Conditions: Non-hodgkin Lymphoma
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 9
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the safety and tolerability of MT-3724 in combination with Lenalidomide in participants with relapsed or refractory B-Cell NHL.

Detailed description:
This is a multi-center, open-label two-part study evaluating the safety and tolerability of MT-3724 in combination with Lenalidomide in relapsed or refractory CD20 positive B-cell Lymphoma participants.

Part 1: (MT-3724 Dose Escalation) Define the maximum tolerated dose (MTD) of MT-3724 in combination with standard treatment of Lenalidomide

Part 2: (MTD Expansion Cohort) Confirm the safety and tolerability of the MTD of MT-3724 from Part 1 in the MTD Expansion Cohort, where MT-3724 will be given at the MTD in combination with Lenalidomide. In addition, the Pharmacokinetics (PK), Pharmacodynamics (PD), immunogenicity and tumor response at the MTD of MT-3724 in combination with Lenalidomide will be more thoroughly evaluated in Part 2.

It is anticipated that up to 64 participants will be enrolled. Treatment will continue until disease progression, withdrawal of consent or any other reason.

Arms:
arm 1: MT-3724 10 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks on Days 1, 3, 5, 8, 10, and 12) of each 28 day cycle in combination with LEN. If the treatment with MT-3724 is continued beyond Cycle 2, then MT-3724 will be administered weekly (Days 1, 3, 5, 8, 10, and 12) of each 28-day cycle arm 2: MT-3724 25 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks on Days 1, 3, 5, 8, 10, and 12) of each 28 day cycle in combination with LEN. If the treatment with MT-3724 is continued beyond Cycle 2, then MT-3724 will be administered weekly Days 1, 3, 5, 8, 10, and 12) of each 28-day cycle arm 3: MT-3724 20 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks on Days 1, 3, 5, 8, 10, and 12) of each 28 day cycle in combination with LEN. If the treatment with MT-3724 is continued beyond Cycle 2 , then MT-3724 will be administered weekly (Days 1, 3, 5, 8, 10, and 12) of each 28-day cycle arm 4: MT-3724 25 mcg/kg dose IV for 4 doses (days 1, 5, 8 and 12 during cycles 1 and 2) of each 28 day cycle in combination with LEN and weekly during cycles 3 and beyond (days 1, 8, 15 and 22). arm 5: MT-3724 50 mcg/kg dose IV for 4 doses (days 1, 5, 8 and 12 during cycles 1 and 2) of each 28 day cycle in combination with LEN and weekly during cycles 3 and beyond (days 1, 8, 15 and 22).

Interventions: intervention 1: MT-3724
Intervention descriptions: intervention 1: Experimental treatment with MT-3724 in combination with LEN therapy.

Protocol document:
Prot_000.pdf: 
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Version 3.0, 14 April 2020 
 
 
 
Page 1 of 115 
  
  
CLINICAL STUDY PROTOCOL 
Protocol Title: 
A Phase 2a Open-label Study to Investigate Safety and Tolerability 
(including the Maximum Tolerated Dose), Efficacy, Pharmacokinetics, 
Pharmacodynamics and Immunogenicity of MT-3724 in Combination 
with Lenalidomide in Subjects with Relapsed or Refractory B-Cell Non-
Hodgkin Lymphoma 
Protocol Number: 
MT-3724_NHL_003  
Compound: 
MT-3724 
Study Phase:  
2a 
Sponsor 
Name 
Molecular Templates, Inc. 
Legal 
registered 
address 
9301 Amberglen Blvd. 
Suite 100 
Austin, TX 78729 
Regulatory Agency 
Identifier Number(s) 
IND: 121918 
EudraCT: Not applicable 
NCT: NCT03645395 
Protocol Version and 
Date: 
Document Version  
Date 
Original (version 1.0) 
18 July 2018 
Version 2.0 
10 December 2018 
Version 3.0 
14 April 2020 
-CONFIDENTIAL- 
This document and its contents are the property of and confidential to Molecular 
Templates. Any unauthorized copying or use of this document is prohibited. 
 
 
 


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MOLECULAR TEMPLATES APPROVAL 
MT-3724_NHL_003: A Phase 2a Open-label Study to Investigate Safety and Tolerability 
(including the Maximum Tolerated Dose), Efficacy, Pharmacokinetics, Pharmacodynamics 
and Immunogenicity of MT-3724 in Combination with Lenalidomide in Subjects with 
Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma 
I, the undersigned, have approved version 3.0 of the clinical trial protocol with the date of 
14 April 2020. 
Name and Title 
Signature and Date 
, MD 
Chief Medical Officer 
Molecular Templates, Inc. 
, PhD 
Senior Director, Clinical Development 
Molecular Templates, Inc. 
DocuSign Envelope ID: 6169EE29-D007-44CA-BF82-5A9526381B97
4/22/2020
4/16/2020


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INVESTIGATOR AGREEMENT  
MT-3724_NHL_003: A Phase 2a Open-label Study to Investigate Safety and Tolerability 
(including the Maximum Tolerated Dose), Efficacy, Pharmacokinetics, Pharmacodynamics 
and Immunogenicity of MT-3724 in Combination with Lenalidomide in Subjects with 
Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma 
 
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. 
 
 
Signature: 
 
 
Date: 
 
 
Name 
(print): 
 
 
 
 
Site Name: 
 
 
 
 
 
 
 
 


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LIST OF CONTACTS 
Sponsor’s Medical Representative: 
 
 
, MD 
Chief Medical Officer 
Molecular Templates, Inc. 
Work: 
 
  
 
Pharmacovigilance and SAE reporting: 
 
Managed by CRO. Refer to Study Contacts 
for MT-3724_NHL_003 for the most up-to-
date contact details.  
Clinical Operations: 
 
 
Clinical Operations 
Molecular Templates, Inc. 
Mobile: 
 
 
 
 


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TABLE OF CONTENTS 
MOLECULAR TEMPLATES APPROVAL ................................................................2 
INVESTIGATOR AGREEMENT.................................................................................3 
LIST OF CONTACTS ...................................................................................................4 
TABLE OF CONTENTS ...............................................................................................5 
LIST OF TABLES .........................................................................................................9 
PROTOCOL SUMMARY ...........................................................................................10 
Synopsis .......................................................................................................................10 
Study Schema...............................................................................................................21 
Schedule of Assessments .............................................................................................22 
1 
INTRODUCTION ................................................................................................27 
1.1 
Non-Hodgkin lymphoma .................................................................................27 
1.1.1 
Anti-CD20 Mab therapy for NHL .............................................................28 
1.2 
MT-3724 ..........................................................................................................28 
1.2.1 
Clinical experience with MT-3724 ............................................................29 
1.3 
Lenalidomide (Revlimid®, LEN) .....................................................................29 
1.3.1 
Rituximab-lenalidomide (R2) in NHL .......................................................30 
1.4 
Rationale for the study design ..........................................................................30 
1.5 
Benefit/risk ratio ..............................................................................................31 
1.6 
Guidance to the investigator ............................................................................31 
2 
OBJECTIVES AND ENDPOINTS ......................................................................32 
2.1 
Primary objectives and endpoints ....................................................................32 
2.2 
Secondary objectives and endpoints ................................................................32 
3 
INVESTIGATIONAL PLAN ...............................................................................34 
3.1 
Description of overall study design and plan ...................................................34 
3.2 
Screening..........................................................................................................34 
3.3 
Treatment .........................................................................................................34 
3.3.1 
MT-3724 ....................................................................................................34 
3.3.2 
Lenalidomide .............................................................................................35 
3.4 
End of Treatment Visit and Short-Term Follow-Up phone call ......................35 
3.5 
Long-Term Follow Up Visit ............................................................................35 
3.6 
Part 1 (MT-3724 Dose Escalation) ..................................................................35 
3.6.1 
Subject evaluable for dose decisions .........................................................37 
3.6.2 
DLT Criteria...............................................................................................37 
3.6.3 
MTD definition ..........................................................................................38 
3.6.4 
MTD communication plan .........................................................................38 
3.7 
Part 2 (MTD Expansion Cohort)......................................................................38 
4 
STUDY POPULATION .......................................................................................39 
4.1 
Inclusion criteria ..............................................................................................39 
4.2 
Exclusion criteria .............................................................................................41 


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4.3 
Subject withdrawal, replacement and study discontinuation ...........................43 
4.3.1 
Subject withdrawal .....................................................................................43 
4.3.2 
Subject replacement ...................................................................................44 
4.3.3 
Study discontinuation.................................................................................44 
5 
TREATMENTS ....................................................................................................44 
5.1 
MT-3724 ..........................................................................................................44 
5.1.1 
MT-3724 drug product ...............................................................................45 
5.1.2 
MT-3724 dose selection .............................................................................45 
5.1.3 
MT-3724 dosing schedule..........................................................................46 
5.1.4 
Premedication before MT-3724 infusion ...................................................47 
5.2 
Lenalidomide (Revlimid®, LEN) .....................................................................47 
5.2.1 
Lenalidomide dose selection ......................................................................47 
5.2.2 
Lenalidomide dosing schedule ...................................................................47 
5.3 
Intra-subject dose escalation ............................................................................48 
5.4 
Treatment modification ....................................................................................48 
5.4.1 
MT-3724 treatment modification ...............................................................48 
5.4.2 
Lenalidomide treatment modification ........................................................49 
5.4.3 
Treatment modification due to IRR or other hypersensitivity event .........50 
5.4.4 
Treatment modification for MT-3724 and LEN due to neutropenia or 
thrombocytopenia .....................................................................................51 
5.4.5 
Treatment modification for MT-3724 and LEN due to increased AST, 
ALT and/or bilirubin levels ......................................................................51 
5.5 
Treatment assignment ......................................................................................52 
5.6 
Blinding............................................................................................................53 
5.7 
Treatment compliance ......................................................................................53 
5.8 
Treatment duration ...........................................................................................53 
5.9 
Prohibited treatment .........................................................................................53 
5.10 
Permitted medication .......................................................................................54 
5.10.1 
Reasons for caution ....................................................................................54 
6 
STUDY ASSESSMENTS ....................................................................................55 
6.1 
General subject characteristics .........................................................................55 
6.1.1 
Demographics ............................................................................................55 
6.1.2 
Body weight ...............................................................................................55 
6.1.3 
Height and BMI .........................................................................................55 
6.1.4 
NHL assessment.........................................................................................55 
6.1.5 
Prior systemic therapy................................................................................56 
6.1.6 
Prior radiotherapy ......................................................................................56 
6.2 
Safety assessments ...........................................................................................56 
6.2.1 
Medical history ..........................................................................................56 
6.2.2 
Prior and concomitant medications ............................................................57 
6.2.3 
Physical examination (PE) .........................................................................57 


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6.2.4 
Eastern Cooperative Oncology Group Performance Status .......................59 
6.2.5 
New York Heart Association .....................................................................59 
6.2.6 
Vital signs ..................................................................................................59 
6.2.7 
Left ventricular ejection fraction ...............................................................60 
6.2.8 
Electrocardiograms ....................................................................................60 
6.3 
Adverse events .................................................................................................61 
6.3.1 
AE reporting period ...................................................................................62 
6.3.2 
Adverse event terminology ........................................................................62 
6.3.3 
Severity ......................................................................................................62 
6.3.4 
Expected and unexpected adverse events and SUSARs ............................64 
6.3.5 
Serious adverse events ...............................................................................64 
6.3.6 
Action taken with study treatment .............................................................66 
6.3.7 
Outcome .....................................................................................................66 
6.4 
Laboratory Tests ..............................................................................................66 
6.4.1 
Hematology, Chemistry and Urinalysis .....................................................67 
6.4.2 
Estimated glomerular filtration rate ...........................................................67 
6.4.3 
Urinalysis ...................................................................................................68 
6.4.4 
Glycated hemoglobin in plasma .................................................................68 
6.4.5 
Thyroid function ........................................................................................68 
6.4.6 
Coagulation ................................................................................................68 
6.4.7 
Immunoglobulins .......................................................................................69 
6.4.8 
Rituximab concentration ............................................................................69 
6.4.9 
Complement, histamine, and cytokines .....................................................69 
6.4.10 
Serum beta-2 microglobulin ......................................................................69 
6.4.11 
Serology/Virology – HIV, HBV and HCV and CD4+ T-cell counts ........70 
6.4.12 
Pregnancy test ............................................................................................70 
6.5 
Pharmacokinetic assessments ..........................................................................71 
6.6 
Efficacy assessments: Radiological Assessment of Tumor Response .............71 
6.6.1 
Central review of efficacy results ..............................................................72 
6.7 
Immunogenicity ...............................................................................................72 
6.8 
Pharmacodynamics assessments ......................................................................72 
6.8.1 
Peripheral blood .........................................................................................72 
6.9 
Tumor tissue.....................................................................................................73 
6.10 
Exploratory Assessments .................................................................................73 
7 
DATA MANAGEMENT AND STATISTICAL ANALYSIS .............................73 
7.1 
Data handling and electronic CRF ...................................................................73 
7.2 
General statistical considerations .....................................................................74 
7.3 
Sample size justification ..................................................................................74 
7.4 
Analysis sets.....................................................................................................74 
7.4.1 
Safety population .......................................................................................74 
7.4.2 
Efficacy analysis population ......................................................................75 


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7.4.3 
Pharmacokinetic population .......................................................................75 
7.4.4 
Immunogenicity population .......................................................................75 
7.4.5 
Pharmacodynamic analysis population ......................................................75 
7.5 
Subject disposition and termination status .......................................................75 
7.6 
Handling missing data ......................................................................................75 
7.7 
Baseline and demographic characteristics .......................................................75 
7.8 
Safety analyses .................................................................................................76 
7.8.1 
Safety data handling ...................................................................................76 
7.9 
Efficacy analyses .............................................................................................77 
7.10 
Pharmacokinetic analyses ................................................................................78 
7.11 
Immunogenicity analysis .................................................................................78 
7.12 
Pharmacodynamic analyses .............................................................................79 
7.13 
Interim analysis ................................................................................................79 
7.14 
Protocol deviations ...........................................................................................79 
8 
STUDY MANAGEMENT ...................................................................................80 
8.1 
Approval and consent ......................................................................................80 
8.1.1 
Regulatory guidelines ................................................................................80 
8.1.2 
Independent ethics committee/Institutional Review Board .......................80 
8.1.3 
Informed consent .......................................................................................80 
8.2 
Protocol amendments and other changes in study conduct .............................81 
8.3 
Discontinuation of the study by the sponsor ....................................................82 
8.4 
Confidentiality .................................................................................................82 
8.5 
Study monitoring, auditing and inspection ......................................................82 
8.6 
Source data .......................................................................................................83 
8.7 
Retention of records .........................................................................................84 
8.8 
Subject insurance .............................................................................................84 
8.9 
Financial Disclosure .........................................................................................84 
8.10 
Study disclosure and publication .....................................................................85 
8.10.1 
Publications of study results ......................................................................85 
REFERENCES ............................................................................................................86 
APPENDIX 1. 
LABORATORY PANELS ............................................................89 
APPENDIX 2. 
STAGING OF NHL .......................................................................90 
APPENDIX 3. 
REVISED LUGANO CLASSIFICATION FOR RESPONSE 
ASSESSMENT IN LYMPHOMA WITH LYRIC MODIFICATION .........92 
APPENDIX 4. 
DLT CRITERIA ............................................................................96 
APPENDIX 5. 
COCKCROFT-GAULT (2009) .....................................................98 
APPENDIX 6. 
ECOG PERFORMANCE STATUS ..............................................99 
APPENDIX 7. 
NEW YORK HEART ASSOCIATION (NYHA) FUNCTIONAL 
CLASSIFICATION .....................................................................................100 
APPENDIX 8. 
ABBREVIATIONS .....................................................................101 
APPENDIX 9. 
SUMMARY OF CHANGES .......................................................106 


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LIST OF TABLES 
Table 1:
MT-3724 Dose Cohorts and Corresponding MT-3724 and LEN Dose 
Levels ...............................................................................................................14
Table 2:
Schedule of Assessments for the Screening Period .........................................22
Table 3:
Schedule of Assessments for Treatment Period ...............................................24
Table 4:
Pharmacokinetic Sampling Schedule ...............................................................26
Table 5: 
MT-3724 Dose Cohorts and Corresponding MT-3724 and LEN Dose 
Levels ...............................................................................................................36
Table 6:
Dose Adjustments of MT-3724 or LEN in Response to Neutrophil and Platelet 
Nadir Counts ....................................................................................................51
Table 7:
Dose Adjustments in Response to the Worst Increase in Aspartate 
Aminotransferase, Alanine Aminotransferase, or Bilirubin ............................52
Table 8:
Classification of Adverse Events by Severity ..................................................62
Table 9:
Classification of Adverse Events by Causality/Relationship to the Study 
Drug(s) .............................................................................................................63
Table 10:
Laboratory Assays ...........................................................................................89
Table 11: 
Ann Arbor Staging System with Cotswold Modification ................................90
Table 12: 
Revised Lugano Classification of Response Assessment in Lymphoma 
adjusted for LYRIC..........................................................................................92
Table 13:
Modified Lugano 5-point scale (5PS) ..............................................................95


