; NAb = neutralizing antibody; NYHA = New York Heart Association; OTC = over-the-counter; PD = 
progressive disease; PK = pharmacokinetic; RNA = ribonucleic acid; RR = respiratory rate; SCR = screening; SCT = stem cell transplant; SD = stable disease; 
STFU = short-term follow-up TIW = three times a week. 
a
The screening period is up to 35 days prior to enrollment. All local/central laboratory safety assessments and radiological assessments must be collected 
within 28 days prior to enrollment. 
b
All assessments are performed any time before dosing unless otherwise indicated. Predose assessments may be performed up to 1 day prior to dosing (except 
for cytokines/immunoglobulins/complement/histamine which should be collected just prior to dosing). 
c
The Day 15 visit is applicable for subjects receiving the weekly dosing schedule. 
d
Upon discontinuation of treatment, as soon as possible (up to 14 days) after the last dose, and before the start of new therapy. 
e
A STFU visit occurs 30 days (± 3 days) after the last dose. The STFU visit can be done via a clinic visit (recommended) or via a telephone call (if subject 
cannot attend a clinic visit or has started a new anticancer treatment or a new NHL treatment). If performed via a telephone call, only AEs and concomitant 
medications will be collected.  
f 
LTFU visits should occur every 3 months (± 14 days) after the last dose of MT-3724 for up to 18 months from the last dose. The LTFU Visits will be 
performed via a telephone call to collect the information about the NHL status (relapsed or not), the start of any new therapy for NHL since the last study 
visit/phone call or death. Subjects with SD or response should also be followed for radiology assessment until progressive disease, start of new anticancer 
treatment, or death. 
g 
When PK, ECG, and vital signs assessments are scheduled to occur at the same time point, the ECG and vital signs should be done first and in that order, 
with the timing of assessments based on collecting the PK sample at the protocolled time (eg, if the PK sample is expected 2 hours after EOI, collect the PK 
sample 2 hour after the infusion, and ECG/VS within 10 minutes before the PK sampling). 
h 
The weekly dosing schedule follows procedures on Days 1, 8 and 15. 


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Table 1-2. Schedule of Pharmacokinetic Samples 
 
Time Points Relative to Dosing 
Notes 
Predose 
During Infusion 
After EOI 
Within 4 h 
Prior SOI 
10 m Before EOI 
5 m 
0.5 h 
1 h 
2 h 
3 h 
4 h 
Window 
 
 
± 1 m 
± 5 m 
± 5 m 
± 5 m 
± 10 m 
± 10 m 
Part 3 
If an MT-3724 dose is rescheduled, then the PK samples 
planned per protocol for that dose should be drawn on the new 
dosing day. For example, if Dose 6 is delayed from D12 to D14, 
then the PK samples planned for D12 should be drawn on D14. 
Unscheduled assessments may be performed at any time at the 
investigator’s discretion. 
 
Samples for PK must be drawn from a different line than that 
used for MT-3724 administration. 
C1D1 
X 
X 
X 
X 
X 
X 
X 
X 
C1D3 
X 
X 
X 
X 
X 
X 
 
 
C1D12 
X 
X 
X 
X 
X 
X 
 
 
CXD1 
X 
X 
X 
 
 
 
 
 
Part 4 
C1D1 
X 
X 
X 
X 
X 
X 
X 
 
C1D3 
X 
X 
X 
 
 
X 
 
 
C1D12 
X 
X 
X 
 
 
X 
 
 
CXD1 
X 
X 
X 
 
 
 
 
 
C = cycle; D = day; PK = pharmacokinetics, SOI = start of infusion; EOI = end of infusion. 
 


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2 INTRODUCTION 
2.1 
Background 
2.1.1 
Advanced Stage Cancer Patient Population 
Starting with Amendment 9.0 (expansion cohort), Parts 3 and 4 will enroll subjects with relapsed 
or refractory (r/r) large B-cell lymphoma after 2 or more lines of systemic non-Hodgkin 
Lymphoma (NHL) therapy and who are not eligible to receive candidates for curative therapy. 
See Section 5 for all eligibility criteria. 
2.1.2 
Epidemiology, Classification, and Treatment Standards 
Non-Hodgkin’s Lymphomas: The 2019 SEER database estimated 74,200 patients in the United 
States (US) would be diagnosed with NHL, or approximately 26,000 people with diffuse large 
B-cell lymphoma (DLBCL) or approximately 7.8/100,000 (Howlader, 2019). Amongst B-cell 
NHL subtypes, DLBCL is the most frequent at approximately 36%, according to the SEER data 
base. Rates, however, vary by region. In the United Kingdom, the annual incidence of DLBCL is 
8.5/100,000 (HMRN, 2020) yet across Europe, the incidence is reported to be approximately 
3.8/100,000 (Vitolo, 2016; Møller, 2004) possibly reflecting differences in genetic and 
environmental risk factors. This latter figure is similar to the incidence of DLBCL in Australia 
(approximately 2/100,000) (NCCI, 2020). In Taiwan, the incidence of DLBCL is approximately 
3/100,000 (Ko, 2018), in South Korea, China and Japan, approximately 3.8/100,000 (Yoo, 2018; 
Miyoshi, 2018; Sun, 2012).  
Lymphoma includes a heterogeneous group of malignancies originating from lymphoid tissues 
(mainly of lymph nodes) with different biology and prognoses divided into 2 large groups of 
neoplasms: (1) non-Hodgkin’s lymphoma and (2) Hodgkin’s disease. Various neoplastic 
malignant cell lines correspond to each of the cellular components of antigen stimulated 
lymphoid follicles. Almost 85% of NHLs are of B-cell origin; only 15% are derived from T-cells 
or Natural Killer cells, and the small remainder arises from macrophages.  
Non-Hodgkin Lymphoma represents a progressive clonal expansion of a lymphoid cell line 
arising from an accumulation of lesions affecting proto-oncogenes or cancer suppressor genes, 
resulting in cell immortalization. Although a variety of laboratory and imaging studies are used 
in the evaluation and staging of suspected NHL, a well-processed section of an excised lymph 
node is the mainstay of pathologic diagnosis. NHL subtypes are characterized by the level of 
differentiation, the size of the cell of origin, the originating cell's rate of proliferation, and the 
histologic pattern of growth. Several cytogenetic lesions are associated with specific NHLs, 
reflecting the presence of specific markers of diagnostic significance in sub-classifying various 
NHL subtypes. 
Non-Hodgkin Lymphoma includes many clinicopathologic subtypes, each with a distinct 
epidemiology, etiology morphology, immunophenotype, genetic features, clinical characteristics 
and response to therapy. For many of the B-cell NHL subtypes, the pattern of growth and cell 


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size may be important determinants of NHL tumor aggressiveness. Non-Hodgkin Lymphoma 
tumors that grow in a nodular pattern are generally less aggressive than lymphomas that 
proliferate in a diffuse pattern. Lymphomas of small lymphocytes generally have a more indolent 
course than those of large lymphocytes, which may have intermediate-grade or high-grade 
aggressiveness. However, some subtypes of high-grade lymphomas are characterized by small 
cell morphology.  
The treatment of B-cell NHL varies greatly, depending on tumor stage, grade, and type as well as 
several clinical factors. The 5-year relative survival rate of patients with NHL is approximately 
63%. The survival rate has steadily improved over the last 2 decades, due to improvements in 
medical and nursing care, the advent of monoclonal antibodies (mAbs), including 
CD20-targeting therapies, validation of biomarkers of response, and the implementation of 
tailored treatment.  
2.1.3 
Anti-CD20 mAb Therapy for Non-Hodgkin Lymphoma  
Anti-CD20 mAb therapy has become a ubiquitous component of treatment regimens for B-cell 
malignancies. Clinically active anti-CD20 mAbs used for the treatment of NHL can be separated 
into 2 types based on cellular effects observed on binding to CD20-expressing B-cells. Type I 
antibodies (rituximab and ofatumumab) induce redistribution of CD20 into large lipid rafts in the 
plasma membrane and have strong complement-dependent cytotoxicity (CDC) and 
antibody-dependent cell-mediated cytotoxicity but have minimal direct antitumor effects. Type II 
antibodies (tositumomab and obinutuzumab) do not induce redistribution of CD20, have minimal 
CDC, strong antibody-dependent cell-mediated cytotoxicity and increased direct antitumor 
effects. Although fully humanized mAbs should be less immunogenic than the chimeric 
rituximab, none of the more recently approved anti-CD20 antibodies appears to be clinically 
more effective against NHL in direct comparisons, perhaps because of patients’ baseline immune 
status (Maloney, 2012). 
A multinational retrospective study (SCHOLAR-1) analyzed overall response rate (ORR) and 
overall survival (OS) in 636 patients with r/r NHL including DLBCL, follicular lymphoma (FL) 
and primary mediastinal B-cell lymphoma (PMBCL)based on 2 Phase 3 trials (LYSA/CORAL, 
CCTG/LY.12) and 2 observational cohorts from MD Anderson and University of Iowa/Mayo 
Clinic (Crump 2017). For patients with refractory (refractory included patients who relapsed 
early ie, within 12 months of stem cell therapy) DLBCL, ORR was 26% (CR 7%) to next line 
therapy, and OS was 6.3 months, with 2-year survival rate of 20%. Overall response rate in 
patients relapsing after 2nd line therapy was 26% (CR 10%). Response significantly correlated 
with survival, especially when patients were able to proceed to stem cell therapy thereafter thus 
emphasizing the importance of novel salvage treatments. 
Most patients across all types of NHL eventually become refractory to all anti-CD20 mAb 
treatments. There are several mechanisms by which this can happen, including increased mAb 
catabolism, initial development or post treatment selection of malignant cells with low levels of 
surface CD20 expression, resistance to mAb effector mechanisms and/or impaired immune cell 
function (Tedder, 1988). It has also been shown that anti-CD20 mAbs induce internalization of 
CD20 by malignant cells, where the degree of internalization is higher with Type I anti-CD20 


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mAbs (Beers, 2010). The internalization requires the binding of the fragment crystallizable 
region (Fc) tail of the mAb to the Fcγ receptor IIb (FcγRIIb) on the malignant B-cell. Differential 
FcγRIIb expression has been correlated with resistance to anti-CD20 therapy in different types of 
B cell malignancies (Lim, 2011). CD20 can also be removed from the B-cell surface following 
the molecular reorganization known as trogocytosis, which occurs during the conjugation 
between the Fcγ receptor on B-cells and the antigen-presenting immune cells (Beum, 2011). 
Further, due to their relatively large size, typically, less than 0.01% of the injected dose of an 
anti-CD20 mAb localizes to NHL tumors in human subjects (Milenic, 1991). 
2.2 
Molecular Templates Investigational Product Background: MT-3724 
MT-3724 is a recombinant homodimeric fusion protein. Each monomer consists of a single chain 
variable fragment (scFv) with affinity for human CD20 cell surface protein fused to the 
enzymatically active Shiga-like toxin-I A1 subunit (SLT-I A1). The primary structure of 
MT-3724 is a single polypeptide chain consisting of 512 amino acids of an approximate 
molecular weight of 55 kiloDaltons (kDa) (data on file). The theoretical molecular weight of the 
MT-3724 homodimer is ~ 110.4 kDa. MT-3724 has been shown to specifically bind and kill 
CD20-expressing malignant B-cells (Rajagopalan, 2013). 
As a direct-kill immunotoxin directed against CD20, MT-3724 could achieve malignant cell lysis 
in refractory or relapsed NHL regardless of the biologic variations of malignant B-cells or 
patient’s immune status. The smaller size of MT-3724 may offer an advantage over anti-CD20 
mAbs enabling better tumor penetration. The scFv in MT-3724 binds to a CD20 epitope within 
rituximab’s binding domain. While able to bind to CD20, the scFv in MT-3724 lacks an intact Fc 
region and does not rely on host antibody-directed cytotoxicity or CDC to induce cell death. The 
scFv in MT-3724 should not be adversely impacted by reduction of CD20 B-cell expression via 
internalization or trogocytosis. Thus, MT-3724 could avoid, mitigate or delay the emergence of 
resistance to anti-CD20 mAb therapy and offer potential benefit in unmet medical need. 
2.2.1 
 Summary of Clinical Experience 
The clinical development program for MT-3724 is being evaluated in 3 ongoing studies: 
1 monotherapy study (MT-3724_NHL_001 [NHL_001]) and 2 combination therapy studies 
(MT-3724_NHL_002 [NHL_002] and MT-3724_NHL_003 [NHL_003]) with gemcitabine and 
oxaliplatin (GEMOX) and lenalidomide (LEN), respectively. Further studies of MT-3724 in 
other subtypes of NHL are planned. 
Data from the MT-3724 monotherapy study, NHL_001, showed clinical antitumor activity in 
heavily pre-treated subjects with relapsed or refractory DLBCL who had low serum level of 
rituximab before the start of treatment.  
Across 3 studies (NHL_001, NHL_002 and NHL_003) as of 28 August 2020, capillary leak 
syndrome (CLS) has been reported in 5 subjects: 2 subjects from NHL_001 dosed at 
75 μg/kg/dose, 2 subjects from NHL_002 dosed at 10 μg/kg/dose, and 1 subject from NHL_003 
dosed at 25 μg/kg/dose. The maximum severity for all events was Grade 2. After the data cutoff, 
1 event of Grade 5 CLS was reported in the NHL_001 study, Part 3 dosed at 50 μg/kg/dose. As a 


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result, more stringent safety measures are implemented in all MT-3724 trials including this 
protocol version. 
Important identified risks for MT-3724 include infections (including pneumonia and viral 
infections), CLS, Neutropenia, and Edema and Peripheral Edema. Important potential risks 
include acute kidney injury, Myalgia/muscle weakness, systemic inflammatory response 
syndrome (SIRS)/ cytokine release syndrome (CRS), Infusion related reactions, Tumor lysis 
syndrome, and Reproductive risk.  
Adverse events of special interest include Neutropenia, acute kidney injury, CLS, SIRS/CRS. 
Please refer to the Investigator’s Brochure for comprehensive information available for MT-3724 
to date. 
2.2.2 
Guidance to the Investigator for Capillary Leak Syndrome 
Capillary leak syndrome typically occurs during earlier cycles of treatment. Capillary leak 
syndrome is suspected if the subject experiences at least 2 of the following signs and/or 
symptoms within the same cycle (unless unequivocally related to underlying condition): 
• 
Hypoalbuminemia 
• 
Hypotension 
• 
Edema (peripheral or central, all types) and/or weight gain 
Subjects should be closely monitored for signs and symptoms of CLS. This includes monitoring 
of vital signs (temperature, heart rate, blood pressure [BP], respiration rate), body weight and 
edema of any type including both peripheral edema and central edema (such as pleural effusion 
or signs of dyspnea), and monitoring of laboratory parameters including hemoconcentration (eg, 
hematocrit, Hb), and especially albumin and creatine phosphokinase (CK) in case of clinical 
symptoms indicative of CLS. 
Refer to the MT-3724 CLS management guide. 
Refer to Section 6.2 for dose modification guidelines. 
3 OBJECTIVES AND ENDPOINTS 
3.1 
Part 3 Objectives and Endpoints 
OBJECTIVES 
ENDPOINTS 
Primary 
• 
To evaluate the safety of MT-3724 as 
monotherapy in subjects with relapsed or 
refractory diffuse large B-cell lymphoma 
(DLBCL) 
• 
adverse events (AE) 
• 
laboratory abnormalities 
• 
vital signs 
Secondary 
• 
To evaluate the efficacy of MT-3724 as 
monotherapy in subjects with relapsed or 
• 
Overall response rate is defined as the proportion 
of subjects with either a complete response (CR) 


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OBJECTIVES 
ENDPOINTS 
refractory DLBCL based on the overall response 
rate (ORR) by the Lugano Classification for 
Lymphoma (Cheson, 2014) 
or a partial response (PR) as determined by 
independent, blinded central review 
x
To evaluate additional measures of efficacy of
MT-3724 as monotherapy in subjects with
relapsed or refractory DLBCL
x
Overall response rate, defined as the proportion of
subjects with either a CR or a PR as determined by
investigator assessment
x
duration of tumor response (DOR), defined as time
from initial documentation of tumor response (CR
or PR) to disease progression
x
disease control rate (DCR), defined as proportion
of subjects who have achieved CR, PR and stable
disease (SD; defined as SD for 6 months or longer)
x
To evaluate the pharmacokinetics (PK) of
MT-3724 as monotherapy in subjects with
relapsed or refractory DLBCL
x
Pharmacokinetics parameters, where calculable,
include: maximum observed plasma concentration
(Cmax), time to achieve Cmax (tmax), and area under
the plasma concentration time curve from 0 to
4 hours (AUC0-4), AUC from 0 to infinity (AUC0-
inf), AUC from dosing to last measurable
concentration (AUClast), half-life (t1/2), volume of
distribution (Vz), and clearance (CL)
x
To evaluate the pharmacodynamics of MT-3724 as
monotherapy in subjects with relapsed or
refractory DLBCL
x
B-cell count
x
Immunophenotyping
x
Circulating immunoglobulins (IgA, IgG, IgM)
x
To evaluate the immunogenicity of MT-3724 as
monotherapy in subjects with relapsed or
refractory DLBCL
x
incidence of anti-drug antibodies (ADA)
Exploratory 
PPD


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3.2 
Part 4 Objectives and Endpoints 
OBJECTIVES 
ENDPOINTS 
Primary 
x 
To determine the efficacy of MT-3724 as 
monotherapy in subjects with relapsed or 
refractory DLBCL based on the ORR by the 
Lugano Classification for Lymphoma (Cheson, 
2014) 
x 
overall response rate is defined as the proportion 
of subjects with either a CR or a PR as determined 
by independent, blinded central review 
Key Secondary 
x 
To determine additional measures of efficacy of 
MT-3724 as monotherapy in subjects with 
relapsed or refractory DLBCL 
x 
Duration of tumor response, defined as time from 
initial documentation of tumor response (complete 
response [CR] or partial response [PR]) to disease 
progression 
Secondary 
x 
To determine the safety of MT-3724 as 
monotherapy in subjects with relapsed or 
refractory DLBCL 
x 
adverse events 
x 
laboratory abnormalities 
x 
vital signs 
x 
To evaluate the effect of MT-3724 on the QT/QTc 
interval in subjects with relapsed or refractory 
DLBCL 
x 
electrocardiograms (ECGs) 
x 
adverse events suggestive of cardiotoxicity 
x 
To determine additional measures of efficacy of 
MT-3724 as monotherapy in subjects with 
relapsed or refractory DLBCL 
x 
overall response rate, defined as the proportion of 
subjects with either a CR or a PR as determined by 
investigator assessment 
x 
disease control rate (DCR), defined as proportion 
of subjects who have achieved CR, PR and SD 
(defined as SD for 6 months or longer) 
x 
progression-free survival (PFS), defined as the 
time from study enrollment to the earliest date of 
disease progression or death from any cause 
x 
overall survival (OS), defined as the time from 
study enrollment to death from any cause 
x 
To determine the pharmacokinetics (PK) of 
MT-3724 as monotherapy in subjects with 
relapsed or refractory DLBCL 
x 
Pharmacokinetics parameters, where calculable, 
include: Cmax, tmax, AUC0-4, AUC0-inf, AUClast, t1/2, 
Vz and CL 
x 
To determine the pharmacodynamics of MT-3724 
as monotherapy in subjects with relapsed or 
refractory DLBCL 
x 
B-cell count 
x 
Immunophenotyping 
x 
Circulating immunoglobulins (IgA, IgG, IgM) 
x 
To determine the immunogenicity of MT-3724 as 
monotherapy in subjects with relapsed or 
refractory DLBCL 
x 
incidence of ADA 
Exploratory 
PPD


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OBJECTIVES 
ENDPOINTS 
4 STUDY DESIGN 
4.1 
Overall Design 
This is a Phase 1-2, multiple ascending dose study: Part 1, enrolled subjects with progressive 
B FHOO1+/ZLWKPHDVXUDEOHGLVHDVHOHVLRQFPRUDEVROXWHSHULSKHUDOEORRGPRQRFORQDO
CD20-positive/CD5-positive B-O\PSKRF\WHFRXQWFHOOVȝ/ZKRKDGUHFHLYHGVWDQGDUG
treatment with at least 1 anti-CD20 antibody containing front-line regimen that resulted in initial 
response, followed by relapse/recurrence and who were not eligible for any further approved 
biologic therapy, chemotherapy and/or autologous stem transplantation and/or refused alternative 
approved therapies and/or were unlikely to achieve clinical benefit from any therapy of higher 
priority by investigator assessment. 
The Part 2 maximum tolerated dose (MTD) expansion cohort was a multi-center, multinational, 
Phase 2 open-label, single-arm evaluation of MT-3724 given as monotherapy in repeat doses in 
subjects with relapsed or refractory DLBCL who had received 2 or more prior lines of systemic 
NHL therapy. Only subjects with relapsed/refractory DLBCL were to be enrolled in Part 2. 
Preliminary data indicated this DLBCL sub-population had a positive response to treatment 
given at doses up to and including the MTD. 
Parts 3 and 4 will be a multi-center, multinational, open-label, single-arm evaluation of MT-3724 
given as monotherapy in repeat doses in subjects with relapsed or refractory DLBCL who have 
received 2 or more lines of prior therapy. 
Eligible subjects will be identified and treated through competitive enrollment across multiple 
global sites. 
4.1.1 
Part 3 
In Part 2 of the study, the MTD of MT-3724 was determined to be 50 μg/kg/dose administered 
on Days 1, 3, 5, 8, 10, and 12 of each 21-day cycle. The dose and schedule is now adjusted due 
to observations of CLS in subjects treated in the Part 3 of the study. 
Part 3 will be a continuation of the expansion of the MTD cohort with the intention to verify the 
safety, dose and dosing schedule in approximately 25 subjects (see Section 6.1). 
Part 3 will include 2 new cohorts of subjects, which will be enrolled sequentially with step-up 
dosing. At least 6 subjects must be enrolled on a cohort with no more than 1 dose-limiting 
PPD


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toxicity (DLT) for that dose and treatment schedule to be declared the MTD. The MTD will be 
used to establish the recommended phase 2 dose (RP2D). 
The DLT assessment period is 21 days. DLTs will be assessed during Cycle 1 of each enrolled 
dose cohort.  
Starting with enrollment into Cohort 1, a minimum of 6 eligible subjects will be enrolled into 1 
of 2 predefined sequential dose cohorts, unless precluded by DLTs. Each dose cohort is deemed 
intolerable if 2 or more DLTs occur at any time in Cycle 1.  
If permitted by the safety results, the MT-3724 dose escalation is planned to proceed in 
sequential dose cohorts. Before each dose escalation decision, the sponsor, investigators and 
independent pharmacovigilance physician will review all available data in the current dose 
cohort. The safety management team must decide by consensus whether it is safe to proceed to 
the next planned dose level, or to another dose not pre-specified in the protocol.  
4.1.1.1 
Subject Evaluable for Dose Decisions  
Subjects in Part 3 will be evaluable for dose decisions if they satisfy one of the following 
criteria:  
• Have had a DLT after at least one dose of MT-3724 in Cycle 1; or  
• In the absence of toxicities that have delayed or caused omission of doses, subjects have 
received at least 4 of 6 (67%) doses of MT-3724 within 21 days 
Subjects who are not evaluable for dose decisions will be replaced. 
4.1.2 
Part 4 
The goal of Part 4 is to provide sufficient evidence to test the null hypothesis that the true 
response rate with MT-3724 ≤ 17% vs the alternative hypothesis that the true response rate with 
MT-3724 ≥ 32% at the 1-sided alpha level of 0.025 with high statistical power. At least 
88 evaluable subjects will be required to test the null hypothesis vs the alternative hypothesis in 
Part 4. If at least 23 of 88 subjects respond at the end of Part 4, then the null hypothesis is 
rejected in favor of the alternative hypothesis and the effectiveness of MT-3724 as monotherapy 
will have been proven. Under the stated null and alternative hypotheses, Part 4 carries 
90.4% power at the 1-sided alpha level of < 0.025. 
4.1.3 
Parts 3 and 4 
All study procedures will be the same for Parts 3 and 4. After eligibility is assessed in the 
screening period (up to 35 days), subjects enter the treatment period. Each treatment cycle will 
be 21 days in length. Treatment will continue until death, disease progression, unacceptable 
toxicity, withdrawal of consent, or another reason for withdrawal, or until study discontinuation. 
Refer to Section 6.1.1.4 for details regarding treatment beyond progression. 


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End of Treatment: After discontinuation from treatment, all subjects should undergo the End of 
Treatment (EoT) Visit as soon as possible (up to 14 days) after the last dose of MT-3724 and 
before start of new therapy. 
Short-term Safety Follow-up: The Short-term Follow-up (STFU) Visit for safety assessment 
should occur 30 days (± 3 days) after the last dose of MT-3724, except for subjects who 
withdrew consent and objected to further data collection, started new therapy for DLBCL or 
started another investigational drug. 
Long-Term Follow-up: Long-term Follow-up (LTFU) Visits should occur every 3 months 
(± 14 days) after the last dose of MT-3724 for up to 18 months from the last dose. Subjects who 
discontinue the study for disease progression will be followed only for OS. Subjects with CR, 
PR, or SD should also be followed for radiology assessment until progressive disease (PD), 
death, or start of new anticancer treatment.  
4.2 
End of Study 
4.2.1 
End of Study Definition 
Primary Completion: The primary completion date is defined as the date when the last subject 
is assessed or receives an intervention for the final collection of data for the primary endpoint(s) 
for the purposes of conducting the primary analysis. This date is defined as when the last subject 
has completed all planned assessments for clinical outcomes. 
End of Study (End of trial): The end of the study is defined as the date of the last visit of the 
last subject in the study or last scheduled procedure shown in the Schedule of Activities for the 
last subject in the trial globally. 
5 STUDY POPULATION 
NOTE: The investigator or sub-investigator must judge all pre-admission vital signs, physical 
examination (PE), laboratory or any safety variables to be within normal limits or clinically 
insignificant. If local standard of care (SoC) procedures or tests were performed prior to signing 
of the informed consent form (ICF) but are still within 35 days (or 28 days for laboratory safety 
and radiographic assessments) of the planned dose Day 1, then those results/data can be used for 
the intended protocol screening procedure. If various parameters within a given procedure are 
missing from the SoC procedures, then only those missing parameters need to be collected. The 
medical monitor will also review all screening data to confirm each subject’s eligibility prior to 
dosing initiation. Any laboratory results that exclude study participation may be repeated to 
confirm accurate exclusion from the study. A subject who is no longer excluded upon retest will 
be reviewed again by the medical monitor prior to dosing initiation. 
In addition, prior to first dose of MT-3724 on Cycle 1 Day 1 (C1D1), the investigator must 
confirm there have been no changes in the subject’s health that would render them medically 
inappropriate to begin protocol therapy.  


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Before any study-specific activities/procedures, the appropriate written informed consent must 
be obtained (see Section 10.1.4). Prospective approval of protocol deviations to recruitment and 
enrollment criteria, also known as protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
Subjects meeting ALL of the following inclusion criteria will be eligible for participation of the 
study: 
1. Subjects must be informed about the study and fully consent to participation as demonstrated
by signing the written ICF before any screening procedure.
2. Male and female subjects ≥ 18 years of age at the time of informed consent
3. Subjects must have relapsed or refractory DLBCL according to the Revised European
American Lymphoma/World Health Organization classification (Swerdlow, 2016). Subjects
must have proof of CD20+ DLBCL, based on either:
a.
historical biopsies (obtained with diagnosis of relapsed or refractory disease), or
b. fresh biopsies
c.
bone marrow biopsy, excisional lymph node biopsy, and core biopsy of any involved
organ are all acceptable methods; Fine Needle Aspirate is not acceptable.
NOTE: Composite lymphoma (DLBCL and indolent histology in the same specimen) is
also acceptable.
4. Subjects must have received at least 2 SoC regimens (including anti-CD20 antibody therapy)
appropriate for DLBCL treatment.
a.
Subjects whose prior therapy includes CAR-T-cell therapy are eligible
b. Subjects who underwent stem cell transplant (SCT) > 100 days for autologous SCT or
> 180 days for allogeneic SCT before study drug administration.
c.
Subjects who have been ineligible for SoC DLBCL treatment(s) may be eligible at the
investigator’s discretion, upon sponsor approval.
5. Subjects must have at least 1 bi-dimensional tumor lesion at screening that is measurable by
CT and/or magnetic resonance imaging (MRI) according to the Lugano criteria (Cheson,
2014). Bi-dimensionally measurable tumor lesion by CT and/or MRI is defined as longest
diameter of > 1.5 cm for lymph nodes and > 1.0 cm for extranodal disease.
6. Subjects must have life expectancy of > 3 months from the start of treatment.
7. Subjects must have ECOG performance status of 0-2.
8. Subjects must have met ALL the following laboratory criteria:
a.
absolute neutrophil count (ANC) ≥ 1.0 × 109/L with no myeloid growth factors
(granulocyte colony-stimulating factor [G-CSF] or granulocyte‐macrophage
colony-stimulating factor preparations) administered within 2 weeks of C1D1
b. platelet count ≥ 50 × 109/L with no Thrombopoietin-receptor agonists agents or platelet
transfusions given within 2 weeks of C1D1


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c. hemoglobin ≥ 8.0 g/dL with no erythropoietin stimulating agents or peripheral red blood 
cell (PRBC) transfusions within 2 weeks of C1D1 
d. creatinine clearance (CLcr) to be ≥ 50 ml/min either measured or estimated using the 
Cockcroft-Gault formula (Section 10.2.2.2).  
e. total bilirubin (or direct bilirubin for patients with Gilbert’s disease) < 1.5 × upper limit 
of normal (ULN) 
f. alanine transaminase (ALT) ≤ 3.0 × ULN (or ≤ 5.0 x ULN if liver involvement). 
g. aspartate aminotransferase (AST) ≤ 3.0 × ULN (or ≤ 5.0 x ULN if liver involvement). 
h. international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN (unless on 
therapeutic anticoagulants) 
i. Activated partial thromboplastin time ≤ 1.5 x ULN (unless on therapeutic anticoagulants) 
9. Have adequate serum albumin, as determined by: 
a. albumin ≥ 3.0 g/dL  
10. QT interval correction for heart rate using Fridericia’s formula (QTcF) ≤ 480 ms determined 
as the average of 3 QTcF values from the triplicate ECG obtained at screening. 
11. Women of reproductive potential must have a negative highly sensitive pregnancy test within 
72 hours before the start of treatment. Women who are postmenopausal or permanently 
sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy) may be considered as 
not of reproductive potential.  
12. Subjects of reproductive potential must agree either to abstain continuously from 
heterosexual intercourse or to use a highly effective birth control method from signing the 
informed consent until the STFU visit for females and until 90 days after the last dose of 
MT-3724 for males. Refer to Section 10.4 for guidance on contraception.  
13. Subject must be able to comply with all study-related procedures and medication use. 
 
5.2 
Exclusion Criteria 
Subjects who meet ANY of the following criteria must be excluded: 
Prior or Current Therapies 
1. Received any amount of anti-CD20 mAbs within the following periods before the start of 
treatment:  
a. Rituximab (Rituxan®/MabThera® or rituximab biosimilar): within 84 days (12 weeks); if 
a subject has received rituximab within 37 weeks before the start of treatment, then serum 
rituximab level must be negative (< 500 ng/mL) at screening. 
b. Obinutuzumab (Gazyva®/Gazyvaro®): 184 days 
c. Ofatumumab (Arzerra®): 88 days 
d. Any other anti-CD20 agents (eg, investigational agents), the washout period is 5 
half-lives. The investigator must contact the medical monitor to discuss the most 


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appropriate washout for non-approved CD20-targeting agents, where the half-life (t1/2) is 
not known. 
2. Received approved or investigational treatment for DLBCL (except anti-CD20 agents where 
exclusion criterion 1 applies and radioimmunoconjugates) within 4 weeks before the start of 
treatment. For small molecules (MW < 0.9 kDa), the washout is 5 half-lives or at least 
2 weeks. Radioimmunoconjugates are excluded within 12 weeks before the start of treatment.  
3. Received radiation therapy to tumor lesions that would serve as target lesions (measurable 
disease) within 4 weeks before the start of treatment, unless the lesion exhibited objective 
progression between radiation therapy and screening according to the Lugano Classification 
(Cheson, 2014).  
a. Palliative radiation therapy to non-target lesions may be permitted at the investigator’s 
discretion after consultation with the medical monitor and sponsor. See Section 6.5 for 
more information on permissible use of palliative radiotherapy. 
4.  Require the use of systemic immune modulators during study treatment: 
a. Systemic immune modulators include, but are not limited to, systemic corticosteroids at 
doses > 20 mg/day of prednisone equivalent, cyclosporine and tacrolimus. Please see 
Section 6.1.3 for more details and exceptions. 
b. The use of non-steroidal anti-inflammatory drugs (NSAIDS) is permitted. 
5. Received any live vaccines within 4 weeks before the start of treatment.  
6. Prior treatment with MT-3724. 
Medical History 
7. Current evidence of Common Terminology Criteria for Adverse Events (CTCAE) Grade > 1 
toxicity (due to prior anticancer therapy) before the start of treatment, except for hair loss and 
those Grade 2 toxicities listed as permitted in other eligibility criteria.  
8. Current evidence of significant (CTCAE Grade ≥ 2) infection or wound within 4 weeks 
before the start of treatment.   
a. Subjects with Grade 2 infection that has stabilized or improved with oral anti-infectives 
before the start of treatment may be eligible at the sponsor’s discretion.  
9. Known or suspected hypersensitivity to the study drug or excipients contained in the study 
drug formulation. 
10. Current evidence of hypersensitivity or other underlying illness requiring systemic 
corticosteroids at doses > 20 mg/day prednisone equivalent 
11. Current evidence of uncontrolled human immunodeficiency syndrome (HIV), HBV or HCV 
at screening. Serology testing is not required if seronegativity is documented in the medical 
history, and if there are no clinical signs suggestive of HIV or hepatitis infections, or 
suspected exposure. The following exceptions apply for subjects with positive viral serology: 
a. Subjects with HIV and an undetectable viral load and CD4+ T-cell (CD4+) counts 
≥ 350 cells/mL may be enrolled, but must be taking appropriate opportunistic infection 
prophylaxis, if clinically relevant. 