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PROTOCOL SUMMARY 
Synopsis 
Protocol Title:  
A Phase 2a Open-label Study to Investigate Safety and Tolerability (including the maximum 
tolerated dose [MTD]), Efficacy, Pharmacokinetics, Pharmacodynamics and Immunogenicity 
of MT-3724 in Combination with Lenalidomide in Subjects with Relapsed or Refractory 
B-Cell Non-Hodgkin Lymphoma.
Objectives and Endpoints: 
OBJECTIVES 
ENDPOINTS 
Primary 
Determine the safety and tolerability 
(including the MTD) of MT-3724 in 
combination with lenalidomide in 
subjects with relapsed or refractory 
B-Cell NHL
Incidence of adverse events (AEs), including DLTs, inclusive of 
physical exam findings, laboratory abnormalities, and/or 
subject-reported symptoms 
Secondary 
Characterize the pharmacokinetics (PK) 
of MT-3724 in combination with 
lenalidomide in subjects with relapsed or 
refractory B-Cell NHL 
PK parameters will be derived from MT-3724 serum 
concentration time data from all eligible subjects; parameters 
will be stratified by dose group. 
Assess the pharmacodynamics (PD) of 
MT-3724 in combination with 
lenalidomide in subjects with relapsed or 
refractory B-Cell NHL 
B-cell count and immunophenotype data by flow cytometry
Assess the immunogenicity of MT-3724 
in combination with lenalidomide in 
subjects with relapsed or refractory 
B-Cell NHL
Anti-drug antibodies (ADA) 
Neutralizing antibodies (NAb) 
Assess the tumor response to MT-3724 
in combination with lenalidomide in 
subjects with relapsed or refractory 
B-Cell NHL
Objective response based on local assessment 
Duration of response 
Progression-free survival (PFS) 
Overall survival (OS) 
Exploratory 
 
 
 
 
 
 
 
 
  
 
Overall Design:  
This will be an open-label dose escalation study of MT-3724 in combination with LEN in 
subjects with relapsed or refractory B-Cell NHL. 
The study will be conducted in two sequential parts (Part 1 and Part 2); in both parts of the 
study, the subject’s participation in the study will comprise of 4 periods: Screening, 
PPD


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Treatment, Short-Term Follow-Up (STFU) and Long-Term Follow-Up (LTFU). All 
assessments will be identical in Parts 1 and 2. 
Screening: 
The screening procedures will be performed within 35 days before Day 1 of cycle 1 (C1D1), 
with the exception of laboratory safety and radiographic assessments which are to be done 
within 28 days of C1D1. 
Treatment: 
Each subject may be treated only in one part of the study. 
Part 1 (MT-3724 Dose Escalation) 
Part 1 will include MT-3724 dose escalation according to the modified 3+3 design to identify 
the MTD of MT-3724 in combination with standard doses of LEN. 
In all dose cohorts, MT-3724 will be administered in combination with LEN at a dose of 
20mg. The LEN starting dose can be decreased per investigator’s discretion based on the 
known safety profile of LEN and subject’s status.  
Before each dose escalation decision, the sponsor and all investigators will review all 
available data in the current dose cohort. These parties 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. The details of the safety review before dose escalation decisions are described in 
the study manual.   
Cohort management and dose escalation decisions will be based on the incidence of 
treatment-emergent adverse events (TEAEs) that fulfill the criteria for a DLT. See 
Section 3.6 for conduct of dose escalation and for dose decisions in Part 1. 
MTD definition: The highest MT-3724 dose that can be given in combination with LEN so 
that no more than 1 of 6 subjects experiences a DLT will be declared as the MTD for 
MT-3724 in Part 1 of this study. At least 6 subjects must be treated at the MTD dose level of 
MT-3724 in combination with LEN and complete cycle 1 or experience a DLT.  
The sponsor will make the decision on the MTD after consultation with all investigators. 
Part 2 (MTD Expansion Cohort) 
The purpose of Part 2 is to confirm the safety, efficacy and tolerability of the MTD of 
MT-3724 in the MTD Expansion Cohort, where MT-3724 will be given at the MTD in 
combination with LEN. In addition, the PK, PD, immunogenicity and tumor response at the 
MTD of MT-3724 in combination with LEN will be evaluated in Part 2. 


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Part 2 can start only after the MTD of MT-3724 in combination with LEN is declared in 
Part 1; however, the screening of prospective subjects for Part 2 may begin during the review 
of the safety data leading to the MTD decision. 
End of Treatment Visit and Short-Term Follow-up phone call: 
The EoT Visit will be performed at the end of the treatment period for each subject in Part 1 
and Part 2. The EoT Visit should occur at the time of discontinuation, as soon as possible 
after the last dose of MT-3724 or LEN (within 14 days of the last dose) for all subjects, 
except those who withdrew consent and objected to further data collection or were lost to 
follow up. End of Treatment Visit assessments should be performed during the clinic visit. 
The EoT Visit may be performed by telephone call only if subject cannot attend a clinic visit 
or has started a new anticancer treatment. The EoT Visit will be followed by a STFU phone 
call at least 30 days (+7 days) after last dose of MT-3724 or LEN, except for subjects who 
withdrew consent and objected to further data collection or were lost to follow up. 
Long-term Follow Up Visit: 
Subjects will be followed every 3 months (±14 days) for 18 months from the last dose of 
MT-3724. Subjects who discontinue treatment for disease progression will be followed only 
for OS. Subjects who discontinue treatment for reasons other than disease progression (e.g., 
toxicity) will be followed for PFS and OS. Subjects with CR, PR, or SD should also be 
followed for radiology assessment until progressive disease, death, or start of new anticancer 
treatment. The LTFU Visits will be performed via a telephone call and radiology data should 
be obtained from medical records. 
Study Treatment and Duration 
MT-3724 Investigational Medical Product (IMP) 
MT-3724 will be administered as intravenous (IV) infusion over 1 hour (window of 54-75 
minutes).  
For subjects enrolled in Cohorts 1-3, in cycles 1 and 2, MT-3724 infusion should be 
administered on Day 1, 3, 5, 8, 10 and 12 (±1) of each 28-day cycle.  
In subsequent cohorts in cycles 1 and 2, MT-3724 infusion should be administered on Days 
1, 5, 8 and 12 of each 28-day cycle. Different dosing days up to D21 may be selected at 
investigator’s discretion.   
In all cohorts, starting with cycles 3 (C≥3), MT-3724 will be administered weekly (Day 1, 8, 
15 and 22) of each 28-day cycle. Different dosing days within ±2 days from Day 1, 8, 15 and 
22 may be selected at the investigator’s discretion. 
MT-3724 doses must be administered at least 48 hours apart. 


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Intra-subject escalation of MT-3724 dose is not permitted in either part of this study. The 
guidance for treatment modification (dose interruption/delay, dose reduction or treatment 
discontinuation) is presented in Section 5.4. 
In Part 1, the starting MT-3724 doses in each of the planned cohorts are described in Table 1.  
If MT-3724 is not tolerated in any of the planned cohorts, then additional MT-3724 doses 
may be evaluated in the interim cohorts at the sponsor’s discretion in consultation with the 
investigator.  
In Part 2, the starting MT-3724 dose will be the MTD of MT-3724 in combination with LEN 
from Part 1. 
Premedication:  
One premedication agent from each of the following 3 therapeutic classes must be given 
within 60 minutes before the start of each MT-3724 infusion in cycle 1 in both parts of the 
study: 
 Oral anti-pyretic agent (325 – 1000mg acetaminophen or equivalent) 
 Intravenous H1 histamine receptor antagonist (50 – 100mg diphenhydramine or 
equivalent) 
 Intravenous corticosteroid agent with a shorter biological half-life (125 – 1000mg 
methylprednisolone or equivalent)  
The specific drugs in each class should be selected at investigator’s discretion or according to 
the institutional guideline. Cases where a subject has a contraindicating medical condition 
that precludes pretreatment with any of the categories above should be discussed with the 
sponsor. Although continued pre-medication is recommended during all cycles, after cycle 1, 
the investigator may adjust the dosage and/or avoid using certain premedication agents 
during the treatment, if supported by the investigator’s assessment of the risk from infusion-
related reaction, anaphylaxis or other hypersensitivity events. 
See Section 5.1.3 for details about the IMP properties and dosing schedule. 
Lenalidomide (Revlimid®, LEN) 
Lenalidomide is available as 2.5-20mg oral capsules. It is available only through a restricted 
program under a Risk Evaluation and Mitigation Strategy (REMS). 
In both parts of the current study, subjects will self-administer LEN once daily (qd) orally 
(PO) with or without food on the first 21 consecutive days (D1-D21) of each 28-day cycle. 
Subjects will record doses taken in a subject diary. 
The starting dose of LEN in each cohort in Part 1 and Part 2 will be 20mg qd. The LEN 
starting dose can be decreased per investigator's discretion based on the known safety profile 
of LEN and subject’s status. For Parts 1 and 2, starting with cycle 2 (after completion of the 


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DLT assessment period for subjects in Part 1), the investigator may increase the LEN dose to 
25mg qd, if clinically indicated, with sponsor approval. 
Modification of LEN treatment in this study will be guided by the reference prescribing 
information, as interpreted by the investigator after consultation with the medical monitor. 
If the LEN dose has been reduced due to a TEAE, the intra-subject escalation of the LEN 
dose is permitted if continued treatment is supported by the investigator’s assessment of the 
benefit-risk ratio after consultation with the medical monitor. In such cases, the LEN dose 
may be increased only up to the level before the most recent dose reduction. 
Table 1: 
MT-3724 Dose Cohorts and Corresponding MT-3724 and LEN Dose Levels 
Planned MT-3724 Dose 
Cohorts 
Interim MT-3724 Dose 
Cohorts1 
Starting  
MT-3724 Dose 
(µg/kg/dose)2 
Starting  
LEN Dose 
(mg)3 
1 
 
10 TIW 
20 
 
-1 (optional) 
≤54 TIW 
20 
2 
 
25 TIW 
20 
 
-2 (optional) 
≤17.54 TIW 
20 
3 
 
20 TIW 
20 
 
-3 (optional) 
154 TIW 
20 
4 
 
25 BIW 
20 
 
-4 (optional) 
<17.54 BIW 
20 
5 
 
50 BIW 
20 
 
-3 (optional) 
≤37.54 BIW 
20 
BIW = twice weekly; LEN = lenalidomide; TIW = three times weekly 
1To be evaluated only if warranted by the safety results in the planned cohorts 
2The administered dose of MT-3724 will be capped at 6000g per infusion  
3LEN dose is once daily  
4The actual MT-3724 doses for ‘interim’ cohorts will be recommended by the sponsor after consultation with 
the investigators.  
Duration: In Part 1 and Part 2, the treatment with MT-3724 and/or LEN in this study may be 
continued until death, disease progression, unacceptable toxicity, withdrawal of consent or 
another reason for withdrawal, or until study discontinuation. LEN dosing may be 
discontinued at investigator’s discretion, after approval by the medical monitor. Treatment 
with MT-3724 as a monotherapy may be permitted to continue with sponsor's approval. 
Number of Subjects:  
Approximately 64 subjects (i.e., 24 subjects in Part 1 and approximately 40 subjects in Part 
2), as well as the appropriate number of replacements (if needed), will be enrolled and treated 
in this study. The actual number will depend on the number of dose cohorts needed to 
identify the MTD of MT-3724 in combination with LEN in Part 1. 
 
 


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Inclusion/Exclusion criteria: 
Inclusion Criteria 
Subjects must meet ALL the following criteria to be eligible for the study. 
1. Be adequately informed about the study and fully consent to participation as 
demonstrated by signing the written informed consent form before any screening 
procedure. 
2. Be aged 18 years on the date of signing the informed consent form.  
3. Have relapsed or refractory CD20-positive B-cell NHL that, in the investigator’s opinion, 
could benefit from MT-3724+LEN therapy. Subjects must have proof of CD20-positive 
NHL, either by: 
a. Historical biopsies (obtained with diagnosis of relapsed or refractory disease), or 
b. Fresh biopsies. 
c. Bone marrow biopsy, excisional lymph node biopsy, or core biopsy of any involved 
organ are all acceptable methods; fine needle aspirates (FNA) are not acceptable. 
4. All subtypes of B-cell NHL may be considered for Part 1 (MT-3724 Dose Escalation). 
Only histologically documented DLBCL (including mixed histology) may be considered 
for Part 2 (MTD Expansion Cohort). 
5. Have received all available approved therapies for NHL, one of which should be anti-
CD20-based therapy.  
a. Subjects whose prior therapy includes chimeric antigen receptor T-cell (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 and exhibited a full 
hematological recovery (consistent with the existing inclusion criteria requirements 
and without PRBC or platelet transfusions within 2 weeks of C1D1) prior to relapse 
are eligible. 
c. Subjects who have been ineligible for approved therapies in the opinion of the 
investigator, or have refused such therapies, may be eligible at the investigator’s 
discretion, upon sponsor approval. 
6. Have bi-dimensionally measurable disease by Lugano Classification for NHL: 
a. >1.5 centimeter (cm) longest diameter (LDi) for lymph nodes 
b. >1.0 cm LDi for extra nodal disease 
7. Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 (Appendix 
6). 
8. Have adequate bone marrow function, as determined by all the following: 
a. Absolute neutrophil count (ANC) 1,000/mm3 and 
b. Platelet count ≥50,000 mm³  
c. Hemoglobin ≥8g/dL 
9. Have adequate kidney function, creatinine clearance (CLcr) to be ≥50mL/min either 
measured or assessed by using the Cockcroft-Gault formula (Appendix 5). 


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a. At the investigator’s discretion, the eGFR result ≤50 mL/min may be verified by 
measurement of CLcr based on the 24-hour urine collection. Subjects with CLcr 50 
mL/min will be eligible irrespective of the eGFR result. 
10. Have adequate hepatic function, as determined by: 
a. Total bilirubin <1.5 x upper limit normal (ULN), or direct bilirubin <1.5 x ULN for 
subjects with elevated total bilirubin secondary to Gilbert’s Syndrome, and 
b. Aspartate aminotransferase (AST) ≤3.0 x ULN (or ≤5 x ULN if liver involvement), 
and 
c. Alanine aminotransferase (ALT) ≤3.0 x ULN (or ≤5 x ULN if liver involvement).  
11. Have adequate coagulation, as determined by: 
a. International normalized ratio (INR) or prothrombin time (PT) 1.5 x ULN (unless on 
therapeutic anticoagulants) 
b. Activated partial thromboplastin time (aPTT) 1.5 x ULN (unless on therapeutic 
anticoagulants) 
12. Albumin ≥3.0 g/dL  
13. Women of reproductive potential must have a negative pregnancy test on 2 occasions 
during the screening period (within 10-14 days and within 24 hours before the start of 
treatment). Women not of reproductive potential are female subjects who are 
postmenopausal (>1 year since last menstrual cycle) or permanently sterilized (e.g., 
hysterectomy, bilateral salpingectomy). 
14. Males must agree to always use a latex or synthetic condom during any sexual contact 
with females of reproductive potential while taking LEN and for up to 4 weeks after 
discontinuing LEN, even if they have undergone a successful vasectomy. Male subjects 
taking LEN must not donate sperm. 
15. Subjects of reproductive potential and their partners must agree to either to abstain 
continuously from heterosexual intercourse or to use 2 methods of reliable birth control 
simultaneously to begin 4 weeks prior to initiating treatment with LEN until 28 days after 
the last dose of MT-3724 or LEN. The investigator or a designated associate should 
advise the subject how to achieve adequate contraception. The following birth control 
methods may be considered: one highly effective form of contraception – tubal ligation, 
intrauterine device (IUD), hormonal (birth control pills, injections, hormonal patches, 
vaginal rings, or implants), or partner’s vasectomy, and one additional effective 
contraceptive method – male latex or synthetic condom, diaphragm, or cervical cap. 
16. Subjects must have a life expectancy of >3 months from the start of treatment.  
 
Exclusion Criteria 
Subjects who meet any of the following criteria must be excluded from the study. 
Medical and surgical history 
1. History or current evidence of neoplastic disease that is histologically distinct from NHL, 
except cervical carcinoma in situ, superficial noninvasive bladder tumors, curatively 


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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.. 
2. 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. Neurological symptoms must be stable and no worse than Grade 2.
c.
Have evidence of stable brain or spinal disease on computer tomography (CT) or
magnetic resonance imaging (MRI) scan obtained within 4 weeks of signing the ICF
and compared with prior imaging results.
d. Do not require chronic steroid therapy (or, if applicable, have been stable on steroid
dose of no more than prednisone 20mg/day or equivalent by C1D1)
3. Current evidence of Graft versus Host Disease.
4. Current evidence of Common Terminology Criteria for Adverse Events (CTCAE) Grade
>1 toxicity before the start of treatment, except for hair loss and those Grade 2 toxicities
listed as permitted in other eligibility criteria.
5. Current evidence of incomplete recovery from surgery or radiotherapy before the start of
treatment, or planned surgery or radiotherapy at any time during the study until the EoT
Visit, except minor elective interventions deemed acceptable by the investigator.
6. 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.
7. 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. Any of the following within 3 months before the start of treatment with MT-3724:
pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade 2),
non-malignant pleural effusion (CTCAE Grade 2) or malignant pleural effusion
(CTCAE Grade 3).
e.
Congestive heart failure (New York Heart Association [NYHA] Class III or IV;
Appendix 7) at Screening or left ventricular ejection fraction (LVEF) <45%, assessed
by Echo or multiple-gated acquisition (MUGA) scan within 1 month before starting
study treatment (inclusion of subjects with LVEF between 40%-45% should be
discussed and approved by the sponsor). Echo or MUGA scan 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 potential cardiotoxic agents
since then.


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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 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. 
8. QT interval corrected according to Fridericia’s formula (QTcF) >480 ms, determined as 
the average from three QTcF values on the triplicate electrocardiogram (ECG) obtained 
at Screening. 
9. Current evidence of uncontrolled 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-cells counts ≥350 
cells/microliter 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 be 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. 
10. Women who are pregnant or breastfeeding. 
11. History or current evidence of hypersensitivity to any of the study drugs, or of current 
hypersensitivity requiring systemic steroids at doses >20 mg/day prednisone equivalent. 
12. History or current evidence of any other medical or psychiatric condition or addictive 
disorder, or laboratory abnormality that, in the opinion of the investigator, 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. 
Prior treatments 
13. Prior treatment with MT-3724. 
14. Received anti-CD20 monoclonal antibody (Mab) therapy within the following periods 
before the start of treatment. 
a. Rituximab (Rituxan®; RTX): 84 days; if a subject has received RTX within 37 weeks 
before the start of treatment, then a serum RTX level must be negative (<500 ng/mL) 
at screening. 
b. Obinutuzumab (Gazyva®): 184 days 
c. Ofatumumab (Arzerra®): 88 days 
15. Received therapy for NHL (except the anti-CD20 Mab therapies listed above and 
radioimmunoconjugates) within 4 weeks before the start of treatment.  
Radioimmunoconjugates are excluded within 12 weeks before the start of treatment. For 
small molecules (MW <0.9kDa), the washout shall be 2 weeks or 5 half-lives, whichever 
is longer (Macielag 2012). 


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16. Any investigational drug treatment from 4 weeks or 5 half-lives of the agent before the 
start of treatment, whichever is longer, until the EoT Visit. 
17. Received radiotherapy to tumor lesions that would be chosen as target lesions 
(measurable disease) within 4 weeks before the start of treatment, unless the lesion 
exhibited objective progression between the radiotherapy and Screening according to the 
Lugano Classification for NHL.  
a. Palliative radiotherapy to non-target lesions may be permitted at the investigator’s 
discretion after consultation with the medical monitor. See Section 5.10 for more 
information on the use of radiotherapy. 
18. Received any live vaccines within 4 weeks before the start of treatment, unless the 
investigator believes benefits outweigh risk, after approval with sponsor. 
19. 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 or prednisone equivalent, cyclosporine and tacrolimus. Please 
see Section 5.9 for more details and exceptions. 
Statistical Considerations:  
All subjects who receive at least one dose of MT-3724 or LEN will be included in the safety 
analysis set, the analysis of tumor response and PD analysis set. All safety and tolerability 
evaluations will be based on this analysis set. 
All subjects who received at least one dose of MT-3724 or LEN and have at least one post-
treatment PK and immunogenicity assessment will be included in the analysis set for the PK 
and immunogenicity analysis, respectively. The subjects who received only LEN will be 
excluded from the PK and immunogenicity analysis. 
Safety Analyses 
Adverse events (AEs), serious adverse events (SAEs) and medical history findings will be 
coded according to MedDRA dictionary and graded for severity using the CTCAE v5.0. The 
AEs and SAEs are treatment-emergent if they have started or worsened after the start of the 
first dose of MT-3724.  
Descriptive summary tables will present 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).  
Efficacy Analyses 
The investigator at each site will determine the objective tumor response (OR) at each time 
point based on the radiologist’s measurement of tumor lesions and using the five-point scale 
(5PS) per the Lugano Classification for Lymphoma (Cheson 2014) adjusted according to 
LYRIC (lymphoma response to immunomodulatory therapy criteria) (Cheson 2016) 
(Appendix 3). The best overall response rate (BORR) of all time points will be reported. 
Subjects who experience disease progression before undergoing the first tumor assessment 
will be added to the disease progression stratum. The best overall response rate (BORR) will 


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be descriptively summarized by the treatment group/cohort; the exact 95% confidence 
intervals will also be produced. 
The OR representing clinically significant clinical benefit in this study will comprise the 
Lugano Score 1, 2 or 3 or the complete response (CR) or partial response (PR). All subjects 
achieving clinically significant clinical benefit according to both response criteria will be 
included in the analysis of the duration of tumor response (DOR). DOR is defined as the time 
from the first documented CR or PR to the actual date of disease progression or death before 
progression. The DOR will be descriptively summarized by the treatment group/cohort; the 
exact 95% confidence intervals will also be produced. 
Pharmacokinetic Analyses 
MT-3724 serum concentration time data from all eligible subjects will be subjected to non-
compartmental analysis using the software package Phoenix WinNonlin (Certera, Princeton 
NJ). Pharmacokinetic parameters will be stratified by MT-3724 dose group and summary 
statistics will be generated.  In addition, the MT-3724 serum concentration time data may be 
evaluated using nonlinear mixed effects modeling using Nonmem (Icon PLC, Dublin 
Ireland). 
Immunogenicity Analyses 
Data for the ADA against MT-3724 will be obtained as titer for ADA samples confirmed as a 
positive result, while the data for the NAb against MT-3724 will be obtained as positive or 
negative.  
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 immunogenicity results will be listed by time point for each subject by 
treatment group/cohort.  Details of the immunogenicity analyses will be provided in a 
separate analysis plan for this study objective. 
Pharmacodynamic Analyses 
B-cell count and immunophenotype data by flow cytometry will be presented as absolute 
values and percentage change from pre- to post-dose time points. The summary statistics by 
time point and graphs of summary statistics over time will be presented by treatment group 
and overall. 
 


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Study Schema  
Figure 1: Study Design for MT-3724_NHL_003  
 
 
 
 
A) For Cohorts 1-3; B) Starting with Cohort 4. 
C1D1 = cycle 1 Day 1; EoT = end of treatment; LEN = lenalidomide; qd = once daily; STFU = Short-Term 
Follow-Up 
Long-Term Follow Up Visits should occur every 3 months (±14 days) for up to 18 months from the last dose of 
MT-3724. 
1See Study Schema for timing of specific activities. 
 
 


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Schedule of Assessments 
a. SCREENING
The schedule of assessments for the Screening period will be the same in Part 1 and Part 2. 
Unscheduled assessments may be performed at any time at the investigator’s discretion. 
Table 2: 
Schedule of Assessments for the Screening Period 
Assessments and Procedures 
Within 35 days of 
dosing on C1D1 
Informed consent 
X 
Demography 
X 
Height, body weight and BMI 
X 
Medical history1 
X 
NHL disease status (at initial diagnosis and after relapse)2 
X 
NHL disease status (current)3 
X 
Prior Medications4 
X 
Prior systemic NHL therapy (including SCT)5 
X 
Prior NHL radiotherapy6 
X 
Full physical examination 
X 
NYHA for subjects with heart failure 
X 
ECOG Performance status 
X 
Blood pressure, heart rate, and respiratory rate7,8 
X 
Body temperature (°F/C) 
X 
12-lead ECG (Triplicate)9 
X 
Radiological tumor assessment (PET-CT or CT/MRI) 10
X11 
LVEF12 
X 
CENTRAL LABORATORY 
  Serum rituximab level (if applicable)13 
X 
  Hematology 
X19 
  Chemistry (including eGFR14) 
X19 
  HbA1c 
X19 
  Coagulation 
X19 
  Thyroid function 
X19 
  Beta-2 Microglobulin 
X 
  MT-3724 Immunogenicity – (ADA/NAb) 
X 
B-cells and immunophenotype (flow cytometry)
X 
  Complement, Histamines, Cytokines, Immunoglobulins 
X 
  Viral Serology & Virology, CD4+ T cell count 15
X 
  Urinalysis (dipstick)16 
X19 
  Pregnancy (serum or urine)17 
X 
AE reporting (new or worsening illness)18 
X 
ADA = anti-drug antibodies; C1D1 = cycle 1, day 1; CT = computed tomography;  DLBCL = diffuse large 
B-cell lymphoma; ECG = electrocardiogram; ECOG = Eastern Cooperative Group of Oncology; eGFR =
estimated glomerular filtration rate; EoT = end of treatment;°F/C = degrees Fahrenheit or Celsius;
FDG =  fluordeoxyglucose; HbA1c = glycated hemoglobin; HBV = hepatitis B virus; HCV = hepatitis C virus;


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HIV = human immunodeficiency virus; LVEF = left ventricular ejection fraction; MRI = magnetic resonance 
imaging; NAb = neutralizing antibodies; NHL = non-Hodgkin lymphoma; NYHA = New York Heart 
Association; OTC = over the counter; PET = positron-emission tomography; RNA = ribonucleic acid; 
r/r = relapsed or refractory; RTX = rituximab; SCT = stem cell transplant; . 
1 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.  
2 NHL disease status (at initial diagnosis and after relapse) will include the type, histology, staging (Ann Arbor 
Classification-Cotswold Modification), grading (low, intermediate or high) 
3 NHL disease status (current) will include the same as for the status at initial diagnosis. Please refer to 
Section 6.1.4 for additional information to collect.  
4 Prior medication is any medication (prescription, OTC and supplements) used within 4 weeks prior to the start 
of treatment. Prior therapy for NHL should be captured separately from prior medications. 
5 Prior systemic therapy for NHL (including SCT) administered at any time before the start of treatment should 
be documented by itemizing each regimen (line of treatment) and the individual agents within each regimen. 
The date of last CD20-based therapy should also be documented in the CRF. 
6 Prior radiotherapy for NHL administered at any time before the start of treatment. 
7 Blood pressure (systolic and diastolic), heart rate and respiratory rate should be measured after 5-10 minutes of 
quiet rest in a sitting or semi-recumbent position. 
8 When ECG and blood pressure assessments are scheduled to occur at the same time point, then the ECG 
should be performed first and the blood pressure/heart rate measurement may begin immediately after ECG 
recording (without additional 5-10 minutes’ rest).  
9 Triplicate 12-lead ECG should be obtained as three 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 5-10 minutes 
before and during the procedure. 
10 A scan of all anatomic regions involved with the measurable disease by PET-CT (in subjects with FDG-avid 
tumor histology) or CT/MRI (in subjects with tumor histology of low or variable FDG avidity). CT of 
diagnostic quality should be collected for all subjects at baseline, whenever possible.  
11 Screening (baseline) radiological tumor assessments should be obtained as close to the start of treatment as 
possible, and within 28 days of C1D1.  
12Done at Screening (within 1 month before starting study treatment). 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.   
13 It is recommended to assess RTX serum concentration prior to performing other screening procedures.  
14 Calculated by the central laboratory using the Cockcroft-Gault equation and the serum creatinine from the 
corresponding chemistry panel. 
15 Serology for HIV, HBV and HCV may be omitted at the investigator’s discretion if seronegativity has been 
previously documented and there are no signs of the corresponding viral infection or suspected exposure.  
If applicable, serology should include anti-HIV1 and anti-HIV2 antibodies, HBsAg, anti-HBsAg and 
anti--HBcAg antibodies, HCV RNA quantitation and anti-HCV antibody as well as virology for HBV, HCV 
and HIV, when applicable. In addition, CD4+ T-cell counts should also be evaluated for subjects with HIV. 
16 Analysis of urine microsediment may be performed at the investigator’s discretion by the local lab. 
17 Two negative pregnancy tests must be obtained prior to initiating therapy. The first test should be performed 
within 10-14 days and the second test within 24 hours of the start of treatment. The pregnancy test performed 
within 24 hours of first dose is listed under C1D1.   
18 Adverse events that occur as a result of a study-related procedures during the screening period should be 
reported on the AE page. 
19 While screening procedures should be done within 35 days of C1D1, these should be within 28 days of C1D1 
 


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b. TREATMENT PERIOD 
The schedule of assessments for the treatment period will be the same in Part 1 and Part 2. Unscheduled assessments may be performed at 
any time at the investigator’s discretion. 
 
Table 3: 
Schedule of Assessments for Treatment Period 
 
Treatment Period (28-day cycles) 
EoT  
STFU  
D1 
D3 
D5 
D8 
D10 
D12 
D15 
D22 
D23 –28 
Study treatment: cycles 1-2 for Cohorts 1-3 
Premedication for MT-37241 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
MT-3724 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
LEN 
Once daily PO on D1 - D21 
 
 
 
Study treatment: cycles 1-2 for subsequent cohorts 
Premedication for MT-37241 
X 
 
X 
X 
 
X 
 
 
 
 
 
MT-3724 
X 
 
X 
X 
 
X 
 
 
 
 
 
LEN 
Once daily PO on D1 - D21 
 
 
 
Study treatment: cycles 3 and beyond (applicable for all cohorts) 
Premedication for MT-37241 
X 
 
 
X 
 
 
X 
X 
 
 
 
MT-3724 
X 
 
 
X 
 
 
X 
X 
 
 
 
LEN 
Once daily PO on D1 - D21 
 
 
 
Study procedures (applicable for all cycles)  
Vital signs 
X5 
 
X 
 
Abbreviated PE 
X2 
 
 
 
 
 
 
 
 
 
 
Full PE 
 
 
 
 
 
 
 
 
 
X 
 
ECOG performance status 
X2 
 
 
 
 
 
 
 
 
X 
 
Body weight 
X 
 
X 
 
Single 12-Lead ECG (single) 
X2 
 
 
 
 
 
 
 
 
X 
 
LVEF8 
 
 
 
 
 
 
 
 
 
X 
 
Radiological tumor assessment 
 
 
 
 
 
 
 
 
X 
X 
 
AE review 
X 


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Treatment Period (28-day cycles) 
EoT  
STFU  
D1 
D3 
D5 
D8 
D10 
D12 
D15 
D22 
D23 –28 
Concomitant medication review 
X 
Local lab analyses 
Urinalysis 
X2 
 
 
X2 
 
 
X2 
 
 
X 
 
Pregnancy 
X 
 
 
X9 
 
 
X 
X9 
 
X 
 
Central lab analyses 
Hematology 
X2 
 
 
X2 
 
 
X2 
 
 
X 
 
Chemistry (incl. eGFR) 
X2 
 
 
X2 
 
 
X2 
 
 
X 
 
Coagulation 
X2,6 
 
 
 
 
 
 
 
 
X 
 
 Thyroid function 
X2,6 
 
 
 
 
 
 
 
 
X 
 
HbA1c 
X2,6 
 
 
 
 
 
 
 
 
X 
 
Complement3 
X 
 
 
 
 
 
 
 
 
X 
 
Immunoglobulins3 
X 
 
 
 
 
 
 
 
 
X 
 
Histamine3 
X 
 
 
 
 
 
 
 
 
X 
 
Cytokines3 
X 
 
 
 
 
 
 
 
 
X 
 
B-cell count and immunophenotype 
X2 
 
 
 
 
X2,10 
X2,11 
 
 
X 
 
MT-3724 Immunogenicity 
X2 
 
 
 
 
 
 
 
 
X 
 
MT-3724 PK7 
X 
X 
 
 
 
X 
 
 
 
X 
 
Tumor tissue biopsy4 
 
 
 
 
 
 
 
 
 
X 
 
AE = adverse events; BP = blood pressure;  C = cycle; CT = computed tomography; CLS = capillary leak syndrome; CR = complete response; CRS = cytokine release 
syndrome; D = day in cycle; ECG = electrocardiogram; ECOG = Eastern Cooperative Group of Oncology; eGFR = estimated glomerular filtration rate; EoT = End of 
Treatment; 0F = degrees Fahrenheit; HbA1c = glycated hemoglobin; HR = heart rate; LEN = lenalidomide; LVEF = left ventricular ejection fraction;; MRI = magnetic 
resonance imaging; NYHA = New York Heart Association; PE = physical examination; PET = positron-emission tomography; PK  = pharmacokinetics; RR = 
respiratory rate; STFU = Short-Term Follow Up; TEAE = treatment-emergent AE. 
1Premedication must be administered within 60 minutes before the start of each MT-3724 infusion in cycle 1. Premedications are encouraged in all subsequent cycles. 
Refer to Section 5.1.4 for more details.  
2Up to 24 hours predose. 
3Immunoglobulins, cytokines, complement and histamine are to be collected D1 of each cycle: predose and 3 h (±10 min) after the start of MT-3724 infusion, and at 
EoT. In addition, if a subject experiences a Grade ≥2 IRR, or another Grade ≥2 hypersensitivity event, Grade ≥2 CRS or Grade ≥2 CLS, the investigator should obtain 
serum samples for 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.  