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b. Subjects with positive HBV serology are eligible if they have an undetectable viral load 
and the subject will receive antiviral prophylaxis for potential HBV reactivation per 
institutional guidelines.  
c. Subjects with positive HCV serology are eligible if quantitative PCR for plasma HCV 
RNA is below the lower limit of detection. Concurrent antiviral HCV treatment per 
institutional guidelines is allowed. 
12. Current evidence of incomplete recovery from surgery or radiotherapy before start of 
treatment, or planned surgery or radiotherapy from the start of treatment until the EoT visit, 
except minor elective surgery deemed acceptable by the investigator or palliative radiation 
therapy to non-target lesions, as described in Section 6.5. 
13. History of cardiovascular, renal, hepatic or any other disease within 3 months before the start 
of treatment that in the investigator’s opinion, may increase the risks associated with study 
participation or require treatments that may interfere with the conduct of the study or the 
interpretation of study results. 
14. History or current evidence of neoplastic disease that is histologically distinct from NHL, 
except cervical carcinoma in situ, superficial noninvasive bladder tumors, curatively treated 
Stage I-II non-melanoma skin cancer. Subjects with prior, curatively treated cancer > 2 years 
ago before the start of treatment can be enrolled.  
15. Current evidence of new or growing brain or spinal metastases during screening. Subjects 
with known brain or spinal metastases may be eligible if they:  
a. Had radiotherapy or another appropriate therapy for the brain or spinal metastases; 
concurrent prophylactic treatment is allowed  
b. Neurologic symptoms must be stable and no worse than Grade 2 
c. Have evidence of stable brain or spinal disease on CT or MRI scan obtained within 
4 weeks before signing the informed consent and compared with prior imaging results 
d. Do not require steroid therapy (or, if applicable, have been stable on dose of no more than 
prednisone 20 mg/day or equivalent by C1D1) 
16. Women who are pregnant or breastfeeding. 
17. History of non-adherence to the schedule of procedures or medication use. 
18. Current evidence of Graft vs Host Disease 
19. History or current evidence of significant cardiovascular disease including, but not limited to, 
the following conditions: 
a. Unstable angina (symptoms of angina at rest) or new-onset angina within 3 months 
before the start of treatment. 
b. Arterial thrombosis or pulmonary embolism within 3 months before the start of 
treatment. 
c. Myocardial infarction or stroke within 3 months before the start of treatment. 
d. Pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade ≥ 2), non-malignant 
pleural effusion (CTCAE Grade ≥ 2) or malignant pleural effusion (CTCAE Grade ≥ 3) 
within 3 months before the start of treatment with MT-3724.  


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e. Congestive heart failure (New York Heart Association [NYHA] Class III or IV) at 
screening or left ventricular ejection fraction (LVEF)  45%, assessed by echocardiogram 
(ECHO) or multigated acquisition (MUGA) scan within 1 month before starting study 
treatment (inclusion of subjects with LVEF between 40% to 45% should be discussed 
with the medical monitor and approved by the sponsor). (ECHO or MUGA performed 
within 6 months before screening and at least 28 days after the last cancer therapy is 
acceptable provided the subject has not received any potentially cardiotoxic agents since 
then). 
f. Cardiac arrhythmia requiring anti-arrhythmic therapy at screening. Subjects receiving 
digoxin, calcium channel blockers, or beta-adrenergic blockers are eligible at the 
investigator’s discretion after consultation with medical monitor and sponsor if the dose 
KDVEHHQVWDEOHIRU 2 weeks before the start of treatment with MT-3724. Subjects with 
sinus arrhythmia and infrequent premature ventricular contractions are eligible at the 
investigator’s discretion. 
5.3 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently entered in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure subjects to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any 
serious adverse event (SAE) deemed related to a protocol screening procedure. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Informed consent is required before subjects can be rescreened if outside the original 
35-day screening window. See Section 10.1.4 for Informed Consent Process details. 
6 STUDY TREATMENT 
6.1 
Study Treatment(s) Administered 
As a standard precaution for all study drugs, subjects must be treated and observed in an area 
with equipment for resuscitation including assisted ventilation and emergency treatments or have 
access to emergency facilities through an emergency call. Adequate management and treatment 
of infusion-related reaction (IRR), anaphylactic reaction or other hypersensitivity events 
according to institutional guidelines must always be assured during the treatment period. 
6.1.1 
Investigational Product: MT-3724 
MT-3724 is the only investigational medicinal product in this study. 
MT-3724 will be supplied as a sterile aqueous solution (pH 
) in a 2 ml vial containing 2.0 mL 
of MT-3724 (0.5 mg/ml) in a formulation buffer comprised of sorbitol 
 mM), sodium citrate 
 mM) and polysorbate-20 
%). Vials are shipped frozen. Each vial will be labeled with the 
PP
D
PPD
PP
D
PP
D


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drug name, lot number, storage conditions, and US Food and Drug Administration 
(FDA)-required Investigational Product statement.  
MT-3724 vials must be stored in a secure facility at 
 until thawed for use. 
It is recommended to use the thawed drug to prepare the final solution for infusion within 
3 hours, although MT-3724 is stable at room temperature for up to 24 hours.  
During preparation of the final solution for infusion, MT-3724 is diluted in
 dextrose in water 
or normal saline for intravenous (IV) administration. All doses should be administered over 
1 hour (54 – 75 minutes) through an IV line. See Pharmacy Manual for detailed instructions and 
worksheets regarding study drug preparation and administration. 
Investigational product must be received at the study site by a designated person, handled and 
stored safely and properly, and kept in a secured location to which only the investigator and 
designated staff have access. Upon receipt, the investigational product should be stored 
according to the instructions specified on the label and in the Pharmacy Manual. Clinical 
supplies are to be dispensed only in accordance with the protocol. Storage conditions must be 
adequately monitored, and appropriate temperature logs maintained as Source data.  
The investigator is responsible for the accountability of the investigational product. Records of 
the receipt and disposition of the investigational product must be maintained in the trial master 
file at the site. Records and drug supplies must be available for inspection by the study monitor. 
6.1.1.1 
Dose Rationale 
Administration of fixed doses of MT-3724 generated early signs and symptoms of an acute 
innate immune response, limiting a tolerable dose to 50 μg/kg/dose in a monotherapy setting. 
However, given the short t1/2 of MT-3724 and its mechanism of action, it is expected that the 
Cmax is critical for cytotoxicity. Furthermore, rapid-onset AEs can be reduced in frequency and 
severity with other antibody therapies by incrementally increasing dose over time, as described 
below.  
To mitigate safety risks, the proposed step-up dose regimen for MT-3724 will not exceed the 
MTD of 50 μg/kg/dose identified in Parts 1 and 2 of the study. In addition, the maximum dose 
will be 1200 μg at the 10 μg/kg dose level, 3000 μg at the 25 μg/kg dose level and 6000 μg at 
the 50 μg/kg dose level.   
6.1.1.2 
Dose Selection 
Part 3: 
Two dosing cohorts are planned to complete Part 3 of the protocol to confirm the tolerable dose 
and schedule. A minimum of 6 subjects will be enrolled in each cohort. Following the 
completion of the Part 3, Part 4 of the protocol will be initiated using the regimen identified as 
tolerable in Part 3. Dose-limiting toxicity will be assessed during Cycle 1 of Cohorts 1 and 2. 
The dose and schedule are described in Table 6-1.  
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Cohort 1: 
The starting MT-3724 dose for each subject will be 10 µg/kg for the first 2 doses (D1, 
D3) and then increased to 25 µg/kg for the remaining doses (D5, D8, D10, D12) of the 
first 21-day cycle and all doses of Cycle 2 (D1, D3, D5, D8, D10, D12). Dosing will then 
continue at 25 µg/kg weekly (D1, D8, D15), beginning with Cycle 3 (Table 6-1).   
If fewer than 2/6 subjects have a DLT in Cohort 1, then the study will proceed to 
Cohort 2. If 2 or more subjects have a DLT in Cohort 1, the study will be stopped. 
Cohort 2: 
The starting MT-3724 dose in each subject will be 10 µg/kg for the first 2 doses (D1, 
D3). The dose will then be increased to 25 µg/kg for 2 doses (D5, D8) and then the dose 
will be increased to 50 µg/kg for the remaining doses (D10, D12) of the first 21-day cycle 
and all doses of Cycle 2. Dosing will then continue at 50 µg/kg weekly (D1, D8, D15) 
beginning with Cycle 3 (Table 6-1). 
If fewer than 2/6 subjects have a DLT in Cohort 2, then the study will continue to Part 4 
using the Cohort 2 dose and schedule. If 2 / 6 subjects experience a DLT in Cohort 2, the 
study will continue to Part 4 using the Cohort 1 dose and schedule. 
Table 6-1. Step-up Dosing Schedule for Cohorts 1 and 2 
Day 
MT-3724 Dose (µg/kg)a,b 
Cohort 1 
(n = 6) 
Cohort 2 
(n = 6) 
Cycle 1 D1, D3 
10 
10 
Cycle 1 D5, D8 
25 
25 
Cycle 1 D10, D12 
25 
50 
Cycle 2 D1, D3, D5, D8, D10, D12 
25 
50 
Cycle 3+ D1, 8, 15 (weekly dosing) 
25 
50 
a 
The total administered dose of MT-3724 must not exceed 1200 µg per infusion for the 10 µg/kg dose; 
3000 µg per infusion for the 25 µg/kg dose and 6000 µg per infusion for the 50 µg/kg dose in all 
treatment cycles. 
b 
Each dose of MT-3724 must be preceded by premedication administered within 60 minutes before the 
start of each infusion (see Section 6.1.2). 
 
 
 
 


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Part 4: 
The study will continue to Part 4 using the tolerable dose and schedule determined in Part 3.   
Parts 3 and 4:  
The dose of MT-3724 in all cohorts will be calculated based on the subject’s baseline body 
weight (in kilograms [kg]). For MT-3724 dose calculation, the body weight will be measured 
before the first dose of MT-3724 in Cycle 1 (baseline for all subsequent assessments). If the 
body weight has changed by ≥ 10% from the baseline value, this will require re-calculation of 
MT-3724 dose or according to institutional policies should they require adjustment for any 
change in body weight.  
The total administered dose of MT-3724 must not exceed 1200 µg per infusion for the 
10 µg/kg dose; 3000 µg per infusion for the 25 µg/kg dose and 6000 µg per infusion for the 
50 µg/kg dose.  
The guidance for treatment modification (dose interruption / delay, dose reduction or treatment 
discontinuation) is presented in Section 6.2. 
6.1.1.3 
Dose Schedule 
All doses of MT-3724 will be administered as IV infusion over 1 hour (window = 54 to 
75 minutes) in a 21-day cycle according to the schedule specified in each cohort (Table 6-1).  
NOTE: Each dose of MT-3724 must be preceded by premedication administered within 
60 minutes before the start of each infusion (see Section 6.1.2)  
All doses should be administered within the first 16 days of the 21-day cycle. For Cycle 1 and 
2 doses are preferably administered on Days 1, 3, 5, 8, 10, and 12 (± 1 d). For Cycle 3 and later 
doses are preferably administered on Days 1, 8, and 15. All cycles should use the following 
guidelines: 
• The first 3 doses of Cycle 1 must be administered at least 2 days (approximately 48 hours) 
apart. 
• All subsequent doses must be at least 20 hours apart (more than 5 half-lives of MT-3724 in 
serum), and must not be administered on more than 2 consecutive days. 
The first dose of the first cycle will require approximately 5 hours in the clinic which include 
approximately 4 hours of post-dose safety assessments. Subsequent doses will require 
approximately 3 hours in the clinic which include approximately 2 hours of safety assessments 
post-dose (see also Section 1.3, Schedule of Activities (SoA)). 
No more than 14 days should elapse between cycles. If more than 14 days elapse, the 
investigator must consult with the medical monitor before initiating the next cycle of treatment. 
Refer to Section 6.2 for dose modification guidelines and management of toxicities.  


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Treatment will continue until death, disease progression, unacceptable toxicity, withdrawal of 
consent, or another reason for withdrawal, or until study discontinuation.  
6.1.1.4 
Treatment Beyond Progression 
For subjects who have radiological, but not clinical, evidence of disease progression within 
3 months of C1D1, in lieu of discontinuation, the investigator may continue treatment at the dose 
they are given at the time progression is identified if s/he believes the benefit outweighs the risk 
and provided the conditions identified below are met.  
Conditions for continued treatment: 
• absence of symptoms and signs, including worsening of laboratory values, indicating 
unequivocal PD, 
• no decline in Eastern Cooperative Oncology Group performance status (ECOG PS) due to 
PD, 
• absence of tumor progression at critical anatomical sites (eg, leptomeningeal disease), 
• subject’s written consent to defer any standard treatment options that may exist in favor of 
continuing MT-3724 treatment at the time of initial progression. 
Radiological assessments should be repeated in 4 to 6 weeks from the time of initial progression. 
6.1.2 
Other Protocol-required Intervention 
Premedication Before MT-3724 Infusion 
Premedication as described in Table 6-2 must be given within 60 minutes before the start of each 
MT-3724 infusion. The specific drugs in each of the 3 classes listed below can be selected at the 
investigator’s discretion or according to the institutional guideline. Cases where a subject has a 
contraindicating medical condition that precludes pre-treatment with any of the categories below 
must be discussed with the Medical Monitor. 
Table 6-2. Premedication  
Premedication Class 
Cycle 1 
Cycle 2 
Cycle 3+ 
Oral anti-pyretic agent 
325-1000 mg 
acetaminophen (or 
equivalent) 
325-1000 mg 
acetaminophen (or 
equivalent) 
325-1000 mg 
acetaminophen (or 
equivalent)1 
Intravenous H1 histamine 
receptor antagonist 
50-100 mg 
diphenhydramine (or 
equivalent) 
50-100 mg 
diphenhydramine (or 
equivalent) 
50-100 mg 
diphenhydramine (or 
equivalent)1 
Intravenous corticosteroid agent 
with a short biological half-life  
250-1000 mg 
methylprednisolone (or 
equivalent) 
250-1000 mg 
methylprednisolone (or 
equivalent)1 
250-1000 mg 
methylprednisolone (or 
equivalent)1 
1 Dose adjustment permitted following MM approval. 
 


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6.1.3 
Excluded Treatments, Medical Devices, and/or Procedures During Study Period 
The following treatments are prohibited during the study: 
• All systemic treatment for lymphoma 
• Radiation therapy to tumor lesions that would serve as target lesions (measurable disease). 
Palliative radiation therapy to non-target lesions may be permitted (see Section 6.5). 
• Systemic immune modulators, unless used for a treatment-emergent adverse event (TEAE) or 
as a premedication for MT-3724.   
o The immune modulators include, but are not limited to, systemic corticosteroids at doses 
> 20 mg/day or prednisone equivalent for more than 1 week, cyclosporin and tacrolimus. 
• Any live vaccines from 4 weeks before the start of treatment, during the treatment and after 
the last dose of MT-3724 while peripheral B cells are depleted. 
6.2 
Dose Modification 
The investigator may modify the MT-3724 treatment in an individual subject by: 
• Dose interruption defined as changes made during the current dose (eg, temporary or 
permanent stop the IV infusion). 
• Dose delay will be used for changes to dose schedule (eg, postpone the date of the next 
dose). A maximal dose delay of 14 days is allowed, a delay exceeding 14 days should be 
discussed with the medical monitor. 
• Dose reduction (according to Table 6-3) 
o Medical monitor must be notified when dose is reduced. 
• Permanent discontinuation.  
Refer to Table 6-4 for guidance on dose modification of MT-3724 treatment (dose interruption, 
dose delay, dose reduction or permanent discontinuation) if deemed at least possibly related to 
MT-3724 by the investigator. Except where expressly prohibited (see Section 6.1.3), the use of 
concomitant medications is allowed at the investigator’s discretion for management of toxicities. 
6.2.1 
Dose Modification for Treatment-emergent Adverse Experiences 
The following actions are recommended after any of the TEAEs listed in Table 6-4 occur. 
• The investigator should notify the medical monitor acting on behalf of the sponsor about the 
TEAE within 24 hours of the awareness. 
• The investigator should monitor the subject and if necessary, perform unscheduled diagnostic 
procedures and therapeutic interventions, including those not specified in the study protocol. 
• If a subject experienced Grade ≥ 2 IRR, or another Grade ≥ 2 hypersensitivity event, 
Grade ≥ 2 CRS or Grade ≥ 2 CLS, then the investigator should obtain serum samples for 


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cytokines, complement, and histamine as soon as possible after the TEAE onset. These 
samples should be marked “STAT” and shipped immediately to the central laboratory. 
• MT-3724 dose may be reduced at the investigator’s discretion. See Table 6-3 for 
recommended dose reduction steps. The number of MT-3724 dose reductions per subject is 
not limited, except that the reduced dose cannot be < 5 µg/kg/dose (this is the lowest dose 
tested in the clinic so far).  
• No intra-subject escalation of MT-3724 dose is permitted after previous MT-3724 dose 
reduction. 
• MT-3724 treatment may be restarted if the TEAE that previously led to treatment 
modification has resolved to Grade ≤1 or the subject’s baseline within the time frame deemed 
appropriate at the investigator’s discretion.   
o After the resolution of the TEAE, the MT-3724 dose for continued treatment may be the 
same or reduced, as determined according to the stopping rules (if applicable) or at the 
investigator’s discretion   
MT-3724 treatment must be permanently discontinued if a TEAE that previously led to 
treatment modification did not resolve to Grade ≤1 or baseline within 14 days. 
Table 6-3. Dose Reduction Steps 
Dose Reductiona 
Dose µg/kg/dose 
Full Dose 
10 
25 
50 
First Reduction (~ 25%) 
8 
19 
38 
Second Reduction (~ 50%) 
5 
13 
25 
a 
Other reductions require consultation and agreement of the medical monitor. 


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Table 6-4. MT-3724 Dose Modification Guidance and Specific Management of Toxicities 
 
Specific Management 
MT-3724 Dose Modificationa 
Neutropenia or Thrombocytopenia 
ANC 
> 500/μl or < 500/μl for < 5 days 
 
No change 
AND 
 
Platelet 
≥ 25,000/μl 
ANC 
< 500/μl for ≥ 5 days, OR febrile 
neutropenia c 
Decrease by 1 dose level 
AND / OR 
 
Platelet 
< 25,000 for ≥ 7 days with or 
without active bleeding, OR 
< 50,000/μl for ≥ 7 days with 
clinically significant bleeding b 
Infusion-related Reaction or Other Hypersensitivity Event 
IRR 
OR 
Hypersensitivity 
reaction 
Grade ≥ 2 
Infusion must be interrupted. 
Treatment may be restarted or permanently discontinued at 
the investigator’s discretion. 
If the MT-3724 re-treatment after Grade 2 IRR is allowed, 
then it must occur: 
• 
Only after the appropriate delay (ie, resolution of 
symptoms).  
• 
At the reduced dose and/or reduced infusion rate, 
where both will be chosen at the investigator’s 
discretion.  
• 
After the appropriate anti-allergic prophylaxis 
according to the premedication guidance in this 
protocol (see Section 6.1.2) or the institutional 
guideline. 
Grade ≥3 
 
MT-3724 treatment must be permanently discontinued 


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Table 6-4. MT-3724 Dose Modification Guidance and Specific Management of Toxicities 
 
Specific Management 
MT-3724 Dose Modificationa 
Nonhematological TEAEs 
Grade ≥ 2 CRS 
Subjects should be closely monitored for 
signs of CRS. This includes: 
• 
Monitoring of vital signs (temperature, 
heart rate, BP, respiration rate), body 
weight and clinical symptoms 
including headache, myalgia, muscle 
weakness, edema, neurological and 
gastro-intestinal symptoms, abdominal 
pain, and fatigue 
• 
Monitoring of laboratory parameters 
of hematology, albumin, kidney and 
liver function and cytokines in case of 
clinical symptoms indicative of CRS 
Investigators should consider supportive 
measures while on trial regardless of 
dosing or timing of dosing.  
May trigger a modification of MT-3724 treatment (dose 
interruption, dose delay, dose reduction or permanent 
discontinuation) if deemed at least possibly related to 
MT-3724 by the investigator. 
 
 


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Table 6-4. MT-3724 Dose Modification Guidance and Specific Management of Toxicities 
 
Specific Management 
MT-3724 Dose Modificationa 
Grade ≥ 2 CLS: 
As defined in CTCAE v5.0, or if at least 2 of the 
following within the same cycle (unless 
unequivocally related to underlying condition) 
reaches the level of Grade 2: 
• 
Hypoalbuminemia 
• 
Hypotension 
• 
Edema (peripheral or central, all types) 
and/or weight gain 
 
Subjects should be closely monitored for 
signs of CLS. This includes: 
• 
Monitoring of vital signs (temperature, 
heart rate, BP, respiration rate), body 
weight, edema of any type including 
both peripheral edema and central 
edema (such as pleural effusion or 
signs of dyspnea).  
• 
Monitoring of laboratory parameters 
including hemoconcentration (eg, 
hematocrit, Hb), and especially 
albumin and CK in case of clinical 
symptoms indicative of CLS. 
Investigators should consider supportive 
measures while on trial regardless of 
dosing or timing of dosing. If a subject 
experiences Grade 2 hypotension, 
orthostasis, edema, or hypoalbuminemia, 
normal saline and/or an albumin infusion 
may be given, as needed. 
 
Treatment modification due to CLS: 
• 
For Grade ≥ 3 CLS, the MT-3724 treatment must be 
permanently discontinued. 
• 
For Grade 2 CLS, the MT-3724 treatment must be 
held, and may only be restarted after:  
o 
a minimum of 7 days has elapsed after onset of 
CLS, and  
o 
all signs and symptoms of CLS have resolved 
to at least grade 1, and  
o 
albumin has remained ≥ 3.0 g/dL for at least 
5 days post last albumin infusion (if required) 
without additional albumin substitution 
  
Subsequent doses of MT-3724 must be:  
• 
reduced by at least 25%, and  
• 
administered once weekly 
or subject may be permanently discontinued at the 
investigator’s discretion. 


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Table 6-4. MT-3724 Dose Modification Guidance and Specific Management of Toxicities 
 
Specific Management 
MT-3724 Dose Modificationa 
SCr increase ≥ 1.5-3.0 times above baseline or 1.5-
3.0 x ULN in the absence of dehydration or bleeding 
 
May trigger a modification of MT-3724 treatment (dose 
interruption, dose delay, dose reduction or permanent 
discontinuation) if deemed at least possibly related to 
MT-3724 by the investigator 
Any Grade ≥ 3 electrolyte abnormality that does not 
resolve, with or without intervention, to Grade < 2 
within 72 hours 
Any other Grade ≥3 nonhematological toxicity 
excluding the following: 
• 
Nausea, vomiting, or diarrhea, if manageable 
with antiemetic or antidiarrheal agents within 
7 days of onset 
• 
Fatigue lasting ≤72 hours 
• 
Grade 3 laboratory abnormalities, if 
asymptomatic and without a clear clinical 
correlate 
Hepatotoxicity 
AST and / or ALT 
≤ 5.0 x ULN (isolated) 
 
• 
No change in treatment 
• 
Monitor subject 
OR 
 
Bilirubin 
≤ 1.5 x ULN (isolated) 
AST and / or ALT 
> 5 x ULN – 8.0 x ULN 
(for subjects enrolled with 
AST/ALT < 3 x ULN) 
 
• 
Temporarily or permanently (see next row) discontinue 
treatment  
• 
Monitor subject  
• 
Continue at dose reduced by 1 dose level after 
abnormal values resolve to Grade ≤ 1 or baseline values 
OR 
 
Bilirubin 
> 1.5 x ULN – 5.0 x ULN 
AST or ALT 
> 8.0 x ULN for any period 
of time (for any subject) 
 
• 
Permanently discontinue treatment 
 


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Table 6-4. MT-3724 Dose Modification Guidance and Specific Management of Toxicities 
 
Specific Management 
MT-3724 Dose Modificationa 
> 5 x ULN for more than 
2 weeks (for subjects 
enrolled with AST/ALT 
3-5 x ULN) 
AST and / or ALT 
> 3.0 x ULN (without 
findings of cholestasis 
defined as serum ALP < 2 
× ULN) 
 
• 
Permanently discontinue treatment 
AND 
 
Bilirubin 
> 2.0 x ULN or INR > 1.5 
AST and / or ALT 
> 3.0 x ULN with the 
appearance of fatigue, 
nausea, vomiting, right 
upper quadrant pain or 
tenderness, fever, rash, 
and/or eosinophilia (> 5%) 
 
• 
Permanently discontinue treatment 
OR 
 
Bilirubin 
> 5.0 x ULN 
NOTE: These are recommendations in situations where a possible relatedness to study drug is assumed. These recommendations cannot consider all clinical 
circumstances; therefore, the investigator is encouraged to contact the sponsor and/or medical monitors to discuss alternative courses of action. 
The number of MT-3724 dose reductions per subject is not limited, except reductions beyond what is outlined in Table 6-3 require consultation with the 
medical monitor. 
ALP = alkaline phosphatase; ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; BP = blood pressure; CLS 
= capillary leak syndrome; CRS = cytokine release syndrome; INR = international normalized ratio; IRR = infusion-related reaction; ULN = upper limit of 
normal; TEAE = treatment-emergent adverse event. 
a 
MT-3724 dose reduction by 1 dose level translates to an approximate reduction by 25% to 33%, see Table 6-3. The actual amounts for either agent will be 
determined by the investigator after consultation with sponsor and medical monitor. 
b 
Clinically significant bleeding is that which requires platelet transfusion. 
c 
Febrile neutropenia is defined as ANC < 1000/μl and fever (a single body temperature reading of > 38.3°C [> 101°F] or a sustained body temperature of 
≥ 38.0°C [≥ 100.4°F] for more than 1 hour).  


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6.3 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1 
Randomization 
The study will be conducted as a single-arm, open-label, non-randomized study, where all 
eligible subjects will be assigned to MT-3724 treatment.  
Assignment of the screening slots and treatment slots will be done on the basis of competitive 
enrollment across multiple sites. 
6.3.2 
Blinding 
Not applicable; this is an open-label study. 
6.4 
Study Treatment Compliance 
Because MT-3724 is administered IV, treatment compliance will be monitored through the 
electronic case report form (eCRF) and source documents (clinic notes and pharmacy records) 
and clinical observations during study drug infusion. Actual dosing schedule vs planned dosing 
schedule will be used to assess compliance. Details will be provided in the standalone Pharmacy 
Manual. 
6.5 
Concomitant Therapy 
New medication (either prescription or OTC) or concomitant medication reported by the subject 
or subject’s medical records between the screening medical history and the start of treatment 
should be reported as concomitant medication. During the treatment and until the STFU visit, 
concomitant medications will be reported by verbal probes at every visit to the clinic or at every 
phone contact; in addition, subject’s spontaneous reports will be captured. 
Except where expressly prohibited (see Section 6.1.3), the use of concomitant medications is 
permitted at the investigator’s discretion for management of toxicities.  
Concomitant use of platelet transfusion for thrombocytopenia, packed red blood cells (RBC) or 
blood transfusion for anemia or G-CSF for leukopenia are permitted for supportive care at the 
investigator’s discretion, but only after the investigator has properly assessed if the MT-3724 
treatment should be modified due to drug-related cytopenia. 
Palliative therapy, such as radiotherapy, which spares at least 50% of bone marrow producing 
regions, to non-target lesions or intrathecal chemotherapy, is allowed at the investigator’s 
discretion after consultation with the medical monitor and sponsor. 
While the use of certain immunomodulators is prohibited as described in Section 6.1.3, the use of 
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Reasons for Caution 
No results are available about the potential for drug-drug interactions between MT-3724 and 
other drugs. Therefore, the investigator should use caution when prescribing concomitant 
medications or vaccines. 
Subjects treated with B-cell depleting mAb, similar to MT-3724, have been shown to have 
impaired humoral and/or cellular immune responses to neo-antigens for variable periods of time 
during or after the treatment. Therefore, investigators should use caution about the potential for 
immune suppression when prescribing concomitant medications or vaccines. 
6.6 
Treatment After the End of the Study 
The sponsor may decide to initiate an open-label rollover study after the study ends. If the 
sponsor decides to initiate an open-label rollover study and that study is approved under 
applicable regulatory requirements and a local ethics committee, or if providing the study drug 
for continued treatment of study subjects is required by the local country’s regulatory 
mechanism, then study subjects may be eligible for continued treatment of MT-3724. However, 
the sponsor reserves the unilateral right, at its sole discretion, to determine whether to supply 
MT-3724 and by what mechanism, after the study and before the product(s) is/are available 
commercially. 
7 SUBJECT WITHDRAWAL, REPLACEMENT AND STUDY 
DISCONTINUATION 
7.1 
Subject Withdrawal 
Subjects must be withdrawn from the study at their own request or at the request of their legally 
acceptable representative. The subject has the right to withdraw from the study at any time for 
any reason, without the need to justify his/her withdrawal. The subject will not suffer any 
disadvantage because of the withdrawal.  
Subjects must also be withdrawn if the β-HCG pregnancy test indicates that they are pregnant at 
any time from signing the consent until the EoT Visit.  
The subject may be withdrawn from the study at the discretion of the investigator due to: 
• Safety concerns  
• Lack of clinical benefit (disease progression is not documented but the investigator 
determines that the subject requires alternative anticancer treatment) 
• Non-compliance with study procedures to the extent that precludes the assessment of study 
objectives 
All subjects who permanently discontinue study treatment for any reason should have an EoT 
Visit performed as described in the Schedule of Activities (Section 1.3).  


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The reason for any discontinuation from the study will be documented in the subject’s medical 
record and recorded on the appropriate eCRF. 
7.2 
Subject Replacement 
Subjects that have signed the informed consent but never received at least 1 dose of study drug 
may be replaced. Subjects who are not evaluable for dose decisions during the DLT assessment 
period will be replaced. 
7.3 
Study Discontinuation 
The sponsor has the right to discontinue the study for any reason. 
7.4 
Lost to Follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. 
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject on the importance of maintaining the assigned visit schedule 
and ascertain whether or not the subject wishes to and/or should continue in the study. 
• Before a subject is deemed lost to follow-up, the investigator or designee must make every 
effort to regain contact with the subject (where possible, 3 telephone calls and, if necessary, a 
certified letter to the subject’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the subject’s medical record. 
• Should the subject continue to be unreachable, he/she will be considered to have withdrawn 
from the study.  
For subjects who are lost to follow-up, the investigator can search publicly available records 
(where permitted) to ascertain survival status. This ensures that the data set(s) produced as an 
outcome of the study is/are as comprehensive as possible. 
8 STUDY ASSESSMENTS AND PROCEDURES 
8.1 
General Study Periods 
Each subject’s participation will comprise of 4 sequential periods: screening, treatment, STFU 
for safety, and LTFU for efficacy. 
8.1.1 
Screening and Enrollment  
A signed written ICF will be obtained before any screening procedure may begin. 


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Screening procedures will be performed within 35 days before the start of treatment on C1D1, 
except for central and local laboratory safety assessments and radiographic assessments (must be 
collected within 28 days of start of treatment) and the determination of LVEF (see Section 8.4.7 
for the permitted windows for this assessment). 
After the investigator determines that all eligibility criteria have been fulfilled (see Section 5), 
the medical monitor should review the screening results and acknowledge the investigator’s 
decision that the subject may start treatment. 
8.1.2 
Treatment Period 
Treatment begins on Day 1 of Cycle 1 when the first dose of investigational product is 
administered to a subject. During clinic visit days all protocol-required predose assessments have 
to be performed prior to administration of MT-3724. 
Treatment will continue until death, disease progression, unacceptable toxicity, withdrawal of 
consent, or another reason for withdrawal, or until study discontinuation. Refer to Section 6.1.1.4 
for details regarding treatment beyond progression. 
8.1.3 
End of Treatment Visit 
The EoT Visit will occur upon discontinuation of treatment, as soon as possible (up to 14 days) 
after the last dose, and before the start of new therapy, except for subjects who withdrew consent 
and objected to further data collection, or were lost to follow-up.  
End of Treatment visit should be performed in-clinic; however the EoT visit may be performed 
by telephone call, but only if a subject cannot attend a clinic visit or has started a new anticancer 
treatment. In such instances, missed assessments (eg, laboratory assessments, PE), are not 
considered deviations. 
8.1.4 
Short-term Follow-up Visit 
The STFU Visit for safety assessment should occur 30 days (± 3 days) after the last dose of 
MT-3724, except for subjects who withdrew consent and objected to further data collection, 
started new therapy for DLBCL or started another investigational drug. 
The STFU Visit can be done via a clinic visit (recommended) or via a telephone call (if subject 
cannot attend a clinic visit or has started a new anticancer treatment or a new DLBCL treatment). 
In such instances, missed assessments (eg, laboratory assessments, PE), are not considered 
deviations. 
8.1.5 
Long-term Follow-up 
The LTFU Visits should occur every 3 months (± 14 days) after the last dose of MT-3724 for up 
to 18 months from the last dose. The LTFU Visits will be performed via a telephone call to 
collect the information about death (if any), the DLBCL status (relapsed or not) and the start of 


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any new therapy for DLBCL or any other investigational drug since the last study visit/phone 
call. Subjects with CR, PR, or SD should also be followed for radiology assessment until PD, 
death, or new anticancer treatment. Radiology data can be obtained from existing medical 
records if assessments were performed as SoC between LTFU visits. 
8.2 
General Assessments 
8.2.1 
Demographics 
Information about date of birth/age, gender, race/ethnicity, detailed smoking history and alcohol 
history will be recorded during screening. 
8.2.2 
Non-Hodgkin Lymphoma Assessment 
The NHL assessment will be performed at screening by documenting the tissue sampling method 
used to confirm the CD20+ DLBCL histology at relapse, and the disease status at the initial 
diagnosis and at screening.  
The following information about NHL will be documented:  
• Status at initial diagnosis:  
o Non-Hodgkin Lymphoma type histology 
o Staging (Ann Arbor Classification-Cotswold Modification) (Lister, 1989)  
o Grading (International Prognostic Index [IPI]) for NHL  
• Status at time of relapse: 
o International Prognostic Index 
o Time to progression after first line therapy (captured as date of first relapse/progression) 
• Status at screening:  
o Histology showing DLBCL and CD20+ status confirmation by historical or fresh biopsy 
(bone marrow, lymph node, organ) in relapse or refractory setting 
o Date of most recent relapse 
o Staging (Ann Arbor Classification-Cotswold Modification) (Lister, 1989)  
o Grading (IPI) 
o Genetic mutational status (eg, MYC, BCL2 and BCL6 rearrangement / overexpression)  
o Molecular subtype (germinal center B cell [GCB] vs activated B cell [ABC]) 
The prognostic assessment instruments (Ann Arbor Classification with Cotswold Modification 
[Lister, 1989] and IPI [NHL Project, 1993]) are described in Section 10.5. 
 