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4Optional FNA biopsy at EoT for subjects in Part 2, who had consented for this procedure, exhibit PD and have accessible peripheral lymph node(s).  
In the absence of PET/CT, a bone marrow biopsy should be assessed to confirm CR. 
5Collect Vital signs (BP, RR, HR, RR and body temperature) 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. 
6Predose on Day 1 of cycle 3 and each odd cycle thereafter 
7SeeTable 4, Pharmacokinetic sampling schedule 
8Only done at the EoT Visit if the subject has received MT-3724 in ≥3 cycles, irrespective of the number of MT-3724 doses in each cycle. 
9Only cycle 1  
10Only cycles 1 and 2 
11Cycles 3 and beyond 
 
Table 4 
Pharmacokinetic Sampling Schedule  
 
Time points relative to dosing 
Notes 
Predose 
During infusion 
After EOI 
Within 4h 
prior SOI 
10m before EOI 
5m 
0.5h 
1h 
2h 
3h 
4h 
Window 
 
 
±1m 
±5m 
±5m 
±5m 
±10m 
±10m 
C1D1 
X 
X 
X 
X 
X 
X 
X 
X 
If a 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 3 is delayed from D5 to D7, then the 
PK samples planned for D5 should be drawn on D7. 
Unscheduled assessments may be performed at any time at the 
investigator’s discretion. 
Samples for PK should be drawn from a different line than that 
used for MT-3724 administration. 
C1D12 
X 
X 
X 
X 
X 
X 
 
 
CXD1 
X 
X 
X 
 
 
 
 
 
C1D1 = cycle 1 Day 1; C1D12 = cycle 1 Day 12; CX = all cycles after cycle 1; EOI = end of infusion; PK = pharmacokinetics; SOI = start of infusion


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1 INTRODUCTION  
1.1 
Non-Hodgkin lymphoma  
CD20 is a B-cell specific differentiation antigen with four transmembrane domains 
(Kuijpers 2010). The CD20 protein plays a critical role in normal B-cell development and is 
expressed on 90% of B-cell NHL (Tedder 1988). 
According to National Cancer Institute (NCI), the number of new NHL cases in the United 
States from 2010-2014 was 19.5 per 100,000 residents per year, and the number of deaths 
from NHL was 5.9 per 100,000 residents per year (SEER). The NCI estimates that in 2017 
there would be 72,240 new NHL cases (4.3% of all cancer diagnoses) and 20,140 deaths 
(3.4% of all deaths) due to cancer. 
Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of NHL 
accounting for approximately 25 percent of NHL cases. In the United States, the incidence of 
DLBCL is approximately 7 cases per 100,000 persons per year (SEER) and varies by 
ethnicity, with Caucasians having higher rates than African Americans, Asians, or Native 
Americans.  
Diffuse large B-cell lymphoma is a heterogeneous group of tumors consisting of large, 
transformed B cells with prominent nucleoli and basophilic cytoplasm, a diffuse growth 
pattern and a high (>40%) proliferation fraction. The immunophenotype of DLBCL can be 
confirmed by immunohistochemistry (IHC) or flow cytometry, with tumor cells generally 
expressing pan B cell antigens (CD19, CD20, CD22, CD79a), as well as CD45.  
The prognosis for a newly diagnosed DLBCL patient depends on many host or tumor 
characteristics including tumor histology, tumor bulk burden and stage of tumor, 
participant’s age and performance status. Current first line treatment for DLBCL is 
chemotherapy (CHOP, EPOCH, ACVBP) in combination with RTX. While 50-70% of 
patients are cured by current standard of care (SOC) chemotherapy (mainly R-CHOP), 30-
40% of patients do not respond to R-CHOP or relapse following CR. Second line therapy 
with curative potential in patients with refractory or relapsed DLBCL (r/r DLBCL) is high 
dose chemotherapy (ICE, DHAP, GDP) + RTX followed by autologous SCT.  
Before the advent of CAR-T therapy, salvage chemotherapy followed by autologous SCT 
was the only potentially curative therapy for patients with r/r DLBCL (Philip 1995).  
However, many patients do not benefit from salvage therapy because they do not respond to 
chemotherapy, are unfit to undergo transplants or lack caregiver support (Crump 2014; 
Kondo 2016); a retrospective analysis (SCHOLR-1) found that only 26% of refractory 
patients responded to salvage therapy, and median OS was only 6.3 months (Crump 2017).   
Approved third line treatment options for DLBCL include CAR-T (Yescarta® axicabtagene 
ciloleucel/”axi-cel”; Tisagenlecleucel/CTL019 [Kymriah®]) and antibody drug conjugates 
such as polatuzumab (Polivy) in combination with RTX and bendamustine. Tafasitamab 
(MOR208) (formerly Xmab®5574) is an anti-CD19 mAb currently investigated in patients 


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with r/r DLBCL who are ineligible for autologous SCT. CAR-T trials show approximately 
50% ORR and approximately 30-40% durable response rate (Neelapu 2017; Locke 2019). 
However, CAR-T remains difficult to access for many patients, and expensive. 
1.1.1
Anti-CD20 Mab therapy for NHL 
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 two types based on cellular effects observed on binding to CD20-expressing
B-cells. Type I antibodies (RTX 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 (ADCC) but have minimal direct
antitumor effects. Type II antibodies (tositumomab and obinutuzumab) do not induce
redistribution of CD20, have minimal CDC, strong ADCC and increased direct antitumor
effects. Although fully humanized mAbs should be less immunogenic than the chimeric
RTX, none of the more recently approved anti-CD20 antibodies appear to be clinically more
effective against NHL in direct comparisons, perhaps because of patients’ baseline immune
status (Maloney 2012).
Of those participants with indolent NHL who relapse >6 months after initial response to 
RTX, only 40% will respond again when retreated with RTX (Davis 2000). The multicenter 
Phase 2 CORAL (Collaborative Trial in Relapsed Aggressive Lymphoma) study showed that 
participants who had previously responded to a RTX containing treatment regimen had a 
worse outcome following RTX containing salvage immunochemotherapy. 
(Gisselbrecht 2010). 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 (Smith 2003). 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 participants (Milenic 1991).  
1.2
MT-3724 
MT-3724 is a recombinant homodimeric fusion protein (theoretical molecular weight of 
~110 kiloDalton), where 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. MT-3724 specifically binds and kills CD20-expressing malignant 
B-cells (Rajagopalan 2013) via a novel mechanism of action of enzymatic and permanent
ribosome inactivation.


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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 patients with unmet medical need. 
1.2.1 
Clinical experience with MT-3724 
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 and 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 anti-tumor activity 
in heavily pre-treated participants with relapsed or refractory DLBCL who had low serum 
level of RTX before the start of treatment.  
Across all 3 studies as of 18 March 2020, CLS has been reported in 5 subjects: 2 subjects 
from NHL_001, 2 subjects from NHL_002, and 1 subject from NHL_003. All CLS events 
resolved, and the maximum severity for all events was Grade 2. 
Neutropenia, acute kidney injury, capillary leak syndrome (including peripheral edema, 
hypotension, weight gain and hypoalbuminemia), systemic inflammatory response/cytokine 
release syndrome, pneumonia, and viral infection were reported as AEs related to MT-3724 
and identified in the Investigator’s Brochure as potential risks for participants receiving 
MT-3724 therapy.  
Please refer to the latest version of the IB for comprehensive information available for 
MT-3724 to date.  
1.3 
Lenalidomide (Revlimid®, LEN) 
Lenalidomide is an analogue of thalidomide with immunomodulatory, antiangiogenic and 
antineoplastic activity in cancer. It was structurally designed to enhance the 
immunomodulatory and antitumor activity of its predecessor thalidomide and is much less 
neurotoxic and in general well tolerated (Anderson 2005). It is approved by the FDA and 
EMA for the treatment of multiple myeloma (MM), mantle cell lymphoma, transfusion-
dependent anemia due to myelodysplastic syndromes associated with deletion 5q 
abnormality, follicular lymphoma ([FL] in combination with RTX) and marginal zone 
lymphoma (in combination with RTX) 


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The most common adverse reactions are neutropenia, thrombocytopenia, anemia, pneumonia, 
rash and venous thromboembolic events (predominantly deep vein thrombosis and 
pulmonary embolism). Allergic reactions including hypersensitivity, angioedema, Stevens-
Johnson Syndrome, and toxic epidermal necrolysis were reported and fatal instances of 
tumor lysis syndrome have been reported during LEN treatment. Please see the reference 
prescribing information on LEN for additional details (Revlimid®).  
1.3.1 
Rituximab-lenalidomide (R2) in NHL 
Following demonstration of activity in MM and chronic lymphocytic leukemia (CLL), LEN 
has been shown to have considerable single agent clinical activity in NHL: overall response 
rates in subjects with aggressive NHL are 28-35% (7-12% complete response [CR]) 
(Witzig 2009). Lenalidomide plus RTX (R2) has been evaluated in multiple phase II trials 
with variable dosing schedules and in multiple NHL subtypes (Witzig 2015).  
In relapsed/refractory DLBCL or Grade 3 FL (n = 45), R2 showed a 33% ORR (22% CR), a 
median DOR of 10.2 months, median PFS of 3.7 months, and median OS of 10.7 months 
(Wang 2013). In an Italian single-center phase II trial, 23 older participants (≥65 years) with 
relapsed/refractory DLBCL received LEN 20mg/day, D1-21/28 with RTX 375mg/m2 on 
Days 1 and 21 for four cycles (Zinzani 2011). Participants with SD or better responses 
received LEN maintenance on the same dosing schedule for an additional eight cycles. At the 
end of induction, R2 produced a 35% ORR and 30% CR. Of 10 participants eligible for 
maintenance, 8 achieved CR and a median DOR of 32 months (Zinzani 2013). 
R2 was generally well tolerated, with hematologic Adverse Event (AE) rates consistent with 
those for single-agent therapy. The rates of Grade 3/4 hematologic toxicity with R2 varied 
across phase II studies, likely reflecting the different patient populations, NHL subtypes, and 
lines of therapy: neutropenia ranged from 30% to 66% and thrombocytopenia from 6% to 
23% (Wang 2012; Ruan 2014; Zinani 2011; Fowler 2014). Non-hematologic toxicity, mainly 
Grade 1/2, also varied across studies, mostly consisting of fatigue, myalgia, rash, and 
infusion related reactions.  
1.4 
Rationale for the study design 
The overall study design includes the dose escalation in the first part and the MTD expansion 
cohort in the second part. This design is typically used to assess the safety and efficacy of a 
novel anticancer agent when it is evaluated for the first time in combination with the SOC 
therapy.  
In Part 1, the dose decisions in sequential cohorts is based on the 3+3 design guided by the 
incidence of DLTs. This is the most commonly used method to identify the MTD of a novel 
anticancer agent in clinical trials. In Part 2, the MTD expansion cohort is also the most 
commonly used method to confirm the MTD and gain more data about the safety and 
efficacy of a novel anticancer agent in a larger number of subjects.  


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All efficacy and safety assessments, as well as the methods used to measure them, are 
standard practice in clinical studies and/or clinical practice. They are widely recognized as 
reliable, accurate, and relevant. 
Long-term follow up will be conducted to determine the impact of MT-3724 on tumor 
response which is part of the secondary objectives of this study.  
1.5 
Benefit/risk ratio 
Most patients with CD20-positive B-cell NHL will eventually become resistant to available 
anti-CD20 therapy. The clinical unmet need is underscored in disease areas like DLBCL 
where the contribution or clinical benefit of anti-CD20 antibody therapies may be diminished 
beyond the front-line treatment setting.  As a direct-kill agent targeted to CD20, where its 
mechanism of action is distinct from ADCC or CDC, 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 current study aims to address this unmet medical need by 
replacing RTX in the R2 regimen with MT-3724. 
In vitro MT-3724 was tested in combination with LEN to assess additive, synergistic or 
antagonistic cytotoxic effects on a CD20-positive cell line. A synergistic effect was observed 
in the combination of LEN and MT-3724 tested on CD20-positive cell line (IB). This in vitro 
data justifies further exploring the benefit-risk of combining MT-3724 with LEN for the 
treatment of NHL. 
In the Phase 1 first-in-human study in NHL subjects, MT-3724 monotherapy was well 
tolerated up to the highest dose planned for the current study (50µg/kg/dose), and the safety 
profile of MT-3724 has been similar to that of RTX. MT-3724 achieved objective tumor 
response at the lowest dose potentially used in the current study (5µg/kg/dose). 
The current study will enroll subjects with advanced progressive B-cell NHL who are not 
eligible for any further approved NHL therapy and/or SCT and/or refuse alternative approved 
therapies and/or are unlikely to achieve clinical benefit from any therapy of higher priority 
according to the investigator’s assessment. MT-3724 has a potential to impart clinical benefit 
when combined with the standard doses of LEN in this population. Thus, the benefit-risk 
ratio in the current study is acceptable.  
1.6 
Guidance to the investigator 
Preclinical studies and the ongoing first-in-human clinical trial MT-3724_NHL_001 have 
indicated several adverse events pertaining to subject safety.  These adverse events should be 
kept in mind prior to treatment of any subject in this study as well as the precautions as 
indicated in the Revlimid® (lenalidomide) reference prescribing information.  
The most common (≥20%) adverse events in the Parts 1 and 2 of the monotherapy study 
(% of subjects) were peripheral edema (63%), diarrhea, fatigue and myalgia (41% each), 
insomnia (30%), cough, pyrexia, and nausea (26% each), and headache, arthralgia, and 
hypotension (22.2% each).  


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DLTs in this trial were symptoms indicative of systemic inflammatory response/cytokine 
release syndrome (CRS) at 100µg/kg (2 subjects) and signs of CLS Grade 2 at 75µg/kg 
(2 subjects). All DLTs occurred in subjects who received a high total MT-3724 dose of 8500, 
10730, 7208, and 11572µg/infusion.  
Subjects should be closely monitored for signs of CLS/CRS.  
 This includes monitoring of vital signs (body temperature, heart rate, blood pressure, and 
respiration rate), body weight and clinical symptoms including headache, myalgia, 
muscle weakness, edema, neurological and gastro-intestinal symptoms, abdominal pain 
and fatigue.  
 Adequate monitoring of laboratory parameters of hematology, albumin, kidney, thyroid 
and liver function and cytokines in case of clinical symptoms indicative of CRS/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. 
In women, pregnancy has to be excluded before onset of treatment and highly effective 
contraceptive measures should be used in both men and women. 
2 OBJECTIVES AND ENDPOINTS 
2.1 
 Primary objectives and endpoints 
OBJECTIVES 
ENDPOINTS 
Determine the safety and tolerability 
(including the MTD) of MT-3724 in 
combination with lenalidomide in 
subjects with relapsed or refractory 
B-Cell NHL 
Incidence of AEs, including DLTs, inclusive of physical exam 
findings, laboratory abnormalities, and/or subject-reported 
symptoms 
   
2.2 
 Secondary objectives and endpoints 
OBJECTIVES 
ENDPOINTS 
Characterize the PK of MT-3724 in 
combination with LEN in subjects with 
relapsed or refractory B-Cell NHL 
PK parameters will be derived from MT-3724 serum 
concentration time data from all eligible subjects; parameters 
will be stratified by dose group. 
Assess the PD of MT-3724 in 
combination with LEN in subjects with 
relapsed or refractory B-Cell NHL 
B-cell count and immunophenotype data by flow cytometry  
Assess the immunogenicity of MT-3724 
in combination with LEN in subjects 
with relapsed or refractory B-Cell NHL 
ADA 
NAb 


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Assess the tumor response to MT-3724 
in combination with LEN in subjects 
with relapsed or refractory B-Cell NHL 
Objective response based on local assessment 
Duration of response 
PFS 
OS 
Exploratory 
 
 
 
 
 
 
PPD


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3 INVESTIGATIONAL PLAN  
3.1 
Description of overall study design and plan  
This is a multi-center, open-label, multiple-dose Phase 2a, dose-escalation study of MT-3724 
in combination with LEN in subjects with relapsed or refractory B-Cell NHL. Eligible 
subjects will be identified and treated through competitive enrollment at multiple global 
study centers. 
There are two sequential parts to this study. Part 1 is an evaluation of doses of MT-3724 in 
combination with LEN in subjects with relapsed or refractory B-cell NHL, to determine the 
MTD; and Part 2 is an expansion of the MTD cohort to evaluate safety, tolerability, and 
potential efficacy in up to 40 additional subjects with DLBCL treated with MT-3724 at the 
MTD in combination with LEN. For LTFU, subjects from both parts of the study will be 
followed for 18 months from the last dose of MT-3724, see study design in Figure 1. 
In both parts of the study, the subject’s participation in the study will consist of 4 periods: 
Screening, Treatment, STFU, and LTFU. 
3.2 
Screening 
Screening procedures will be performed within 35 days before the start of treatment on 
C1D1, with the exception of laboratory safety and radiographic assessments which are to be 
done within 28 days of C1D1. A signed written informed consent form (ICF) will be 
obtained before any screening procedure may begin. Screening assessments will be the same 
for Part 1 and Part 2. 
After the investigator determines that all eligibility criteria have been fulfilled (Section 4.1 
and Section 4.2.) the medical monitor will review the screening results and acknowledge that 
the subject may enter the treatment phase of the study. 
3.3 
Treatment  
Each subject may be treated only in one part of the study. The treatment procedures will be 
identical in Part 1 and Part 2.  
3.3.1 
MT-3724 
MT-3724 will be administered as an IV infusion over 1 hour (54 to 75 minutes). 
Treatment with MT-3724 will be administered for cycles of 28 days each until death, disease 
progression, unacceptable toxicity, withdrawal of consent or another reason for withdrawal, 
or until study discontinuation.   


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3.3.2 
Lenalidomide 
In both parts of the current study, subjects will self-administer LEN qd PO with or without 
food, around the same time each day, on the first 21 consecutive days (D1-D21) of each 
28-day cycle. LEN cannot be administered between D22-D28 in any cycle. 
3.4 
End of Treatment Visit and Short-Term Follow-Up phone call 
The EoT Visit will be performed at the end of the treatment period for each subject in Part 1 
and Part 2. The EoT Visit should occur at the time of discontinuation, as soon as possible 
after the last dose of MT-3724 or LEN (within 14 days of last dose) for all subjects, except 
those who withdrew consent and objected to further data collection, or were lost to follow up. 
The EoT Visit should be performed during the clinic visit. 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 (e.g., laboratory assessments, 
PE), are not considered deviations. 
The STFU phone call will take place at least 30 days (+7 days) after the last dose of 
MT-3724 or LEN (except for subjects who withdrew consent and objected to further data 
collection, or were lost to follow up). 
3.5 
Long-Term Follow Up Visit  
The LTFU Visits should occur every 3 months (±14 days) for up to 18 months from the last 
dose of MT-3724. Subjects who discontinue treatment for disease progression will be 
followed only for OS. Subjects who discontinue for reasons other than disease progression 
(e.g., toxicity) will be followed for PFS and OS. Subjects with CR, PR, or SD should also be 
followed for radiology assessment until progressive disease, death, or start of new anticancer 
treatment. The LTFU Visits will be performed via a telephone call to collect the information 
about death (if any), the NHL status (relapsed or not) and the start of any new therapy for 
NHL or any other investigational drug since the last study visit/phone call and radiology data 
should be obtained from medical records.  
3.6 
Part 1 (MT-3724 Dose Escalation) 
Twenty-four subjects will be enrolled in Part 1; the actual number will depend on the number 
of dose cohorts needed to identify the MTD of MT-3724 in combination with LEN. 
The first two subjects in each MT-3724 dose cohort will be enrolled in a staggered fashion, 
where at least 7 days elapse between D1 of the first and D1 of the second subject (the next 
subject(s) can be included at the same time as the second subject) to allow for adequate 
safety monitoring. Prospective subjects for all 3 treatment slots may be consented and 
screened in parallel with the treatment of previous subjects in the same cohort. 
If permitted by the safety results, the MT-3724 dose escalation is planned to proceed in 
sequential dose cohorts. Interim MT-3724 doses may be evaluated in additional cohorts at the 
sponsor’s discretion in consultation with the investigator(s). 


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In all dose cohorts, MT-3724 will be administered in combination with a starting dose of 
LEN 20mg. The LEN starting dose can be decreased per investigator’s discretion based on 
the known safety profile of LEN and subject’s status.  
The planned dose-escalation scheme is summarized in Table 5 
Table 5:  MT-3724 Dose Cohorts and Corresponding MT-3724 and LEN Dose Levels 
Planned MT-3724 Dose 
Cohorts 
Interim MT-3724 Dose 
Cohorts1 
Starting  
MT-3724 Dose 
(µg/kg/dose)2 
Starting 
LEN Dose 
(mg)3 
1 
10 TIW 
20 
-1 (optional)
≤ 54 TIW 
20 
2 
25 TIW 
20 
-2 (optional)
≤ 17.54 TIW 
20 
3 
20 TIW 
20 
-3 (optional)
154 TIW 
20 
4 
25 BIW 
20 
-4 (optional)
< 17.54 BIW 
20 
5 
50 BIW 
20 
-3 (optional)
≤ 37.54 BIW 
20 
BIW = twice weekly; LEN = lenalidomide; TIW = three times weekly 
1To be evaluated only if warranted by the safety results in the planned cohorts 
2The administered dose of MT-3724 will be capped at 6000g per infusion 
3The LEN dose is once daily 
4The actual MT-3724 doses for ‘interim’ cohorts will be recommended by the sponsor after consultation with 
the investigators and Medical Monitor. 
Before each dose escalation decision, the sponsor and all available investigators will review 
all available data in the current dose cohort. The listed stakeholders 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. The details of the safety review before dose escalation decisions 
are described in the study manual. 
Cohort management and dose escalation decisions (including the MTD) will be based on the 
incidence of TEAEs that fulfill the criteria for a DLT, as follows: 
a.
The first dose escalation decision in the current MT-3724 dose cohort will be made
after at least 3 subjects complete cycle 1 or experience a DLT. Up to 4 subjects may
be initially treated in each MT-3724 dose cohort; this aims to ensure that at least 3
evaluable subjects are available for the first dose escalation decision.
b. If none of the first 3 or 4 subjects in the current MT-3724 dose cohort experience a
DLT, then dose escalation may proceed to the next planned MT-3724 dose level.
c.
If 1 of the initial 3 or 4 subjects in the current MT-3724 dose cohort experiences a
DLT, then this cohort will be expanded to 6 subjects. Subjects for the expanded
current cohort may be enrolled simultaneously through competitive enrollment.


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d. If no more than 1 of 6 subjects in the expanded current MT-3724 dose cohort 
experiences a DLT, then dose escalation may proceed to the next planned MT-3724 
dose level.  
e. If a DLT occurs in ≥2 of initial 3 or 4 subjects in the current MT-3724 dose cohort, or 
in ≥2 of 6 subjects in the expanded current cohort, one of the following 2 steps may 
be undertaken at the sponsor’s discretion after consultation with the investigator(s): 
 If not previously done, up to 6 subjects may be treated at the planned MT-3724 
dose level immediately below the non-tolerable dose. 
 Alternatively, up to 4 subjects may be initially treated at the ‘interim’ MT-3724 
dose level and schedule between the non-tolerable dose level and the planned 
MT-3724 dose level immediately below the non-tolerable dose. The MT-3724 
doses proposed for the ‘interim’ cohorts are listed in Table 5; however the actual 
MT-3724 doses and schedule for ‘interim’ cohorts will be recommended by the 
sponsor after consultation with all investigators.  
f. If at least 4 subjects in the cohort have no DLTs, dose re-escalation can be attempted 
in up to 6 subjects at the original target dose of the previous cohort under the new 
schedule after consultation with the investigators and medical monitor.  
g. The same principles as listed above will apply to the cohort management and dose 
decisions in the ‘interim’ MT-3724 dose cohorts.  
Treatment in the expanded current MT-3724 dose cohort or the next cohort may start only 
after the dose decision in the current cohort has been made; however, prospective subjects 
may be consented and screened during the review of the safety data leading to the dose 
decision. 
3.6.1 
Subject evaluable for dose decisions 
Subjects in Part 1 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 DLT, have received at least 4 of 6 (67%) doses of MT-3724 (if 6 doses 
are planned) or 3 of 4 doses (75%) of MT-3724 (if 4 doses are planned) and at least 14 of 
21 (67%) doses of LEN.  
Subjects who are not evaluable for dose decisions will be replaced.  
3.6.2 
DLT Criteria  
A 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 of Part 1.  
a. If a TEAE that fulfills a DLT criterion is observed in cycle ≥2 of Part 1, 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). 


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Note: TEAEs related to LEN will not be declared a DLT unless they exceed in severity the 
worst grade described or are not mentioned in the reference prescribing information. If a 
Grade ≥3 TEAE related to LEN is more severe than the worst grade described in the 
reference prescribing information or has not been reported in the reference prescribing 
information, then the sponsor may declare this event a DLT 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.  
See Appendix 4 for the type and severity of TEAEs that may qualify as DLT. 
3.6.3 
MTD definition  
The highest MT-3724 dose that can be given in combination with LEN so that no more than 
1 of 6 subjects experiences a DLT will be declared as the MTD for MT-3724 in Part 1 of this 
study. At least 6 subjects must be treated at the MTD dose level of MT-3724 in combination 
with LEN and complete cycle 1 or experience a DLT.  
The MTD decision will be made by the sponsor after consultation with all investigator. 
3.6.4 
MTD communication plan 
The investigators and medical monitor will monitor the occurrence of TEAEs that could 
qualify as DLT and assess the number of subjects with DLT in real time during the conduct 
of Part 1. If the medical monitor becomes aware that the MTD may be declared in the current 
dose cohort (e.g. based on the occurrence of qualifying AE/serious adverse event [SAE] in 
≥2 subjects), then they will inform the investigators that recruitment should be suspended 
pending the safety review meeting. The details of cohort management and safety review 
during Part 1 will be described in the study manual.  
3.7 
Part 2 (MTD Expansion Cohort) 
The purpose of Part 2 is to confirm the safety and tolerability of MT-3724 in the MTD 
Expansion Cohort, where MT-3724 will be given at the MTD in combination with LEN. In 
addition, the PK, PD, immunogenicity and tumor response at the MTD of MT-3724 in 
combination with LEN will be more thoroughly evaluated in Part 2. 
Up to 40 subjects will be enrolled in Part 2. Subjects in Part 2 may be enrolled and treated 
simultaneously through competitive enrollment at multiple global study centers. 
Part 2 can start only after the MTD of MT-3724 in combination with LEN is declared in 
Part 1; however, the screening of prospective subjects for Part 2 may begin during the review 
of the safety data leading to the MTD decision.  
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4 STUDY POPULATION  
In addition to evaluating eligibility during the screening period, prior to first dose of 
MT-3724 on 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. 
4.1 
Inclusion criteria 
Subjects must meet ALL the following criteria to be eligible for the study. 
1. Be adequately informed about the study and fully consent to participation as 
demonstrated by signing the written ICF before any screening procedure. 
2. Be aged 18 years on the date of signing the informed consent form.  
3. Have relapsed or refractory CD20-positive B-cell NHL that, in the investigator’s opinion, 
could benefit from MT-3724+LEN therapy. Subjects must have proof of CD20-positive 
NHL, either by:  
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; FNA are not acceptable. 
4. All subtypes of B-cell NHL may be considered for Part 1 (MT-3724 Dose Escalation). 
Only histologically documented DLBCL (including mixed histology) may be considered 
for Part 2 (MTD Expansion Cohort). 
5. Have received all available approved therapies for NHL, one of which should be 
anti-CD20-based therapy. 
a. Subjects whose prior therapy includes chimeric antigen receptor t-cell (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 and exhibited a full 
hematological recovery (consistent with the existing inclusion criteria requirements 
and without PRBC or platelet transfusions within 2 weeks of C1D1) prior to relapse 
are eligible. 
c. Subjects who have been ineligible for approved therapies in the opinion of the 
investigator, or have refused such therapies, may be eligible at the investigator’s 
discretion, upon sponsor approval. 
6. Have bi-dimensionally measurable disease by Lugano Classification for NHL. 
a. >1.5 cm LDi for lymph nodes  
b. >1.0 cm LDi for extranodal disease  
7. Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 (Appendix 
6). 


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8. Have adequate bone marrow function, as determined by all the following: 
a. Absolute neutrophil count (ANC) 1,000/mm3 
b. Platelet count ≥50,000 mm³ 
c. Hemoglobin ≥8.0g/dL 
9. Have adequate kidney function, CLcr to be ≥50 mL/min either measured or estimated 
using the Cockcroft-Gault formula (Appendix 5). 
a. At the investigator’s discretion, the eGFR result 50 mL/min may be verified by 
measurement of CLcr based on the 24-hour urine collection. Subjects with CLcr 50 
mL/min will be eligible irrespective of the eGFR result. 
10. Have adequate hepatic function, as determined by: 
a. Total bilirubin <1.5 x ULN, or direct bilirubin <1.5 x ULN for subjects with elevated 
total bilirubin secondary to Gilbert’s Syndrome, and 
b. Aspartate aminotransferase ≤3.0 x ULN (or ≤5 x ULN if liver involvement), and 
c. Alanine aminotransferase ≤3.0 x ULN (or ≤5 x ULN if liver involvement).  
11. Have adequate coagulation, as determined by: 
a. International normalized ratio or PT 1.5 x ULN (unless on therapeutic 
anticoagulants) 
b. Activated partial thromoplastin time 1.5 x ULN (unless on therapeutic 
anticoagulants) 
12. Albumin ≥3.0 g/dL.  
13. Women of reproductive potential must have a negative pregnancy test on 2 occasions 
during the screening period (within 10-14 days and within 24 hours before the start of 
treatment). Women not of reproductive potential are female subjects who are 
postmenopausal (>1 year since last menstrual cycle) or permanently sterilized (e.g., 
hysterectomy, bilateral salpingectomy). 
14. Males must agree to always use a latex or synthetic condom during any sexual contact 
with females of reproductive potential while taking LEN and for up to 4 weeks after 
discontinuing LEN, even if they have undergone a successful vasectomy. Male subjects 
taking LEN must not donate sperm. 
15. Subjects of reproductive potential and their partners must agree to either abstain 
continuously from heterosexual intercourse or to use 2 methods of reliable birth control 
simultaneously to begin 4 weeks prior to initiating treatment with LEN until 28 days after 
the last dose of MT-3724 or LEN. The investigator or a designated associate should 
advise the subject how to achieve adequate contraception. The following birth control 
methods may be considered: one highly effective form of contraception – tubal ligation, 
IUD, hormonal (birth control pills, injections, hormonal patches, vaginal rings, or 
implants), or partner’s vasectomy, and one additional effective contraceptive method – 
male latex or synthetic condom, diaphragm, or cervical cap. 
16. Subjects must have life expectancy of >3 months from the start of treatment. 
 