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8.2.3 
Prior Systemic Therapy 
Prior systemic therapy for NHL (including SCT and CAR-T) administered at any time before the 
start of treatment will be assessed. 
Each regimen (line of treatment) should be documented in sequential order of past use with the 
outcome of therapy. The start and stop dates of each individual agent / regimen (ie, line of 
treatment) should be recorded. The date of the last CD20-based therapy should also be 
documented in the eCRF. 
8.2.4 
Prior Radiotherapy 
Prior radiation therapy for NHL administered at any time before the start of treatment will be 
assessed and documented. 
8.3 
Efficacy Assessments 
Planned time points for all efficacy assessments are provided in the SoA (Section 1.3). 
8.3.1 
Radiological Assessment of Tumor Response 
At baseline, both a positron emission tomography-computed tomography (PET-CT) and a 
computed tomography of diagnostic quality (CT-dq; or MRI) should be collected. Note, if the 
CT-portion of the PET-CT is of diagnostic quality, a separate CT-dq scan need not be obtained. 
For follow-up scans, while the same methodology (eg, PET-CT, CT-dq) should be used 
throughout the study (both PET-CT/CT-dq whenever possible), PET-CT should be used in 
subjects with fluorodeoxyglucose (FDG)-avid tumor histology while CT-dq and/or MRI should 
be used in subjects with tumor histology of low or variable FDG avidity. Irrespectively, CT-dq 
and/or MRI should be used at baseline and in subsequent follow-up scans in lieu of PET-CT if 
the latter cannot be used at the frequency prescribed per protocol because of access limitations. 
Methodology may vary per imaging availability, upon consultation with the sponsor. The same 
technique (eg, slice thickness, field of view) should be used for all scans during the study 
treatment period. 
The radiological tumor response assessment should be performed as indicated in the SoA 
(Section 1.3). The original schedule needs to be maintained even if there is a delay is dosing. 
Unscheduled tumor response assessment by fluorodeoxyglucose-positron emission tomography-
CT (or CT-dq and/or MRI) may be obtained at the investigator’s discretion. Complete remission 
and PR should be confirmed by repeated radiologic evaluation between 4 weeks to 8 weeks after 
the initial response assessment. For subjects treated beyond progression, radiological evaluation 
must be repeated in 4 to 6 weeks from initial scan showing progression. 
The investigators at each investigational site will determine the preliminary tumor response 
based on the radiologist’s measurement of all anatomic regions involved with the measurable 
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Preferably, all scans from 1 subject should be interpreted by the same investigator and the same 
radiologist at each investigational site. 
8.3.2 
Independent Centralized Review of Efficacy Results 
Digital images from all tumor response assessments must be available to be sent to the 
independent central review (ICR) service at any time during the study. All images sent to the 
ICR service must be anonymized by the investigational sites and provided digitally as Digital 
Imaging and Communications in Medicine (DICOM) format. The investigator must assure that 
the images are of acceptable diagnostic quality and fulfill the requirements outlined in the 
Imaging Manual. Additional specific information on the handling (ie, collection, shipment, 
tracking) of the images sent to the ICR will be provided in the Imaging Manual. 
The definitive treatment response assessment will be determined by the ICR service at the central 
imaging laboratory using the Lugano Classification (Cheson, 2014). 
The reviewers at the central imaging laboratory will be board-certified radiologists, experienced 
and independent radiologists with strong expertise in clinical radiology as well as the use of 
Lugano Classification in clinical trials with novel hematology-oncology agents. The central 
reviewers must not be otherwise involved in this study, ie, listed or identified as investigator or 
sub-investigator who is directly involved in the treatment or evaluation of study subjects. Central 
reviewers will be isolated from knowledge of investigator PD assessments through read lock 
procedures and communication controls. Except for the baseline visit, the ICR will be blinded to 
the subject’s identity and all other data (eg, demography, MT-3724 dose modification, TEAEs, 
disease characteristics). 
8.3.3 
Quality of Life 
The standardized EuroQol Group Quality of Life (QoL) – 5-dimensions (EQ-5D) questionnaire 
with 5 questions will be used for the QoL assessment. 
8.4 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
Subjects will be monitored for signs of CLS and CRS during and after their infusions. Vital signs 
will be monitored up to 4 hours after the start of infusion on C1D1, and up to 2 hours after the 
start of infusion for each subsequent infusion. In addition, subjects will remain in-clinic for PK 
sampling for 5 hours from the start of infusion on C1D1 and for 3 hours from the start of 
infusion on C1D3 and C1D12, where they will be observed for signs of CLS and CRS.   
8.4.1 
Medical History 
Relevant medical history will be recorded at screening. This will include prior surgery, prior and 
concomitant illnesses and allergy history. The prior systemic anticancer therapy, radiotherapy 
and tumor related biopsies or surgery will be collected and documented on separate eCRF forms.   


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New illnesses and/or worsening of concomitant illnesses detected by verbal probes or subject’s 
spontaneous reports between the signing of informed consent and the start of treatment should be 
reported under medical history, unless they are due to study-mandated procedures, in which case 
they should be reported as AEs. 
8.4.2 
Prior and Concomitant Medications 
Any medication (both prescription and over-the-counter [OTC] medications and supplements, 
including herbals, and palliative treatments such as radiation or intrathecal chemotherapy, when 
permitted) used within 4 weeks prior to the start of treatment until the STFU Visit will be 
recorded in the eCRF, together with the main reason for its prescription. 
Medications taken within 4 weeks before the start of treatment on C1D1 will be regarded as prior 
medications (prior NHL therapy will be captured separately). The medications taken after the 
start of treatment on C1D1 will be regarded as concomitant medications.  
8.4.3 
Physical Measurements 
Height (in meters [m]) and weight (in kilograms [kg]) will be measured; body-mass index (BMI) 
will be then be calculated. 
The body weight measured before the start of treatment on C1D1 will be used to calculate the 
MT-3724 dose in all subsequent cycles. The dose must be re-calculated when the body weight 
has changed by ≥ 10% from the baseline value; or according to institutional policies should they 
require adjustment for any change in body weight. 
All body weight measurements will contribute to the safety assessment. Unscheduled body 
weight measurements could be made for safety assessment at the investigator’s discretion. 
8.4.4 
Physical Examinations 
Physical examination (PE) will be performed by a physician or a qualified delegate at the 
investigating site.  
A complete PE including neurological examination and ECOG assessment will be performed at 
the following time points:  
• At screening  
• At the EoT Visit  
An abbreviated PE including ECOG will be performed at the following time points:  
• Before MT-3724 dose on D1 of each cycle 
The investigator or delegate at the site will perform the PE and evaluate the results. The overall 
PE result will be categorized as ‘normal’, ‘abnormal, not clinically significant (abnormal NCS)’, 


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or ‘abnormal, clinically significant (abnormal CS)’. All abnormal CS results of the PE should be 
reported as AE(s) in the eCRF and followed up at the investigator’s discretion. Comments about 
abnormal NCS results, either overall or for individual aspects or body parts, will not be collected 
in the eCRF. 
The performance status will be assessed by the Eastern Cooperative Oncology Group (ECOG) 
scale (see Section 10.7) at the same time points as complete and abbreviated PEs. 
8.4.4.1 
Complete Physical Examination 
At a minimum, the following aspects/body parts should be assessed during the complete PE: 
• General appearance 
• Skin (paleness, jaundice, redness/rash, acneiform changes) 
• Extremities (petechial bleedings, ulcers, signs of thrombosis), hands and feet (signs of 
hand-foot syndrome/palmar-plantar erythrodysesthesia) 
• Ears, eyes (jaundice, inflammation), nose and throat (presence of petechial bleedings, 
gingival bleeding) 
• Head and neck 
• Lungs 
• Heart 
• Abdomen (pain, tenderness, peristaltic, ascites, organomegaly) 
• Lymph nodes 
• Neurological examination to include the following assessments: 
o Oculomotor testing, pupil accommodation, double images 
o Motor system: muscle strength of arms 
o Sensory system: pain and touch sensation of thighs 
o Mental Status 
o Posture 
o Coordination: finger-to-nose and heel-to-shin test 
o Reflexes: biceps, patella and plantar (Babinski’s sign) test 
o Gait: walking freely, on toes and on heels 
o Romberg test 
 
Other aspects/body parts or organ systems may be assessed at the investigator’s discretion. 
 
8.4.4.2 
Abbreviated Physical Examination 
At a minimum, the following aspects/body parts should be assessed during the abbreviated PE: 
• General appearance 


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• Skin (paleness, jaundice, redness/rash, acneiform changes) 
• Ears, eyes (jaundice, inflammation) nose, throat (presence of petechial bleedings, gingival 
bleeding) 
• Lungs 
• Heart 
• Abdomen (pain, tenderness, peristaltic, ascites, organomegaly) 
• Lymph nodes 
• Extremities (petechial bleedings, ulcers, signs of thrombosis), hands and feet (signs of 
hand-foot syndrome/palmar-plantar erythrodysesthesia) 
• Abbreviated neurological examination to include the following assessments: 
o Oculomotor testing, pupil accommodation, double images  
o Motor system: muscle strength of arms 
o Sensory system: pain and touch sensation of thighs 
o Mental Status (awareness of self and environment) 
o Posture 
o Coordination: finger-to-nose and heel-to-shin test 
 
Other aspects/body parts or organ systems may be assessed at the investigator’s discretion. 
8.4.5 
New York Heart Association 
The classification of cardiac function will be performed for subjects with heart failure according 
to the NYHA (Section 10.8). 
8.4.6 
Vital Signs 
Vital sign assessments (BP; systolic and diastolic, respiratory rate [RR], heart rate [HR] and 
body temperature) will be assessed at time points indicated in the SoA (Section 1.3). 
Body temperature will be measured in Fahrenheit (°F) or Celsius (°C). BP, RR, and HR will be 
measured using an automated digital (preferred) or manual assessment.  
Unscheduled vital signs measurements may be performed at investigator’s discretion in each 
cycle. 
For BP and HR assessments, the subject must rest quietly in a sitting or semi-recumbent position 
for at least 5 minutes before and during the assessments. When the PK, ECG and vital signs 
assessments are scheduled to occur at the same time point, refer to the SoA for timing of 
collection. 
Any clinically-significant abnormality of vital signs should be followed up by repeat 
assessment(s), where number and timing will be determined at the investigator’s discretion. If 


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confirmed on repeat assessment(s), the abnormal CS results should be reported as AE(s) in the 
eCRF and followed up at the investigator’s discretion. Comments about abnormal NCS result 
will not be collected in the eCRF. 
8.4.7 
Left Ventricular Ejection Fraction 
The LVEF assessment will be performed at screening. A pre-study LVEF assessment is 
acceptable if obtained within 6 months before screening and at least 28 days after the last cancer 
therapy provided the subject has not received any potentially cardiotoxic agents since then. 
Left ventricular ejection fraction should be assessed by ECHO. If ECHO is not available or 
appropriate according to the institutional standard, then MUGA scan is permitted. The same 
modality should be used throughout the study. 
8.4.8 
Electrocardiograms 
All ECG recordings will be obtained using standardized equipment supplied for this study by the 
sponsor or contract research organization (CRO). The investigator or delegate at the site will 
assess the ECG results for the bedside safety assessment. All recordings will be transferred to a 
central review facility. The sponsor may initiate to have the ECG recordings analyzed by an ICR 
service at the central facility. 
Standard resting 12-lead ECG assessments will be performed after the subject has rested quietly 
for at least 5 minutes in supine or semi-recumbent position.  
All ECG recordings will be obtained in triplicate (3 standard ECGs obtained in close succession, 
and no more than 2 minutes apart). 
When the PK, ECG and vital signs assessments are scheduled to occur at the same time point, 
refer to the SoA (Section 1.3) for timing of collection.  
If any of the ECG printouts in a triplicate is of poor quality, additional ECG(s) may be obtained 
as soon as possible at the same time point until 3 ECGs of adequate quality are obtained. Such 
additional ECG(s) do not have to be reported as unscheduled assessments. 
The investigator or delegate at the site will assess the ECG results for the bedside safety 
assessment. The QT interval corrected according to the Fridericia’s formula (QTcF) will be used 
for safety assessment. The 3 QTcF values from a triplicate ECG should be averaged to yield the 
mean QTcF value. If not available on the ECG printout, the QTcF value will be calculated using 
an online calculator.  
The overall ECG assessment will be categorized as ‘normal’, ‘abnormal, not clinically 
significant (abnormal NCS)’, or ‘abnormal, clinically significant (abnormal CS)’. The overall 
ECG assessment by the ECG recorder and the related diagnostic comments will not be entered in 
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Any clinically-significant abnormality of ECGs should be followed up by repeat assessment(s), 
where number and timing will be determined at the investigator’s discretion. If confirmed on 
repeat assessment(s), the abnormal CS results should be reported as AE(s) in the eCRF and 
followed up at the investigator’s discretion. Comments about abnormal NCS result will not be 
collected in the eCRF. 
NOTE: If a subject reports an AE post-dose while in the clinic, a 12-lead ECG should be 
obtained and reviewed as part of the AE evaluation if clinically indicated. This AE will be 
reported in the eCRF, and the ECG analyzed and reported according to site specific procedures. 
8.4.9 
Clinical Safety Laboratory Assessments 
See Section 10.2 for the list of clinical laboratory tests to be performed and to the SoA 
(Section 1.3) for the timing and frequency. 
In the event of an unexplained clinically-significant abnormal laboratory test value, the test 
should be repeated and followed up until it has returned to the normal range and/or an adequate 
explanation of the abnormality is found. Any clinically-significant laboratory abnormality 
considered an AE should be recorded in the eCRF. 
Laboratory test results will be graded according to the CTCAE v. 5.0 criteria. Out of range 
results considered to be CS should be verified by repeat testing as soon as possible. In general, a 
confirmed Grade 3 or Grade 4 abnormal laboratory test result will be a CS AE and needs to be 
reported as such in the eCRF, unless associated with disease progression. Confirmed Grade 2 
abnormal laboratory results will be assessed on a case by case basis for clinical significance 
based upon the subject’s baseline value, the duration of the abnormal result, the need for and 
type of treatment and/or further evaluation required. Abnormal laboratory test results meeting 
SAE criteria will be reported as such. 
8.4.10 
Safety Follow-up Phone Calls 
A safety follow-up phone call should be performed to evaluate ongoing AEs, occurrence of new 
AEs and use of concomitant medication the third week of each cycle, unless the subject is 
receiving weekly dosing. 
8.5 
Adverse Events and Serious Adverse Events 
The definitions of an AE and SAE can be found in Section 10.3. For AEs of CLS, CRS/ SIRS, 
and IRRs, individual symptoms and grade should be reported on the appropriate eCRF. 
8.5.1 
Time Period and Frequency for Collecting Adverse Event Information 
The AE reporting period will begin on the day of the first dose of study drug unless deemed 
related to a protocol screening procedure after signing informed consent until the STFU visit or 
phone call, or until the start of new cancer therapy (unless the investigator believes the AE is 
related to MT-3724), whichever occurs first.  


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Grade ≥ 2 AEs related to MT-3724 that are ongoing at the STFU Visit should be followed by the 
investigator until all events have resolved to Grade ≤ 1.  
Those AEs that occur after the first dose on C1D1 will be considered treatment-emergent. 
All AEs that occur in enrolled subjects during the AE reporting period specified in the protocol 
must be recorded, regardless of the relationship of the AE to MT-3724. Any serious known 
untoward event that occurs beyond the AE reporting period that the investigator assesses as 
at least possibly related to MT-3724 should also be reported to the sponsor. 
8.5.2 
Method of Detecting Adverse Events and Serious Adverse Events 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrences. 
8.5.3 
Regulatory Reporting Requirements for Serious Adverse Events 
If an SAE occurs at any time from the time of start of treatment until the STFU Visit, it must be 
reported to the CRO responsible for clinical safety management and the medical monitor acting 
on behalf of the sponsor (see list of contacts). The investigator must report any SAE due to any 
cause, whether or not related to the study drug(s), within 24 hours of the time when s/he became 
aware of the event. The investigator must send a preliminary report of any such SAE to the study 
safety monitor via the electronic data capture (EDC) system within 24 hours or if this is not 
possible, via email or fax using an SAE Report Form, or at a minimum by telephone.   
The event must be recorded on the electronic SAE eCRF page. Preliminary reports of SAEs must 
be followed by detailed descriptions later, including clear copies of hospital case reports, 
consultant reports, autopsy reports, and other documents when requested and applicable. All 
copies should be redacted to remove subjects’ personal details and annotated with the subject’s 
unique study identifiers. 
Appropriate remedial measures should be taken to treat the SAE, and the response to treatment 
should be recorded. Subjects must be closely followed until sufficient information is obtained to 
indicate a return to normal status or until the event stabilizes at a level acceptable to the 
investigator. Clinical, laboratory, and diagnostic measures should be employed as needed to 
determine the etiology of the problem. The results will be reported promptly to the sponsor. 
Comprehensive SAE reporting instructions will be provided in the study manual. 


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8.5.3.1 
SUSAR 
An unexpected SAE that is at least possibly related to the study drug will be considered a 
Suspected Unexpected Serious Adverse Reaction (SUSAR).  
The sponsor will determine if a reported SAE meets the criteria for SUSAR and confirm the 
decision with the medical monitor and the CRO responsible for clinical safety management. The 
sponsor has a legal responsibility to notify regulatory authorities, investigators, and in some 
locations Ethics Committees (ECs)/Institutional Review Boards (IRBs) regarding potentially 
serious risks from clinical trials. The sponsor will comply with country-specific regulatory 
requirements relating to safety reporting to the regulatory authority, IRBs/ ECs, and 
investigators. 
8.5.3.2 
Pregnancy Reporting Instructions 
Pregnancy should be avoided from 4 weeks before the start of treatment, until the STFU Visit. 
Acceptable contraception is specified in the inclusion criteria, see Section 5.1 and Section 10.4. 
Subjects must be advised to immediately notify the investigator of pregnancy.  
If pregnancy occurs during treatment in a subject the investigator must immediately discontinue 
MT-3724 and report the pregnancy to the CRO responsible for clinical safety management and 
the medical monitor acting on behalf of the sponsor, along the same timelines as a SAE (see 
Section 8.5.3).The subject must be referred to an obstetrician/gynecologist experienced in 
reproductive toxicity for further evaluation and counseling.  
For a study subject, the outcome of the pregnancy should be followed up carefully, and any 
abnormal outcome of the mother or the child should be reported. For the pregnancy of a study 
subject’s partner, all efforts should be made to obtain similar information on course and 
outcome, subject to the partner’s consent. 
8.6 
Pharmacokinetics 
Blood samples will be collected prior to, during, and at specified times following the MT-3724 
infusion for determination of free MT-3724 concentrations in serum, which will be used for the 
assessment of the single-dose and repeat-dose PK of MT-3724 (refer to Table 1-2 for specific 
time points). If warranted, select serum samples collected for the MT-3724 concentration may 
also be analyzed for any other anti-CD20 biologic agent that the subject may have received prior 
to enrollment. Please note, samples for PK must be drawn from a different line than that used for 
MT-3724 administration. 
In addition, for subjects who will have cerebrospinal fluid (CSF) collected at any time point in 
the study as part of their SoC, a portion of the sample collected will be used by the sponsor to 
evaluate for the presence of MT-3724 in CSF. 


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8.7 
Pharmacodynamics 
8.7.1 
Peripheral Blood 
Pharmacodynamic markers will be the B-cell count and the immunophenotype in peripheral 
blood, as determined by flow cytometry, and circulating immunoglobulins (IgA, IgG, IgM).  
Serial blood samples for pharmacodynamic assessment will be collected as indicated in the SoA 
(Section 1.3). Unscheduled assessments may be performed at any time at the investigator’s 
discretion. 
8.7.2 
Optional Tumor Tissue Biopsy 
Optional biopsy of the tumor tissue may be performed at the EoT Visit in those subjects who had 
been discontinued due to PD, had consented for this procedure and have accessible peripheral 
lymph node(s). 
The purpose of the biopsy is to assess if the disease progression is associated with the loss of 
CD20 positivity of tumor cells. 
Subjects may also have a biopsy to confirm CR, in the absence of PET/CT scans. 
8.8 
Immunogenicity Assessments 
Antibodies to MT-3724 will be evaluated in blood samples collected from all subjects according 
to the SoA (Section 1.3). Additionally, blood samples should also be collected at the final visit 
from subjects who discontinued study intervention or were withdrawn from the study. These 
samples will be tested by the sponsor or sponsor's designee. 
Blood samples will be screened for anti-drug antibodies (ADA) that bind MT-3724. All ADA 
positive samples will have the titer reported and screened for neutralizing antibodies (NAb), 
reported as positive or negative. Other analyses may be performed such as verifying the stability 
of antibodies to MT-3724. 
The detection and characterization of antibodies to MT-3724 will be performed using a validated 
assay method by or under the supervision of the sponsor. All samples collected for detection of 
antibodies to MT-3724 will also be evaluated for MT-3724 serum concentration to enable 
interpretation of the antibody data. Antibodies may be further characterized and/or evaluated for 
their ability to neutralize the activity of the study intervention(s). Refer to the appropriate 
informed consent for the maximum duration of storage. Samples will be stored at a facility 
selected by the sponsor to enable further analysis of immune responses to MT-3724. 
 


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9 STATISTICAL CONSIDERATIONS 
The statistical analysis of the clinical data will be performed by Molecular Templates’ 
representative. Analysis of the PK, pharmacodynamic and immunogenicity data may be 
performed separately and entered into a separate database. Data from the clinical, PK and 
pharmacodynamic databases will be integrated in the clinical study report. 
Summary statistics for continuous variables will include the mean, standard deviation, median, 
and range (minimum/maximum); categorical variables will be presented as frequency counts and 
percentages; and time-to-event variables will be summarized by Kaplan-Meier plots, medians 
and range. Where confidence limits are appropriate, the confidence level will be 95% (2-sided), 
unless otherwise stated. There are no inferential statistical methods for this study design. 
Individual data (including relevant derived variables) will be presented by variable in by-subject 
listings. Results of statistical analyses, descriptive summary statistics and supportive listings will 
also be presented. 
Detailed methodology for summary and statistical analyses of the data collected in Parts 3 and 4 
of this study will be documented in a statistical analysis plan, which will be maintained by the 
sponsor. This document may modify the plans outlined in the protocol; however, any major 
modifications will also be reflected in a protocol amendment and documented in the clinical 
study report. 
Statistical analyses will be performed using SAS® v9.4 or higher (SAS Institute, Cary NC, 
USA). 
9.1 
Statistical Hypothesis and Sample Size Determination 
In Part 3, approximately 25 subjects will be enrolled as a continuation of the expansion of the 
MTD cohort with the intention to verify the safety, dose and dosing schedule (completion of the 
Phase 1b).  
In Part 4, approximately 88 evaluable subjects will be enrolled. If at least 23 of 88 evaluable 
subjects respond at the end of Part 4, then the null hypothesis is rejected in favor of the 
alternative hypothesis and the effectiveness of MT-3724 as monotherapy will have been proven. 
Under the stated null and alternative hypotheses, Part 4 carries 90.4% power at the 1-sided alpha 
level of < 0.025. 


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9.2 
Populations for Analyses 
For purposes of analysis, the following populations are defined: 
Population 
Description 
Full analysis set (FAS) 
population 
All subjects who received at least 1 dose of MT-3724 
monotherapy treatment. This will be the primary population for 
the assessment of efficacy endpoints. 
Modified full analysis set 
(mFAS) population 
All subjects who have at least 1 post-baseline efficacy 
assessment; subjects without a post-baseline efficacy assessment 
will not be considered evaluable for the primary efficacy 
analysis. Subjects who discontinue due to disease progression or 
die, prior to disease assessment will be included. 
PK analysis population 
All subjects who received any amount of MT-3724 and for 
whom the on-treatment PK data are considered to be sufficient 
and interpretable. 
Immunogenicity analysis 
population 
All subjects who have received any amount of MT-3724 and 
have valid post-baseline immunogenicity assessment will be 
included in the analysis set for the immunogenicity analysis. 
Pharmacodynamic 
analysis population 
All subjects who have received any amount of MT-3724 and 
have at least 1 valid post-baseline pharmacodynamic assessment. 
Safety analysis population 
All subjects who received at least 1 dose of MT-3724 
monotherapy treatment. For this study, this is equivalent to the 
FAS population. 
9.3 
Statistical Analyses 
9.3.1 
General Considerations 
Starting with Amendment 9 of the study protocol MT-3724_NHL_001, the study will be a 
multi-center, single-agent, open-label study consisting of 2 parts: Part 3 will complete the Phase 
1b portion of this to verify the safety, dose and dosing schedule. Part 4 is a Phase 2 design and 
will provide independent confirmation of the efficacy of MT-3724.  
Each of the 2 parts (Parts 3 and 4) will include LTFU after the last dose of MT-3724 for up to 
18 months from the last dose. Subjects who discontinue the study for disease progression will be 
followed only for OS. Subjects who discontinue the study for reasons other than disease 
progression will be followed for PFS, as reported by investigators and OS.  
9.3.1.1 
Baseline Definition 
The assessment obtained (and entered into EDC) at the most recent time before the start of 
MT-3724 treatment will be the baseline for all post-baseline assessments.  


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For all efficacy endpoints, the tumor scan obtained before MT-3724 Dose 1 during the screening 
(if available) will serve as the baseline; Pre-study tumor scan should be collected as close as 
possible to the start of treatment and evaluable for the ICR (ie, performed according to the 
Imaging Acquisition Guidance provided in the Imaging Manual). 
9.3.1.2 
Subject Disposition 
A detailed description of subject disposition will be provided. It will include: 
• The number of subjects who were included in the FAS, safety and efficacy evaluable analysis 
sets 
• A summary of subjects who complete the protocol 
• A summary of reasons for subject discontinuation 
• A summary of reasons for subjects with treatment failure 
• An account of all identified protocol violations 
All subjects enrolled in the study will be accounted for in the summation. 
9.3.1.3 
Demographic and Baseline Characteristics 
Demographic characteristics including age, gender, race, and ethnicity will be presented in the 
form of tabular summary statistics for all FAS subjects. Other subject baseline characteristics 
including weight, height, BMI, initial stage of disease, and performance status will be presented 
similarly. 
9.3.2 Efficacy Analysis 
The primary efficacy variable (Part 4) is the overall tumor response rate (ORR). 
The secondary efficacy variables in Part 3 are overall response rate, DCR, DOR; and in Part 4 
the secondary efficacy variables are the DCR, DOR, PFS, and OS. 
The definitive treatment response assessment (ie, the tumor response used to derive the primary 
and secondary efficacy endpoints) will be determined by response assessment using the Lugano 
Classification (Cheson, 2014). The sponsor will have the definitive treatment response 
assessment determined by the blinded, ICR service at the central imaging laboratory using the 
Lugano Classification. 
9.3.2.1 
Primary Efficacy Variable (for Part 4) 
The primary efficacy variable is the ORR. The ORR is defined as the percent of subjects with 
CR or PR determined by the blinded, ICR according to the Lugano Classification for Lymphoma 
(Cheson, 2014), relative to the FAS population. 


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Overall response rate  will be summarized by number and percentage of subjects meeting the 
definition of ORR along with the corresponding 2-sided 95% binomial exact confidence intervals 
(CI), separately for Parts 3 and 4. 
In Part 4, with n = 88 subjects, if ≥ 23 ORRs are seen, the null hypothesis is rejected in favor of 
the alternative hypothesis and the effectiveness of MT-3724 as monotherapy will have been 
proven. 
Subjects with missing disease assessments such that objective response cannot be determined 
will be assumed to be non-responders in the analysis. 
9.3.2.2 
Secondary Efficacy Variables 
The secondary efficacy variables will be PFS, DCR, DOR and OS. All secondary efficacy 
variables will be determined from the radiological tumor scans according to the Lugano 
Classification for Lymphoma (Cheson, 2014) relative to the FAS population. 
Secondary efficacy variables will be evaluated separately for Parts 3 and 4. 
The DCR will be defined as the percent of subjects with objective response of CR, PR, or SD, 
(defined as SD for 6 months or longer). The DCR will be analyzed using similar methods as the 
ORR. 
For subjects who continue to receive treatment after radiographic PD, and have confirmed PD at 
next assessment, the time of PD will be that of the first detection. 
The DOR will be defined as the time from the first documented objective response (CR or PR) to 
the date of PD or death from any cause. Subjects who have not progressed at the time of data 
base lock will be censored at the date of their last tumor assessment. 
The PFS will be defined as the time from the start of treatment with MT-3724 on C1D1 to the 
date of PD or death from any cause. Subjects who have not progressed at the time of data base 
lock will be censored at the date of their last tumor assessment.  
For both DOR and PFS, those subjects who have no data on progression (eg, subjects who 
discontinued the study due to other reasons than progression and who were not followed up until 
progression) and/or have no data on tumor assessment after baseline and are still alive will be 
censored at the subject’s date of first dose. 
The OS will be defined as the time from the start of treatment with MT-3724 until death from 
any cause. 
The DOR, PFS and OS will be summarized descriptively using the Kaplan-Meier methods (K-M 
median and corresponding 95% CI, quartiles, number of events, number censored, Kaplan-Meier 
figure). Since these methods assume missing data are missing at random, supportive analyses 
will be conducted assuming data are missing not at random. 


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As a secondary sensitivity analysis for efficacy (eg, study drug exposure, lines of prior therapy, 
DOR to prior therapy, subject subsets), the mFAS population will be utilized. The same 
statistical techniques will be applied on each efficacy endpoint on the mFAS population.  
Data listings will be created to support each analysis and to present all efficacy data.   
The value for the percent change from baseline in the sum of product of perpendicular diameters 
(SPD) as the measurement of tumor lesion size in each individual subject will be listed by time 
points. The values for the percent change from baseline in SPD values at each time point will be 
plotted for individual subjects (“spider plot”). The largest value for the percent change from 
baseline in SPD will be plotted on a histogram (‘waterfall’ plot). 
9.3.2.3 
Quality of Life 
Quality of life is assessed via the EQ-5D. The EQ-5D consists of the EQ-5D descriptive system 
and the EQ visual analogue scale. The EQ-5D descriptive system includes 5 dimensions: 
mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The response for 
each of the dimensions is ordered categorical: 1 = no problems, 2 = slight problems, 3 = 
moderate problems, 4 = severe problems and 5 = unable to/extreme problems. The EQ-5D 
domains will be summarized descriptively in terms of the percent of subjects falling into each 
ordered category at any given timepoint; the data will also be explored by cumulative and 
adjacent logit analyses. 
The EQ visual analogue scale records the respondent’s self-rated health on a vertical, visual 
analogue scale where the extremes are ‘100 = Best imaginable health state’ and ‘0 = Worst 
imaginable health state’. The change in visual analog scale score from baseline to any given time 
point will be summarized descriptively. 
9.3.3 
Safety Analysis 
All subjects who receive any dose (any amount) of MT-3724 monotherapy treatment will be 
included in the summaries and listings of safety data. Overall safety profile will be characterized 
by type, frequency, severity, timing, duration, AEs’ relationship to study drug, laboratory 
abnormalities, and vital signs. All analyses will be descriptive. All AE data will be summarized 
separately for Parts 3 and 4 and also combined (Parts 3 and 4). 
Baseline values are defined as the last valid value prior to study drug administration. Baseline 
safety data will be presented along with subsequent safety values assessed during or after drug 
administration. 
9.3.3.1 
Adverse Events 
Adverse events will be classified using the Medical Dictionary for Regulatory Activities 
(MedDRA) classification system and the severity of the toxicities will be graded according to the 
NCI CTCAE v 5.0. Adverse event data will be summarized separately for Parts 3 and 4 and also 
combined (Parts 3 and 4). 


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In all summaries, emphasis will be placed on TEAEs, namely, those with initial onset or those 
that worsen in severity after the first dose of MT-3724. Adverse events will be summarized by 
the frequency of subjects experiencing TEAEs corresponding to MedDRA System organ class 
and preferred term and by worst NCI CTCAE grade. Summaries will also be provided of 
treatment related TEAEs, namely, those judged by the investigator to be related or likely related 
to MT-3724.  
Adverse events resulting in discontinuation of MT-3724 treatment or withdrawal from the study, 
Grade 3 or higher, SAEs, and deaths on-study will be tabulated. 
9.3.3.2 
Laboratory Tests 
Laboratory data will be summarized for the observed values at each scheduled assessment, 
together with the corresponding changes from baseline using descriptive statistics.  
For those analytes with CTCAE version 5.0 severity criteria specified, abnormal laboratory 
values will be summarized by shift tables displaying numerical values and percentages classified 
by baseline grade and maximum grade on treatment.   
All laboratory data will be presented in data listings. 
9.3.3.3 
Vital Signs and Physical Examination Findings 
Vital signs data will be summarized by the observed valued at each scheduled assessment, 
together with the corresponding changes from baseline using descriptive statistics.  
Physical examination findings will be presented in data listings. 
9.3.4 
Other Analyses 
9.3.4.1 
Pharmacokinetic Analysis 
Pharmacokinetics data will be summarized separately for Part 3 and Part 4. The PK parameters 
will be estimated using standard noncompartmental methods as data permit. Pharmacokinetics 
parameters, where calculable, include: Cmax, tmax, AUC0-4, AUC0-inf, AUClast, t1/2, Vz, and CL. 
Actual sample collection times will be used rather than scheduled collection times. Serum 
concentrations below the limit of quantification will be treated as 0. Embedded missing serum 
concentrations (ie, missing values between 2 observed values) will be estimated using linear 
extrapolation. This is consistent with using the trapezoidal rule to calculate AUC. Other missing 
serum concentrations will be excluded from calculations to estimate PK parameters. 
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9.3.4.2 
Pharmacodynamic Analysis 
B-cell count and immunophenotyping results obtained by flow cytometry will be presented as 
absolute values and percentage change from pre- to post-dose time points. The absolute values 
and changes from baseline by time point during the treatment will be tabulated and plotted for 
the pharmacodynamic analysis set.  
Details of the descriptive statistical analyses of pharmacodynamic data will be provided in a 
separate statistical analysis plan. Pharmacodynamic data will be summarized separately for 
Part 3 and Part 4. 
 