 


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4.2 
Exclusion criteria 
Subjects who meet any of the following criteria must be excluded from the study. 
Medical and surgical history 
1. 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. 
2. 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 of signing the ICF and compared with prior imaging results 
d. Do not require chronic steroid therapy (or, if applicable, have been stable on steroid 
dose of no more than prednisone 20mg/day or equivalent by C1D1) 
3. Current evidence of Graft versus Host Disease.  
4. Current evidence of CTCAE Grade >1 toxicity (due to prior cancer therapy) before the 
start of treatment, except for hair loss and those Grade 2 toxicities listed as permitted in 
other eligibility criteria. 
5. Current evidence of incomplete recovery from surgery or radiotherapy before the start of 
treatment, or planned surgery or radiotherapy at any time until the EoT Visit, except 
minor elective interventions deemed acceptable by the investigator.  
6. 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. 
7. 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. Any of the following within 3 months before the start of treatment with MT-3724: 
pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade2), 
non-malignant pleural effusion (CTCAE Grade 2) or malignant pleural effusion 
(CTCAE Grade 3).  
e. Congestive heart failure (NYHA Class III or IV; Appendix 7) at Screening or LVEF 
<45%, assessed by Echo or multiple-gated acquisition (MUGA) scan within 1 month 
before starting study treatment (inclusion of subjects with LVEF between 40%-45% 


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should be discussed and approved by the sponsor). Echo or MUGA scan 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 potential 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 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. 
8. QTcF >480 ms, determined as the average from three QTcF values on the triplicate ECG 
obtained at screening. 
9. 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: 
a. Subjects with HIV and an undetectable viral load and CD4+ T-cells counts ≥350 
cells/microliter 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 be 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 limit of detection. Concurrent antiviral HCV treatment and have 
an undetectable viral load. 
10. Women who are pregnant or breastfeeding. 
11. History or current evidence of hypersensitivity to any of the study drugs, or of current 
hypersensitivity requiring systemic steroids at doses >20 mg/day prednisone equivalent 
12. History or current evidence of any other medical or psychiatric condition or addictive 
disorder, or laboratory abnormality that, in the opinion of the investigator, 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. 
Prior treatments 
13. Prior treatment with MT-3724. 
14. Received anti-CD20 mAb therapy within the following periods before the start of 
treatment:  
a. Rituximab (Rituxan®): 84 days; if a subject had received RTX within 37 weeks 
before the start of treatment, then a serum RTX level must be negative (<500 ng/mL) 
at screening. 
b. Obinutuzumab (Gazyva®): 184 days 
c. Ofatumumab (Arzerra®): 88 days 


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15. Received therapy for NHL (except the anti-CD20 mAb therapies and 
radioimmunoconjugates) within 4 weeks before the start of treatment. 
Radioimmunoconjugates are excluded within 12 weeks before the start of treatment. For 
small molecules (MW <0.9kDa), the washout shall be 2 weeks or 5 half-lives, whichever 
is longer (Macielag 2012). 
16. Any investigational drug treatment from 4 weeks or 5 half-lives of the agent before the 
start of treatment, whichever is longer, until the EoT Visit. 
17. Received radiotherapy to tumor lesions that would be chosen as target lesions 
(measurable disease) within 4 weeks before the start of treatment, unless the lesion 
exhibited objective progression between the radiotherapy and screening according to the 
Lugano Classification for NHL.  
a. Palliative radiotherapy to non-target lesions may be permitted at the investigator’s 
discretion after consultation with the medical monitor. See Section 5.10 for more 
information on the use of radiotherapy. 
18. Received any live vaccines within 4 weeks before the start of treatment, unless the 
investigator believes benefits outweigh risk, after approval with medical monitor.  
19. 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 or prednisone equivalent, cyclosporine and tacrolimus. Please 
see Section 5.9 for more details and exceptions. 
 
4.3 
Subject withdrawal, replacement and study discontinuation 
4.3.1 
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 from the treatment period if the -human chorionic 
gonadotropin (-HCG) pregnancy test indicates that they are pregnant at any time between 
the consent and the EoT Visit.  
The subject may be withdrawn from the treatment period 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 
Discontinuation of the study drug(s) for documented disease progression is considered study 
completion and not as premature withdrawal from the study. 


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All subjects who permanently discontinue study treatment for any reason should have an EoT 
Visit performed and an STFU phone call as described in the Schedule of Assessments before 
discontinuation.  
The reason for any discontinuation from the study will be documented in the subject’s 
medical record and recorded on the appropriate case report form (CRF). 
4.3.2 
Subject replacement  
In both parts of the study, the sponsor will determine if a subject should be replaced. All 
subject data collected will be analyzed in the Safety Analysis set. The additional subject(s) 
included to replace non-evaluable subjects will be given new unique subject IDs. 
Part 1 (MT-3724 Dose Escalation) 
Subjects who discontinue in cycle 1 and are not evaluable for dose decisions (Section 3.6.1) 
must be replaced in the current dose cohort to ensure that a sufficient number of subjects are 
available for dose decisions. Non-evaluable subjects may remain on treatment if supported 
by the investigator’s assessment of the benefit-risk ratio after consultation with medical 
monitor. 
Subjects who discontinue for any reason after cycle 1 will not be replaced. 
Part 2 (MTD Expansion Cohort) 
Subjects in Part 2 of the study who have insufficient safety, PD, PK or immunogenicity data 
in cycle 1 may be replaced at the sponsor’s discretion, unless they experienced a TEAE 
leading to treatment modification.  
4.3.3 
Study discontinuation 
The sponsor has the right to discontinue the study for any reason. 
5 TREATMENTS 
As a standard precaution for all study drugs, subjects must be treated and observed in an area 
with equipment/personnel for resuscitation and emergency treatments or have access to 
emergency facilities through an emergency call. Adequate management and treatment of 
infusion-related reaction, anaphylactic reaction or other hypersensitivity events according to 
institutional guidelines must always be assured during the treatment period. 
5.1 
MT-3724 
MT-3724 is the investigational medicinal product (IMP) in this study.   
MT-3724 is a recombinant fusion protein consisting of an scFv with affinity for human CD20 
cell surface protein, fused to the enzymatically active A1 subunit of Shiga-like Toxin 1.   


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5.1.1 
MT-3724 drug product 
MT-3724 will be supplied as a sterile aqueous solution (pH 5.5) in a 2 ml vial containing 
2.0ml of MT-3724 (0.5mg/ml) in a formulation buffer comprised of Sorbitol (200mM), 
Sodium Citrate (20mM) and Polysorbate-20 (0.1%). Vials are shipped frozen. Each vial will 
be labeled with the drug name, lot number, storage conditions, and US FDA-required 
Investigational Product statement.  
MT-3724 vials must be stored in a secure facility at -20 (-10 to -25) °C 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 5% dextrose in 
water or normal saline for IV administration. All doses should be administered over 1 hour 
through an IV line (54 – 75 minutes). See Pharmacy Manual for detailed instructions and 
worksheets regarding study drug preparation and administration. 
Investigational medicinal 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 IMP 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 IMP. Records of the receipt and 
disposition of IMP must be maintained in the trial master file at the site. Records and drug 
supplies must be available for inspection by the study monitor. 
5.1.2 
MT-3724 dose selection 
The dose of MT-3724 will be calculated based on the subject’s 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 the 
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 will be capped at 6000 µg per infusion in all 
subjects in both parts of the study. 
The guidance for treatment modification (dose interruption/delay, dose reduction or 
treatment discontinuation) is presented in Section 5.4. 
Part 1 (MT-3724 dose escalation) 
The planned starting dose of MT-3724 in Part 1 will depend on the cohort. Please see Table 5 
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If MT-3724 is not tolerated by any subject in any planned cohort, then additional MT-3724 
doses may be evaluated in the interim cohort at the sponsor’s discretion in consultation with 
the investigator(s).   
The actual MT-3724 doses in the interim cohorts will be recommended by the sponsor after 
consultation with the investigator(s). The actual MT-3724 dose in the interim Cohort -1 
should not be <5µg/kg/dose, as this was the lowest dose evaluated in the clinic so far.   
Part 2 (MTD Expansion Cohort) 
The starting dose of MT-3724 in Part 2 will be the MTD of MT-3724 from Part 1. 
5.1.3 
MT-3724 dosing schedule 
MT-3724 will be administered as an IV infusion over 1 hour (window of 54-75 minutes).  
Cohort 1-3 
For subjects enrolled in Cohorts 1-3, in cycles 1 and 2, MT-3724 infusion should be 
administered on Day 1, 3, 5, 8, 10 and 12 (±1) of each 28-day cycle.  
 
Cohorts ≥4 
In subsequent cohorts in cycles 1 and 2, MT-3724 infusion should be administered on Days 
1, 5, 8 and 12 (±1) of each 28-day cycle. Different dosing days up to D21 may be selected at 
investigator’s discretion after consultation with the medical monitor.  
All Cohorts 
Starting with cycle 3, MT-3724 will be administered weekly (Day 1, 8, 15 and 22) of each 
28-day cycle. Different dosing days within ±2 days from Day 1, 8, 15 and 22 may be selected 
at investigator’s discretion. 
Time windows for days of MT-3724 dosing 
Cycles 1-2 
Any of the scheduled MT-3724 doses may be administered on different dosing days at 
investigator’s discretion up to D21.  
MT-3724 doses must be administered at least 48 hours apart.  
Cycles 3 and beyond 
Any of the scheduled weekly MT-3724 doses may be administered within ±2 days at 
investigator’s discretion.  
For all cycles 
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. 
 


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5.1.4 
Premedication before MT-3724 infusion 
One premedication agent from each of the following 3 therapeutic classes must be given 
within 60 minutes before the start of each MT-3724 infusion in cycle 1 in both parts of the 
study:  
 Oral anti-pyretic agent (325 – 1000mg acetaminophen or equivalent) 
 Intravenous H1 histamine receptor antagonist (50 – 100mg diphenhydramine or 
equivalent) 
 Intravenous corticosteroid agent with a shorter biological half-life (125 – 1000mg 
methylprednisolone or equivalent) 
 
The specific drugs in each class should be selected at investigator’s discretion or according to 
the institutional guideline. Cases where a subject has a contraindicating medical condition 
that precludes pretreatment with any of the categories above should be discussed with the 
sponsor. Although continued pre-medication is recommended during all cycles, after cycle 1, 
the investigator may adjust the dosage and/or avoid using certain premedication agents 
during the treatment, if supported by the investigator’s assessment of the risk from infusion-
related reaction, anaphylaxis or other hypersensitivity events.  
5.2 
Lenalidomide (Revlimid®, LEN) 
LEN is an analogue of thalidomide with immunomodulatory, antiangiogenic and 
antineoplastic activity in cancer. 
LEN is available as 2.5-20mg oral capsules. It is available only through a restricted REMS 
program (REVLIMID REMS®). 
This medicinal product does not require any special storage conditions. 
See Section 5.4.2 for guidance about the LEN treatment modification. In addition, the 
modification of LEN treatment in this study should be guided by the reference prescribing 
information, as interpreted by the investigator. 
5.2.1 
Lenalidomide dose selection 
The starting dose of LEN in each cohort in Part 1 and Part 2 will be 20mg qd. The LEN 
starting dose can be decreased per investigator’s discretion based on the known safety profile 
of LEN and subject’s status. For Parts 1 and 2, starting with cycle 2 (after completion of the 
DLT assessment period for Part 1), the investigator may increase the LEN dose to 25mg qd, 
if clinically indicated, with sponsor approval. 
5.2.2 
Lenalidomide dosing schedule 
In both parts of the current study, subjects will self-administer LEN qd PO with or without 
food on the first 21 consecutive days (D1-D21) of each 28-day cycle. Subjects will be 


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directed to self-administer LEN at about the same time every day and record doses taken in 
subject diary.  
Treatment with LEN in the current study will continue until death, disease progression, 
unacceptable toxicity, withdrawal of consent or another reason for withdrawal, see 
Section 4.3. If pregnancy occurs during treatment, immediately discontinue the drug.  
LEN dosing may be discontinued at investigator’s discretion, after approval by the medical 
monitor. Treatment with MT-3724 as a monotherapy may be permitted to continue with 
sponsor's approval. 
 
5.3 
Intra-subject dose escalation 
Intra-subject escalation of MT-3724 dose is not allowed in either part of the study.  
If the LEN dose has been reduced due to a TEAE, the intra-subject escalation of LEN dose is 
permitted if continued treatment is supported by the investigator’s assessment of the benefit-
risk ratio after consultation with the medical monitor. In such cases, LEN dose may be 
increased only up to the level before the most recent dose reduction. Starting with cycle 2 
(after the DLT assessment period for subjects in Part 1), the dose of LEN may be increased to 
25mg qd, as described in Section 5.2.1. 
5.4 
Treatment modification 
Treatment modification due to a TEAE (dose interruption/delay, dose reduction, or 
permanent discontinuation) could be done in an individual subject at the investigator’s 
discretion after consultation with the medical monitor. By convention in this study, the term 
‘dose interruption’ will be used for the interventions during the IV infusion, and the term 
‘dose delay’ will be used for the changes in the dosing schedule (e.g., date of the next dose) 
for both MT-3724 and LEN. 
The severity of TEAEs requiring treatment modification will be graded according to the 
CTCAE v.5.0. 
5.4.1 
MT-3724 treatment modification 
Any of the following TEAEs in any treatment cycle may trigger MT-3724 treatment 
modification, if deemed at least possibly related to MT-3724 by the investigator after 
consultation with the medical monitor. 
 Any TEAE irrespective of the time of onset, that would otherwise fulfill the DLT criteria 
(Appendix 4) 
 Grade ≥2 IRR, or another Grade ≥2 hypersensitivity reaction 
 Any other toxicity related to MT-3724, irrespective of the type or severity or time of 
onset, that warrants dose modification in the opinion of the investigator after consultation 
with the medical monitor. This may be Grade 1 or Grade 2 toxicity that notably limits the 


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activities of daily life (e.g. long-lasting fatigue or anorexia), making a dose reduction 
necessary to ensure the subject’s compliance. 
The following actions are recommended after any of the above TEAEs occur. 
 The investigator should notify the medical monitor about the TEAE within 24 hours of 
the awareness. 
 The investigator should monitor the subject and if necessary, perform diagnostic 
procedures and therapeutic interventions. 
 If a subject experiences a TEAE in cycle 1 that is related to MT-3724 and qualifies as a 
DLT, then the MT-3724 treatment should be discontinued, except if continued treatment 
is supported by the investigator’s assessment of the benefit-risk ratio. In this case, the 
MT-3724 re-treatment should be delayed until the TEAE resolves to Grade ≤1. Further, 
the MT-3724 re-treatment should start at a ≥25% reduced MT-3724 dose. 
 If a subject experienced a Grade ≥2 IRR, or another Grade ≥2 hypersensitivity event, 
Grade ≥2 CRS or Grade ≥2 CLS, the investigator should obtain serum samples for 
cytokines, complement and histamine as soon as possible after the TEAE onset. These 
samples should be marked “STAT” and shipped immediately to the laboratory. 
 MT-3724 dose may be reduced by ≥25% at the investigator’s discretion after 
consultation with the medical monitor. The number of dose reductions per subject is not 
limited, except that the reduced dose cannot be <5 µg/kg/dose (this was 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 should be permanently discontinued if a TEAE that previously led to 
dose interruption/delay or reduction didn’t resolve to Grade 1 within 4 weeks after 
treatment modification, except if continued treatment is supported by the investigator’s 
assessment of the benefit-risk ratio after consultation with the medical monitor.  
5.4.2 
Lenalidomide treatment modification 
Any of the following TEAEs in any treatment cycle may trigger LEN treatment 
modification, if deemed at least possibly related to LEN by the investigator. 
 Any TEAE that would fulfill the DLT criteria irrespective of the time of onset 
 Grade ≥2 venous or arterial thrombosis or thromboembolic event 
o LEN treatment should be temporarily discontinued immediately after the onset of the 
thrombosis or thromboembolic event to assess the causality and clinical risk  
o If the thrombosis is confirmed as at least possibly related to LEN, the LEN treatment 
may be continued at the investigator‘s discretion after consultation with the medical 
monitor after the thrombosis resolves to Grade ≤1. If the treatment is continued, the 
LEN dose may remain the same dose or be reduced by ≥5 mg qd at the investigator’s 
discretion. 