 
 The details of the exposure-response modeling analysis will be described in a 
separate Modelling and Simulation (M&S) Analysis Plan and the results will be presented in a 
separate M&S report. 
9.3.4.3 
Immunogenicity Analysis 
Data for the ADA against MT-3724 will be obtained. The ADA titer will be determined for ADA 
samples confirmed as a positive result. The data for the NAb against MT-3724 will be reported 
as positive or negative. These data will be summarized separately for Part 3 and Part 4. 
The number and percent of subjects with a detectable ADA titer, and separately with a positive 
NAb result, will be summarized by time point for each treatment group/cohort. The individual 
subject’s ADA and NAb results will be listed by time point during the treatment; the listings will 
be presented for the pharmacodynamic analysis set. The individual subject’s ADA titer will be 
plotted by time point during the treatment. 
Details of the descriptive statistical analyses of immunogenicity data will be provided in a 
separate statistical analysis plan. 
9.4 
Data Safety Monitoring Board 
A Data Safety Monitoring Board (DSMB) will be established to monitor and evaluate the safety 
of subjects on an ongoing basis and to maintain oversight of the study data and monitoring 
process. The committee will consist of at least 1 independent experienced oncologist, statistician, 
and pharmacovigilance physician, the sponsor and its representatives and any other person the 
study team considers necessary to assist with study decisions. The committee will meet prior to 
starting Part 4, and according to the DSMB Charter established at the beginning of the trial. The 
DSMB will meet periodically during the expansion cohort. The DSMB will meet to discuss the 
overall incidence of serious related AEs (SAEs and AEs with CTCAE Grade 3 or 4) and Adverse 
Events of Special Interest to ensure that subject safety is addressed appropriately. The sponsor 
has the discretion to suspend enrollment for safety or efficacy reasons at any time pending 
DSMB review. The DSMB will also meet at unscheduled times according to clinical necessity. 
All SAEs and suspected Adverse Events of Special Interests will be reported to the DSMB by the 
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sponsor in accordance with regulatory timelines. Refer to the DSMB Charter for additional 
details. 
 


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10 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1 
Investigators and Study Administrative Structure 
Physician Responsible for Study and Data Monitoring Committee Contact: 
, M.D., MBA 
Chief Medical Officer, Molecular Templates, Inc. 
Harborside Plaza 5, Suite 1510 
185 Hudson Street  
Jersey City, NJ 07311 
Tel:
Contract Research Organization: A Contract Research Organization (CRO) will be managing 
all or part of this clinical trial on behalf of Molecular Templates. All contact information 
including each site’s assigned clinical research associate and medical monitor will be provided in 
the Site Reference Manual provided at the site initiation visit. 
Safety Laboratory Tests: All standard safety laboratory tests (see Section 10.2) will be 
performed by a central laboratory. Unscheduled safety labs for critical AE management may be 
performed by the site’s local laboratory. Results from these laboratories will be entered into the 
study’s data base by electronic transfer for central lab results or manually for local lab results.  
Central Laboratory Tests: Flow cytometry, serum cytokines, PK (serum and CSF), serum 
Rituximab, anti-drug antibodies (ADA)/Immunogenicity, and the optional biopsy analyses will 
be performed by a central laboratory. All contact information will be provided in the Laboratory 
Manual provided at the site initiation visit. 
Central Review Services: Electrocardiogram recordings will be obtained using standardized 
equipment supplied for this study by the sponsor or CRO. The investigator or delegate at the site 
will assess the electrocardiograms (ECG) results for the bedside safety assessment. All 
recordings will be transferred to a central review facility. The sponsor may initiate to have the 
ECG recordings analyzed by an independent central review (ICR) service at the central facility.   
All radiology data collected for this study will be transferred to a central imaging laboratory. The 
sponsor will have the definitive treatment response assessment determined by the ICR service at 
the central imaging laboratory. 
Clinical Trial Supply: MT-3724 will be shipped frozen to sites by a central vendor. Specific 
instructions for ordering study drug and contact information for each site will be provided in the 
Study and Pharmacy Manuals provided at the site initiation visit. 


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10.1.2 
Regulatory and Ethical Considerations 
The procedures set out in this study protocol, pertaining to the conduct, evaluation, and 
documentation of this study, are designed to ensure that the sponsor, its authorized representative 
and investigators abide by Good Clinical Practice (GCP) as described in International 
Conference on Harmonisation (ICH) guideline E6 (ICH, 2016), and in 21 Code of Federal 
Regulations (CFR) Parts 50, 54, 56, and 312. Compliance with these regulations also constitutes 
compliance with the ethical principles described in the most recent revision of the Declaration of 
Helsinki (WMA, 2013) that is recognized by the US Food and Drug Administration (US FDA) 
and the European Medicines Agency. 
The investigator should ensure that all persons assisting with the trial are adequately qualified, 
informed about the protocol, any amendments to the protocol, the study treatments, and their 
trial-related duties and functions. The investigator should maintain a list of sub-investigators and 
other appropriately qualified persons to whom significant trial-related duties have been 
delegated. 
Prior to initiation, the principal investigator will submit the study protocol, Investigator’s 
brochure, sample ICF, and any other documents that pertain to subject information, recruitment 
methods and advertisements, to the Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC). The principal investigator must also submit any other information that may be 
requested to the IRB/IEC for review and approval. Each investigator’s IRB/IEC will review 
these materials in accordance with GCP guidelines. The investigator will request that the 
IRB/IEC provide written approval and will keep on file records of initial study approval.  
After approval by the committee, the following documentation will be sent to the study manager 
before the study commences: 
• Confirmation of IRB/IEC approval of the protocol. 
• Confirmation of IRB/IEC approval of the ICF and applicable addenda. 
• A list of IRB/IEC members, their representative capacity, and their affiliation (a current 
Health and Human Services General Assurance number will suffice). 
The investigator must submit and, where necessary, obtain approval from the IRB/IEC for all 
subsequent protocol amendments and changes to the ICF provided by Molecular Templates or its 
agents. The investigator may not make changes to this protocol without Molecular Templates 
agreement.  
The investigator must conduct the study according to the most recent, approved protocol version. 
For deviations, the investigator or designee must document and explain any deviation from the 
protocol. The investigator should also notify the IRB/IEC of deviations from the protocol or SAE 
occurring at the site as per the IRB/IEC standard operating procedure, as well as other AE 
reports received from Molecular Templates or its representative and provided to the investigator, 
in accordance with local procedures. 


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The principal investigator will be responsible for obtaining annual IRB/IEC approval or renewal 
throughout the duration of the study. Copies of the investigator’s reports and the IRB/IEC 
continuance of approval must be sent to Molecular Templates’ representative. 
10.1.3 
Financial Disclosure 
All described guidelines and procedures apply equally to investigators and sites enrolling in 
Parts 1, 2, 3 and 4 of this study. In accordance with the FDA regulation (21 CFR Part 54) on 
Financial Disclosure by Clinical Investigators, Molecular Templates is required to include in 
marketing applications to the FDA either: 
• Certification of the absence of certain financial interests or arrangements of clinical 
investigators,  
OR 
• Disclosure of certain financial interests or arrangements of clinical investigators. 
Molecular Templates will request a statement attesting to any such financial arrangements. 
Disclosure is required for those financial interests other than the Clinical Study Agreement for 
this study. A statement will be required from all investigators and sub-Investigators who 
participate in a clinical study (defined as those directly involved in the treatment or evaluation of 
research subjects). This includes the financial interests of spouses and dependent children of the 
investigators. Any changes to the disclosure statement must be submitted in writing to Molecular 
Templates. 
10.1.4 
Informed Consent Process 
• The investigator will not undertake any measures specifically required only for the clinical 
study until valid consent has been obtained. If local SoC procedures or tests were performed 
prior to signing of the ICF but are still within 35 days of initiation of dosing, unless otherwise 
specified (eg, LVEF), then those results/data can be used for the intended protocol screening 
procedure. If various parameters within a given procedure are missing from the SoC 
procedures, then only those missing parameters need to be collected. 
• The investigator’s IRB/IEC will review and approve the study protocol and subject ICF and 
any other materials the investigator prepares for recruitment of subjects (eg, advertisements, 
study information brochures). All investigator generated subject information and recruitment 
materials must also be provided to Molecular Templates and its agents for review and 
approval. The ICF will contain all the elements required by the ICH E6 Guideline for GCP 
and any additional elements required by local regulations. 
• Before being enrolled, the principal investigator or one of his/her sub-investigators must 
explain orally and in writing the nature, duration, purpose of the study, and the action of the 
study drug in such a manner that the subject or legally authorized representative is aware of 
possible risks, inconveniences, or adverse effects that may occur. The ICF must be in a 
language that is understandable to the subject or legally authorized representative. The 
subject or legally authorized representative will have sufficient time to read the document 


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prior to being asked if there are any questions about the study procedures. A qualified and 
trained member of the study team must respond to these questions (eg, a study staff member 
who has been specifically trained on the protocol). Where required by local law, the person 
who informs the subject must be the investigator or another physician designated by the 
investigator. The subject should be informed that they may withdraw from the study at any 
time. The subject will receive all information that is required by the local regulatory 
authorities and ICH guidelines. 
• The subject’s consent must be confirmed at the time of consent by the personally dated 
signature of the subject. If the subject is unable to read, oral presentation and explanation of 
the written ICF and information to be supplied to subjects must take place in the presence of 
an impartial witness. Consent must be confirmed at the time of consent orally and by the 
personally dated signature of the subject or by a local legally recognized alternative (eg, the 
subject's thumbprint or mark). The witness to the informed consent discussions must also 
sign and personally date the ICF. A copy of the ICF must be given to the subject. The 
original signed ICF will be retained by the investigator. 
10.1.5 
Data Protection 
• Subject names will not be supplied to the sponsor. Only the subject number will be recorded 
in the electronic case report form (eCRF), and if the subject name or any other personal 
identifier appears on any other document (eg, pathologist report), it must be obliterated 
before a copy of the document is supplied to the sponsor. 
• Study findings stored on a computer will be stored in accordance with local data protection 
laws. 
• The subjects will be told that representatives of the sponsor, IRB/IEC, or regulatory 
authorities may inspect their medical records to verify the information collected, and that all 
personal information made available for inspection will be handled in strictest confidence 
and in accordance with local data protection laws. 
10.1.6 
Study Monitoring 
Contract research organization personnel may monitor the conduct of this study on behalf of the 
sponsor. Monitoring will include on-site visits, remote online access, and telephone 
communication to assure that the study is conducted according to the protocol and to assess the 
site’s compliance with GCP guidelines and other regulations. On-site or online review of eCRFs 
will assess the completeness and clarity, and consistency with source documents available for 
each subject.  
10.1.7 
Source Documents 
10.1.7.1 
Case Report Forms and Study Records 
It is a regulatory obligation of the investigator to maintain adequate and accurate case histories 
(source documentation) designed to record all observations and data pertinent to the investigation 
for each subject. Source Documents are the documents where information regarding a subject is 


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first recorded. Investigator subject files or hospital records are generally the basis of source 
document information. All source documentation must be available during site visits for the 
assigned Monitor to review and compare with the completed eCRFs. The investigator must 
maintain source documents. 
If the site is required to use a subject’s medical / hospital record to submit to sponsor/CRO, all 
subject identifiers must be made invisible to maintain subject’s anonymity and confidentiality. 
For this trial Monitors will perform source document verification as per the monitoring plan. It is 
critical that all information contained in the eCRF can be corroborated by the Source Documents 
that are used. Source documents may include but are not limited to all original documents, data, 
and records (eg, hospital records, clinical and office charts, laboratory notes, memoranda, 
subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified after verification as being accurate and 
complete, photographic negatives, microfilm or magnetic media, X-rays, subject files and 
records kept at the pharmacy, at the laboratories and at technical departments involved in the 
clinical study) that pertain to a study subject during the course of the clinical study. Source 
documents may also include past and current medical and medication history, documentation of 
informed consent (signed ICF, including all amendments as required by local authorities), 
subject study identification (eg, subject number, protocol number), ECOG assessments, 
International Working Group Criteria, documentation of dosing and study 
procedures/evaluations, all AE records and any protocol deviations.  
All data will be collected on study specific eCRFs, with the exception of central laboratory data, 
which will be provided to the investigator on a laboratory report and submitted to the clinical 
database via electronic transfer from the testing laboratory. Local laboratory data will be entered 
into the case report form (CRFs) by trained and qualified study staff. 
Monitors and auditors must have access to original records (unless copies are certified as 
authentic copies). Source data must be legible, written concurrently with the subject visit, and no 
data may be obliterated.  
All potentially eligible and appropriately consented study candidates will be entered into the 
study’s electronic data base with the initiation of screening. This information will be retained for 
all dosed subjects as well as subjects who fail 1 or more screen procedures or withdraw consent 
following screening and never progress to receive study drug.  
For all enrolled subjects, eCRF pages will be completed for all study activities (eg, MT-3724 
administration/dosing, safety assessments, procedures) These entries will be completed from the 
baseline visit forward until the end of the study (early termination or study completion) and 
combined with the screen entries be included in each subject’s complete study documentation 
package.   
All protocol-required information collected during the study must be entered by the investigator, 
or designated representative, in the eCRF. Details of eCRF completion and correction will be 
provided in the eCRF completion guidelines and will be explained to the investigative staff. If 


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the investigator authorizes other persons to make entries in the eCRF, the names, positions, 
signatures, and initials of these persons must be supplied to the sponsor/CRO. 
The eCRFs must be reviewed by the principal investigator and signed by the principal 
investigator named in the clinical study protocol at the end of the study. Any changes to the 
eCRF after retrieval using data clarification forms or queries must also be authorized/signed by 
the principal investigator and/or the study coordinator and/or the data entry coordinator. (Note: 
Study Coordinators and Data Entry Coordinators are sometimes allowed to sign Data 
Clarification Forms.) The sponsor or CRO acting as an agent of the sponsor will retain the final, 
complete electronic data base with all eCRFs. The investigator will retain a copy of all eCRF 
pages completed at their site. 
10.1.7.2 
Access to Source Documentation 
Domestic and foreign regulatory authorities, the IRB/IEC, and an auditor authorized by the 
sponsor may request access to all source documents, eCRF, and other study documentation for 
on-site audit or inspection. Direct access to these documents must be guaranteed by the 
investigator, who must provide support at all times for these activities. Medical records and other 
study documents may be copied during audit or inspection provided that subject names are 
obliterated on the copies to ensure confidentiality. If the investigator is informed of an 
impending regulatory authority audit, the sponsor must be notified within 24 hours of the 
investigator’s notification by the inspecting authority. 
10.1.7.3 
Retention of Data 
Study documents for all parts of this study must be retained until at least 5 years after the last 
marketing approval in an ICH region or at least 5 years have elapsed since the formal 
discontinuation of clinical development of the investigational product (eg, via notification of the 
FDA or local regulatory authority). The investigator/institution may not destroy records without 
written authorization from the sponsor. If an investigator leaves the institution at which the study 
was conducted, arrangements must be made to ensure another responsible party is designated to 
maintain the records. 
Unless otherwise noted, all described guidelines and procedures apply equally to subjects 
enrolled in all parts of this study. The following records must be retained by the 
investigator/institution for a minimum of 2 years after the sponsor has notified the FDA that 
investigations have been discontinued or after the FDA has approved the new drug application:  
• Signed ICFs for all subjects 
• Subject identification code list, screening log (if applicable), and enrollment log 
• Record of all communications between the investigator and the IRB 
• Composition of the IRB or other applicable statement  
• Record of all communications between the investigator and Molecular Templates and/or 
CRO 


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• List of sub-Investigators and other appropriately qualified persons to whom the investigator 
has delegated significant trial-related duties, together with their roles in the study and their 
signatures 
• Copies of CRFs and of documentation of corrections for all subjects 
• Drug accountability records 
• Record of any body fluids or tissue samples retained 
• All other source documents (subject records, hospital records, laboratory records, etc.) 
• All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial) 
Normally, these records will be held in the investigator's archives. If the investigator is unable to 
meet this obligation, he or she must ask the sponsor for permission to make alternative 
arrangements. Details of these arrangements must be documented in writing to the sponsor. 
10.1.8 
Data Quality Assurance 
• Data will be recorded in an FDA CFR Part 11-compliant eCRF, also known as the electronic 
data capture (EDC) system. 
• Data reported on the eCRF must accurately reflect the corresponding source documents, or 
the discrepancies must be explained. No data are to be recorded directly on the eCRFs (ie, the 
eCRF is not to be considered as source data). 
• The investigator should agree to have completed source documents and eCRFs available for 
inspection by the Monitor on behalf of the sponsor at the time of each scheduled monitoring 
visit. The investigator must sign the completed eCRF for each subject after the study 
completion. 
• All data obtained either from the eCRFs or from an external laboratory will be provided in 
descriptive summary tables presenting the number of subjects (n), mean, standard deviation, 
median, minimum and maximum for continuous variables and number of subjects (n) and 
percent for categorical variables. 
• The sponsor or designee is responsible for the data management of this study including 
quality checking of the data. All clinical parameters should be entered into the eCRF /EDC as 
soon as possible after each study visit, preferably within 5 business days of the visit. 
10.1.9 
Publication and Disclosure Policy 
All described guidelines and requirements apply equally to investigators and sites enrolling in all 
parts of this study. The information developed in the clinical study will be used by Molecular 
Templates in connection with the development of the investigational product. As such, the 
information may be disclosed to other investigators or regulatory authorities to obtain marketing 
approval. In order for Molecular Templates to use the clinical research information, the 
investigator is obligated to provide all of the information they obtain regarding the 
investigational product.   


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Both Molecular Templates and the investigator are free to present or publish the results of the 
study. Any party proposing a publication will provide the other with a copy of the proposed 
publication for review and comment prior to the submission for publication. Manuscripts must be 
submitted 30 days in advance of submission and abstracts within 10 days. The sponsor must be 
acknowledged in all publications. 
 
 


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10.2 Appendix 2: Clinical Laboratory Tests 
10.2.1 
General Guidance 
• The tests detailed in Table 10-1 will be performed by the central laboratory or local 
laboratory as indicated. All screening laboratory tests must be collected within 28 days of 
start of treatment. 
• The same laboratory should analyze all scheduled laboratory tests throughout the study. 
• Local laboratory for chemistry and hematology should be collected to assess subject status / 
safety if results from central laboratory will not be available predose, whenever central 
laboratory assessments are scheduled. These results need only be entered in the electronic 
data capture (EDC) if there is a clinically significant (CS) finding, related to an AE except 
albumin and creatine phosphokinase (CK) collected during Cycle 1 which are collected 
locally and should be entered in the case report form (CRF) irrespective of clinical 
significance.  
• For serial blood samples (PK analyses), an in-dwelling catheter (“hep lock”) placed in an 
extremity other than that used for MT-3724 infusion can be used to obtain the multiple blood 
samples stipulated in the protocol on dosing days. 
• A standalone Laboratory Manual will provide complete instructions regarding how these 
samples should be collected, stored, and shipped. 
• Additional tests may be performed at any time during the study as determined necessary by 
the investigator or required by local regulations. 
Table 10-1. 
Protocol-Required Laboratory Assessments 
Central Laboratory 
Local Laboratory 
Hematology 
Chemistry 
Local Chemistry 
hematocrit 
hemoglobin 
platelet count 
RBCb 
WBCc 
Albumin 
ALP 
ALT (SGPT) 
amylase 
AST (SGOT) 
β-HCGa 
β-2 microglobulin 
bicarbonate 
bilirubin (total 
and direct) 
BUN 
calcium 
chloride 
CKe 
creatinine 
eCrCla 
GGT 
glucose (fasting, 
plasma) 
HbA1c 
LDH 
lipase 
magnesium 
phosphorous  
potassium 
protein (total) 
sodium 
uric acid 
Albumin 
CKe 
Urinalysis macroscopica 
glucose 
ketones 
leukocytes 
nitrites 
occult blood 
pH 
protein 
specific gravity 
Coagulation 
Urinalysis microscopic (optional)a 
aPTT 
INR or PT 
bacteria 
casts 
crystals 
epithelial cells 
mucous threads 
RBC 
WBC 
Thyroid function 
Viral Serology (if applicabled) 
free T4 
TSH 
anti-HIV-1 antibody 
anti-HIV-2 antibody 
HBsAg 
anti-HBsAg antibody 
anti-HBcAg antibody 
HCV- RNA 
quantitation 
anti-HCV antibody 
Other Central Laboratory Analytes 
Virology (if applicable)  
anti-drug antibodies (ADA and NAb titer) 
HIV viral load 


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Table 10-1. 
Protocol-Required Laboratory Assessments 
B-cell count and immunophenotype (flow cytometry) 
complementa 
cytokines (serum)a 
histaminea 
immunoglobulins (IgA, IgG, IgM) 
serum MT-3724 concentration (PK) 
CSF MT-3724 concentration (PK) 
serum rituximab concentration (if applicable) a 
HBV viral load 
HCV viral load 
Other local laboratory tests 
CD4+ T-cell counts (if applicable) 
Pregnancy test (if applicable) 
NOTES: 
ADA = anti-drug antibody; ALP = alkaline phosphatase; ALT = alanine aminotransferase; aPTT = activated 
partial thromboplastin time; AST = aspartate aminotransferase; β-HCG = beta human chorionic gonadotropin; 
BUN = blood urea nitrogen; CK = creatinine phosphokinase; CSF = cerebrospinal fluid; eCrCl = estimated 
creatinine clearance; freeT4 = free thyroxin; GGT = gamma-glutamyl transferase; HBsAg = hepatitis B surface 
antigen; HbA1c = glycated hemoglobin; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; Ig = immunoglobulin; INR = international normalized ratio; LDH = lactate 
dehydrogenase; NAb = neutralizing antibodies; PK = pharmacokinetic; PT = prothrombin time; RBC = red blood 
cell; SGOT = serum glutamic-oxaloacetic transaminase; SGPT = serum glutamic-pyruvic transaminase; TSH 
= thyroid-stimulating hormone; ULN = upper limit of normal; WBC = white blood cell. 
a 
See Section 10.2.2 for analyte-specific guidance. 
b 
RBC indices (mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin 
concentration) and distribution widths (red cell and platelet). 
c 
WBC with differential (including neutrophils, basophils, eosinophils, lymphocytes, monocytes) reported 
as percentage and absolute values. 
d 
The serology for individual virus(es) may be omitted at the investigator’s discretion if seronegativity is 
documented in the medical history and there are no clinical signs of HIV or hepatitis infections, or suspected 
exposure. 
e 
If CK is elevated > ULN, CK isoenzymes must be analyzed. 
10.2.2 
Analyte-specific Guidance 
10.2.2.1 
Pregnancy Test 
Only applicable for women of childbearing potential. Women who are postmenopausal (> 1 year 
since last menstrual cycle) or permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral 
salpingectomy) may be considered as not of reproductive potential. 
Treatment with MT-3724 may proceed only if the pregnancy test is documented as negative at 
the most recent assessment. See Section 8.5.3.2 for the guidance about reporting the onset of 
pregnancy during the study. 
10.2.2.2 
Creatinine Clearance 
The creatinine clearance (CLcr) will be derived from the serum creatinine (SCr) values obtained 
from the blood chemistry assessment. The CLcr will be calculated using the Cockcroft-Gault 
formula: 
 
CLcr = {((140–age) x weight) / (72 x SCr)} x 0.85 (if female) 


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Where CLcr = mL/minute; SCr = serum creatinine (mg/dL); age = years; and weight = kg. 
At the investigator’s discretion, the CLcr results at screening that fall outside the limit required 
for eligibility may be verified by the formal measurement of CLcr based on the 24-hour urine 
collection. Furthermore, if warranted by the CLcr result at any other time point, the investigator 
may order CLcr (measured from the 24-hour urine) as unscheduled assessment. 
10.2.2.3 
Complement, Histamine, and Cytokines 
,IDVXEMHFWH[SHULHQFHGD*UDGH 2 infusion-related reaction (IRR)RUDQRWKHU*UDGH 2 
K\SHUVHQVLWLYLW\HYHQW*UDGH 2 cytokine release syndrome (CRS) RU*UDGH 2 CLS, the 
investigator should obtain serum samples for complement, and histamine, and cytokines as soon 
as possible after the treatment-emergent adverse event (TEAE) onset. These samples should be 
marked “STAT” and shipped immediately to the central laboratory. 
10.2.2.4 
Rituximab Concentration 
Serum rituximab (RTX) concentration must be assessed at screening if a subject received RTX 
within 37 weeks before the start of treatment on C1D1. Subjects will be eligible only if the serum 
RTX concentration is below 500 ng/mL. Serum RTX does not need to be re-evaluated once 
determined to be “negative”, in cases of rescreening. 
The serology for RTX concentration should not be assessed in subjects who have received RTX 
within 84 days before the start of treatment (automatically ineligible based on this criterion). 
When 37 weeks have elapsed since the last treatment with RTX,
 
The serology for RTX 
concentration should not be assessed for subjects who never received RTX. 
It is recommended to assess RTX serum concentration prior to performing other screening 
procedures. 
10.2.2.5 
Urinalysis 
Any clinically-significant abnormality in the dipstick urinalysis should be investigated by repeat 
urinalysis coupled with the microscopic analysis of the urine sediment. The confirmed CS 
abnormalities should be reported as per standard medical practice and reported as an AE in the 
eCRF. 
 
 
PPD


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10.3 Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
10.3.1 
Definition of Adverse Event 
The term adverse event (AE) is defined as any untoward medical occurrence in a subject or 
clinical investigation in a subject administered a pharmaceutical product(s) and which does not 
necessarily have to have a causal relationship with this experimental treatment(s).  
An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study 
or, if present at screening, worsens during the study, regardless of the suspected cause of the 
event. All AEs that occur in enrolled subjects during the AE reporting period specified in the 
protocol must be recorded, regardless of the relationship of the AE to study drug. 
All medical and psychiatric conditions (except those related to the indication under study) 
present at screening will be documented on the Medical History eCRF page. Clinically 
significant (CS) worsening in these conditions and new symptoms, physical signs, syndromes, or 
diseases should be noted on the AE eCRF page during the rest of the study. Laboratory, vital 
signs and electrocardiogram (ECG) abnormalities should also be recorded as AEs when 
considered CS and representing a change from pre-treatment baseline. 
Surgical procedures themselves are not AEs; they are therapeutic measures for conditions that 
require surgery. The condition for which the surgery is required may be an AE. Planned surgical 
measures for preexisting, non-worsening conditions permitted by the clinical study protocol and 
the condition(s) leading to these measures are not AEs, except when the event would qualify as 
serious (eg, leading to hospitalization). 
Adverse events will be assessed by verbal probes and subject’s spontaneous reports from the 
start of treatment until the STFU Visit or until the start of new anticancer therapy (unless the 
investigator believes the AE is related to MT-3724), whichever occurs first. Any AEs that occur 
during screening which are due to study-mandated procedures should also be reported. 
Information will be collected by trained, qualified study staff and the information will be 
recorded in the appropriate eCRFs. At a minimum, all relevant information regarding the AE and 
concomitant medication use will be captured.  
All AE reports (solicited or volunteered) will be reviewed and followed by the responsible 
investigator or qualified delegate for completeness, relatedness and accuracy of severity grading 
to ensure appropriate reporting practice. Medical Monitor acting on behalf of the sponsor will 
review cumulative AE data at appropriate intervals, as well as the serious AEs as they are 
reported. 
Natural disease progression of the malignancy or deterioration of the subject’s condition under 
study (including new sites of metastasis and death due to disease progression) will be recorded as 
part of the efficacy evaluation and should not be reported as an AE or as an SAE. 


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Discontinuation from study treatment because of disease progression or deterioration of the 
subject’s condition of the disease under study should be recorded on the Study Completion page 
of the eCRF as disease progression and not as an AE. 
10.3.2 
Definition of Serious Adverse Event 
An SAE is defined as any AE that meets 1 or more of the following criteria: 
• The event is fatal or life-threatening. 
• The event is permanently disabling (incapacitating or interfering with the ability to resume 
usual life patterns). 
• The event results in unplanned in-patient hospitalization or prolongation of an existing 
hospitalization. 
• Is or results in a congenital abnormality or birth defect. 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the subject or may require medical or surgical intervention to prevent 1 
of the outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. 
An AE does not need to be severe in order to be classified as an SAE. In this protocol, the term 
"severe" is used to describe the intensity (severity) of a specific event according to the CTCAE 
v.5.0. However, the nominally severe AE may be of relatively minor medical significance (such 
as short-term severe headache or nausea). This is not the same as "serious," which is based on 
patient/event outcome or action criteria. Seriousness (not severity) serves as a guide for defining 
regulatory reporting obligations. 
10.3.3 
Adverse Event Terminology 
All AEs should be recorded in standard medical terminology rather than the subject’s own 
words. Each AE will also be described in terms of duration, frequency, severity/intensity, 
association with the study medication, assessment of possible causes, actions taken, and 
outcome, using choices given on the eCRF. 
10.3.4 
Severity 
Severity will be classified according to the criteria provided by the Common Toxicity Criteria 
guidelines from the National Cancer Institute (CTCAE) v5.0. Accessible at 
https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_5.0/ 
If the AE is not listed in the CTCAE v5.0, then the highest severity level reached according to 
the scale in Table 10-2 will be assigned. Every effort should be made to find the appropriate AE 
term and definitions of severity in the modified CTCAE v. 5.0. 


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Table 10-2. 
Classification of Adverse Events by Severity 
Grade  
Definition 
Grade 1  
(mild) 
An AE that is easily tolerated by the subject. It incurs only a minimum of discomfort 
and does not influence ordinary daily tasks. 
Grade 2  
(moderate) 
An AE that is of sufficient severity to have a negative influence on ordinary daily 
tasks. 
Grade 3  
(Severe) 
An AE that effectively hinders ordinary daily tasks, often requiring intervention. 
Grade 4  
(life-threatening or 
disabling) 
An AE that puts the subject’s life at risk. 
Grade 5  
(fatal) 
Death related to an AE. 
10.3.5 
Causality / Relatedness 
Causality should be assessed for the study drug (MT-3724) as detailed in the eCRF. Causal 
relationship to protocol-required procedure(s) should also be considered and reported 
accordingly in the eCRF.  
The following should be considered when assessing causality: 
• temporal associations between the agent and the event 
• effect of de-challenge and/or re-challenge 
• pre-existing risk factors 
• a plausible mechanism 
• concurrent illnesses. 
The investigator will determine the causal relationship / relatedness to the study drug according 
to the classification in Table 10-3. 


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Table 10-3. 
Classification of Adverse Events by Causality / Relationship to the Study 
Drug 
Causality / Relatedness 
Definition 
Definitely related 
Follows a reasonable temporal sequence from drug administration, abates 
upon discontinuation of the drug (de-challenge), is confirmed by reappearance 
of the reaction on repeat exposure (re-challenge). 
Probably related 
Follows a reasonable temporal sequence from drug administration, abates 
upon discontinuation of the drug, cannot be reasonably explained by the 
known characteristics of the subject’s clinical state. 
Possibly related 
Follows a reasonable temporal sequence from drug administration, could have 
been produced by the subject’s clinical state or by other modes of therapy 
administered to the subject. 
Unlikely to be related 
Does not follow a reasonable temporal sequence from drug administration, is 
readily explained by the subject’s clinical state or by other modes of therapy 
administered to the subject. 
Unrelated 
The AE is definitely produced by the subject’s clinical state or by other modes 
of therapy administered to the subject. 
For all purposes of subject management, dose-limiting toxicity (DLT) assignment and treatment 
modification, the causality assessment of: 
• “probably”, “possibly” or “definitely” will be treated as “related” 
• “unlikely” and “not related” will be treated as “unrelated”. 
10.3.6 
Expected and Unexpected Adverse Events and SUSARs 
The expectedness of AEs will be determined by the sponsor according to the applicable reference 
document(s) and the requirements of the health authorities.  
An unexpected AE is an AE that is not identified by type, severity grade, or frequency in the 
Reference Safety Information (RSI) section of the Investigator’s Brochure for MT-3724 (IB, 
2020) or in the MT-3724 safety reports to the health authorities (eg, DSUR). 
The Safety Department of the CRO responsible for clinical safety management must report any 
suspected, unexpected serious adverse reaction (SUSAR) to the regulatory authorities within the 
required timeframes. The investigator must report any SUSARs to the Institutional Review 
Boards (IRBs)/Independent Ethics Committees (IECs) in accordance with local requirements. 
10.3.7 
Action Taken with Study Treatment 
Any action with the study treatment during the AE management and follow-up should be 
documented in the eCRF using the categories listed below.  
• Drug withdrawn 
• Dose interrupted 
o Infusion interrupted and resumed 


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o Infusion stopped 
o Dose delayed 
• Dose reduced 
• Dose not changed 
• Not applicable 
• Unknown 
The action “dose increased” is not available in this study.  
10.3.8 
Outcome 
The outcome of the AE should be documented as follows:  
• Recovered / resolved 
• Recovered / resolved with sequelae 
• Not recovered / not resolved 
• Fatal 
• Unknown 
 
 


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10.3.9 
Dose Limiting Toxicity (DLT) Criteria 
GENERAL PRINCIPLES  
A treatment-emergent adverse event (TEAE) will be declared as DLT if both of the following 
criteria are met:  
1. The TEAE occurred after the start of infusion in Cycle 1   
a. 
If a TEAE that fulfills a DLT criterion is observed in cycle ≥ 2 of Part 3, then the 
sponsor may declare this event a DLT after consultation with the investigator(s).  
2. The TEAE is at least possibly related to MT-3724, as determined by the sponsor after 
consultation with the investigator(s).  
 
The severity of TEAEs potentially fulfilling the DLT criteria will be graded according to the 
CTCAE v 5.0.  
POTENTIALLY QUALIFYING TREATMENT-EMERGENT ADVERSE EVENTS: Any 
TEAE listed below may represent a DLT for MT-3724 in this study.  
Hematological Treatment-Emergent Adverse Events  
● Grade ≥ 3 febrile neutropenia (absolute neutrophil count [ANC] < 1000/μl and a single body 
temperature reading of > 38.3°C [101°F] or a sustained body temperature of ≥ 38.0°C 
[100.4°F] for more than 1 hour)  
● Grade 4 neutropenia (ANC < 500/μl) for > 5 days; if the investigator determines that 
granulocyte colony-stimulating factor (G-CSF) therapy for Grade 4 neutropenia is essential 
within ≤ 5 days of onset, then this AE will also qualify as DLT  
● Grade 3 thrombocytopenia (< 50,000/μl and ≥ 25,000/μl) with CS bleeding (ie, bleeding 
requiring platelet transfusion)  
● Grade 4 thrombocytopenia (< 25,000/μl) with or without bleeding  
● Grade 4 anemia  
Nonhematological Treatment-Emergent Adverse Events  
● Grade ≥ 2 Cytokine Release Syndrome (CRS) 
● Grade ≥ 2 Capillary Leak Syndrome (CLS), (change in albumin must be a decrease by at 
least 0.5 g/dL compared to C1D1) 
● Grade ≥ 3 Acute kidney injury  
● Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) increase 
≥ 5.0 times upper limit of normal (ULN) (> 8.0 times for those with liver involvement)  
● Aspartate aminotransferase and/or ALT increase ≥ 3.0 times ULN with concomitant increase 
in total bilirubin ≥ 2.5 times ULN  


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● Total bilirubin ≥ 4.0 times ULN  
Note: for AST, ALT and bilirubin the investigator in consultation with the Medical Monitor and 
the sponsor should diligently assess if the value above either 5.0, 3.0, or 1.5 × ULN (depending 
on laboratory values as specified above), could be interpreted as non-DLT in light of the elevated 
baseline value (see CTCAE v 5.0) and liver involvement.  
● Grade ≥ 3 infusion-related reaction or other Grade ≥ 3 hypersensitivity reaction  
● Any Grade ≥ 3 electrolyte abnormality that does not resolve, with or without intervention, to 
Grade < 2 within 72 hours.  
● Any other Grade ≥ 3 nonhematological toxicity excluding the following:  
o Nausea, vomiting, or diarrhea, if manageable with antiemetic or antidiarrheal agents 
within 7 days of onset  
o Fatigue lasting ≥ 72 hours  
• Grade 3 laboratory abnormalities, if asymptomatic and without a clear clinical correlate, as 
determined by the sponsor after consultation with investigator(s). 
 
Any other toxicity at least possibly related to MT-3724, irrespective of the type or severity, that 
would qualify as DLT, as determined by the sponsor after consultation with investigator, 
considering the severity, duration, poor response to remedial therapy and/or inadequate 
resolution. This may be Grade 1 or Grade 2 toxicity that notably limits the activities of daily life 
to the extent that makes dose reduction necessary to ensure subject’s compliance (eg, 
long-lasting fatigue or anorexia). 
 
 


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10.4 Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP: 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the above, 
(eg, mullerian agenesis, androgen insensitivity), investigator discretion should be applied to 
determining study entry. 
Note: Documentation can come from the site personnel’s: review of the subject’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause.  
• A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be 
used to confirm a postmenopausal state in women not using hormonal contraception or 
hormonal replacement therapy (HRT). However, in the absence of 12 months of 
amenorrhea, confirmation with more than 1 FSH measurement is required.  
• Females on HRT and whose menopausal status is in doubt will be required to use 1 of the 
non-estrogen hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation 
of postmenopausal status before study enrollment. 
Contraception Guidance: 
Female subjects of reproductive potential must agree either to abstain continuously from 
heterosexual intercourse or to use a highly effective birth control method from signing the ICF 


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until the STFU. Male subjects of reproductive potential must agree to abstain continuously from 
heterosexual intercourse, have had a vasectomy, or use a condom with or without spermicidal 
agent from time of signing the ICF until 90 days after the last treatment with study drug. 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency  
• 
Implantable progestogen-only hormone contraception associated with inhibition of ovulationc 
• 
Intrauterine device 
• 
Intrauterine hormone-releasing systemc 
• 
Bilateral tubal occlusion 
• 
Azoospermic partner (vasectomized or due to a medical cause) 
Azoospermia is a highly effective contraceptive method provided that the partner is the sole sexual partner 
of the woman of childbearing potential and the absence of sperm has been confirmed. If not, an additional 
highly effective method of contraception should be used. Spermatogenesis cycle is approximately 90 days. 
Note: documentation of azoospermia for a male subject can come from the site personnel’s review of the 
subject’s medical records, medical examination, or medical history interview. 
Highly Effective Methodsb That Are User Dependent  
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of 
ovulationc 
o 
oral 
o 
intravaginal 
o 
transdermal 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
o 
oral 
o 
injectable 
• 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study intervention. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of 
the subject. 
a) Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b) Failure rate of < 1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
c) If locally required, in accordance with Clinical Trial Facilitation Group guidelines, acceptable contraceptive 
methods are limited to those which inhibit ovulation as the primary mode of action. 
Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method are not acceptable methods of contraception for this study. 
Male condom and female condom should not be used together (due to risk of failure from friction). 


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Collection of Pregnancy Information 
Male subjects with partners who become pregnant 
• The investigator will attempt to collect pregnancy information on any male subject’s female 
partner who becomes pregnant while the male subject is in this study. This applies only to 
male subjects who receive MT-3724. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the appropriate form and 
submit it to the sponsor within 24 hours of learning of the partner’s pregnancy. The female 
partner will also be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and child will be forwarded to the sponsor. Generally, the follow-up will 
be no longer than 6 to 8 weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported regardless of fetal status (presence or absence of anomalies) or 
indication for the procedure.  
Female subjects who become pregnant 
• The investigator will collect pregnancy information on any female subject who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the sponsor within 24 hours of learning of a subject's pregnancy.  
• The subject will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the subject and the neonate and the information will be 
forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 to 
8 weeks beyond the estimated delivery date. Any termination of pregnancy will be reported, 
regardless of fetal status (presence or absence of anomalies) or indication for the procedure. 
• A spontaneous abortion (occurring at < 22 weeks gestational age) or still birth (occurring 
at > 22 weeks gestational age) is always considered to be an SAE and will be reported as 
such.  
• Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in Section 8.5.3 
and Section 8.5.3.1. While the investigator is not obligated to actively seek this information 
in former study subjects, he or she may learn of an SAE through spontaneous reporting. 
• Any female subject who becomes pregnant while participating in the study will discontinue 
study intervention. 
 
 


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10.5 Appendix 5: Staging of NHL 
Ann Arbor Staging System With Cotswold Modification (Lister, 1989) 
Ann Arbor stage is determined as outlined in Table 10-4, for calculation of the prognostic index 
for disease status at initial diagnosis and at baseline. The Cotswold modification maintains this 
original 4-stage clinical and pathologic staging but also adds information regarding the 
prognostic significance of bulky disease (denoted by an X designation), regions of lymph node 
involvement (denoted by an E designation) and the absence or presence of symptoms (denoted 
by the A/B designations). 
Table 10-4. 
Ann Arbor Staging System With Cotswold Modification 
Ann Arbor Staging System Features 
Stagea 
I 
Involvement of a single lymph node region or lymphoid structure (eg, spleen, thymus, 
Waldeyer's ring) 
II 
Involvement of 2 or more lymph node regions on the same side of the diaphragm 
IIIb 
Involvement of lymph regions or structures on both sides of the diaphragm 
IV 
Involvement of extranodal site(s) beyond that designated E 
Cotswold Modifications 
For All Stages 
A 
No symptoms 
B 
Fever (> 38oC), drenching sweats, weight loss (10% body weight over 6 months) 
X 
Massive mediastinal disease has been defined by the Cotswold meeting as a thoracic ratio of 
maximum transverse mass diameter greater than or equal to 33% of the internal transverse 
thoracic diameter measured at the T5/6 intervertebral disc level on chest radiography. 
For Stages I to III 
E 
Involvement of a single, extranodal site contiguous or proximal to known nodal site 
a. The number of anatomic regions involved should be indicated by a subscript (eg, II3).  
b. Stage III may be subdivided into: III1, with or without splenic, hilar, celiac, or portal nodes; III2, with para-aortic, iliac, 
mesenteric nodes. 
International Prognostic Index for Aggressive Non-Hodgkin's Lymphoma (NHL Project, 
1993) 
The International Prognostic Index (IPI) for Aggressive non-Hodgkin Lymphoma (NHL) is used 
to assess the prognostic score of subjects at diagnosis with aggressive NHL.  
One point is assigned for each of the following risk factors: 
1. age > 60 years 
2. Ann Arbor Stage III or IV disease  
3. serum lactic dehydrogenase (LDH) ≥ 450 IU/L  
4. ECOG performance status of 2, 3, or 4  
5. extranodal sites ≥ 2 


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Subjects will be documented to be in 1 of 4 risk groups: 
Low risk 
0-1 risk factors 
Low-intermediate risk (2 points) 
2 risk factors 
High-intermediate risk (3 points) 
3 risk factors 
High risk (4-5 points) 
4-5 risk factors 
 


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10.6 Appendix 6: Lugano Classification for Response Assessment in Lymphoma 
(Including the 5PS) 
Tumor response will be evaluated according to the Lugano Classification for Lymphoma 
(Cheson, 2014) (Table 10-5). 
Table 10-5. 
Lugano Classification of Response Assessment in Lymphoma  
Response and Site 
PET-CT-Based Response 
CT and/or MRI-Based Response 
Complete 
Complete metabolic response (CMR) 
Complete radiologic response 
(all of the following) 
Lymph nodes and 
extralymphatic sites  
5PS score of 1, 2, or 3a with or without 
residual mass (see Table 10-6) 
It is recognized that in Waldeyer’s ring or 
extranodal sites with high physiologic 
uptake or with activation within spleen or 
marrow (eg, with chemotherapy or myeloid 
colony-stimulating factors), uptake may be 
greater than normal mediastinum and/or 
liver. In this circumstance, CMR may be 
inferred if uptake at sites of initial 
involvement is no greater than surrounding 
normal tissue even if the tissue has high 
physiologic uptake 
Target nodes/nodal masses must regress to 
≤ 1.5 cm in LDi 
No extralymphatic sites of disease 
Nonmeasured lesion 
Not applicable 
Absent 
Organ enlargement 
Not applicable 
Regress to normal 
New lesion(s) 
None 
None 
Bone Marrow 
No evidence of FDG-avid disease in marrow 
Normal by morphology; if indeterminate, 
IHC negative 
Partial 
Partial metabolic response 
Partial remission (all of the following) 
Lymph nodes and 
extralymphatic sites  
Score 4 or 5 on the 5PS (see Table 10-6) 
with reduced uptake compared with baseline 
and residual mass(es) of any size. 
At interim, these findings suggest 
responding disease. 
At end of treatment (EoT), these findings 
indicate residual disease 
≥ 50% decrease in SPD of up to 6 target 
measurable nodes and extranodal sites. 
When a lesion is too small to measure on 
CT, assign 5 mm x 5 mm as the default 
value; 
when no longer visible, 0 x 0 mm. 
For a node > 5 mm x 5 mm, but smaller than 
normal, use actual measurement for 
calculation. 
Nonmeasured lesion 
Not applicable 
Absent/normal, regressed, but no increase 
Organ enlargement 
Not applicable 
Spleen must have regressed by > 50% in 
length beyond normal. 
New lesion(s) 
None 
None 


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Table 10-5. 
Lugano Classification of Response Assessment in Lymphoma  
Response and Site 
PET-CT-Based Response 
CT and/or MRI-Based Response 
Bone Marrow 
Residual uptake higher than uptake in 
normal marrow but reduced compared with 
baseline (diffuse uptake compatible with 
reactive changes from chemotherapy 
allowed). If there are persistent focal 
changes in the marrow in the context of a 
nodal response, consideration should be 
given to further evaluation with MRI or 
biopsy or an interval scan 
Not applicable 
No response or 
stable disease 
No metabolic response 
Stable disease 
Target nodes/nodal 
masses, extranodal 
lesions 
Score 4 or 5 with no significant change in 
FDG uptake from baseline at interim or EoT 
< 50% decrease from baseline in SPD of up 
to 6 dominant, measurable nodes and 
extranodal sites; no criteria for progressive 
disease are met 
Nonmeasured lesion 
Not applicable 
No increase consistent with progression 
Organ enlargement 
Not applicable 
No increase consistent with progression 
New lesion(s) 
None 
None 
Bone Marrow 
No changes from baseline 
Not applicable 
Progressive 
Disease  
Progressive metabolic disease 
Progressive disease requires 
at least 1 of the following  
Individual target 
nodes/nodal masses  
Score 4 or 5 with an increase in intensity of 
uptake from baseline and/or 
PPD progression 
Extranodal lesions 
New FDG-avid foci consistent with 
lymphoma at interim or end-of-treatment 
assessment 
An individual node/lesion must be abnormal 
with: 
LDi > 1.5 cm and 
Increase by 2: 50% from PPD nadir and 
An increase in LDi or SDi from nadir 
0.5 cm for lesions ≤ 2 cm 
1.0 cm for lesions > 2 cm 
In the setting of splenomegaly, the splenic 
length must increase by > 50% of the extent 
of its prior increase beyond baseline (eg, a 
15-cm spleen must increase to > 16 cm). If 
no prior splenomegaly, must increase by at 
least 2 cm from baseline 
New or recurrent splenomegaly 
Nonmeasured lesion 
None 
New or clear progression of preexisting 
nonmeasured lesions 
New lesion(s) 
New FDG-avid foci consistent with 
lymphoma rather than another etiology (eg, 
infection, inflammation). If uncertain 
regarding etiology of new lesions, biopsy or 
interval scan may be considered 
Regrowth of previously resolved lesions 
A new node > 1.5 cm in any axis 
A new extranodal site > 1.0 cm in any axis; 
if < 1.0 cm in any axis, its presence must be 
unequivocal and must be attributable to 
lymphoma 
Assessable disease of any size unequivocally 
attributable to lymphoma 


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Table 10-5. 
Lugano Classification of Response Assessment in Lymphoma  
Response and Site 
PET-CT-Based Response 
CT and/or MRI-Based Response 
Bone Marrow 
New or recurrent FDG-avid foci 
New or recurrent involvement 
5PS = 5-point scale; CT: computed tomography; FDG = fluorodeoxyglucose; IHC = immunohistochemistry; LDi = longest 
transverse diameter of a lesion; MRI = magnetic resonance imaging; PET = positron emission tomography; PPD = cross product 
of the LDi and perpendicular diameter; SDi = shortest axis perpendicular to the LDi; SPD = sum of the product of the 
perpendicular diameters for multiple lesions. 
a 
A score of 3 in many patients indicates a good prognosis with standard treatment, especially if at the time of an interim 
scan. However, in trials involving PET where de-escalation is investigated, it may be preferable to consider a score of 
3 as inadequate response (to avoid undertreatment). Measured dominant lesions: Up to 6 of the largest dominant nodes, 
nodal masses, and extranodal lesions selected to be clearly measurable in 2 diameters. Nodes should preferably be 
from disparate regions of the body and should include, where applicable, mediastinal and retroperitoneal areas. Non-
nodal lesions include those in solid organs (eg, liver, spleen, kidneys, lungs), GI involvement, cutaneous lesions, or 
those noted on palpation. Nonmeasured lesions: Any disease not selected as measured, dominant disease and truly 
assessable disease should be considered not measured. These sites include any nodes, nodal masses, and extranodal 
sites not selected as dominant or measurable or that do not meet the requirements for measurability but are still 
considered abnormal, as well as truly assessable disease, which is any site of suspected disease that would be difficult 
to follow quantitatively with measurement, including pleural effusions, ascites, bone lesions, leptomeningeal disease, 
abdominal masses, and other lesions that cannot be confirmed and followed by imaging. In Waldeyer’s ring or in 
extranodal sites (eg, GI tract, liver, bone marrow), FDG uptake may be greater than in the mediastinum with complete 
metabolic response, but should be no higher than surrounding normal physiologic uptake (eg, with marrow activation 
as a result of chemotherapy or myeloid growth factors). 
b 
See original paper Cheson, 2014 for more detailed information on immune related response. 
 
Lugano 5PS Range (Cheson, 2014) 
The 5PS ranges from a score of 1 (where no uptake is discernible in the lesion) to a score of 5 
(where the uptake in the lesion is markedly increased compared to the uptake in the liver 
parenchyma). A single 5PS score, which represents the most FDG-avid (ie, metabolically 
intense) area of disease (across all index and non-index lesions), is assigned for each PET/CT 
scan in the study, see Table 10-6. 
Table 10-6. 
Modified Lugano 5-Point Scale (5PS) 
Score 
Description 
1 
No uptake 
2 
Uptake ≤ mediastinum 
3 
Uptake > mediastinum but ≤ liver 
4 
Uptake moderately increased above liver at any site 
5 
Markedly increased uptake above liver at any site 
NE 
Not evaluable 
X 
Any areas of uptake not likely to be related to lymphoma 
 


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10.7 Appendix 7: ECOG Performance Status 
ECOG will be recorded per the investigator’s assessment of patient performance status: 
Grade 
Description 
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 
Death 
 


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10.8 Appendix 8: New York Heart Association Functional Classification 
The stages of heart failure will be assessed according to the New York Heart Association 
(NHYA) functional classification system. This system relates symptoms to everyday activities 
and the patient’s quality of life. 
NYHA Functional Classification 
Class 
Patient symptoms 
Class I (mild) 
No limitation of physical activity. Ordinary physical activity does not cause undue 
fatigue, palpitation, or dyspnea (shortness of breath). 
Class II (mild) 
Slight limitation of physical activity. Comfortable at rest, but ordinary physical 
activity results in fatigue, palpitation, or dyspnea. 
Class III (moderate) 
Marked limitation of physical activity. Comfortable at rest, but less than ordinary 
activity causes fatigue, palpitation, or dyspnea. 
Class IV (severe) 
Unable to carry out any physical activity without discomfort. Symptoms of cardiac 
insufficiency at rest. If any physical activity is undertaken, discomfort is increased. 
 
 
 


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10.9 Appendix 9: Abbreviations 
Abbreviation 
Definition 
ABC 
activated B cell 
ADA 
anti-drug antibodies 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT (SGPT) 
alanine aminotransferase 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST (SGOT) 
aspartate aminotransferase 
AUC0-4 
area under the plasma concentration time curve from 0 to 4 hours 
AUC0-inf 
area under the plasma concentration time curve from 0 to infinity 
AUClast 
area under the plasma concentration time curve from dosing to last measurable 
concentration 
BP 
blood pressure 
BUN 
blood urea nitrogen 
C1D1 
Cycle 1 Day 1 
CAR-T 
chimeric antigen receptor T-cell 
CDC 
complement-dependent cytotoxicity 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CK 
creatine phosphokinase 
CL 
clearance 
CLcr 
creatinine clearance 
CLS 
capillary leak syndrome 
cm 
centimeter 
Cmax 
maximum observed plasma concentration 
CR 
complete remission; complete response 
CRF 
case report form 
CRO 
contract research organization 
CRS 
cytokine release syndrome 
CS 
clinically significant 
CSF 
cerebrospinal fluid 
CT 
computerized tomography 
CT-dq 
computed tomography of diagnostic quality 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCR 
disease control rate 
DLBCL 
diffuse large B-cell lymphoma 


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Abbreviation 
Definition 
DLT 
dose-limiting toxicity 
DOR 
duration of tumor response 
DSMB 
Data Safety Monitoring Board  
ECG 
electrocardiogram 
ECHO 
echocardiogram 
ECOG PS 
Eastern Cooperative Oncology Group performance status 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EoT 
end of treatment 
EQ-5D 
EuroQol Group Quality of Life – 5-dimensions 
FAS 
Full analysis set 
Fc 
fragment crystallizable region 
FDA 
Food and Drug Administration 
GCB 
germinal center B cell 
GCP 
Good Clinical Practice 
G-CSF 
granulocyte colony-stimulating factor 
GGT 
gamma glutamyl transferase 
HBsAg 
hepatitis B surface antigen 
 
 
HIV 
human immunodeficiency virus 
IB 
Investigator Brochure 
ICF 
Informed Consent Form  
ICH 
International Conference on Harmonisation  
ICR 
independent central review 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IND 
investigational new drug  
INR 
international normalized ratio 
IPI 
International Prognostic Index  
IRB 
Institutional Review Board 
IRR 
infusion-related reactions 
IV 
intravenous  
kDa 
kiloDaltons 
Kg 
kilogram 
L 
liter 
LDH 
lactic dehydrogenase 
LTFU 
long-term follow-up 
PPD


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Abbreviation 
Definition 
LVEF 
left ventricular ejection fraction 
mAb 
monoclonal antibody 
µg 
microgram 
MedDRA 
Medical Dictionary for Regulatory Activities 
mFAS 
modified full analysis set 
mg 
milligram 
ml 
milliliter 
mM 
millimolar 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
MUGA 
multigated acquistion 
NAb 
neutralizing antibody  
NCI 
National Cancer Institute 
NCS 
not clinically significant 
NHL 
non-Hodgkin Lymphoma 
NSAIDS 
non-steroidal anti-inflammatory drugs 
NYHA 
New York Heart Association 
ORR 
objective response or overall response rate 
OS 
overall survival 
PD 
progressive disease 
PE 
physical examination  
PET 
positron emission tomography 
PFS 
Progression-free survival 
PK 
pharmacokinetics 
PR 
partial response 
PRBC 
peripheral red blood cell 
PT 
prothrombin time  
QTcF 
QT interval correction for heart rate using Fridericia’s formula 
RBC 
red blood cell (count) 
RP2D 
recommended phase 2 dose 
RR 
respiratory rate 
SAE 
serious adverse event 
scFv 
single chain variable fragment 
SCr 
serum creatinine 
SCT 
stem cell transplant 
SD 
stable disease 
SGOT (AST) 
serum glutamic-oxaloacetic transaminase 


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Abbreviation 
Definition 
SGPT (ALT) 
serum glutamic-pyruvic transaminase 
SIRS 
systemic inflammatory response syndrome 
SLT-I A1 
Shiga-like toxin-I A1 subunit  
SoC 
standard of care 
SPD 
sum of product of perpendicular diameters 
STAT 
urgent, rush 
STFU 
short-term follow-up 
t1/2 
half-life 
TEAE 
treatment-emergent adverse event 
TIW 
three times a week 
tmax 
time to achieve Cmax 
ULN 
upper limit of normal  
US 
United States 
Vz 
volume of distribution 
WBC 
white blood cell (count) 
 
 
 


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11 REFERENCES 
Beers SA, F. R. Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications 
for antibody selection. Blood. 2010;115:5191–201. 
Beum PV, P. E. Loss of CD20 and bound CD20 antibody from opsonized B cells occurs more 
rapidly because of trogocytosis mediated by Fc receptor-expressing effector cells than direct 
internalization by the B cells. J Immunol. 2011;3438-447. 
Cheson BD, F. R. Recommendations for initial evaluation, staging and response assessment of 
Hodgkin and Non-Hodgkin Lymphoma. The Lugano Classification. J Clin Oncol. 
2014;32:3059-67. doi:10.1200/JCO.2013.54.8800 
HMRN. Haematological Malignancy Research Network (HMRN). Retrieved from 
https://www.hmrn.org/statistics/incidence, 30 March 2020. 
Howlader N, N. A. SEER Cancer Statistics Review, 1975-2016, National Cancer Institute. 
Bethesda, MD. Retrieved from https://seer.cancer.gov/csr/1975_2016/, based on November 2018 
SEER data submission. posted to the SEER web site, April 2019. 
IB. MT-3724 Investigator’s Brochure (IB); version 6.0, effective date: November 2020.  
ICH. ICH, Integrated addendum of ICH E6(R1): Guideline for Good Clinical Practice E6 (R2). 
2016. 
Ko BS, et al. Subtype-specific epidemiology of lymphoid malignancies in Taiwan compared to 
Japan and the United States, 2002-2012. Cancer Med. 2018;7(11):5820-31. 
Lim SH, V. A.-K. Fc gamma receptor IIb on target B cells promotes rituximab internalization 
and reduces clinical efficacy. Blood. 2011;2530-40. 
Lister TA, C. D. Report of a committee convened to discuss the evaluation and staging of 
patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol. 1989;7(11):1630-6. 
Maloney, D. Anti-CD20 antibody therapy for B-cell lymphomas. N Engl J Med. 
2012;336(21):2008-16. 
Milenic DE, Y. T. Construction, Binding Properties, Metabolism, and Tumor Targeting of a 
Single-Chain Fv Derived from the Pancarcinoma Monoclonal Antibody CC49. Cancer Research. 
1991;6363-71. 
Miyoshi H, O. K. Epidemiology of malignant lymphoma and recent progress in research on adult 
T-cell leukemia/lymphoma in Japan. Int J Hematol. 2018;107(4):420-7. 
Møller MB, et al. Diffuse large B-cell lymphoma: clinical implications of extranodal versus 
nodal presentation--a population-based study of 1575 cases. Br J Haematol. 2004;124(2):151-9. 


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NCCI. National Cancer Control Indicators. Retrieved from 
https://ncci.canceraustralia.gov.au/diagnosis/cancer-incidence/cancer-incidence. 30 March 2020. 
NHL Project, T. I.-H. A Predictive Model for Aggressive Non Hodgkin's Lymphoma. N Engl J 
Med. 1993;(329):987-994. doi:10.1056/NEJM199309303291402 
Rajagopalan S, et al. CD20-Specific Engineered Toxin Body Demonstrates Direct Cell Kill Of 
Multiple B-Cell Non-Hodgkin's Lymphoma Types. Blood. 2013;122(21):5152. 
Sun J, et al. Distribution of lymphoid neoplasms in China: analysis of 4,638 cases according to 
the World Health Organization classification. Am J Clin Pathol. 2012;138(3):429-34. 
Swerdlow SH, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. In: 
IARC. In World Health Organization Classification of Tumours. Lyon, France. 2016. 
Tedder TF, S. M. Isolation and structure of a cDNA encoding the B1 (CD20) cell-surface antigen 
of human B lymphocytes. Proc Natl Acad Sci USA. 1988;208-12. 
Vitolo U, S. J. Extranodal diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B 
cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann 
Oncol. 2016;27(suppl 5), v91 v102. 
WMA. World Medical Association (WMA), Declaration of Helsinki – Ethical Principals of 
Medical Research Involving Human Subjects, 2013, Adopted by the WMA General Assembly in 
Helsinki (1964) and as amended by the WMA General Assembly. 2013. 
Yoo KH, et al. Lymphoma epidemiology in Korea and the real clinical field including the 
Consortium for Improving Survival of Lymphoma (CISL) trial. Int J Hematol, 
2018;107(4):395-404. 
 


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12 SUMMARY OF CHANGES 
12.1 Version 11 
Version 11.0 (12 February 2021) replaces versions 10.0 (14 August 2020), 9.0 (14 April 2019) 
and 9.1 (29 June 2020) 
Rationale for changes:  
Considering a recent Grade 5 CLS event, MTEM has completed the CLS safety assessment and 
has proposed CLS mitigation strategies and safety monitoring plans for all protocols evaluating 
MT-3724. This includes the addition of 2 dose-escalation cohorts to evaluate step-up dosing, 
modified dose caps, CLS-management, including increased monitoring of albumin and CK, and 
DLT-assessment. These changes, as well as administrative changes, and other necessary changes to 
account for these additions, are described below.  
 
Editorial changes that do not impact meaning were made and are not listed below. 
Summary of changes made: 
Change 
Rationale 
Affected protocol sections 
Increased number of subjects from 
20 to 25 in Part 3, thereby increasing 
the total number of subjects from 
108 to 113. 
 
To account for evaluation of 2 
additional cohorts 
Synopsis 
Overall Design 
4.1.1 Part 3 (overall study design) 
9.1 Statistical Hypothesis and 
sample size determination 
Added description of 2 dose 
escalation cohorts with step-up 
dosing. Subjects will start at 
10 µg/kg and increase in dose will 
be based on cohort. After the first 2 
cycles, subjects will be dosed 
weekly.  
An analysis of available data showed 
that dose and dose-associated PK 
parameters were associated with an 
increased risk for CLS. This, in 
conjunction with the observation that 
all CLS events occurred within a few 
days post initial dosing (or re-dosing 
after an initial CLS), suggests that 
lower doses at start of treatment may 
reduce the risk of CLS events.  
1. Synopsis 
Study treatment 
1.2 Study schema 
1.3 Schedule of activities 
4.1.1 Part 3 (overall study design) 
4.1.1.1 Subject evaluable for dose 
decisions (new section added in this 
amendment) 
6.1.1.1 Dose Rationale 
6.1.1.2 Dose Section 
6.3.1 Randomization 
Removed reference to switching to 
weekly dosing in cases of clinical 
benefit 
All subjects will be switched to 
weekly dosing staring with Cycle 3 
with this amendment, therefore this 
no longer applies 
Synopsis 
Study treatment 
Treatment beyond progression 
1.3 Schedule of activities 
6.1.1.3 Dose Schedule 
6.1.1.4 Treatment beyond 
progression  
Added DLT criteria  
Added criteria since dose escalation 
was reintroduced to this protocol 
10.3.9 Dose Limiting Toxicity 
(DLT) Criteria 


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Change 
Rationale 
Affected protocol sections 
Updated dose cap so that it is based 
on max of 120 kg body weight rather 
than absolute total dose of 6000 µg 
per infusion 
An analysis of available data showed 
an association with total dose 
administered and CLS, therefore 
dose caps have been updated to 
potentially reduce the risk of CLS 
events. 
6.1.1.1 Dose Rationale 
6.1.1.2 Dose Selection 
Modified dose reduction steps  
To account for different doses 
introduced with step-up dosing 
6.2.1 Dose Modification for 
Treatment Emergent Adverse 
Experiences 
Added guidance to the investigator 
for CLS, including dose 
modification 
Provide additional information on 
signs and/or symptoms of CLS, and 
management of CLS 
2.2.2 Guidance to the Investigator 
for Capillary Leak Syndrome 
6.2.1 Dose Modification for 
Treatment Emergent Adverse 
Experiences – Table 6-4. MT-3724 
Dose Modification Guidance and 
Specific Management of Toxicities. 
Added requirement for collection of 
albumin and CK (local lab) prior to 
each dose in Cycle 1, and require 
albumin to be reviewed prior to 
dosing 
Added collection and review of 
albumin prior to each dose of 
Cycle 1 to mitigate CLS. 
Added collection of CK prior to each 
dose of Cycle 1 to evaluate if this is 
a potential biomarker of CLS. 
1.3 Schedule of activities 
10.2.1 General Guidance (Appendix 
2: Clinical Laboratory Tests) 
Table 10-1 
Updated premedication 
requirements, including requirement 
to premedicate prior to each dose 
Added more clarification on 
premedication  
1.3 Schedule of activities 
6.1.2 Other Protocol-required 
Intervention 
Updated requirement for first 3 
doses of Cycle 1 to be at least 2 days 
(approx. 48 hours) apart rather than 
at least 48 hours apart 
To allow for flexibility with respect 
to dosing while maintaining window  
Synopsis 
Study treatment 
1.3 Schedule of activities 
6.1.1.3 Dose Schedule 
Removed reference to reverting to 
TIW dosing in case of progression 
and clarified that subjects will 
remain on dose received at time of 
progression 
All subjects will be on weekly 
dosing schedule starting Cycle 3 
with this amendment, therefore this 
no longer applies; and clarified dose 
administration at time of progression 
since dose escalation has been re-
introduced to this protocol 
Synopsis 
Overall design, treatment 
beyond progression 
6.1.1.4 Treatment beyond 
progression 
Added clarification under dose 
modification that MT-3724 
treatment may be restarted if the 
TEAE that led to modification 
resolved to Grade ≤ 1 (new text: “or 
the subject’s baseline”) 
To allow for treatment to be 
restarted if subject’s baseline 
condition that led to modification 
was more severe than grade 1 
6.2.1 Dose Modification for 
Treatment Emergent Adverse 
Experiences 
Added updated clinical experience to 
reflect IB update (vs 6) 
Provided update of clinical 
experience based on IB version 6, 
given grade 5 CLS event 
2.2.1 Summary of Clinical 
Experience  
Added clarification regarding 
subject replacement 
To account for replacement of 
subjects ineligible for DLT 
assessment 
7.2 Subject replacement 


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Change 
Rationale 
Affected protocol sections 
Added requirement for DSMB 
assembly prior to starting Part 4, and 
other administrative changes  
To ensure sufficient oversight prior 
to initiating Part 4, 
Administrative changes made to 
reflect DSMB charter and best 
practices 
9.4 Data Safety Monitoring Board 
Updated action taken with study 
treatment for AE management 
Administrative change to correspond 
with CDISC  
10.3.7 Action Taken with Study 
Treatment (Adverse Events) 
 
12.2 Version 10 
Version 10.0 (14 August 2020) replaces versions 9.0 (14 April 2019) and 9.1 (29 June 2020) 
Rationale for changes:  
1. Updated schedule of activities (Tables 1-1 and 1-2) to correct errors that were inadvertently 
made when version 8 was updated to version 9. 
2. Language permitting the administration of live vaccines during treatment has been removed, 
as use of live vaccines with anti-CD20 products and subsequent B-cell depletion is not 
recommended. 
3. Updated the inclusion criterion #4 to specify that the required prior 2 lines of treatment 
should be appropriate for DLBCL and not any NHL. 
4. Updated requirement to change dose if body weight changes from > 10% to ≥ 10%. 
5. Updated entry criterion on LVEF to be at least 45% rather than greater than 45%. 
6. Clarification has been added on the duration of the in-clinic visit during which subjects will 
be monitored for signs of CLS and CRS. 
7. Additional changes to the summary of changes for amendment 9.0 were added as they were 
erroneously left out. Those items are in bolded text. 
8. Other editorial changes that do not impact meaning were made and are not listed below. 
List of changes made: 
Section 
Revision Made 
Schedule of 
activities:  
Table 1-1 
• 
Added ECG at EoT 
• 
Added Chemistry and removed coagulation at STFU 
• 
Added samples missing from screening: complement, histamine, immunoglobulins, 
cytokines, B-cells and immunophenotype, and MT-3724 ADA/NAb and removed 
concomitant medication review during screening    
• 
Provided clarification on how prior systemic therapy should be recorded 
• 
Provided clarification that the safety calls are not required for subjects dosed on 
weekly schedule 
• 
Provided clarification regarding radiological exams for subjects who continue to 
receive MT-3724 beyond progression and that they are every 6 weeks starting from 
C1D1 
• 
Reworked note for triplicate ECGs for clarification 


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Section 
Revision Made 
• 
Changed that subject has to have rested quietly from 5 to 10 minutes to at least 
5 minutes. 
• 
Updated footnotes to match protocol text and provide clarification on Day 15 visit 
• 
Updated requirement to change dose if body weight changes from > 10% to ≥ 10% 
• 
Pregnancy test moved from central lab to local lab to allow for real-time assessment 
Schedule of 
activities 
Table 1-2 
• 
Removed PK samples from C1D3 and C1D12 at both the 0.5 h- and 1 h-after end of 
infusion timepoints for subjects in Part 4 
• 
Added “within” to “4 hr prior to SOI” to clarify that the PK samples can be drawn 
within 4 hours prior to SOI and not at 4 hr prior to SOI 
Synopsis, Number 
of subjects 
• 
Removed “who have received at least 2 standard of care systemic NHL treatment 
regimens (including anti-CD20 antibody therapy) will be enrolled” to avoid 
redundancy 
Synopsis,  
Sections 3.1, 3.2 
and 8.7.1 
• 
Provided clarification that immunoglobulins are collected as pharmacodynamic 
endpoints 
Synopsis;  
Section 4.1.3 
• 
Removed “Safety” from Long Term Safety follow-up since LTFU visits are not done 
for safety; and also removed “Visits may occur by telephone contact when radiology 
data can be obtained from medical records” as it was less clear than what is stated in 
the section on LTFU (Section 8.1.5)  
Synopsis,  
Section 5.1 
• 
Updated inclusion criterion #4 to specify that the prior treatments need to be 
appropriate for DLBCL (changed from “Subjects must have received at least 2 
standard of care regimens (including anti-CD20 antibody therapy) for NHL treatment” 
to “Subjects must have received at least 2 standard of care regimens (including 
anti-CD20 antibody therapy) for appropriate for DLBCL treatment.” 
• 
Updated inclusion criterion 4b to remove reference to hematologic recovery (deleted: 
“and exhibited a full hematological recovery (consistent with the existing inclusion 
criteria requirements and without peripheral red blood cell [PRBC] or platelet 
transfusions within 2 weeks of C1D1) prior to relapse are eligible.” 
• 
Updated inclusion criteria #8 to include guidance on use of treatments affecting bone 
marrow function 
• 
Updated inclusion criteria numbering as #11 was skipped in version 9. 
• 
Updated inclusion criterion #11 to require pregnancy test within 72 hours of C1D1 
rather than 7 days of C1D1, for consistency. 
• 
Updated inclusion criterion #12 to clarify contraception requirements after treatment, 
in alignment with Appendix 4. 
Synopsis; 
Section 5.2 
• 
Exclusion criterion #1 – added sub-bullet D to provide more guidance for 
investigational CD20 agents.  
• 
Exclusion criterion #2 – added clarification on CD20 agents “except anti-CD20 agents 
where exclusion criterion 1 applies” 
• 
Exclusion criterion #5 - removed "unless the investigator believes the benefits 
outweigh risks, after consultation with the medical monitor and with sponsor 
approval." 
• 
Exclusion criterion #12 – added “or palliative radiation therapy to non-target lesions, 
as described in Section 6.5” as it was erroneously removed with amendment 9 
• 
Exclusion criterion #19e – corrected LVEF requirement from < 45% to ≤ 45% 
Synopsis; 
Section 6.1.1.2 
• 
Changed requirement for all doses to be administered within 14 days to within 16 days 
to allow for more flexibility while maintaining roughly 2-week dosing window. 
• 
Added clarification on the duration of the clinic visit post-dose. 