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o If the thromboembolic event re-occurs after the LEN continuation and is confirmed as 
at least possibly related to LEN, then the treatment should be permanently 
discontinued,  
 Grade ≥2 skin reactions: skin rash (acneiform or maculo-papular); angioedema or other 
types of hypersensitivity manifest on the skin, Stevens-Johnson Syndrome, toxic 
epidermal necrolysis; any other skin reaction that warrants treatment modification at the 
investigator’s discretion  
o LEN treatment should be temporarily discontinued immediately after the onset of the 
skin reactions to assess the causality and clinical risk 
o If the skin reaction is confirmed as at least possibly related to LEN 
 If Grade 2 (except for Grade 2 non-blistering rash), hold LEN until toxicity 
resolves to Grade ≤1 and reduce LEN dose by ≥5mg qd.  
 If Grade 2 non-blistering rash, hold until toxicity resolves to ≤ Grade 1 and 
continue at same LEN dose or reduce LEN dose by ≥5mg qd  
 If Grade >3, the LEN treatment should be permanently discontinued 
 
In addition, the modification of LEN treatment in this study will be guided by the reference 
prescribing information (REVLIMID®), as interpreted by the investigator after consultation 
with the medical monitor. 
5.4.3 
Treatment modification due to IRR or other hypersensitivity event 
This guidance is applicable to any among the 2 study drugs that, in the investigator’s opinion, 
is at least possibly related to IRR or other hypersensitivity event. 
If a subject experienced a Grade 2 IRR or other Grade 2 hypersensitivity reaction, the 
infusion must be immediately interrupted. The following additional actions are recommended 
in case of a Grade ≥2 IRR: 
 In case of a Grade 2 IRR or other Grade 2 hypersensitivity reaction 
o Continued treatment with the study drug causally related to IRR may be allowed at 
the investigator’s discretion. 
o If continued treatment is indicated, then  
 it must occur after the appropriate delay (i.e., resolution of symptoms)  
 Upon restarting infusion (and for subsequent doses), if study drug is causally 
related to IRR, the infusion rate must be reduced by 50% (2-hour duration) 
preceded by appropriate anti-allergic prophylaxis (see premedication, 
Section 5.1.4 or the institutional guideline)  
 In case of a CTCAE Grade 3 IRR or other Grade 3 hypersensitivity reaction, the study 
drug causally related to IRR should be permanently discontinued. 


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5.4.4
Treatment modification for MT-3724 and LEN due to neutropenia or 
thrombocytopenia 
This guidance is applicable to any neutropenia and/or thrombocytopenia that, in the 
investigator’s opinion, is at least possibly related to any of the study drugs. 
If treatment modification of MT-3724 or LEN is warranted due to neutropenia or 
thrombocytopenia, and the continuation of treatment is appropriate at investigator’s 
discretion after consultation with the medical monitor, then the dose of MT-3724 or LEN 
will be adjusted as described in Table 6. 
Table 6: 
Dose Adjustments of MT-3724 or LEN in Response to Neutrophil and 
Platelet Nadir Counts 
Absolute neutrophil 
nadir count 
Platelet nadir count 
MT-3724 and/or LEN 
dose 
modification 1 
500/μl or 500/μl for
5days
and 
25,000/μl
No change 
500/μl for 5 days
and/or 
25,000 for 7 days with
or without active bleeding,
OR 50,000/μl for 7 days
with clinically significant
bleeding 2 
Decrease by ≥25% 
or according to reference 
prescribing information 
Febrile neutropenia 3 
and/or 
25,000/μl for 7 days
with or without active
bleeding, OR 50,000/μl 
for 7 days with clinically 
significant bleeding 2 
Decrease by ≥25% 
or according to reference 
prescribing information 
LEN = lenalidomide 
1MT-3724 dose reduction translates to a reduction by ≥25%, and LEN dose reduction by 1 level translates 
to a reduction by ≥5 mg once daily; the actual amounts for either agent will be determined by the 
investigator after consultation with the medical monitor.  
2Clinically significant bleeding is that which requires platelet transfusion. 
3Febrile neutropenia is defined as absolute neutrophil count 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 one 
hour).  
Repeated dose reductions are permitted if continued treatment is supported by the investigator’s 
assessment of the benefit-risk ratio, but not below 5 µg/kg/dose for MT-3724. 
5.4.5
Treatment modification for MT-3724 and LEN due to increased AST, ALT 
and/or bilirubin levels 
This guidance is applicable to increased serum AST, ALT and/or bilirubin levels that, in the 
investigator’s opinion, is at least possibly related to any of the study drugs. 
If treatment modification of MT-3724 or LEN is warranted due to increased AST, ALT 
and/or bilirubin levels, and the continuation of treatment is appropriate at investigator’s 


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discretion after consultation with the medical monitor, then the dose of MT-3724 or LEN 
will be adjusted as described in Table 7. 
Table 7 
Dose Adjustments in Response to the Worst Increase in Aspartate 
Aminotransferase, Alanine Aminotransferase, or Bilirubin 
Worst AST and/or ALT increase  
Worst bilirubin increase 
MT-3724 and/or LEN dose 
modification  
≤5 x ULN (isolated) 
or 
≤1.5 x ULN (isolated) 

No change in study drug
Monitor subject
5 x ULN – 8.0 x ULN (for subjects
enrolled with AST/ALT <3 x ULN)
and/or 
>1.5 x ULN – 5.0 x ULN

Temporarily or permanently
(see next row) discontinue
study drug

Monitor subject

Continue at dose reduced by
1 dose level after abnormal
values resolve to Grade ≤1 or
baseline1
AST or ALT >8.0 x ULN for any 
period of time (for any subject) 
or AST or ALT >5x ULN for more 
than 2 weeks (for subjects enrolled 
with AST/ALT 3-5 x ULN) 

Permanently discontinue
study drug
>3.0 x ULN (without findings of
cholestasis defined as serum alkaline
phosphatase <2×ULN)
and 
> 2.0 x ULN or INR >1.5

Permanently discontinue
study drug
>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
study drug
>5.0 x ULN

Permanently discontinue
study drug
ALT = alanine aminotransferase; AST = aspartate aminotransferase; LEN = lenalidomide; ULN = upper limit 
normal 
These are recommendations in situations where a possible relatedness of liver enzyme elevations to study drug 
is assumed. Further these being recommendations that cannot consider all clinical circumstances, the 
investigator is encouraged to contact the medical monitor to discuss alternative course of action. 
1MT-3724 dose reduction by 1 dose level translates to an approximate reduction by ≥25%-33%, and LEN dose 
reduction translates to a reduction by ≥5 mg once daily; the actual amounts for either agent will be determined 
by the investigator after consultation with the medical monitor.  
Repeated dose reductions are permitted if continued treatment is supported by the investigator’s assessment of 
the benefit-risk ratio, but not below 5 µg/kg/dose for MT-3724. 
5.5
Treatment assignment 
This is an open label, non-randomized study. Subjects will be assigned to MT-3724 treatment 
either in one of the sequential dose cohorts (Part 1) or in the MTD expansion cohort (Part 2). 
MT-3724 treatment assignment may occur only after the investigator declares the subject 


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eligible and the medical monitor reviews the screening results and acknowledge the 
investigator’s eligibility decision.  
All subjects in all cohorts will receive the same standard dose of LEN (Section 5.2). 
Assignment of screening slots and treatment slots will be done on the basis of competitive 
enrollment (i.e. “first-come first-served”). The details will be described in the standalone 
Cohort Management Plan. 
5.6 
Blinding 
Not applicable; this is an open-label study. 
5.7 
Treatment compliance 
MT-3724  
Because MT-3724 is administered IV, treatment compliance will be monitored through the 
eCRF and source documents (subject 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. 
Lenalidomide 
LEN tablets will be dispensed to subjects to be taken on an out-patient basis. LEN may also 
be administered to subjects during clinic visits. During the study the subjects will be 
instructed to document intake of LEN tablets in a diary by entering the date and time of 
dosing as well as the administered dose. Subjects will be instructed to return all packages of 
used and unused LEN to the study unit. Returned LEN tablets will be counted by the study 
center to evaluate treatment compliance. The data from the subject diary will be transferred 
into the eCRF to capture any dose delays and modifications. Any discrepancies between 
actual and expected amount of returned study medication must be discussed with the subject 
at the time of the visit and any explanation must be documented in the source records. 
5.8 
Treatment duration 
In Part 1 and Part 2, the treatment with MT-3724 and/or LEN in this study may be continued 
until death, progressive disease, AE requiring discontinuation or withdrawal of consent, any 
other reason for study discontinuation, or until study discontinuation. Thereafter, the subject 
will undergo the EoT Visit and STFU phone call. 
5.9 
Prohibited treatment 
The following treatments are not permitted during the study: 
 All systemic treatments for NHL.  
 Radiotherapy to tumor lesions that would be chosen as target lesions (measurable 
disease).  


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 Palliative radiotherapy to non-target lesions may be permitted (Section 5.10). 
 Systemic immune modulators from C1D1 until the EoT Visit, unless used for a TEAE or 
as pre-medication for MT-3724.  
o The immune modulators include, but are not limited to, systemic corticosteroids at 
doses >20mg/day or prednisone equivalent for >1 week, cyclosporine and tacrolimus. 
 Vaccines: Subjects should not receive any live vaccines from 4 weeks before the start of 
treatment until 28 days after the last dose of MT-3724, unless the investigator believes 
benefits outweigh risk, after approval by the sponsor. 
 
5.10 Permitted medication 
The use of G-CSF, GM-CSF, platelet and blood transfusions and concomitant medications is 
permitted during the treatment phase at the investigator’s discretion for management of 
appropriate toxicities.  In particular, G-CSF is required for the treatment of Grade 3 
neutropenia. 
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. Please note: palliative therapy is not 
allowed up to 2 weeks of C1D1 through and not during the DLT assessment period (cycle 1).  
While the use of certain immunomodulators is prohibited as described in Section 5.9, the use 
of NSAIDs is permitted. 
5.10.1 
Reasons for caution 
No results are available about the potential for drug-drug interactions between MT-3724 and 
LEN, or between MT-3724 and other drugs. Therefore, investigators should use caution 
when prescribing concomitant medications 
 
 


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6 STUDY ASSESSMENTS 
Please refer to the schedule of assessments to see which assessments need to be performed at 
each visit (Schedule of Assessments). 
Unscheduled visits may occur when indicated at the investigator’s discretion. The results 
obtained at unscheduled visits should be entered into the eCRF (where applicable) and 
recorded in the source documentation. 
All assessments will be performed by the investigator or medically qualified designee or 
other personnel at the investigating site. 
6.1 
General subject characteristics  
6.1.1 
Demographics 
Information about date of birth/age, gender, race/ethnicity, detailed smoking history and 
alcohol history will be recorded during screening. 
6.1.2 
Body weight 
Body weight (kg) will be measured at the following time points: 
 At screening 
 Pre-dose on each dosing day for MT-3724  
 At the EoT Visit 
The body weight measured before the start of MT-3724 dose 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. 
6.1.3 
Height and BMI  
Height in meters (m) and body mass index (BMI) will be measured at screening. 
6.1.4 
NHL assessment 
The NHL assessment will be performed at screening by documenting the biopsy method by 
which the NHL histology and CD20 status has been confirmed at the initial diagnosis and at 
baseline.  
The following information will be documented:  
 NHL assessment (status at initial diagnosis):  


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o NHL type (histology)  
o Staging (Ann Arbor Classification-Cotswold Modification) 
o Grading (low, intermediate, high)  
 NHL assessment (status at Screening) 
o NHL type [histology 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 
o Grading at relapse 
o Grading at screening 
o Time to first relapse 
o Mutational status (e.g., MYC and/or BCL2 and/or BCL6 
rearrangement/overexpression; del 9p32. TP53, MLL2 mutations) 
o Molecular subtype (GCB vs ABC) 
The prognostic assessment instruments (Ann Arbor Classification with Cotswold 
Modification and (follicular lymphoma) International Prognostic Index) are described in 
Appendix 2. 
6.1.5 
Prior systemic therapy 
Prior systemic therapy (including SCT and CAR-T) for NHL 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 the regimen (i.e., line of treatment) should be recorded along with each individual 
agent given in the regimen. The date of the last CD20-based therapy should also be 
documented. 
6.1.6 
Prior radiotherapy 
Prior radiotherapy for NHL administered at any time before the start of treatment will be 
assessed and documented at screening. 
6.2 
Safety assessments 
Note that the AE are described in the Section 6.3, and the laboratory safety tests are 
described together with all laboratory tests in the Section 6.4 and Appendix 1. 
6.2.1 
Medical history 
Medical history will be recorded at screening. This will include prior surgery, prior and 
concomitant illnesses and allergy history. The prior antitumor chemotherapy, radiotherapy 
and tumor related biopsies or surgery will be collected and documented on a separate eCRF 
form.   


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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. Those illnesses that are active at the time of 
informed consent will be regarded as concomitant illnesses.  
New illnesses and/or worsening of concomitant illnesses detected by verbal probes or 
subject’s spontaneous reports between the screening and the start of treatment should be 
reported medical history unless they are due to study-mandated procedures, in which case 
they should be reported as AEs. 
6.2.2 
Prior and concomitant medications 
Any medication (both prescription and over-the-counter [OTC] medications and 
supplements, 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. 
The medications taken before the start of treatment on C1D1 will be regarded as prior 
medications (prior NHL therapy will be captured separately, Section 6.1.5). The prior 
medications will be captured at the following time points: 
 During the screening period 
 Before the start of treatment on C1D1. 
The medications taken after the start of treatment on C1D1 will be regarded as concomitant 
medications. Concomitant medications will be captured at all visits and telephone contacts 
from the start of treatment until the STFU Visit.  
6.2.3 
Physical examination (PE) 
A PE will be performed by a physician or a qualified delegate at the investigating site.  
The full PE will be performed at the following time points:  
 At screening  
 At the EoT Visit  
 
Abbreviated PE:  
 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 PE 
can be captured up to 24 hours before dosing and must be done before dosing is allowed.  
The overall PE result will be categorized as ‘normal’, ‘abnormal, not clinically significant 
(NCS)’, or ‘abnormal, clinically significant (CS)’. Any abnormal CS result of the PE should 
be followed up at the investigator’s discretion and reported as an AE in the electronic CRF 


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(eCRF). Comments about abnormal NCS result of the PE, either overall or for individual 
aspects or body parts, will not be collected in the eCRF. 
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. 
Abbreviated physical examination 
At a minimum, the following aspects/body parts should be assessed during the abbreviated 
PE: 
 General appearance 
 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) 


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 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. 
6.2.4 
Eastern Cooperative Oncology Group Performance Status  
ECOG performance status will be done at the same timepoints as physical examination, see 
Appendix 6. 
6.2.5 
New York Heart Association 
NYHA classification will be performed at screening, see Appendix 7 for subjects with heart 
failure. 
6.2.6 
Vital signs  
Vital signs include blood pressure (BP), heart rate (HR), respiratory rate (RR), and body 
temperature (°F or °C). BP and HR will be measured after 5-10 minutes of quiet rest in a 
sitting or semi-recumbent position using an automatic (preferred) or manual BP measuring 
device.  
Vital signs will be assessed at the following time points:  
 At screening 
 Before the start of each MT-3724 infusion in each cycle;  
 At 0.5h, 1h and 2h (±10 min allowed at each time point) after the start of each MT-3724 
infusion in each cycle  
 At 3h and 4h (±10 min allowed at each time point) after the start of MT-3724 infusion on 
C1D1  
 At the EoT Visit 
 
Unscheduled VS measurements may be performed at investigator’s discretion in each cycle. 
Any clinically-significant abnormality in VS should be investigated by repeat assessments 
(number and timing at investigator’s discretion). The confirmed clinically significant 
abnormalities should be reported as AE in the eCRF. 


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6.2.7 
Left ventricular ejection fraction 
Left ventricular ejection fraction assessment should be assessed by echocardiography 
(ECHO).  If ECHO is not available or appropriate according to the institutional standard, 
then multi-gated acquisition (MUGA) scan is permitted. The same modality should be used 
throughout the study. Left ventricular ejection fraction will be assessed at the following time 
points: 
 At screening (within 1 month before starting study treatment) 
o 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. 
 At the EoT Visit (only if the subject has received MT-3724 in ≥3 cycles irrespective of 
the number of MT-3724 doses in each cycle). 
 
6.2.8 
Electrocardiograms 
Standard resting 12-lead ECG assessments will be performed after the subject had rested rest 
quietly for 5-10 minutes in supine or semi-recumbent position. The ECG recordings will be 
obtained at the following time points: 
 At screening (triplicate ECG, i.e. 3 ECG recordings obtained in close succession and not 
more than 2 minutes apart) 
 Before the start of MT-3724 infusion on D1 of each cycle (single ECG recording will be 
performed) 
 At the EoT Visit (single ECG) 
 
If the ECG printout is of poor quality, additional ECG(s) may be obtained at the same time 
point until an ECG of adequate quality is obtained. Such additional ECG(s) do not have to be 
reported as unscheduled assessments. 
When PK, ECG and VS assessments are scheduled to occur at the same time point, the ECG 
and VS should be done first and in that order, with the timing of assessments based on 
collecting the PK sample at the protocolled time.  
The investigator or delegate at the site will assess the ECG results. The three QTcF values 
from a triplicate ECG should be averaged to yield the QTcF value for the purpose of 
eligibility assessment. The derived variable will be calculated according to the formula of 
Fridericia using an online calculator.  
The overall ECG assessment will be categorized as ‘normal’, ‘abnormal, not clinically 
significant (NCS)’, or ‘abnormal, clinically significant (CS)’. The overall ECG assessment 
by the ECG recorder and the related diagnostic comments will not be entered in the eCRF. 