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Section 
Revision Made 
• 
Rearranged paragraph on weekly dosing for clarity.  
• 
Updated requirement to change dose if body weight changes from > 10% to ≥ 10%. 
Synopsis;  
Section 6.1.1.3 
Added language to clarify that subjects for who have disease progression within 3 months 
of switching to weekly dosing, the investigatory may revert to the original dosing 
schedule, if conditions already outlined in that section are met. 
Section 6.1.3   
Removed: “unless the investigator believes the benefits outweigh risks, after consultation 
with the medical monitor and with sponsor approval” and added further prohibition on use 
of live vaccinations: “during the treatment and after the last dose of MT-3724 while 
peripheral B cells are depleted.” 
Section 6.4 
Changed “subject notes” to “clinic notes” to clarify that compliance is not based on 
subject diary as treatment is given in-clinic. 
Section 8.2.2 
Status at screening – clarified that histology at screening is specifically for DLBCL rather 
than NHL 
Section 8.2.3  
Provided clarification on how prior systemic therapy should be recorded (to allow for 
flexibility based on EDC capabilities) 
Section 8.4  
Added: “Subjects will be monitored for signs of CLS and CRS during and after their 
infusions. Vital signs will be monitored up to 4 hours after the start of infusion C1D1, and 
up to 2 hours after the start of infusion for each subsequent infusion. In addition, subjects 
will remain in-clinic for PK sampling for 5 hours from the start of infusion on C1D1 and 
for 3 hours from the start of infusion on C1D3 and C1D12, where they may also be 
observed for signs of CLS and CRS.” 
Section 8.4.2 
Added clarification that medications taken within 4 weeks before the start of treatment on 
C1D1 will be regarded as prior medications 
Section 8.4.3 
Updated requirement to change dose if body weight changes from > 10% to ≥ 10%. 
Section 8.4.6 
Changed that subject has to have rested quietly from 5 to 10 minutes to at least 5 minutes. 
Section 8.4.8 
Changed “Any clinically significant abnormality of vital signs should be followed…” to 
“Any clinically significant abnormality of ECGs should be followed…” 
Reworked note for triplicate ECGs for clarification (removed “ie, the maximum 4 minutes 
total for 3 ECGs.” 
Section 8.4.9 
Removed “immediately” from “In the event of an unexplained clinically-significant 
abnormal laboratory test value, the test should be repeated immediately and followed 
up…”    
Section 8.4.10 
Added clarification that the safety follow-up call is not applicable for subjects dosed on 
the weekly schedule since subjects are seen in-clinic on weekly basis 
Section 10.1 
Updated that MT-3724 will be shipped frozen instead of “on dry ice”  
Section 10.1.2 
Changed requirement for investigator to obtain written approval of all study-related 
documents to only obtaining written documentation for initial study approval. 
Changed “The investigator must conduct the study according to the signed, written 
protocol” to “The investigator must conduct the study according to the most recent, 
approved protocol version”. 
These changes were made to better accurately reflect what is done in practice. 
Section 10.1.4 
Informed consent process updated to more accurately reflect what is done in practice in 
this global clinical trial. 
Section 10.1.5 
Removed that “subject initials” will be collected in the eCRF and added that any personal 
identifiers should be obliterated. 
Section 10.1.7.1 
Removed mention of site reference manual as it not needed to be stated, and also removed 
examples of source documentation. 


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Section 
Revision Made 
Clarified that subject identifiers should be made invisible without prescribing method of 
making it so (changed “lined through with black marker” to “made invisible”) 
Deleted “/Medical records” from “Source Documents/Medical records” since medical 
records are source documents.  
Deleted “microfiches” as they are not likely to be used as source documents. 
Added clarification that ICF for amendments are to be saved as source documents per 
local authorities. 
Section 10.2 
Removed histamine from under chemistry; added pregnancy test to local laboratory 
Section 10.2.1 
Deleted “If possible, the blood for chemistry assessments should be drawn after a subject 
has fasted for at least 2 hours, to facilitate a more reliable interpretation of the plasma 
glucose result. The compliance with this recommendation (Yes / No) will be entered in the 
eCRF for every chemistry assessment.” since this is not required to assess MT-3724 
safety.  
Administrative 
Global Changes 
Changed abbreviation for standard of care from SOC to SoC to avoid confusion with 
System Organ Class and spelled out System organ class as it only appeared once. 
Spelled out abbreviation for NHL upon first appearance.  
Changed CT/MRI to CT and/or MRI for more clarity. 
Updated CRF to eCRF. 
Updated name of European Agency for the Evaluation of Medicinal Products to European 
Medicines Agency 
Updated Appendix 9, Abbreviations, to include the new terms introduced in this 
amendment 
Updated NHL to DLBCL where appropriate 
Editorial updates for inclusion/exclusion criteria in synopsis to match that in body of 
protocol 
 
12.3 Version 9 
Version 9.0 (14 April 2020) replaces version 8.0 (15 February 2019) 
Amendment 9.0 is applicable to all investigators participating in this protocol. For practical 
reasons, this amendment only specifies the study conduct of Part 3 and Part 4 of the protocol.  
Rationale for changes: 
1. The statistical aspect of the study design that had been a Simon 2-stage in 100 subjects 
(termed "Part 3") has been changed. Instead, the statistical aspect of the study includes a 
continuation of an expansion cohort at the Recommended Phase 2 Dose (RP2D) (now termed 
"Part 3") in approximately 20 subjects and a new Phase 2 portion (termed "Part 4") that will 
evaluate approximately 88 subjects. The total sample size has increased from 100 to 
approximately 108. Importantly, the primary endpoints were adjusted to safety for Part 3 and 
efficacy for Part 4. 
o The first 20 subjects enrolled will contribute to the completion of the MTD expansion 
cohort (Part 3). This is considered to be important because the existing sample size of 
subjects evaluated at the RP2D included only 6 subjects, and only 3 were treated for more 
than one cycle. Thus, these additional subjects will better inform the safety and 


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tolerability of monotherapy at the RP2D before starting the Phase 2 portion of the trial 
(Part 4). 
2. The goal of Part 4 is to provide sufficient evidence to test the null hypothesis that the true 
response rate with MT 3724 ≤ 17% versus the alternative hypothesis that the true response 
rate with MT 3724 ≥ 32% at the 1-sided alpha level of 0.025 with high statistical power. 
Under the stated null and alternative hypotheses, Part 4 carries 90.4% power at the 1-sided 
alpha level of < 0.025. Since this is an open-label trial, formal futility analysis has been 
removed from the protocol, as this will occur on an ongoing basis with input from a Data 
Safety Monitoring Board. 
3. Subjects are now required to have histologically confirmed CD20+ DLBCL obtained at the 
time of relapse to be eligible for this study. This is to confirm the study enrolls the 
appropriate patient population whose disease has the potential to respond to this therapy 
based upon based upon the mechanism of action of MT-3724. 
4. Other changes to inclusion/exclusion criteria have been made to ensure consistency across 
the MT-3724 program of studies and to modify criteria which were unnecessarily stringent. 
These latter changes include allowing subjects with seropositive human immunodeficiency 
virus (HIV)/hepatitis B virus (HBV)/hepatitis C virus (HCV) the option to enroll in this study 
provided they have non-detectable viral loads (HIV/HBV/HCV), a minimum number of 
CD4+ cells (for subjects with HIV) and receive appropriate prophylactic treatments; also, a 
reduced washout period (consistent with the relevant half-life for subjects whose last 
treatment included small molecules [as opposed to monoclonal antibodies]). The current 
safety data do not indicate a heightened risk for study subjects to have new or reactivated 
viral infectious diseases.   
5. Predose medication requirements have been updated to clarify that subjects must receive 
predose medications with all doses in Cycle 1, rather than allowing predose medications at 
the investigator’s discretion, which may reduce incidence and/or severity of innate immune 
responses typically observed early in Cycle 1.  
6. The protocol was modified to allow subjects continued treatment with MT-3724, rather than 
the prior limitation of therapy to a maximum of 12 cycles, contingent upon demonstration of 
continued clinical benefit and tolerability of study treatment. Given the current safety profile 
which includes subjects’ exposure for up to 9 cycles, it is reasonable to allow subjects 
continued treatment with MT-3724 provided there is a favorable benefit-risk ratio, in the 
opinion of the treating investigator. 
7. The clinical assessment tool termed LYRIC has been removed and replaced with Lugano 
(Cheson, 2014) since LYRIC was designed primarily for use with checkpoint inhibitors. 
Instead, the protocol now allows for treatment beyond progression if the investigator believes 
the benefits outweigh the risks, while requiring certain standard criteria to be met (ie, 
ensuring the subject is not exhibiting clinical deterioration, has no impending organ 
impairment, and agrees to sign an ICF again, acknowledging the potential risks of continuing 
investigational therapy and foregoing other treatment options). 
8. The screening period has been increased from 28 days to 35 days to allow for central 
laboratory processing of screening samples. 


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9. The safety event collection period starting point has been updated from “signing of the 
informed consent” to “Cycle 1 Day 1”. This was implemented to avoid collecting unrelated 
pre-treatment AEs; and to avoid confounding understanding of MT-3724 safety profile with 
toxicities from other cancer therapies. An AE/SAE during the screening period will only be 
collected if it is deemed related to a protocol screening procedure. 
10. Respiratory rate and temperature assessments have been added to vital signs and quality of 
life analysis language has been added as these were inadvertently omitted from previous 
versions of the protocol. 
11. Please note, the protocol has been transferred into a new TransCelerate-based protocol 
template for improved organization, readability, and reduction in redundancy of information. 
Some sections are new to the protocol (eg, Sections 5.3, 6.6, 7.4, 8.8, and 10.4) and utilized 
template language to offer additional guidance to investigators, sites, IRB/IECs, and health 
authorities. In line with the template transfer, the background material formerly provided in 
Section 2 has been drastically reduced to provide a concise summary on disease and 
investigational product (MT-3724) background. Appropriate references to the Investigator’s 
Brochure have been included which contains detailed information. 
12. Vast majority of changes made were to provide clarifications to existing language. 
High-level summary of changes made: 
Section 
Revision Made 
Global 
Administrative and editorial changes were made throughout the protocol (including 
updates to protocol version, approval date, and study contact information; and correction 
of typographical, grammatical, and formatting errors). 
Global 
Objective response will be based on the Lugano Classification for Lymphoma; the 
“adjustment according to LYRIC” has been removed (and its associated reference). 
Global 
Screening window increased from 28 days to 35 days. 
Global 
Long-term follow-up visit frequency has increased to every 3 months (instead of every 6 
months). Long-term follow-up now ends up to 18 months after the last dose (instead of 
“until death or loss to follow-up”). 
Schedule of 
Activities 
Added predose ECG collections  
Other changes made are covered in text relevant protocol sections 
Synopsis; 
Sections 3.1 and 3.2 
x 
Add Part 3 and Part 4 study objectives and endpoints 
x 
Part 4 revisions: 
o 
Move duration of tumor response to key secondary endpoint 
o 
Additional exploratory objectives and endpoints were added 
o
Synopsis; 
Section 4.1 
Updated to indicate Parts 1 and 2 are closed and add design language for Parts 3 and 4. 
Synopsis; 
Sections 4.1, 6.1.1.2 
Removed limitation of 6 cycles of treatment, subjects will now be treated until death, 
disease progression, unacceptable toxicity, withdrawal of consent, or another reason for 
withdrawal, or until study discontinuation 
Synopsis; 
Section 6.1.1.3 
Added option to treat subjects beyond progression if certain criteria are met. 
Synopsis; 
Sections 4.1, 8.1.5 
Frequency of long-term follow-up visits have been increased from every 6 months to 
every 3 months (for up to 18 months from the last dose of MT-3724). 
PPD


Compound: MT-3724 
 
Protocol MT-3724_NHL_001 
Protocol Date and Version: 12 February 2021, v11.0 
 
CONFIDENTIAL 
 
Page 120 of 123 
Section 
Revision Made 
Synopsis; 
Sections 1.3, 6.1.1.2 
Cycle 1 dose schedule was clarified to indicate that the first 3 doses of Cycle 1 must be 
administered at least 48 hours apart. 
Synopsis 
Number of subjects has been updated to reflect expected number of subjects that are to be 
enrolled in Parts 3 and 4 of this study. 
Synopsis; 
Section 9.1 
Number of subjects has been updated to reflect expected number of subjects that are to be 
enrolled in Parts 3 and 4 of this study. 
Section 5  
Modified text to remove information that is already described in the 
inclusion/exclusion criterion to avoid redundancy 
Synopsis; 
Section 5.1 
Inclusion criteria have been updated to include patients with proof of CD20+ DLBCL 
based on historical biopsies; fresh biopsies; bone marrow biopsy; excisional lymph node 
biopsy, or core biopsy of any involved organ 
Synopsis; 
Section 5.1 
Inclusion criteria have been updated as follows: to include anti-CD20 antibody therapy for 
NHL treatment; the amount of time before study drug administration for autologous SCT 
or allogenic SCT have been clarified to be ≥ 100 and ≥ 180 days, respectively; 
hematological recovery has been clarified to be consistent with the existing inclusion 
criteria requirements and without PRBC or platelet transfusions within 2 weeks of C1D1 
Synopsis; 
Section 5.1 
Inclusion criteria have been updated to clarify tumor lesion at screening must be bi-
dimensional and that only CT or MRI methods according to the Lugano criteria are 
acceptable 
Synopsis; 
Section 5.1 
Peripheral blood total lymphocyte count has been removed as an inclusion criteria 
Synopsis; 
Section 5.1 
Total bilirubin has been updated to be < 1.5 only, as an inclusion criteria 
Synopsis; 
Section 5.1 
LVEF criteria have been removed as inclusion criteria (combined with exclusion criterion 
on cardiovascular disease) 
Synopsis;  
Section 5.1 
ALT and AST criteria have been updated to ≤ 3.0 x ULN (or ≤ 5.0 x ULN if liver 
involvement) from ≤ 2.5 (or ≤ 5.0 x ULN if liver involvement) 
Synopsis;  
Section 5.1 
Inclusion criteria have been updated to change reliable birth control methods to highly 
effective birth control methods; specific methods have been replaced with a reference to 
Section 10.4 for guidance 
Synopsis;  
Section 5.2 
Exclusion criteria have been updated to provide washout periods for small molecules 
Synopsis;  
Section 5.2 
Exclusion criteria regarding palliative radiation therapy within 4 weeks before the start of 
treatment has been removed and is now permitted at investigators discretion with 
consultation with the medical monitor and sponsor. 
Synopsis;  
Section 5.2 
Exclusion criteria has been updated to require the use of systemic immune modulators 
during study treatment and permit the use of NSAIDS 
Synopsis;  
Section 5.2 
Exclude potential subjects if they received any live vaccines except injectable flu 
(inactivated or recombinant) vaccine within 4 weeks before the start of treatment, unless 
the investigator believes the benefits outweigh risks, after consultation with the medical 
monitor and with sponsor approval. 
Synopsis;  
Section 5.2 
Removed exclusion criteria “received allogeneic stem cell transplant” and added 
exclusion criteria of “Current evidence of Graft vs Host Disease”. 
Synopsis;  
Section 5.2 
Exclude prior treatment with MT-3724 
Synopsis;  
Section 5.2 
Remove exclusion criteria: subjects with grade 2 neuropathy may be eligible at 
investigator’s discretion 


Compound: MT-3724 
 
Protocol MT-3724_NHL_001 
Protocol Date and Version: 12 February 2021, v11.0 
 
CONFIDENTIAL 
 
Page 121 of 123 
Section 
Revision Made 
Synopsis;  
Section 5.2 
Updated language regarding HIV, HBV, and HCV exclusion; added that subjects with 
HIV and an undetectable viral load and CD4+ T-cell (CD4+) counts ≥ 350 cells/mL may 
be enrolled, but must be taking appropriate opportunistic infection prophylaxis, if 
clinically relevant. 
Synopsis;  
Section 5.2 
Subjects with positive HBV serology are eligible if they have an undetectable viral load 
and will receive antiviral prophylaxis for potential HBV reactivation per institutional 
guidelines. 
Synopsis;  
Section 5.2 
Subjects with positive HCV serology are eligible if quantitative PCR for plasma HCV 
RNA is below the lower limit of detection. Concurrent antiviral HCV treatment per 
institutional guidelines is allowed. 
Synopsis;  
Section 5.2 
Serology testing is not required if seronegativity is documented in the medical history and 
there are no clinical signs suggestive of HIV or hepatitis infections, or suspected exposure. 
Synopsis;  
Section 5.2 
Current evidence of incomplete recovery from surgery or radiotherapy must be before 
start of treatment, not at screening. Also changed that planned surgeries/radiotherapy 
restriction is only up until EOT and not STFU. 
Synopsis;  
Section 5.2 
History of another primary malignancy within the past 3 years (except for ductal breast 
cancer in situ, non-melanoma skin cancer, prostate cancer not requiring treatment, and 
cervical carcinoma in situ) that required systemic drug therapy or radiotherapy. Has been 
revised to: History or current evidence of neoplastic disease that is histologically distinct 
from NHL, except cervical carcinoma in situ, superficial noninvasive bladder tumors, 
curatively treated Stage I-II non-melanoma skin cancer or any previous cancer curatively 
treated > 2 years before the start of treatment 
Synopsis; 
Section 5.2 
Subjects with radiotherapy or other appropriate therapy for known brain or spinal 
metastases may be eligible and concurrent prophylactic treatment is allowed. Neurologic 
symptoms must be stable and no worse than grade 2. They may be eligible if they have 
evidence of stable brain or spinal disease on CT or MRI scan obtained within 4 weeks 
before signing informed consent and compared with prior imaging results. They must not 
require steroid therapy or if applicable, have been on dose of no more than 20 mg a day of 
prednisone or equivalent by C1D1. 
Synopsis; 
Section 5.2 
Exclusion criteria have been updated to include history or current evidence of significant 
cardiovascular disease 
Section 5.3 
Screen failures procedures have been defined and a minimal set of screen failure 
information has been listed 
Section 6.1.1 
Dose administration timing has been added: all doses should be administered over 1 hour 
(54 – 75 minutes). 
Section 6.1.1.1 
Removed language referring to Part 2 and the measuring of weight before the first dose of 
MT-3724 in subsequent cycles. The re-calculation of dosage based on bodyweight change 
is no longer at investigator’s discretion but according to institutional policies.  
Section 6.1.1.2 
 
The dosage administration window has been updated to 54 to 75 minutes rather than the 
previously used +15 minutes.  
Section 6.1.1.2 
Clarified that each dose of MT-3724 should be preceded by premedication administered 
within 60 minutes before the start of infusion in Cycle 1. 
Section 6.1.1.2 
Removed: The choice of premedication agents and their doses for MT-3724 doses after 
C1D1 may be determined at the investigator’s discretion or according to the institutional 
guideline. 
Section 6.1.1.2 
Added: The first 3 doses of Cycle 1 must be administered at least 48 hours apart while all 
other doses remain at least 20 hours apart. 
Section 6.1.1.2 
Updated information regarding treatment dose schedule and discontinuation criteria.  


Compound: MT-3724 
 
Protocol MT-3724_NHL_001 
Protocol Date and Version: 12 February 2021, v11.0 
 
CONFIDENTIAL 
 
Page 122 of 123 
Section 
Revision Made 
Synopsis; 
Section 6.1.1.3 
Added option to treat subjects beyond progression if certain criteria are met. 
 Section 6.1.2 
Provided acceptable dosage ranges for 3 classes of premedications before MT-3724 
infusion and updated adjustment language. 
Section 6.1.3 
Updated excluded treatments, medical devices, and/or procedures during study period to 
all systemic treatment for lymphoma, radiation therapy to target tumor lesions, systemic 
immune modulators and any live vaccines. 
Section 6.2 
Restructured entire section, all former subsections and lists of hematological and 
nonhematological TEAEs have been converted into Table 6-2 “MT-3724 Dose 
Modification Guidance and Specific Management of Toxicities” to provide clear guidance 
in a more organized manner. 
Section 6.2 
Removed immunoglobulins from list of serum samples for the investigator to obtain if the 
subject experienced grade 2 or greater adverse events 
Section 6.2 
Replaced the time frame determined at investigators discretion with baseline to within 
14 days for discontinuation of MT-3724 in the case of TEAE 
Section 6.2  
Updated language and footnotes regarding infusion-related reaction or other 
hypersensitivity events in Table 6-2 
Section 6.5 
Removed language permitting inactivated or recombinant flu vaccines (these are 
permitted; only live vaccines are excluded though with exceptions). 
Updated to include palliative therapy, such as radiotherapy, which spares at least 50% of 
bone marrow producing regions, to non-target lesions or intrathecal chemotherapy, is 
allowed at the investigator’s discretion after consultation with the medical monitor and 
sponsor. 
While the use of certain immunomodulators is prohibited as described in Section 6.1.3, the 
use of NSAIDS is permitted. 
Section 6.6 
Added language allowing for possible initiation of an open-label rollover study. 
Section 7.1 
Removed language regarding premature withdrawal from study and early termination. 
Section 7.3 
Removed language regarding continuation of treatment. 
Section 7.4 
Added section to define lost to follow-up and give guidance to sites on how to handle 
subjects that may be lost to follow-up. 
Section 8.2.2 
Screening NHL assessment revised to clarify what information is to be collected from 
various time points in disease history. 
Section 8.2.3 
Clarifications made regarding what type of information is to be collected for prior 
systemic therapies. 
Section 8.3.1 
Clarifications made regarding what types of scans should be used and when for 
radiological assessments of tumor response. Also added clarification that the original 
schedule needs to be maintained even if there is a delay is dosing. 
Section 8.3.2 
Removed “(ie, the tumor response used to derive the primary efficacy endpoint)” 
since it is not applicable to Part 3 and is extraneous.  
Section 8.4.1 
Clarifications made regarding new illnesses and/or worsening of concomitant illnesses 
detected during the screening period (medical history vs AE). 
Section 8.4.2 
Clarified definition of concomitant medication. 
Section 8.4.3 
Clarified language regarding changes of > 10% in body weight resulting in dose 
adjustments. 
Section 8.4.4  
Added subsections to clarify what constitute complete and abbreviated physical 
examinations and removed window of 72 hours. 


Compound: MT-3724 
 
Protocol MT-3724_NHL_001 
Protocol Date and Version: 12 February 2021, v11.0 
 
CONFIDENTIAL 
 
Page 123 of 123 
Section 
Revision Made 
Section 8.4.6 
Added respiratory rate as a vital sign measurement and that temperature should be 
assessed at same time as BP, HR, and RR. Also clarified language regarding timing of PK, 
ECG, and vital signs measurements. 
Section 8.4.7 
Updated when a pre-study LVEF assessment would be acceptable for screening purposes 
(protocol now allows up to 6 months before screening and at least 28 days after last cancer 
therapy); also updated that ECHO is preferred over MUGA. 
Section 8.4.8 
Clarified language regarding timing of PK, ECG, and vital signs measurements. 
Section 8.4.9 
Clarified language regarding Grade 3 or Grade 4 abnormal laboratory tests; should be 
reported as a clinically significant AE unless associated with disease progression. 
Section 8.5 
Added statement “For AEs of CLS, CRS/SIRS, and IRRs, individual symptoms and grade 
should be reported on the appropriate CRF.” 
Section 8.5.1; 
Section 8.5.3 
AE/SAE reporting period redefined to start at first dose of study drug. AEs/SAEs will be 
reported during the screening period only if they are deemed related to a protocol 
screening procedure. 
Section 8.5.2.3 
Removed mention that MT-3724 needs to be discontinued if partner of male subject 
becomes pregnant  
Section 8.5.6 
Clarified that PK samples should not be drawn from the same line as that used for study 
drug administration. 
Also added language that if CSF is collected at any time as part of standard of care, a 
portion of the sample collected will be used to evaluate for presence of study drug. 
Section 8.7.2 
Added language that biopsies may be used to confirm CR, in absence of PET/CT scans. 
Section 8.8 
Added details regarding collection and analysis of immunogenicity samples. 
Section 9 
The entire statistical considerations sections has been updated to provide appropriate 
information addressing the new parts of the study (Parts 3 and 4), the associated sample 
size, objectives/endpoints, etc. 
Section 9.3.2.3 
Quality of life analysis was added as a new section in this amendment. 
Section 10.1.6 
Language has been altered to allow remote online monitoring of sites in light of recent 
guidance released on global pandemic. 
Section 10.1.7 
Text regarding examples of source documentation has been deleted as it was inaccurate.  
Text describing screen procedures CRF has been removed as it was also inaccurate. 
Section 10.3 
Updated classification of adverse events for clarification and removed “For example, an 
overnight hospitalization for a diagnostic procedure must be reported as an SAE 
even though the occurrence is not medically serious” since it was inaccurate. 
Section 10.5 
For Cotswold modifications, X, moved this to be applicable for all stages and not just 
Stages I to III. In addition, removed reference to different tumor types since Parts 3 
and 4 are specific to DLBCL and 5-year survival rates based on risk since it’s 
extraneous information.  
 

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN 
Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Multiple 
Dose Regimens of MT-3724 for the Treatment of Subjects with Relapsed non-
Hodgkin’s B-Cell Lymphoma and B-Cell Chronic Lymphocytic Leukemia, 
and Extended Treatment Access Study for Subjects who Have Completed the 
Main Study 
Protocol Numbers: 
Protocol Versions and 
Dates: 
MT-3724_NHL_001_US 
MT-3724_NHL_001_EXT_US 
MT-3724_NHL_001_US: 
Original Version 1.0: 30 July 2014 
Version 7.0: 08 February 2018 
MT-3724_NHL_001_EXT_US: 
Original Version 1.0: 15 April 2015 
Version 2.0: 18 April 2016 
Name of Test Drug: 
MT-3724 
Phase: 
Phase 1/1b 
Methodology: 
Open-label, Dose-escalation, Multicenter, Rollover 
Sponsor: 
Molecular Templates, Inc. 
111 W. Cooperative Way, Suite 201 
Georgetown, TX, 78626 
Tel: (512) 930-0304 
Sponsor Representative: 
, MD 
SVP, Clinical Development 
Analysis Plan Date: 
15 August 2018 
Analysis Plan Version: 
Final Version 3.0 
Confidentiality Statement 
The information contained herein is confidential and the proprietary property 
of Molecular Templates, Inc. and any unauthorized use or disclosure  
of such information without the prior written authorization of  
Molecular Templates, Inc. is expressly prohibited. 
NCT Number: NCT02361346
This NCT number has been applied to the document
for the purposes of posting on clinicaltrials.gov




Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 3 
TABLE OF CONTENTS 
Section 
Page 
1. 
INFORMATION FROM THE STUDY PROTOCOLS ......................... 9 
1.1. 
Introduction ...................................................................................... 9 
1.1.1. 
Introduction ....................................................................... 9 
1.2. 
Study Objectives .............................................................................. 9 
1.2.1. 
Main Study ...................................................................... 10 
1.2.2. 
Extension Study .............................................................. 11 
1.3. 
Study Design .................................................................................. 11 
1.3.1. 
Synopsis of Study Design ............................................... 11 
1.3.2. 
Randomization Methodology .......................................... 17 
1.3.3. 
Stopping Rules ................................................................ 17 
1.3.4. 
Study Procedures ............................................................ 18 
1.3.5. 
Safety, Efficacy, and Pharmacokinetic Parameters ........ 29 
2. 
SUBJECT POPULATION ...................................................................... 32 
2.1. 
Population Definitions ................................................................... 32 
2.2. 
Protocol Violations ........................................................................ 32 
2.3. 
Withdrawals and Subject Replacement .......................................... 32 
2.3.1. 
Main Study ...................................................................... 32 
2.3.2. 
Extension Study .............................................................. 33 
3. 
GENERAL STATISTICAL METHODS ............................................... 34 
3.1. 
Sample Size Justification ............................................................... 34 
3.2. 
General Methods ............................................................................ 34 
3.3. 
Computing Environment ................................................................ 35 
3.4. 
Baseline Definitions ....................................................................... 35 
3.5. 
Methods of Pooling Data ............................................................... 35 
3.6. 
Adjustments for Covariates ............................................................ 35 
3.7. 
Multiple Comparisons/Multiplicity ................................................ 35 
3.8. 
Subpopulations ............................................................................... 35 
3.9. 
Withdrawals, Dropouts, Loss to Follow-up ................................... 36 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 4 
Section 
Page 
3.10. Missing, Unused, and Spurious Data ............................................. 36 
3.11. Visit Windows ................................................................................ 37 
3.12. 
Interim Analyses ............................................................................ 37 
4. 
STUDY ANALYSES ................................................................................ 38 
4.1. 
Subject Disposition ........................................................................ 38 
4.2. 
Demographics and Baseline Characteristics .................................. 39 
4.2.1. 
Demographic characterstics ............................................ 39 
4.2.2. 
Medical history ............................................................... 39 
4.2.3. 
Disease history ................................................................ 39 
4.2.4. 
Prior Medications ............................................................ 40 
4.2.5. 
Serum Rituximab levels .................................................. 40 
4.2.6. 
Other baseline characteristics.......................................... 40 
4.3. 
Exploratory Efficacy Evaluation .................................................... 40 
4.4. 
Pharmacokinetic Evaluation........................................................... 42 
4.5. 
Study Drug Exposure ..................................................................... 42 
4.6. 
Safety Analyses .............................................................................. 42 
4.6.1. 
Adverse Events ............................................................... 42 
4.6.2. 
Laboratory Data .............................................................. 44 
4.6.3. 
Vital Signs ....................................................................... 44 
4.6.4. 
Physical Examination ...................................................... 45 
4.6.5. 
Electrocardiogram ........................................................... 45 
4.6.6. 
Concomitant Medications ............................................... 45 
4.6.7. 
ECOG Performance Status ............................................. 45 
5. 
CHANGES TO PLANNED ANALYSES .............................................. 47 
6. 
REFERENCES ......................................................................................... 48 
 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 5 
TABLES AND FIGURES INCLUDED IN THE TEXT 
 
Page 
Table 1: 
Schedule of Assessments – Main Study Core Study ....................................................... 19 
Table 2: 
Schedule of Assessments – Main Study Repeat Dosing ................................................. 22 
Table 3: 
Schedule of Assessments – Extension Study .................................................................. 25 
 
Figure 1:  
Part 1 Study Schematic .................................................................................................... 17 
Figure 2:  
Part 2 (MTD Expansion) Study Schematic ..................................................................... 12 
Figure 3:  
Extended Access Schematic ............................................................................................ 21 
 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 6 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition 
AE 
Adverse event 
ALT 
Alanine transaminase 
ANC 
Absolute neutrophil count 
AST 
Aspartate transaminase 
ATC 
Anatomical therapeutic chemical 
AUC 
Area under the concentration versus time curve 
AUC0-4 
Area under the concentration versus time curve from time 0 to the end of 
the dosing interval 4 hours later, calculated using linear trapezoid rule 
β-HCG 
Beta human chorionic gonadotropin 
BLQ 
Below the limit of quantification 
BSA 
Body surface area 
BUN 
Blood urea nitrogen 
C 
Celsius 
Cmax 
Maximum serum concentration 
Cmin 
Trough serum concentration, taken 24 hours after dose and prior to 
subsequent dose 
CBC 
Complete blood count 
CI 
Confidence interval 
CK 
Creatine kinase 
CL 
Clearance 
cm 
Centimeter 
CNS 
Central nervous system 
CO2 
Carbon dioxide 
CR 
Complete remission 
CRu 
CR/unconfirmed 
CSR 
Clinical study report 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
dL 
Deciliter 
DLCO 
Diffusion capacity of carbon dioxide 
DLT 
Dose-limiting toxicity 
DNA 
Deoxyribonucleic acid 
DOR 
Duration of response 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EE 
Efficacy-evaluable 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 7 
Abbreviation 
Definition 
EEG 
Electroencephalography 
FDA 
Food and Drug Administration 
FEV1 
Forced expiratory volume in 1 second 
g 
Gram 
GGT 
Gamma glutamyl transferase 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
IWG 
International Working Group 
IV 
Intravenous 
kg 
Kilogram 
L 
Liter 
LDH 
Lactic dehydrogenase 
m2 
Square meter 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
mEq 
Milliequivalence 
mg 
Milligram 
mL 
Milliliter 
mm 
Millimeter 
mm3 
Cubic millimeter 
Msec 
Millisecond 
MTD 
Maximum tolerated dose 
μL 
Microliter 
N 
Number 
NCI 
National Cancer Institute 
ORR 
Objective response rate 
OS 
Overall survival 
PASS 
Power and Sample Size 
PD 
Progressive disease 
PDn 
Pharmacodynamic 
% 
Percent 
PET 
Positron emission tomography 
PFS 
Progression-free survival 
PFT 
Pulmonary function test 
pH 
Hydrogen ion concentration 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 8 
Abbreviation 
Definition 
PK 
Pharmacokinetic 
PR 
Partial remission 
PT 
Preferred term 
PTT 
Partial thromboplastin time 
QT 
Interval between Q and T waves 
QTc 
Corrected interval between Q and T waves 
RBC 
Red blood cell (count) 
RECIST 
Response evaluation criteria in solid tumors 
Rel Day 
Relative study day 
RTF 
Rich text format 
SAP 
Statistical analysis plan 
SC 
Subcutaneous 
SD 
Stable disease  
SDR 
Stable disease rate 
SI 
International System of Units 
SOC 
System organ class 
SPD 
Sum of the Product of Diameters 
T1/2 
Terminal half-life 
TEAE 
Treatment-emergent adverse event 
tmax 
Time to maximum serum concentration 
TTP 
Time to progression 
ULN 
Upper limit of normal 
US 
United States 
VC 
Vital capacity 
Vdss 
Volume of distribution at steady state 
WBC 
White blood cell (count) 
WHO 
World Health Organization 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 9 
1. 
INFORMATION FROM THE STUDY PROTOCOLS 
1.1. 
Introduction 
1.1.1. 
Introduction 
According to American Cancer Society statistics non-Hodgkin’s Lymphoma (NHL) is the most 
prevalent hematopoietic neoplasm, representing approximately 4% of all cancer diagnoses in 
men and women and ranking seventh in frequency among all cancers. Since the early 1970s, the 
incidence rates of NHL have nearly doubled. Lymphoma includes a heterogeneous group of 
malignancies originating from lymphoid tissues (mainly of lymph nodes) with different biology 
and prognoses divided into 2 large groups of neoplasms: (1) non-Hodgkin’s lymphoma and (2) 
Hodgkin’s disease. Various neoplastic tumor cell lines correspond to each of the cellular 
components of antigen-stimulated lymphoid follicles. Almost 85% of NHLs are of B-cell origin. 
NHL includes many clinicopathologic subtypes, each with a distinct epidemiology; etiology 
morphology, immunophenotype, genetic features, clinical characteristics and response to 
therapy. For many of the B-cell NHL subtypes, the pattern of growth and cell size may be 
important determinants of tumor aggressiveness. 
MT-3724 is a single polypeptide chain consisting of 512 amino acids and a recombinant 
homodimeric fusion protein. Each monomer consists of a single chain variable fragment (scFv) 
with affinity for human CD20 cell surface protein fused to the enzymatically active Shiga-like 
toxin-I A1 subunit (SLT-I A1). MT-3724 has not yet been given to human subjects. 
The main study, a Phase I, multiple ascending dose study will seek to enroll subjects with 
progressive B-cell NHL with measurable disease (lesion > 1.5 cm) who have received standard 
treatment with at least one anti-CD20 antibody containing front-line regimen that resulted in 
initial response, followed by relapse/recurrence and who are not eligible for any further 
approved biologic therapy, chemotherapy and/or autologous stem transplantation and/or refuse 
alternative approved therapies and/or are unlikely to achieve clinical benefit from any therapy of 
higher priority by Investigator assessment. The extended access, compassionate use study is 
available only to those subjects who have successfully completed the MT-3724 NHL main study 
and require continued treatment for their NHL.  
1.2. 
Study Objectives 
This statistical analysis plan (SAP) contains detailed information on definitions of analysis 
populations, derived variables, and statistical methods for the analysis of safety and efficacy 
data from the Phase I/ Ib clinical studies: MT-3724_NHL_001_US and 
MT-3724_NHL_001_EXT_US. The statistical analyses and summary tabulations described in 
this SAP will provide the basis for the results sections of the clinical study report (CSR) for this 
trial. This SAP will also outline any differences in the currently planned analytical objectives 
relative to those planned in the study protocol. 
The SAP is based upon the following study documents: 
• Study protocols v7.0 dated 08 February 2018 for MT-3724_NHL_001_US and v2.0 
dated 16 April 2016 for MT-3724_NHL_001_EXT_US. 
• Electronic Case Report Form (eCRF), v10.0 dated 16 May 2018. 


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Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 12 
Parts 1 and 2: Retreatment under a separate extension protocol will be considered for subjects 
who exhibit PR or SD after completing 5 cycles (or 2 cycles after a complete remission) in 
consultation with the Sponsor.  
Schematics of Parts 1 & 2 of the main study is presented in Figures 1 and 2. 
Figure 1:  
Part 1 Study Schematic 
 
 
 
 
 
 
 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 13 
Figure 2:  
Part 2 (MTD Expansion) Study Schematic 
Core Study (Cycle 1, Days 1 to 28) 
Subjects will receive a single course of study drug via a 2 to 4 hour intravenous (IV) infusion of 
MT-3724 on Days 1, 3, 5, 8, 10 and 12. The first dosing cohort will receive 5 micrograms per 
kilogram (mcg/kg) per dose of MT-3724. Each cohort is planned to have from 3 to 6 subjects, 
but additional subjects may be added to one or more dosing cohorts to further explore safety 
and/or efficacy signals. Following the first dose in the Core Study, there will be a minimum 28-
day observation period for each subject to document safety and tolerability prior to initiating 
any additional treatment cycles in the Repeat Dosing Study (see below). Subjects experiencing a 
dose limiting toxicity (DLT) in the Core Study (Days 1-28) must be withdrawn from the study 
and receive no further doses of MT-3724. Subjects will have successfully completed the Core 
Study if they receive at least 4 of the 6 infusions in their first cycle and they are followed for 28 
days after their first dose. If a subject in the Core Study completes less than 4 of the 6 infusions 
in the first 12 days and the missed infusions were not due to an MT-3724-related DLT or AE 
that contraindicates further dosing then the Investigator in consultation with the Sponsor may 
attempt to achieve a minimum 4 infusions by administering the missed doses in the third week 
(Days 15 - 19) of the Core Study. In such instances, subjects must still be observed for 28 days 
following the first dose in the Core Study prior to initiating any further study drug dosing.  
 
Following Data Monitoring Committee (DMC) safety review and approval to escalate, the 
subsequent cohorts are planned to be dosed at 10, 20, 50, 100, 150, and 200 mcg/kg/dose.  
 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 14 
• Dose Escalation: Additional dose cohorts may be added above the 200 mcg/kg/dose 
cohort if (1) less than two DLTs are observed at the completion of that cohort’s first 
cycle and (2) maximum PK/PD parameter changes have not yet been observed. The 
incremental increases of cohorts beyond 200 mcg/kg/dose/day will be determined by the 
PK/PD observations and all safety data.  
• Dose-De-escalation: Additional cohorts at dose levels below an identified toxic dose 
level will be added to more accurately identify the MTD. At the identification of the first 
dose cohort that has > 33% DLTs, the maximal administered dose, an interim cohort will 
be added at a dose that is approximately 25 mcg/kg/dose lower than the maximal 
administered dose. If that lower dose has > 33% DLTs then the next highest cohort by a 
further 25 mcg/kg/dose reduction will be studied. For example, if there are > 33% DLTs 
at the 150 mcg/kg/dose, it will become the maximal administered dose and a 125 
mcg/kg/dose cohort will be added. If the 125 mcg/kg/dose cohort has > 33% DLTs then 
the next lowest dose cohort (100 mcg/kg/dose in this example) will be expanded to 6 
subjects if not previously done. Cohorts will be explored at ~25 mcg/kg/dose reductions 
until the MTD has been identified by documenting < 33% DLTs in a cohort expanded to 
the required 6 subjects. If the MTD cohort identified in the Core Study is expanded 
beyond 6 subjects for further PK, PD and/or efficacy exploration then from their first 
cycle, the subjects added to this expansion cohort will be dosed according to the Repeat 
Dosing 21-day cycle.  
 
Part 1 Repeat Dosing (Cycles 2-5) 
Following successful completion of the 28-day Core Study of Part 1, subjects may continue to 
receive up to 4 more cycles of treatment as long as they have experienced no AE attributable to 
MT-3724, which would contraindicate further dosing and provided their disease has not 
progressed.  
 
If a subject has tolerated repeat cycles of MT-3724 without evidence of a toxicity that would 
prohibit further dosing or evidence of disease progression, but their dose is subsequently 
determined to be above the MTD, he/she may continue to receive additional cycles at the 
highest studied dose in Part 1 that has been confirmed to be below the MTD or at the dose 
confirmed to be the MTD.  
 
Part 2 
Up to 40 subjects will be enrolled in Part 2. Subjects may be enrolled and treated simultaneously 
through competitive enrollment at multiple study centers in North America and Europe. 
All subjects will receive a single course of study drug via a 2 (±15 minutes) IV infusion of MT-
3724 on Days 1, 3, 5, 8, 10 and 12. Each dose of MT-3724 will be at the adjusted MTD (50 
mcg/kg/dose).  Three subjects were started in Part 2 at 75 mcg/kg/day but later had possibly 
related TEAEs that required dose reduction or a treatment discontinuation Following the first 
dose in each cycle, there will be a minimum 21-day observation period for each subject prior to 
initiating the next treatment cycle. Subjects experiencing a serious adverse event (SAE) 
attributable t MT-3724 may be withdrawn from the study or depending upon the nature of the 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 15 
event, the Investigator, in consultation with the DMC, may, once the event has resolved, resume 
dosing at a dose reduced by 25-33%. Subjects will have successfully completed a cycle if they 
receive at least 4 of the 6 infusions in that cycle, and they are followed for 21 days after their 
first dose in that cycle. If a subject completes less than 4 of the 6 infusions in the first 12 days of 
a cycle and the missed infusions were not due to an event that would contraindicate further 
dosing, then the Investigator in consultation with the Sponsor may attempt to achieve a 
minimum of 4 infusions by administering the missed doses in the third week (Days 15 - 19) of 
that cycle. In such instances, subjects must still be observed for a minimum of 21 days 
following the first dose in Cycle 1 prior to initiating any further study drug dosing.  
No dose escalation will be permitted above the adjusted MTD (50 mcg/kg/dose) identified by 
the DMC. However, at the Investigator’s discretion, the dose for any subject in the Part 2 
expansion cohort may be reduced by 25-33% for one or more doses in any cycle (see below) 
based upon a subject’s response at the adjusted MTD (50 mcg/kg/dose). 
 
Subjects must receive a minimum of 4 of the 6 infusions in a cycle in order to successfully 
complete that cycle and continue in the study. For subjects in Parts 1 and 2 who complete at 
least 4 of the 6 infusions in any cycle, and the missed infusions were not due to an MT-3724-
related event that contraindicates further dosing (see above for criteria for continued dosing), 
then up to 5 total cycles may be administered on the same schedule (Days 1, 3, 5, 8, 10 and 12) 
and at the same dose (as long as that dose is not subsequently identified to be a toxic dose).  
 
If the adjusted MTD (50 mcg/kg) is determined to be causing adverse effects for a subject, at the 
Investigator’s discretion, that subject may continue to receive additional cycles at a dose that is 
25-33% lower than the adjusted MTD.  
 
For both Parts 1 & 2, subjects in any cohort who complete less than 4 of the 6 infusions in any 
cycle and the missed infusions were not due to an MT-3724-related AE that would 
contraindicate further dosing, the Investigator (in consultation with the Sponsor) may attempt to 
achieve a minimum of 4 infusions by administering the missed dose(s) in the third week (Days 
15-19) of the cycle. In such instances, subjects must still be observed for at least 21 days after 
their first dose in one cycle prior to initiating their next cycle in Part 1, repeat dosing cycles, or 
Part 2, all cycles.  
Long Term Safety Follow-up 
Following the Final Safety Assessment, subjects will be contacted by telephone every 6 months 
from the date of their first dose for up to 2 years or until they initiate further treatment for their 
B-cell NHL, CLL, or other malignancies or take any other investigational new drug for any 
reason. Subjects will be asked about their current medical status and if they have experienced 
any new AE attributable to their MT-3724 treatment. If the subject continues to participate in 
the MT 3724 extension study, no AEs will be captured with respect to long-term safety within 
this parent study, as they will be captured in the extension study.  
1.3.1.2. 
Extension Study 
This is an active treatment, extended access study open solely to those subjects who have 
successfully completed the Core and Repeat Dosing portions of the MT-3724_NHL_001_US 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 16 
clinical study and who, in the Investigator’s judgment (i) have not had progressive disease while 
on MT-3724 treatment (i.e., have shown a complete or partial response or stable disease), (ii) 
have experienced no clinical or laboratory toxicities that would contraindicate further MT-3724 
dosing, and (iii) have no acceptable and better alternative treatment available to them. Each 
treatment cycle will consist of 6 doses of MT-3724 to be administered over 12 days followed by 
at least 9 days of observation; longer intervals between dosing cycles will be allowed at the 
Investigator’s discretion (e.g., 6 doses of MT-3724 over 12 days followed by 16 days 
observation). Subjects in this extension study may continue to receive up to 6 additional cycles 
in the absence of clear disease progression or toxicity. If a subject achieves complete remission 
(CR), two additional cycles will be attempted, after which dosing may be suspended prior to 
completion of the maximum 6 cycles. 
A schematic of the extension study is presented in Figure 3, and schedule of assessments are 
provided in Table 3. 
Figure 3:  
Extended Access Schematic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dosing Cycles  
As in the MT-3724_NHL_001_US Repeat Dosing Study each subject will continue to receive 
six (6) MT-3724 intravenous (IV) infusions over approximately 12 days (Days 1, 3, 5, 8, 10 and 
12) followed by at least 9 days observation (Days 13 – 21) observation for a maximum of 6 
cycles. At the Investigator’s discretion the observation period between treatment periods may be 
extended to 16 days for one or more cycles following discussion with the Sponsor. Each subject 
may continue to receive the same dose (mcg/kg) which they had been receiving in the Repeat 
Dosing Study OR, in consultation with the Sponsor, a subject may be reassigned to receive the 
maximum tolerated dose (MTD) identified in the MT-3724_NHL_001_US Core Study. If a 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 17 
subject enrolls in this study prior to the identification of the MTD in the Core Study, the subject 
must continue at their originally assigned dose (mcg/kg) until the MTD is identified. If a subject 
has tolerated repeat cycles of MT-3724 without evidence of (i) a toxicity that would prohibit 
further dosing or (ii) disease progression, but their dose is subsequently determined to be above 
the MTD, they may continue to receive additional cycles at the highest studied dose that has 
been confirmed to be below the MTD or at the dose confirmed to be the MTD. Following the 
successful completion of a treatment cycle in this extended access study, subjects are eligible to 
receive the next cycle (to a maximum of 6 cycles) as long as (i) they have experienced no AE 
attributable to MT-3724 which contraindicates further dosing AND (ii) their disease has not 
progressed. For subjects in any dosing cohort who complete less than 4 of the 6 infusions in a 
cycle, and the missed infusions were not due to an MT-3724 related AE that would 
contraindicate further dosing then the Investigator may attempt to achieve a minimum 
of 4 infusions by administering the missed doses in the third week of that dosing cycle. In such 
an instance, for that cycle only, at the Investigator’s discretion and in consultation with the 
Medical Monitor, a subject may be observed for less than 9 days prior to initiating their next 
cycle. 
Long Term Safety Follow-up (Extension) 
Following the assessment performed 14 - 28 days after the last MT-3724 dose in this study, 
subjects will be contacted by telephone every 6 months from the date of their first dose in the 
MT-3724_NHL_001_US Core Study for up to 2 years OR until they initiate further treatment 
for their B-cell Non-Hodgkin’s Lymphoma (NHL) or B-cell Chronic Lymphocytic Leukemia 
(CLL) OR until they take any other investigational new drug for any reason. During these 
telephone contacts subjects will be asked about their current medical status and if they have 
experienced any new AE attributable to their MT-3724 treatment. 
1.3.2. 
Randomization Methodology 
Not applicable as this is an open label study. 
1.3.3. 
Stopping Rules  
The list of study stopping rules that follows is based on key safety parameters. This list will be 
used to determine whether:  
Part 1: 
• dosing may proceed to a subsequent dosing cohort (per protocol or alternate dose based 
upon DMC recommendation),  
• the cohort must be stopped and no additional subjects dosed at that dose level,  
• dosing must be suspended for an individual subject pending DMC review, or  
• the subject must be withdrawn because an AE is determined to be a DLT or it is 
determined to be in the subject’s best interest to receive no further doses of MT-3724.  
Part 2: 
• Dosing must be suspended for an individual subject pending DMC review, or 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 18 
• The Investigator and Medical Monitor and/or the DMC approve dosing be resumed for 
an individual subject at a dose 25-33% less than the MTD, or 
• The subject must be withdrawn, because it is determined to be in the subject’s best 
interest to receive no further doses of MT-3724. 
Additional DMC and/or Investigator meetings may be triggered by occurrence of specific 
stopping rules (see the list that follows) or may be called at the request of an Investigator or of 
the DMC. Based on the event and the study stopping rules, it may or may not be reasonably safe 
to proceed with dose administration of the next subject in a cohort and/or to continue the study 
per the current protocol. A subject will be withdrawn from further MT-3724 treatment if any of 
the stopping rules outlined in Section 6.13 (main study) or Section 6.12 (extension study) of the 
protocol are met. 
1.3.4. 
Study Procedures 
The schedules of assessments for the main study are provided in Table 1 (Core Study) and 
Table 2 (Repeat Dosing). The schedule of assessments for the extension study is presented in 
Table 3. 
 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 19 
Table 1: 
Schedule of Assessments – Main Study Cycle 1 – Parts 1 and 2 
 
 
 
 
Assessment 
Qualification 
Screen 
MT-3724 Infusion Schedule 
Safety 
Assessment 
Safety 
Assessment 
Part 1 
ONLY 
Final Safety 
Assessment 
 
Visit 1 
Day -28 
 to Day -1 
 
Visit 2 
Day 1 
Dose 1 
 
Visit 3 
Day 3 
Dose 2 
 
Visit 4 
Day 5 
Dose 3 
 
Visit 5     
Day 8 
Dose 4  
 
Visit 6 
Day 10 
Dose 5 
 
Visit 7 
Day 12  
Dose 6 
 
Visit 8 
Day 16-19 
(If early 
withdrawal, 
must still be 
performed) 
 
 
Visit 9 
Day 23-25 
(If early 
withdrawal, 
must still be 
performed) 
 
(If withdrawing 
replaces Day 28 
safety assessment 
prior to Cycle 2)  
Day 28-35 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion  
X 
 
 
 
 
 
 
 
 
 
Medical History Review and 
Physical Exam including 
ECOG1 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
X 
Baseline Disease Assessments 
X 
 
 
 
 
 
 
 
 
 
Vital Signs2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Laboratory  
CBC w/differential 
X 
X 
 
X 
(post 
infusion) 
 
 
 
X 
X 
X 
Serum Chemistry 
X 
X 
 
 
 
 
 
X 
X 
X 
Β2 microglobulin  
X 
 
 
 
 
 
 
 
 
X 
Serum Rituximab 
X 
 
 
 
 
 
 
 
 
 
For CLL subjects ONLY: 
soluble CD23 and thymidine 
kinase 1 
X 
 
 
 
 
 
 
 
 
X 
For CLL subjects ONLY: 
anti-globulin test  
X 
 
 
 
 
 
 
 
 
 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 20 
 
 
 
Assessment 
Qualification 
Screen 
MT-3724 Infusion Schedule 
Safety 
Assessment 
Safety 
Assessment 
Part 1 
ONLY 
Final Safety 
Assessment 
 
Visit 1 
Day -28 
 to Day -1 
 
Visit 2 
Day 1 
Dose 1 
 
Visit 3 
Day 3 
Dose 2 
 
Visit 4 
Day 5 
Dose 3 
 
Visit 5     
Day 8 
Dose 4  
 
Visit 6 
Day 10 
Dose 5 
 
Visit 7 
Day 12  
Dose 6 
 
Visit 8 
Day 16-19 
(If early 
withdrawal, 
must still be 
performed) 
 
 
Visit 9 
Day 23-25 
(If early 
withdrawal, 
must still be 
performed) 
 
(If withdrawing 
replaces Day 28 
safety assessment 
prior to Cycle 2)  
Day 28-35 
PT, aPTT, INR 
X 
 
 
 
 
 
 
 
 
 
Urinalysis 
X 
 
 
 
 
 
 
 
 
X 
Estimated Cr Clearance3  
X 
 
 
 
 
 
 
 
X 
X 
Pregnancy Test (urine)4  
X  
X  
(-72 hrs) 
 
 
 
 
 
 
 
 
Complement (CH50 and C3) 
X 
 
 
 
 
 
 
 
 
 
Quantitative Serum 
Immunoglobulins 
X 
 
 
 
 
 
 
 
 
 
X 
Viral Serology:  HepBAb 
HepBsAg HepCAb and/or HIV 
if clinically indicated 
X 
 
 
 
 
 
 
 
 
 
Flow Cytometry ,                 
Lymphocyte subsets5 
X 
 
 
 
X   
(pre-
infusion) 
 
 
 
 
X 
X  
(including MRD 
analysis for CLL) 
Serum Cytokines6 
X 
X 
 
X 
 
 
 
 
 
X 
X 
MT-3724 Administration7 
 
 
MT-3724 
MT-3724 
MT-3724 
MT-3724 
MT-3724 
MT-
3724 
 
 
 
MT-3724 Serum Levels 
(PK)8 
 
 
X 
(pre- and 
post-
infusion) 
 
X 
(post-
infusion) 
X 
(pre-
infusion) 
 
X 
(post-
infusion) 
 
X 
X 
 
ADA/Immunogenicity9 
X 
Additional specimens tob e drawn as clinically indicated. 
 
X 
X 
12-Lead ECG10 
X 
X 
 
 
 
 
 
 
 
 
Malignancy Histology 
X 
 
 
 
 
 
 
 
 
 


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15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 21 
 
 
 
Assessment 
Qualification 
Screen 
MT-3724 Infusion Schedule 
Safety 
Assessment 
Safety 
Assessment 
Part 1 
ONLY 
Final Safety 
Assessment 
 
Visit 1 
Day -28 
 to Day -1 
 
Visit 2 
Day 1 
Dose 1 
 
Visit 3 
Day 3 
Dose 2 
 
Visit 4 
Day 5 
Dose 3 
 
Visit 5     
Day 8 
Dose 4  
 
Visit 6 
Day 10 
Dose 5 
 
Visit 7 
Day 12  
Dose 6 
 
Visit 8 
Day 16-19 
(If early 
withdrawal, 
must still be 
performed) 
 
 
Visit 9 
Day 23-25 
(If early 
withdrawal, 
must still be 
performed) 
 
(If withdrawing 
replaces Day 28 
safety assessment 
prior to Cycle 2)  
Day 28-35 
Radiological Response 
Assessment11 
X 
 
 
 
 
 
 
 
 
X 
(optional) 


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CONFIDENTIAL 22 
Table 2: 
Schedule of Assessments – Main Study Cycles 2-5 – Parts 1 and 2 
 
 
 
Assessment 
MT-3724 Infusion Schedule 
Repeated for Each Course 
 
Safety Assessment 
Exploratory 
Efficacy 
Assessment 
Final Safety 
Assessment 
 
Visit 1 
Day 1 
Dose 1 
 
Visit 2 
Day 3 
Dose 2 
 
Visit 3 
Day 5 
Dose 3 
 
Visit 4     
Day 8  
Dose 4 
 
Visit 5 
Day 10 
Dose 5 
 
Visit 6 
Day 12 
Dose 6  
 
Telephone Contact 
Day 16-18 
 
Days 15-21of each 
even-numbered 
cycle 
(replaces 
interim safety 
assessment after 
last infusion)  
Day 14-28 
Medical History Review 
and Physical Exam 
including ECOG1 
X 
 
 
 
 
 
 
 
 
 
X 
Vital Signs2 
X 
X 
X 
X 
X 
X 
 
 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
 
X 
Clinical Laboratory  
CBC w/differential 
X 
 
 
 
 
 
 
 
 
 
 
X 
Serum Chemistry 
X 
 
 
 
 
 
 
 
X 
Β2 microglobulin  
 
 
 
 
 
 
 
 
X 
Urinalysis 
 
 
 
 
 
 
 
 
X 
Estimated Cr Clearance3 
 
 
 
 
 
 
 
 
X 
Pregnancy Test (urine)4 
X 
 
 
 
 
 
 
 
 
Quantitative Serum 
Immunoglobulins 
 
 
 
 
 
 
 
 
 
X 
NHL Flow Cytometry,  
Lymphocyte Subsets5 
X  
(Day 1 of 
Cycle 4, 
pre-
infusion) 
 
 
 
 
 
 
 
 
 
X 
Serum Cytokines6 
Specimens to be drawn as clinically indicated. 
X 
MT-3724 Administration7 
MT-3724 
MT-
3724 
MT-
3724 
MT-
3724 
MT-3724 
MT-
3724 
 
 
 
ADA/Immunogenicity9 
X 
Additional specimens to be drawn as clinically indicated. 
 
X 
MT-3724 serum levels 
(PK)8 
X 
A concurrent MT-3724 serum level (PK) sample should be drawn whenever an 
Immunogenicity (ADA) sample is drawn for clinical indication(s). 
 
X 


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15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 23 
 
 
 
Assessment 
MT-3724 Infusion Schedule 
Repeated for Each Course 
 
Safety Assessment 
Exploratory 
Efficacy 
Assessment 
Final Safety 
Assessment 
 
Visit 1 
Day 1 
Dose 1 
 
Visit 2 
Day 3 
Dose 2 
 
Visit 3 
Day 5 
Dose 3 
 
Visit 4     
Day 8  
Dose 4 
 
Visit 5 
Day 10 
Dose 5 
 
Visit 6 
Day 12 
Dose 6  
 
Telephone Contact 
Day 16-18 
 
Days 15-21of each 
even-numbered 
cycle 
(replaces 
interim safety 
assessment after 
last infusion)  
Day 14-28 
12-Lead ECG10 
(at investigator’s discretion) 
Radiological Response 
Assessment11 
 
 
X 
X 
(optional) 
1 Height and weight are collected at the Screen visit. Weight is collected again at final safety visit 14-28 days after last infusion. The MT-3724 dose is calculated 
using Screening visit weight.  
2 For the first two infusions in Cycle 1 (Doses 1 & 2), vital signs (temperature, blood pressure, pulse, and respiration rate) will be collected at pre-dose prior to 
initiation of dosing on each dosing day, at 20, 40 and 60 min (± 5 min), at 90 min (± 10 min), at 2 hours (± 15 min) and no less than hourly (± 15 min) until the 
infusion is completed. For all other infusions, vital signs should be collected prior to the initiation of the infusion and at the conclusion of the infusion (±15 
min). Beyond these times and at all other infusions, subjects should be monitored as clinically indicated. The frequency of interim monitoring during and 
following all infusions beyond the second infusion should be determined by the Investigator based on the subject’s clinical condition. In addition, in all 
subjects, orthostatic vital signs will be performed as needed after all doses prior to the subject standing or ambulating for any reason during the observation 
period. 
3 Calculate estimated creatinine clearance by Cockcroft Gault formula. 
4 All female subjects of child bearing potential must have a urine pregnancy test performed prior to the first dose of each new cycle of MT-3724 beginning 
with the first cycle and continuing through the last cycle. Pregnancy test should be done within 72 hours prior to the first dose of each new cycle. 
5 Lymphocyte subset samples must be processed and shipped to the Central Laboratory according to Site Reference Manual and Laboratory Manual instructions. 
The baseline flow cytometry sample should be drawn at the Screening Visit whenever possible. If not obtained at the Screening Visit, the baseline flow 
cytometry sample may be drawn on Dose Day 1 prior to initiation of dosing. The sample drawn on Cycle 1 Day 8 (Visit 5, Dose 4) during the first cycle of 
MT-3724 should be drawn PRIOR to the initiation of Dose 4 infusion. Additionally, Part 1 only: FOR SUBJECTS WITH CLL, flow assessment for 
minimal residual disease (MRD) will be obtained at Baseline and the Final Safety Assessment respectively.  
6 During the first cycle, serum cytokine samples will be obtained at the Screening Visit (Days -28 to -1) or on Dose Day 1 prior to initiation of dosing and then 
at 2 hours post infusion on Visit 2 (Day 1, Dose 1) and Visit 4 (Day 5, Dose 3) and again at the Visit 9 (Days 23-25). Serum cytokine samples must always be 
obtained at the Final Safety Assessment Visit regardless of how many doses have been administered (any cycle). Additional samples may be drawn at the 
Investigator’s discretion as clinically indicated. Serum will be assayed for TNFα, IFN-γ, IL1β, IL-6, IL-8, IL-10 and IL-12. For suspected CRS, SIRS, or TLS, 
unscheduled tests for LDH, D-dimer and PT should be sent to the site’s local laboratory. If the reaction is considered to be a possible hypersensitivity reaction 
then a serum histamine level should also be sent. 
7 MT-3724 will be administered according to Site Reference Manual directions over a period 2 hours ±15 minutes. During the first cycle, all subjects should 
remain in the clinic for a minimum of 4 hours after completion of the first dose of MT-3724 and for a minimum of 2 hours after completion of the second and 
third doses. For these and all subsequent infusions, subjects will not be discharged to home until any signs or symptoms consistent with an adverse reaction to 
study drug or study procedures have completely cleared.  


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CONFIDENTIAL 24 
8 During Cycle 1, serum PK samples will be taken at the following times: 
• 
Day 1 (First Infusion, Dose 1): Samples: Baseline sample within 4 hours prior to initiation of infusion (concurrent baseline ADA/immunogenicity 
sample and cytokine samples may be obtained simultaneously), within 10 minutes prior to the end of primary infusion, and then starting at the 
completion of the infusion, post-infusion samples at 5 minutes (+ 1 min); 0.5, 1, 2, 3 and 4 hours (±5 minutes).  
• 
Day 5 (Third Infusion, Dose 3): Samples at 10 minutes prior to the end of primary infusion, and then at 5 minutes (+ 1 min) and 2 hours (+ 5 
minutes) after completion of infusion.  
• 
Day 8 (Fourth Infusion, Dose 4):    Single sample pre infusion.   
• 
Day 12 (Sixth Infusion, Dose 6): Samples within 10 minutes prior the the end of primary infusion, and at 5 minutes (+ 1 min) and 2 hours (+ 5 
minutes) after completion of infusion. 
• 
Day 23-25 (Visit 9): Sample should be drawn concurrent with ADA/Immunogenicity sample and other safety lab tests at this visit. 
During the Repeat Dosing Study, at the first visit starting each cycle, an ADA/immunogenicity sample should be drawn prior to the initiation of MT-3724 
infusion and a PK sample should be drawn at 5 minutes (+1 minute) following the end of that infusion. Whenever an unscheduled ADA/immunogenicity 
sample is drawn for clinical indication(s), a serum PK sample should be drawn concurrently. 
During Cycles 2 - 5, at the first visit starting each cycle, an ADA/Immunogenicity sample should be drawn prior to the initiation of MT-3724 infusion and a 
PK sample should be drawn at 5 minutes (+1 minute) following the end of that infusion. Whenever an unscheduled ADA/Immunogenicity sample is drawn for 
clinical indication(s), a serum PK sample should be drawn concurrently. 
Final Safety Assessment: A single MT-3724 serum PK sample will be obtained concurrent with the immunogenicity (ADA) sample no matter how many 
doses have been administered (all cycles). Additional samples may be requested if indicated. 
9 Serum samples for ADA/Immunogenicity will be collected during the Core Study during Screening (Day -28 to -1) or on Dose Day 1 prior to initiation of 
dosing and at the Visit 9 Safety Assessment 11 to 14 days following the sixth dose of the first course (Day 23-25). Additional ADA/immunogenicity samples 
will be obtained pre-dose on Day 1 of each Repeat Dosing Study cycle and at the Final Safety Assessment 14-28 days following infusion of the final dose in 
the Core Study or Repeat Dosing Study. For subjects who withdraw early, a serum ADA/Immunogenicity sample will be collected at the Final Safety 
Assessment 14-28 days following their last infusion. Additional samples may be requested if clinically indicated. Additional ADA/immunogenicity samples 
obtained for any “clinical indication” should have a PK sample obtained at the same time. 
10 Standard 12-lead ECG printouts will be obtained at screening, during Cycle 1 (Table 5) on Day 1 (Visit 2, Dose 1) within 3 hours prior to initiation of dosing 
and then at 1 hour (± 15 min) and 2 hours (± 15 min) post start of infusion. For Cycles 2-5, standard 12-lead ECG printouts will be captured at any time it is 
clinically indicated. 
11 See Study Protocol Appendix 3. CT scans will be performed for disease assessment. Where clinically indicated, PET scan will also be performed per 
investigator discretion. 
 


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CONFIDENTIAL 25 
Table 3: 
Schedule of Assessments – Extension Study 
Assessment 
Qualification 
Screen 
MT-3724 Infusion Schedule 
(21-28 day cycles, up to 6 cycles) 
Safety 
Observation 
Final Safety 
Assessment 
Visit 1 
Day -14  to Day -1 
Visit 2 
Day 1 
Dose 1 
Visit 
3 Day 
3 
Dose 
2 
Visit 4 
Day 5 
Dose 3 
Visit 5 
Day 8 
Dose 4 
Visit 6 
Day 10 
Dose 5 
Visit 7 
Day 12 
Dose 6 
Day 16-25 
(If 
withdrawing 
replaces 
interim safety 
assessment 
after last 
infusion) Day 
26-40 
Informed Consent 
X 
 
Inclusion/Exclusion  
X 
 
Medical History Review and Physical 
Exam including ECOG1 
X 
X (directed history and PE as clinically indicated) 
X 
Disease Assessments2 
X 
X (only when clinically indicated) 
X 
Vital Signs3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Laboratory   
CBC w/differential 
X 
X (only when clinically indicated) 
X 
Serum Chemistry 
Na,K,Cl,CO2,  BUN, Cr, LDH, 
Bilirubin, AST (SGOT),  ALT (SGPT), 
GGT, CPK, albumin, total protein, Ca, 
Mg, glucose, uric acid, phosphate, 
amylase, lipase, alkaline phosphatase 
X 
X (only when clinically indicated) 
X 
Β2 microglobulin 
X (only when 
clinically indicated) 
 
 
PT, aPTT, INR 
X (only when clinically indicated) 
Urinalysis 
X 
X (only when clinically indicated) 
X 


Molecular Templates, Inc. 
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15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 26 
Assessment 
Qualification 
Screen 
MT-3724 Infusion Schedule 
(21-28 day cycles, up to 6 cycles) 
Safety 
Observation 
Final Safety 
Assessment 
Visit 1 
Day -14  to Day -1 
Visit 2 
Day 1 
Dose 1 
Visit 
3 Day 
3 
Dose 
2 
Visit 4 
Day 5 
Dose 3 
Visit 5 
Day 8 
Dose 4 
Visit 6 
Day 10 
Dose 5 
Visit 7 
Day 12 
Dose 6 
Day 16-25 
(If 
withdrawing 
replaces 
interim safety 
assessment 
after last 
infusion) Day 
26-40 
Estimated Cr Clearance4 
X 
X (only when clinically indicated) 
X 
Pregnancy Test (urine)5 
X  
X  
(-72 hrs 1st 
dose of 
each 
cycle) 
X (only when clinically indicated) 
X 
Complement (CH50 and C3) 
X (only when clinically indicated) 
Quantitative Serum Immunoglobulins 
X (only when clinically indicated) 
Viral Serology:  Hepatitis and/or HIV if 
clinically indicated 
X (only when clinically indicated) 
Flow Cytometry, Lymphocyte subsets5 
X (including MRD 
analysis for CLL) 
X (only when clinically indicated) 
X (including 
MRD analysis 
for CLL) 
Serum Cytokines6 
 
X  
(Cycle 1) 
X (only when clinically indicated) 
MT-3724 Administration7 
 
MT-3724 
MT-
3724 
MT-
3724 
MT-
3724 
MT-
3724 
MT-
3724 
 
 
MT-3724 Serum Levels (PK)8 
X (Concurrent with ADA only when clinically indicated) 
ADA/Immunogenicity9 
X 
X (only if 
not drawn 
at 
Screening 
Visit) 
X (additional specimens to be drawn as clinically indicated) 
X 


Molecular Templates, Inc. 
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CONFIDENTIAL 27 
Assessment 
Qualification 
Screen 
MT-3724 Infusion Schedule 
(21-28 day cycles, up to 6 cycles) 
Safety 
Observation 
Final Safety 
Assessment 
Visit 1 
Day -14  to Day -1 
Visit 2 
Day 1 
Dose 1 
Visit 
3 Day 
3 
Dose 
2 
Visit 4 
Day 5 
Dose 3 
Visit 5 
Day 8 
Dose 4 
Visit 6 
Day 10 
Dose 5 
Visit 7 
Day 12 
Dose 6 
Day 16-25 
(If 
withdrawing 
replaces 
interim safety 
assessment 
after last 
infusion) Day 
26-40 
12-Lead ECG10 
X (only when clinically indicated) 
Cancer Histology 
X (Confirm history) 
X (repeat only when clinically indicated) 


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15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 28 
Abbreviations: ADA: anti-drug antibodies; ALT: alanine aminotransferase; AST: aspartate aminotransferase; BUN: blood urea nitrogen; Ca: calcium; CBC: 
complete blood count; Cl: chloride; CO2: carbon dioxide; CPK: creatine phosphokinase; Cr: creatinine; CT: computed tomography; ECG: electrocardiogram; 
ECOG: Eastern Cooperative Oncology Group; GGT: gamma-glutamyl transferase; HepBAb: hepatitis B antibody; HepBAg: hepatitis B surface antigen; 
HepCAb: hepatitis C antibody; HIV: human immunodeficiency virus; IFN-γ: interferon gamma; IL-6: interleukin 6; K: potassium; LDH: lactate dehydrogenase; 
Mg: magnesium; MRD: minimal residual disease; NA: sodium; PET: positron emission tomography; PK: pharmacokinetic; TNFα tumor necrosis factor alpha 
1 Height and weight are collected at the Screening Visit. Weight is collected again at Final Safety Visit 14-28 days after last infusion. MT-3724 dose is re-
calculated using Screening Visit weight if subject’s weight has changed by ± 10% from MT-3724_NHL_001_US study, the dose OR subject’s mcg/kg/dose 
must be changed due to MTD identification. 
2 See Protocol Appendix 3. CT scans will be performed for tumor assessment at screening and Final Safety Visit. Additional tumor assessment (s) will be 
performed per investigator. Where clinically indicated, PET scan may also be performed per Investigator discretion. 
3 For all infusions, all cycles, vital signs (temperature, blood pressure, pulse, and respiration rate) should be collected prior to the initiation of the infusion and at 
the conclusion of the infusion. Beyond these times subjects should be monitored as clinically indicated. The frequency of interim monitoring during and 
following all infusions should be determined by the Investigator based on the subject’s clinical condition. In addition, in all subjects, orthostatic vital signs will 
be performed as needed after all doses prior to the subject standing or ambulating for any reason during the observation period 
4 Calculate estimated creatinine clearance by Cockcroft Gault formula. 
5 All female subjects of child bearing potential must have a urine pregnancy test performed prior to the first dose of each new cycle of MT-3724. Pregnancy 
test should be done within 72 hours prior to the first dose of each new cycle at their Final Safety Assessment and at any other time deemed clinically indicated.  
6 A sample for serum cytokines samples will be obtained prior to first dose, first cycle for baseline. Additional samples should be drawn as clinically 
indicated. Serum will be assayed at study’s central laboratory for TNFα, IFN-γ, IL1β, IL-6, IL8, IL10 and IL12. For suspected CRS, SIRS, or TLS 
unscheduled tests for LDH, D-dimer and PT should be sent to the site’s local laboratory. If an adverse event is considered to be a possible hypersensitivity 
reaction then a serum histamine level should also be sent. 
7 MT-3724 will be administered according to Site Reference Manual directions over a period not less than 2 hours and not more than 4 hours. Subjects will not 
be discharged to home until any signs or symptoms consistent with an adverse reaction to study drug or study procedures have completely cleared.  
8 A serum PK sample will be taken concurrently whenever an unscheduled ADA/Immunogenicity sample is drawn for clinical indication(s). Additional samples 
may be requested if indicated. 
9 Serum samples for ADA/Immunogenicity will be collected prior to first dose, first cycle at Screening Visit or on Day of first dose, first cycle prior to 
initiation of dosing for baseline and again at the Final Safety Assessment 14-28 days following the last infusion. Additional samples may be requested 
if clinically indicated. (n.b., for any additional ADA/Immunogenicity samples obtained “when clinically indicated” a concurrent PK sample must be 
obtained.). 
10 Standard 12-lead ECG printouts will be captured at any time it is clinically indicated. 


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CONFIDENTIAL 29 
1.3.5. 
Safety, Efficacy, and Pharmacokinetic Parameters 
1.3.5.1. 
Safety Parameters 
The safety and tolerability of MT-3724 will be evaluated by means of drug related DLT, AE 
reports, physical examinations, and clinically significant changes in the laboratory safety 
evaluations. Adverse events will use the descriptions and grading scales found in the revised 
National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03. 
The evaluation of the MTD and DLT will be performed on all subjects enrolled in Part 1 of the 
main Core Study who receive at least one infusion of MT-3724. MTD is defined as the highest 
dose level at which ≤33% (or 2/6) of subjects experience a DLT. 
A DLT will be defined as a toxic effect that is presumed to be related to MT-3724 and 
considered unacceptable because of its severity and/or irreversibility and as such may limit 
further dose escalation. Dose-limiting toxicities will be defined based upon any toxic effects 
seen in the Core Study. Adverse events during Repeat Dosing will not be classified as DLTs. If 
a toxicity can be satisfactorily documented to be unrelated to MT-3724, then that specific 
toxicity will not be considered to impact the stopping or dose escalation rules.  
A DLT will be determined as follows: 
1. Grade 3 or greater AE: Any Grade 3 or greater adverse event that cannot clearly be 
determined to not be related to MT-3724 or disease progression will be considered to be a 
DLT. 
2. Grade 3 or greater non-hematologic laboratory abnormality: Any Grade 3 or greater non-
hematologic laboratory abnormality that fails to spontaneously recover to less than Grade 3 
on retest prior to the next scheduled dose of MT-3724 or within 10 days (whichever is 
shorter) unless the event can be clearly determined to not be related to MT-3724 or tumor 
progression will be considered a DLT excepting the following: 
• Parameters for liver function test (AST, ALK, PT [INR], aPTT, Bilirubin, and Alk Phos) 
abnormalities to be considered a DLT are detailed in Section 1.3.3. 
3. Grade 3 or greater hematologic laboratory abnormality: Because subject treated with anti-
CD20 MAb develop Grade 3 or higher lymphopenia and because it is an expected 
pharmacodynamic effect of MT-3724, lymphopenia will not be considered a DLT. 
• Unless the event can be clearly determined to not be related to MT-3724 or disease 
progression changes in the following specific hematologic parameters will qualify as a 
DLT: 
i. Febrile neutropenia (absolute neutrophil count <1000/mcl and temperature ≥ 38.5°C) 
ii. Grade 4 neutropenia for > 10 days 
iii. Grade 3 thrombocytopenia with bleeding 
iv. Grade 4 thrombocytopenia  
v. Grade 4 anemia not due to underlying disease  


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CONFIDENTIAL 30 
For all other hematologic laboratory abnormalities, any grade 3 or greater hematologic toxicity 
that fails to spontaneously recover to less than grade 3 within 10 day (and prior to additional 
doses of MT-3724) unless the event can be clearly determined to not be related to MT-3724 or 
tumor progression will be considered a DLT. 
4. A grade 2 (moderate) AE might invoke a stopping rule if:  
• It is not pre-existing 
• It is not due to disease progression 
• It is not manageable with standard outsubject therapies AND 
• It persists in the judgment of the Investigator(s) for an unreasonable people.  
5. Any new Grade 1 (Mild) AE attributable to MT-3724 will not be considered a DLT. 
1.3.5.2. 
Efficacy Parameters 
As this is a dose finding study and is designed to assess the safety and tolerability of MT-3724, 
all efficacy analyses are exploratory in nature, based on documented tumor responses.  
Tumor response following completion of even numbered (e.g., 2, 4, etc.) courses of MT-3724 
and at final safety assessment following termination of MT-3724 will be assessed according to 
the Tumor Response Criteria for malignant lymphoma (Cheson et al 2007) defined by the 
International Working Group. 
In addition, source document verified tumor lesion measurement data that was not reported in 
the EDC was collected and tallied by the Sponsor via an Excel Spreadsheet. The data in this 
Spreadsheet will be used for the analysis of percent change in tumor size. 
Endpoints will include: 
• Best Overall Response. 
• Objective response rate (ORR) - Objective response will be determined as the proportion 
of subjects with either CR or PR using the tumor response criteria described below. 
• Disease Control Rate (DCR) will be calculated as the proportion of subjects who achieve 
either CR, PR or stable disease status. 
• Duration of tumor response (DOR) - Duration of response is defined as the time from the 
first occurrence of either complete or partial response to first documented evidence of 
disease recurrence or progression. Subjects without evidence of progression will be 
censored at time of last disease assessment.Only responders (CR or PR) will be included 
for this analysis. 
• Progression-free survival (PFS) – Progression-free survival is calculated from the date of 
first infusion of MT-3724 to first documented evidence of disease recurrence or 
progression or death due to any cause. Subjects who are last known to be alive and 
without evidence of progression will be censored at time of last disease assessment. 
• Duration of stable disease (i.e., duration of disease control) - Duration of at least stable 
disease is defined as the time from the date of first infusion of MT-3724 to first 


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CONFIDENTIAL 31 
documented radiologic evidence of disease recurrence or progression. Subjects without 
evidence of progression will be censored at time of last disease assessment. 
• Overall survival (OS) – Overall survival is calculated from the date first dose of study 
treatment to the date of death. Subjects who are still alive prior to the data cutoff for 
final efficacy analysis, or who dropout prior to study end, will be censored at the day 
they were last known to be alive. 
• Percent change from baseline in lesion size based on the Sum of the Product of 
Diameters (SPD). 
1.3.5.3. 
Pharmacokinetic and Pharmacodynamic Parameters 
During the study, PK serum samples will be analyzed for concentrations of free MT-3724 and if 
indicated may also be analyzed for any other anti-CD20 biologic agent which the subject may 
have received prior to enrolment. Analysis of PK/PDn parameters will be described in a separate 
PK/PDn analysis document. 
1.3.5.4. 
Immunogenicity 
Immunogenicity parameters will be described in a separate analysis document. 


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CONFIDENTIAL 32 
2. 
SUBJECT POPULATION 
2.1. 
Population Definitions 
The following subject populations will be evaluated and used for presentation and analysis of 
the data: 
• Safety Set (SS): All subjects who received any amount of MT-3724. 
• Pharmacokinetic Analysis Set (PAS): All subjects from the Safety Set with sufficient 
serum concentration data to determine the primary PK parameters. 
• Full Analysis Set (FAS): All subjects from the Safety Set who have at least one tumor 
re-evaluation performed (scheduled or unscheduled). 
The Safety Set is the primary population for the analysis of safety. The PAS is the primary 
population for all PK and PDn analyses. The FAS is the primary population for all exploratory 
efficacy analyses. 
2.2. 
Protocol Violations 
The Sponsor or designee will be responsible for producing the final protocol violation file 
(formatted as a Microsoft Excel file), in collaboration with Veristat and the data monitoring 
group as applicable; this file will include a description of the protocol violation. This file will be 
finalized prior to hard database lock. 
All protocol violations will be presented in a data listing. 
2.3. 
Withdrawals and Subject Replacement 
Subjects may be withdrawn at any time for reasons including the following:  
• at their own request or at the request of their legally authorized representative, 
• if, in the Investigator’s or Sponsor’s opinion, continuation in the study would be 
detrimental to the subject’s well-being, and/or 
• when Stopping Rules have been met. 
2.3.1. 
Main Study 
Part 1: If a subject terminates study participation prior to per protocol Core Study completion 
the Investigator or their representative should notify Molecular Templates and the CRA 
immediately. In all cases, the reason for withdrawal must be recorded in the eCRF and in the 
subject’s medical records. If the reason is not known, the subject must be followed to establish 
whether the reason was an AE, and, if so, this must be recorded. If a subject withdraws for 
reasons other than a DLT and prior to completing the Core Study Molecular Templates and the 
CRA must be informed immediately so a timely decision can be made regarding replacement of 
the subject. If a subject withdraws because of disease progression prior to completion of the 
Core Study, Molecular Templates and the CRA must be informed immediately so a timely 
decision can be made regarding replacement of the subject. Subjects in any cohort will not be 
replaced if they are withdrawn because of a DLT in the Core Study or they are withdrawn 
because of an AE or disease progression in the Repeat Dosing Study.  


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 33 
 
Part 2: If a subject terminates study participation prior to per-protocol post-Cycle 2 tumor 
assessment for any reason other than progressive disease, the Investigator or their 
representative should notify Molecular Templates and the CRA immediately. In all early 
withdrawal cases, the reason for withdrawal must be recorded in the CRF and in the subject’s 
medical records. If the reason is not known, the subject must be followed up to establish 
whether the reason was an AE, and, if so, this must be recorded. If a subject terminates study 
participation prior to per-protocol post-Cycle 2 tumor assessment for any reason other than 
progressive disease, the Investigator or theirrepresentative should notify Molecular Templates  
and the CRA immediately. The DMC must review the study data from any subject who 
withdraws from the study prior to completing at least eight of twelve infusions in Cycles 1 and 2 
and completing the post-Cycle 2 tumor reassessment. If withdrawal is for any reason other than 
disease progression, the DMC must review all safety data available for that subject and 
determine if the subject should be replaced in the MTD expansion cohort. 
2.3.2. 
Extension Study 
If a subject terminates study participation prior to per protocol completion of 6 cycles the 
Investigator or their representative should notify Molecular Templates and the CRA 
immediately. In all cases, the reason for withdrawal must be recorded in the case report form 
(CRF) and in the subject’s medical records. If the reason is not known, the subject must be 
followed to establish whether the reason was an adverse event, and, if so, this must be recorded. 
The Investigator will make every effort to contact subjects lost to follow-up.  Subjects 
withdrawing from this open access extension study due to an MT-3724 related toxicity will not 
be eligible for further MT-3724 treatment. 
If a subject is discontinued early from the study for any reason after receiving one or more doses 
of MT-3724, they will be requeted to undergo all the same safety assessments as outlined for the 
final assessment and exploratory efficacy examinations within 14 to 28 days of withdrawal that 
the subjects who complete the study are required to undergo.  


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 34 
3. 
GENERAL STATISTICAL METHODS 
3.1. 
Sample Size Justification 
Part 1: An estimated 20 to 40 subjects will be enrolled in this standard 3+3 cohort expansion 
safety and tolerability dose escalation study. The dose escalation cohorts will proceed per 
protocol as follows:  
• Cohort 1: 5mcg/kg/dose/day 
• Cohort 2: 10mcg/kg/dose/day 
• Cohort 3: 20mcg/kg/dose/day 
• Cohort 4: 50mcg/kg/dose/day 
• Cohort 5: 100mcg/kg/dose/day 
• Cohort 6: 75mcg/kg/dose/day 
If the MTD is not reached at or prior to completion of Cohort 6 (75 mcg/kg/day) then 
additional cohorts will be added in incremental increases based upon analysis of PK/PD data 
and all safety data for previous cohorts. Additional dose exploration may be required to more 
accurately identify an MTD. 
 
Part 2: A maximum of 40 DLBCL subjects will be treated in Part 2 (MTD Expansion). The 
cohort designation for Part 2 is Cohort 7 (50 mcg/kg/dose/day).  Three patients started in Part 2 
on 75 mcg/kg/day.  
3.2. 
General Methods 
All data listings that contain an evaluation date will contain a relative study day (Rel Day). Pre-
treatment and on-treatment study days are numbered relative to the day of the first dose of study 
medication which is designated as Day 1. The preceding day is Day -1, the day before that is 
Day -2, etc.  
All output will be incorporated into Rich Text Format (RTF) files, sorted and labeled according 
to the International Conference on Harmonisation (ICH) recommendations, and formatted to the 
appropriate page size(s). 
Tabulations will be produced for appropriate demographic, baseline, efficacy, and safety 
parameters. For categorical variables, summary tabulations of the number and percentage of 
subjects within each category (with a category for missing data) of the parameter will be 
presented. For continuous variables, the number of subjects, mean, median, standard deviation 
(Std Dev), minimum, and maximum values will be presented. Time-to-event data will be 
summarized using Kaplan-Meier methodology using 25th, 50th (median), and 75th percentiles 
with associated 2-sided 95% confidence intervals (CIs), as well as percentage of censored 
observations.  
This study is primarily descriptive in nature; therefore, there are no formal statistical hypothesis 
tests planned.  Hypothesis testing may be employed if warranted.  


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 35 
3.3. 
Computing Environment 
All descriptive statistical analyses will be performed using SAS statistical software v9.4, unless 
otherwise noted. Medical history and adverse events will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA) v17.0. Concomitant medications will be coded using the 
World Health Organization (WHO) Drug Dictionary version March 2014. 
3.4. 
Baseline Definitions 
For both the Main and Extension studies, unless noted otherwise, baseline will be defined as the 
most recent measurement prior to the first administration of MT-3724 in the Main Study.  
3.5. 
Methods of Pooling Data 
Subject data from all study centers will be combined for analysis. 
3.6. 
Adjustments for Covariates 
No formal statistical analyses that adjust for possible covariate effects are planned. 
3.7. 
Multiple Comparisons/Multiplicity 
Multiplicity is not of concern for this study with a descriptive interpretation. 
3.8. 
Subpopulations 
All safety and efficacy analyses will be conducted in the following subsets in addition to the 
overall population: 
1. DLBCL vs. “mixed” or “transformed” DLBCL histology (where data allows), 
designated as NHL histological subtype.  
2. Patients with negative  vs. positive serum rituximab (RTX) level at screening in the 
overall population, designated as serum rituximab status at screening.  
3. Patients with negative  vs. positive serum RTX levels at screening in the DLBCL subsets 
as defined in point #1 (where data allows). 
For Part 1, subjects who have a reported disease histology of Follicular Lymphoma at their 
initial screening diagnosis and who subsequently have a DLBCL histology at their diagnosis 
screening review visit will be considered as “Mixed” or “transformed” DLBCL. For Part 2, 
“mixed” or “transformed” histology is an allowed entry on the disease histology field on the 
eCRF, and is reported as such. 
The distinction between negative and positive serum RTX level is as follows: 
• For subjects tested using the RUO assay with a quantitative readout in ng/mL, RTX 
status will be based on the Sponsor-preferred clinical cut off defined as:  <500 ng/mL = 
negative; >=500 ng/mL = positive. 
• For subjects tested using the GLP assay with a semi-quantitative readout of ‘Negative’, 
‘Low Positive’ or ‘High Positive’, RTX status will be defined as Positive if the readout 
is either ‘Low Positive’ or ‘High Positive’, and Negative if the readout is ‘Negative. 
Both types of results will be pooled for the analyses by serum RTX status.  


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 36 
3.9. 
Withdrawals, Dropouts, Loss to Follow-up 
Subjects withdrawing from a cohort in Part 1/Core Study for reasons other than a DLT will be 
replaced. Subjects participating in Part 2 (MTD Expansion) who are withdrawn any time before 
Day 21 due to disease progression will be replaced. Subjects participating in Part 2 who 
withdraw prior to completion of the post-Cycle 4 tumor reassessment may be replaced at the 
Sponsor’s discretion. 
3.10. 
Missing, Unused, and Spurious Data 
There will be no substitutions made to accommodate missing data points. All data recorded on 
the case report form will be included in data listings that will accompany the clinical study 
report. 
When tabulating AE data, partial start dates will be handled as follows: 
• If the year, month, and day are all missing, then set the onset day to the date of the first 
dose. 
• If the month and day are missing, and the year is: 
o the same as the year of first dose, then set the onset day as the first day of 
the month of the first dose; 
o earlier than the year of first dose, then set the onset day as December 31; 
o after the year of the first dose, then set the onset day as January 1. 
• If only the day is missing, then 
o if the month/year is the same as the first dose, then set the onset day as 
the date of first dose; 
o if the month/year is earlier than the month/year of the first dose, then set 
the onset day as the last day of the month; 
o if the month/year is later than the month/year of the first dose, then set the 
onset day as the first day of the month. 
Partial end dates will only be imputed if the year is non-missing: 
• If the month and day are missing, and the year is the same as the year of the last dose 
then set the end day as the last day of the month of the first dose. Otherwise, set the end 
date as December 31. 
• If only the day is missing, then set the end day as the last day of the month. 
If the imputed start date is later than the imputed/non-imputed end date then set the imputed 
start date to the imputed/non-imputed end date. 
 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 37 
3.11. 
Visit Windows 
It is expected that all visits should occur according to the protocol schedule. All data will be 
tabulated per the evaluation visit as recorded on the eCRF even if the assessment is outside of 
the visit window. In data listings, the relative day of all dates will be presented. 
3.12. 
Interim Analyses 
There are no planned formal interim statistical analyses of the data. Interim safety data will be 
examined on an ongoing basis to ensure subject safety and to comply with the clinical trial dose 
escalation rules. Interim efficacy data may be examined on an ad hoc basis.  


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 38 
4. 
STUDY ANALYSES 
All analyses will be presented by the following MT-3724 treatment groups: 
• Cohort 1 (5 mcg/kg/dose) 
• Cohort 2 (10 mcg/kg/dose) 
• Cohort 3 (20 mcg/kg/dose) 
• Cohort 4 (50 mcg/kg/dose) 
• Cohort 5 (100 mcg/kg/dose) 
• Cohort 6 (75 mcg/kg/dose)  
• Cohort 7 / MTD Expansion Cohort (50 mcg/kg/dose) 
o Although 3 subjects enrolled in the original MTD of 75 mcg/kg/dose in Cohort 7, 
only those enrolled at a starting dose of 50 mcg/kg will be considered for the 
purpose of analysis 
• A cohort which combines all patients with a starting dose of 75 mcg/kg, hereafter 
referred to as the 'Combined 75 mcg/kg/dose' Cohort  
• A cohort which combines all patients with a starting dose of 50 mcg/kg, hereafter 
referred to as the 'Combined 50 mcg/kg/dose' Cohort  
In addition, overall tabulations will be presented in appropriate analyses. 
All analyses will be performed on integrated Main and Extention studies. 
4.1. 
Subject Disposition 
Summary statistics (arithmetic mean, standard deviation, median, minimum and maximum for 
quantitative variables) will be presented by MT-3724 treatment group. Frequency tables for 
qualitative data will be provided. If not otherwise mentioned the summary statistics will be 
based on all subjects who received at least one dose of any study medication, the safety analysis 
set. 
Subject disposition will be tabulated and include the following: 
• The number of subjects screened 
• The number of subjects treated in total 
• The number of subjects in each population for analysis, and the reasons for exclusion, as 
applicable 
• The number of subjects who withdrew prior to completing the study and reason(s) for 
withdrawal 
• The number of subjects who completed the core study, and the number continuing into 
the repeat cycles and/or extension study. 
A by-subject data listing of study completion information including the reason for premature 
study withdrawal, if applicable, will be presented. 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 39 
4.2. 
Demographics and Baseline Characteristics 
4.2.1. 
 Demographic characterstics 
The following baseline demographic characteristics will be summarized:   
• age at enrollment 
• gender 
• race 
• height 
• weight 
4.2.2. 
 Medical history 
Medical history findings include previous diagnoses, diseases and surgeries, excluding study 
indication, and meeting the following criteria: start before signing of the informed consent and 
considered relevant for the subject’s study eligibility.  
These data will be summarized using frequency tables for subject count by MedDRA v17.0 
system organ class (SOC) and preferred term (PT). Summary statistics will be provided by MT-
3724 treatment group and overall. Medical history will be provided in a by-subject data listing 
by treatment group. 
 
4.2.3. 
 Disease history 
The following disease history parameters will be summarized:  
• Age at diagnosis 
o In Part 1, the age at initial diagnosis will be assumed to be based on the first 
entry on the disease diagnosis field of the eCRF. In Part 2, the initial diagnosis 
will be indicated on the updated eCRF.The age at diagnosis will be computed as 
date of initial diagnosis – date of birth + 1. For patients enrolled under Protocol 
Version 7.0, the date of birth is not available; therefore, the year of birth will be 
used to approximate the age at diagnosis.  
• Duration of disease 
o In Part 1, the duration of disease will be assumed to be based on the first entry on 
the disease diagnosis field of the eCRF.In Part 2, the initial diagnosis will be 
indicated on the updated eCRF. 
• Tumor burden 
• Tumor stage at diagnosis 
• NHL histological diagnosis.  If any data is missing from the initial disease diagnosis 
assessment, data will be taken from the disease diagnostic review assessment.  
Disease history will be provided in by-subject data listings by treatment group. 


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Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 43 
category, subjects are only counted once. If a patient has the same AE on multiple occasions, the 
worst severity grade (fatal > life threatening > severe > moderate > mild) recorded for the event 
will be summarized. 
Pre-treatment adverse events 
All AEs that occurred before the first administration of MT-3724 are considered to be pre-
treatment AEs.  
Pre-treatment AEs will be summarized using frequency tables for subject count by CTCAE 
grade and worst CTCAE grade. Separate summary tables will be provided for serious and non-
serious events. By-subject listings of pre-treatment AEs will be provided separately for serious 
and non-serious events. Summary statistics and listings of pre-treatment AEs will be provided 
for the overall safety population.  
Treatment-emergent adverse events 
All AEs that have started or worsened after the first administration of MT-3724 up until the last 
study assessment visit are considered to be treatment-emergent adverse events (TEAEs).  
For each TEAE, the investigator will assess the causal relationship to MT-3724 as related and 
unrelated,  where related = possibly, probably or definitely related, and unrelated = unlikely or 
definitely not related. 
TEAEs will be summarized by treatment group using frequency tables for subject count by 
CTCAE grade and worst CTCAE grade. Separate tables will be provided for non-serious 
TEAEs, serious TEAEs and all TEAEs (non-serious and serious combined). The following 
tables will be provided for each of the above categories: 
• TEAEs by MedDRA and Worst CTCAE Grade  
• TEAEs by MedDRA and Worst CTCAE Grade, Only Grade 3/4/5 Events  
• Related TEAEs by MedDRA and Worst CTCAE Grade  
• Related TEAEs by MedDRA and Worst CTCAE Grade, Only Grade 3/4/5 Events  
• Common TEAEs (occurring in ≥10% of subjects) by MedDRA and Worst CTCAE 
Grade – Only for the overall population and MTD expansion 
The following additional tables will be provided for all TEAEs (non-serious and serious 
combined) 
• TEAEs Leading to Permanent Discontinuation by MedDRA and Worst CTCAE Grade 
• Related TEAEs Leading to Permanent Discontinuation by MedDRA and Worst CTCAE 
Grade 
• TEAEs Leading to Dose Reduction by MedDRA and Worst CTCAE Grade  
• Related TEAEs Leading to Dose Reduction by MedDRA and Worst CTCAE Grade 
• TEAEs Leading to Dose Interruption / Delay by medDRA and Worst CTCAE Grade 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 44 
• Related TEAEs Leading to Dose Interruption / Delay by medDRA and Worst CTCAE 
Grade 
The following by-subject listings of TEAEs with the corresponding MedDRA PT, worst 
CTCAE grade, relatedness outcome and seriousness (where applicable) will be provided: 
• Non-serious TEAEs Grade 3/4/5  
• Serious TEAEs (all CTCAE grades) 
• TEAEs Leading to Dose Interruption / Delay  
• TEAEs Leading to Dose Reduction  
• TEAEs Leading to Permanent Discontinuation  
 
• TEAEs Declared as Dose Limiting Toxicities  
• TEAEs Leading to Death 
4.6.2. 
Laboratory Data 
Clinical laboratory values will be expressed in SI units. 
Quantitative laboratory data will be summarized by treatment group, parameter and scheduled 
time points using descriptive statistics. The summary tables will be presented for the original 
data as well as for the difference from baseline. In the event of repeat values, the average value 
per study day/time will be used. Local hematology lab results will be primarily considered for 
summary tables; if no local lab results are available, central lab results will be used. Non-
negative results will be listed for qualitative variables. Microglobulin, immunology, and 
complement samples, as well as Serum cytokine results from the central lab will be included in 
the summary tables. 
Shift tables will be produced that summarize the maximum shifts from baseline to worst value 
for hematology, chemistry, and coagulation lab categoriesusing CTCAE toxicity grades for 
relevant laboratory parameters. Scatter plots or box and whisker plots of selected lab tests over 
time may be presented where appropriate. Unscheduled visits may contribute to worst visits, as 
applicable. Both local and central hematology lab results will be considered for worst values.  
All laboratory data will be provided in data listings, where laboratory values outside the normal 
range will be flagged with “H” (high) or “L” (low), as well as the CTCAE grade, if applicable.   
Unscheduled visits will not be summarized in tabulations. They will only be included in data 
listings and/or shift tables, as appropriate. 
4.6.3. 
Vital Signs  
Vital signs parameters include systolic and diastolic blood pressure, heart rate, respiration rate, 
body temperature and body weight. 
The actual value and change from baseline within each on-study evaluation will be summarized 
by treatment group. The pre-dose measurement will act as baseline for a given visit; post-dose 
measurements will be compared to pre-dose measurements within each visit. 
Vital sign measurements will be presented for each subject in a data listing by treatment group. 


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Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
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CONFIDENTIAL 45 
4.6.4. 
Physical Examination 
Physical examination results at each time point will be summarized using shift tables to indicate 
change in status (normal/abnormal) from baseline to each post-baseline assessment.  
Those findings on physical examination that represented a changes from baseline will be 
presented in by-subjec tdata listing for each treatment group. 
4.6.5. 
Electrocardiogram 
Electrocardiogram (ECG) parameters include the heart rate, PR interval, QRS interval, QT 
interval, QT interval corrected for heart rate according to Fredericia’s formula (QTcF), sinus 
rhythm (yes/no), overall ECG interpretation by the investigator or designee (normal, abnormal 
clinically not significant and abnormal clinically significant) and comments from the overall 
ECG interpretation by the investigator or designee. 
The ECG recording obtained at screening will represent the baseline for all on-treatment 
observations. 
Actual values and changes from baseline in ECG intervals and the heart rate will be summarized 
by descriptive statistics and presented in tables and by-subject listings for each treatment group. 
Categorical analysis of the QT and QTcF intervals (absolute value ≤450, 451-480, 481-500, and 
>500 msec and change from baseline <30, 31-60, and >60 msec) will also be performed and 
frequencies (number and percent of subjects) in each category will be presented in tables and 
by-subject listings for each treatment group. The specific value for each subject will be provided 
in the listing of categorical analysis results. 
The overall ECG assessment results will be summarized by category (normal, abnormal 
clinically not significant, abnormal clinically significant) in frequency tables for each treatment 
group. In addition, the overall ECG assessment results will be listed by category for each 
treatment group. For abnormal clinically significant result, the corresponding AE term and 
CTCAE grade will be specified in the listing, if available.  
4.6.6. 
Concomitant Medications 
Concomitant medications will be coded using the WHO Drug Dictionary. Results will be 
tabulated by anatomic therapeutic class (ATC) and preferred term. 
Concomitant medications will be tabulated by treatment group, where any medications that did 
not end prior to first dose will be included. If an end date is missing or the medication is 
ongoing, the medication will be included.  
 The concomitant medication dates and terms will be presented in by-subject listings for each 
treatment group. 
4.6.7. 
ECOG Performance Status 
ECOG performance status will be summarized using a shift table to indicate change in score 
from baseline to each post-baseline assessment. 
All ECOG data will be presented in a by-subject data listing for each treatment group. 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 46 
 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 47 
5. 
CHANGES TO PLANNED ANALYSES 
Changes from Version 1.0 to Version 2.0 of this SAP was the result from a change in CRO 
providing biostatistical services to Molecular Templates for Study MT-3724_NHL_001_US.  
Changes from Version 2.0 to Version 3.0 of this SAP are the result from the changes that 
occurred between Protocol Version 4.0 and Protocol Version 7.0 for Study MT-
3724_NHL_001_US and between Protocol Version 1.0 and Protocol Version 2.0 for Study MT-
3724_NHL_001_US_EXT. 


Molecular Templates, Inc. 
Statistical Analysis Plan, Main Study Protocol Version 7.0, Extension Study Protocol Version 2.0 
15 August 2018, Final Version 3.0 
 
CONFIDENTIAL 
 
 
48 
6. 
REFERENCES 
 
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised 
response criteria for malignant lymphoma. J Clin Oncol. 2007;25:579-86.