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Any clinically significant abnormality in the ECG should be investigated by unscheduled 
ECG assessment(s) (number and timing at investigator’s discretion). The confirmed 
clinically significant abnormalities should be reported as AE in the eCRF. 
6.3 
Adverse events 
The term adverse event 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 CRF page. Clinically 
significant 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, VS, 
and ECG abnormalities should also be recorded as AEs when considered clinically 
significant 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 (e.g. leading to hospitalization). 
Adverse events will be assessed by verbal probes and subject’s spontaneous reports at 
screening and during every post-baseline clinic visit and telephone contact from the start of 
treatment until the STFU Visit. 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 and medical monitor qualified delegate for completeness, relatedness and 
accuracy of severity grading in order to ensure appropriate reporting practice. Cumulative 
AE data will be reviewed periodically by the medical monitor as well as ad hoc review of 
serious and/or severe 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. 
Discontinuation from the 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. 


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6.3.1
AE reporting period 
The AE reporting period will begin on the day of the first dose of study drug until the STFU 
call, or until the start of new cancer therapy (unless the investigator believes the AE is related 
to MT-3724), whichever occurs first.  
Grade 2 AEs related to MT-3724 and/or LEN that were 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 or LEN. 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. 
For AEs of CLS, CRS/SIRS, and IRRs, individual symptoms and grade should be reported 
on the appropriate CRF. 
6.3.2
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. 
6.3.3
Severity 
Severity will be classified according to the criteria provided by CTCAE v5.0. If the AE is not 
listed in the CTCAE v5.0, then the highest severity level reached according to the scale in 
Table 8 will be assigned.  
Table 8: 
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. 
AE =adverse event 


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Every effort should be made to find the appropriate AE term and definitions of severity in the 
modified CTCAE v. 5.0. 
Causality/Relatedness 
Causality should be assessed separately for each study drug (MT-3724 and LEN) as detailed 
in the eCRF. If the investigator feels that the event cannot be firmly attributed to one of the 
study drugs, then the same assessment should be documented for each study drug. 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(s)
according to the classification in Table 9.
Table 9 
Classification of Adverse Events by Causality/Relationship to the Study 
Drug(s) 
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. 
AE = adverse event 
For all purposes of subject management, 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”


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6.3.4 
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 IB for MT-3724 or in the MT-3724 safety 
reports to the health authorities (e.g. development safety update report) and for LEN any 
ADR that is not described in the Revlimid® reference prescribing information. 
The Safety Department of the Contract Research Organization (CRO) 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. 
6.3.5 
Serious adverse events 
An SAE is defined as any AE that meets one 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 one 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 in-
patient 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 adverse event 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 subject/event outcome or action criteria. Seriousness (not 
severity) serves as a guide for defining regulatory reporting obligations. 
SAE reporting instructions 
If an SAE occurs at any time from the time of start from C1D1 until the STFU Visit (or 
during screening if deemed related to study-procedure), it must be reported to the Safety 
Department of the CRO and the medical monitor (See List of Contacts). The investigator 


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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 CRF 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 in order to determine the etiology of the problem. The results will be 
reported promptly to the sponsor. 
Pregnancy reporting instructions 
Pregnancy should be avoided from 4 weeks prior to first dose of LEN, during treatment, 
during dose interruptions and for 4 weeks following the last dose of LEN or MT-3724. 
Reliable contraception is specified in the exclusion criteria, see Section 4.2. 
Subjects must be advised to immediately notify the investigator of pregnancy.  
If pregnancy occurs during treatment in a subject, the investigator must immediately 
discontinue the study drugs (MT-3724 and LEN) and report the pregnancy to the Safety 
Department of the CRO and the medical monitor (See List of Contacts), along the same 
timelines as an SAE (Section 6.3.5).The subject must be referred to an 
obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and 
counseling.  
The investigator maintains the responsibility for reporting pregnancy in accordance with the 
Revlimid REMS program (REVLIMID REMS®). 
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. 
Suspected Unexpected Serious Adverse Reaction  
An unexpected SAE that is at least possibly related to the study drug will be considered a 
Suspected Unexpected Serious Adverse Reaction (SUSAR). Please see Section 6.3.4 for the 
definition of the unexpected event. 


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The sponsor will determine if a reported SAE meets the criteria for SUSAR.  
Clinical Laboratory Adverse Events 
Laboratory test results will be graded according to the CTCAE v.5.0 criteria. Out of range 
results considered to be clinically significant 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 
considered to be a clinically significant AE and need to be reported as such in the eCRF, 
unless related to 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 screening, 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.  
6.3.6 
Action taken with study treatment 
Any action with any of the study treatments to manage the AE should be documented using 
the categories in the eCRF completion guidelines and the study treatment action should be 
recorded separately for MT-3724 and LEN. 
6.3.7 
Outcome 
The outcome of the AE should be documented as described in the eCRF completion 
guidelines. 
6.4 
Laboratory Tests 
The following laboratory tests are to be performed as indicated by the Schedule of 
Assessment and Safety Laboratory Panel.  
The following tests will be performed by the central laboratory:  
 Hematology 
 Chemistry (with eGFR) 
 HbA1c 
 Coagulation 
 Thyroid function 
 Beta-2 microglobulin 
 Serum cytokines 
 Complement 
 Immunoglobulins  
 Histamine 
 B-cell count and immunophenotype (flow cytometry) 
 Immunogenicity of MT-3724; Anti-drug antibodies (ADA and NAb titer)  


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
Serum RTX concentration (if applicable)
The following laboratory tests will be performed by a local laboratory: 

Urinalysis (dipstick)

Pregnancy test (serum or urine)

Serology/Virology for HIV, HBV and HCV (if applicable)
The same laboratory should analyze all scheduled laboratory tests throughout the study. 
In the event of an unexplained clinically-significant abnormal laboratory test value, the test 
should be repeated immediately 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. 
A standalone Laboratory Manual will provide complete instructions regarding how these 
samples should be collected, stored and shipped.  
6.4.1
Hematology, Chemistry and Urinalysis 
The hematology, chemistry (with eGFR) and urinalysis assessments will be performed at the 
following time points:  

At screening

Before the MT-3724 infusion on D1, D8

On D15 of each cycle (at any time in C1-C2 and before the MT-3724 infusion in C3 and
beyond)

At the EoT Visit
If possible, the blood for chemistry assessments should be drawn after a subject has fasted for 
at least 2 hours, in order to facilitate a more reliable interpretation of the serum glucose 
result. The compliance with this recommendation (Yes/No) will be entered in the eCRF for 
every chemistry assessment. 
Local laboratory for chemistry and hematology should be collected to assess subject 
status/safety if results from central laboratory will not be available pre-dose, whenever 
central laboratory assessments are scheduled. See Schedule of Assessments (Study Schema) 
for details. These results need only be entered in the EDC if there is a clinically significant 
finding, related to an adverse event. 
6.4.2
Estimated glomerular filtration rate 
The eGFR will be assessed as a measure of renal function and will be calculated using the 
Cockcroft-Gault creatinine equation (Appendix 5). 


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The eGFR will be derived from the serum creatinine values obtained from the blood 
chemistry assessment at all time points listed above (Section 6.4.1).   
At the investigator’s discretion, the eGFR 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 eGFR result at any other time 
point, the investigator may order CLcr (measured from the 24-hour urine) as an unscheduled 
assessment. 
6.4.3 
Urinalysis 
A standard dipstick urinalysis will be initially performed at the time points listed above 
(Section 6.4.1). 
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 
clinically significant abnormalities should be reported as per standard medical practice and 
reported as AE in the eCRF. 
6.4.4 
Glycated hemoglobin in plasma  
The HbA1c will be assessed at the following time points: 
 At Screening 
 Before MT-3724 dose on D1 of cycle 3 and every odd cycle thereafter 
 At the EoT Visit 
  
6.4.5 
Thyroid function 
The thyroid function parameters (see Appendix 1) will be assessed at the following time 
points: 
 At Screening 
 Before MT-3724 dose on D1 of cycle 3 and every odd cycle thereafter  
 At the EoT Visit 
 
6.4.6 
Coagulation  
Coagulation will be assessed at the following time points: 
 At Screening  
 Before MT-3724 dose on D1 of cycle 3 and each odd cycle thereafter 
  At the EoT Visit 
 


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6.4.7 
Immunoglobulins 
The immunoglobulins (IgG, IgA, IgM) will be assessed at the following time points: 
 At screening 
 Before the start of MT-3724 infusion on D1 of each cycle 
 At 3h (±10 min) after the start of MT-3724 infusion on D1 of each cycle 
 At the EoT Visit 
 
6.4.8 
Rituximab concentration 
Serum RTX concentration must be assessed at screening if a subject had received RTX 
within 37 weeks before the start of treatment on C1D1.  Subject will be eligible only if the 
serum RTX concentration is <500ng/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 had 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, serum RTX will 
be assessed for exploratory purposes because these results will not impact eligibility. 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. 
6.4.9 
Complement, histamine, and cytokines 
Complement, histamine, and cytokines will be assessed at the following time points: 
 At screening 
 Before the start of MT-3724 infusion on D1 of each cycle.  
 At 3 h (±10 min) after the start of MT-3724 infusion on D1 of each cycle 
 At the EoT Visit 
If a subject experienced a Grade ≥2 IRR, or another Grade ≥2 hypersensitivity event, Grade 
≥2 CRS or Grade ≥2 CLS, the investigator should obtain serum samples for 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. 
6.4.10 
Serum beta-2 microglobulin  
A blood sample for the collection of beta-2 microglobulin will be collected at Screening. 


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6.4.11 
Serology/Virology – HIV, HBV and HCV and CD4+ T-cell counts 
Viral serology and viral load assessment will be assessed at screening and will include the 
following parameters: 
Human immunodeficiency virus 
 Anti-HIV-1 antibody 
 Anti-HIV-2 antibody 
 HIV viral load 
 CD4+ T-cell counts 
Hepatitis B virus 
 HBsAg 
 Anti-HBsAg antibody 
 Anti-HBcAg antibody 
 HBV viral load 
Hepatitis C Virus 
 HCV-RCV-RNA quantitation 
 Anti-HCV antibody 
 HCV viral load 
The serology for individual virus(es) may be omitted at the investigator’s discretion if 
seronegativity has been previously documented and there are no signs of the corresponding 
viral infection. 
6.4.12 
Pregnancy test 
The pregnancy test (urine or serum at the investigator’s discretion) will be assessed for 
women of childbearing potential at the following time points: 
 At screening (within 10-14 days and within 24 hours before the start of treatment) 
 Within 24 hours before D1, D8, D15, D22 in cycle 1.  
 Starting with cycle 2, within 24 hours before D1 and D15. If the biweekly pregnancy test 
is scheduled for the day of MT-3724 dosing, the result must be known before the start of 
treatment. 
 At the EoT Visit 
 
For pregnancy tests scheduled to occur when there is no corresponding on-site visit, the 
subject should use a commercial pregnancy test kit on their own and contact the site to report 
the test result. The site should follow up if the subject has not contacted the site to confirm 
that the test was done.  


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If the scheduled pregnancy test coincides with the dosing of MT-3724, then the result must 
be known before the start of MT-3724 infusion. 
6.5 
Pharmacokinetic assessments 
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.  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.  
The PK samples for the free concentration of MT-3724 will be collected at prespecified times 
in Table 4. 
The PK of LEN will not be assessed in this study. 
6.6 
Efficacy assessments: Radiological Assessment of Tumor Response 
The tumor response assessment should be performed at the following time points: 
 At Screening:  
o The investigator is encouraged to obtain the screening tumor scan as close as possible 
to the start of treatment within 28 days of C1D1. 
 Within 7 days before the start of treatment on C3D1 and every other cycle thereafter (i.e. 
Between D23 and D28 of the cycle). The original schedule needs to be maintained even if 
there is a delay is dosing. 
 Within 7 days of the EoT Visit (only if the previous tumor scan has been performed 
>4 weeks before the EoT Visit) 
 
The investigator and the radiologist should carefully consider if the increase from baseline in 
tumor size could be “pseudoprogression” due to the tumor flare induced by the study drug(s). 
Unscheduled tumor response assessment by FDG-PET-CT (or CT/MRI, where applicable) 
may be ordered at the investigator’s discretion. 
Efficacy of the study drugs (tumor response) will be assessed by the scan of all anatomic 
regions involved with the measurable disease.  Positron emission tomography-computed 
tomography should be used in subjects with FDG-avid tumor histology. Computed 
tomography or MRI should be used in subjects with tumor histology of low or variable FDG 
avidity.  Diagnostic quality CT should be collected for all subjects at baseline, whenever 
possible. 
Tumor response in subjects with FDG-avid tumor histology will be determined using the 
5-point scale (5PS) according to the Lugano Classification for Lymphoma (Cheson 2014) 
adjusted according to LYRIC (lymphoma response to immunomodulatory therapy criteria) 
(Cheson 2016). An overview of NHL response criteria for FDG avid and non-avid NHL is 
presented in Appendix 3. 


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The same technique (e.g. slice thickness, field of view) should be used for all scans during 
the study treatment period. Preferably, all scans should be interpreted by the same 
investigator during the study whenever possible. Scans must meet the SOC for imaging of 
lesions in the respective organ system(s). 
6.6.1 
Central review of efficacy results  
If the sponsor considers it necessary at any time during the study, a third-party radiology 
service may perform a blinded independent central review of digital images used for the 
tumor response assessment by the investigators at the sites, coupled with relevant clinical 
data from the eCRF.   
Sites should archive imaging in standard DICOM format in readiness for data transfer. All 
data will be transferred to a central database by the end of the study.  
6.7 
Immunogenicity 
Blood samples will be collected at pre-specified time points for the assessment of 
immunogenicity of MT-3724 ADA and NAb titer. 
The immunogenicity samples will be collected at prespecified time points listed below: 
 At Screening 
 Pre-dose on D1 in each cycle: Before the start of MT-3724 infusion 
 At the EoT Visit 
 
Please also see the Schedule of Assessments. Unscheduled assessments may be performed at 
any time at the investigator’s discretion.  
6.8 
Pharmacodynamics assessments 
6.8.1 
Peripheral blood 
The B-cell count will be the PD marker in this study and the immunophenotype in peripheral 
blood, as determined by flow cytometry. Serial blood samples for the assessment of PD 
markers will be collected at the following time points: 
 At Screening 
 D1 in each cycle (at any time before the start of MT-3724 infusion) 
 D12 of cycles 1-2 (at any time before the start of MT-3724 infusion on the dosing day) 
 D15 of cycle 3-and beyond (at any time before the start of MT-3724 infusion on the 
dosing day) 
 At the EoT Visit 
 
Unscheduled assessments may be performed at any time at the investigator’s discretion. 


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6.9 
Tumor tissue  
Optional FNA biopsy will be collected at EoT for subjects in Part 2 who had consented for 
this procedure, exhibit PD and have accessible peripheral lymph node(s) at time of 
collection. CD20-positive status of DLBCL in the fine needle aspirate of the peripheral 
lymph node will be determined by IHC staining. Subjects with mediastinal or abdominal 
lymph nodes will not be considered for FNA biopsy. 
In the absence of PET/CT, a bone marrow biopsy should be assessed to confirm CR.  
6.10 Exploratory Assessments 
 
7 DATA MANAGEMENT AND STATISTICAL ANALYSIS 
All clinical parameters should be entered into the eCRF/EDC as soon as possible after each 
study visit.  
The statistical analysis of the clinical data will be performed by Molecular Templates’ 
representative. Analysis of the PK, PD and immunogenicity data may be performed 
separately and entered into a separate database. Data from the clinical, PK and PD databases 
will be integrated in the clinical study report. 
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. 
7.1 
Data handling and electronic CRF 
Data will be recorded in an FDA CFR Part 11-compliant eCRF, also known as the EDC 
system. 
Data reported on the CRF must accurately reflect the corresponding source documents, or the 
discrepancies must be explained. No data are to be recorded directly on the CRFs (i.e. the 
CRF 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. 
PPD


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7.2 
General statistical considerations 
Statistical analysis will be performed using the Statistical Analysis System®; the version 
used will be specified in the statistical analysis plan (SAP). 
All data will be listed, and descriptive summary tables will be provided by treatment 
group/cohort irrespective of the study part. In addition, appropriate variables will be 
summarized in a separate treatment group comprising the subjects treated at the MTD of 
MT-3724 in Part 1 (dose escalation) and in Part 2 (expansion). These variables will be 
specified in the SAP. 
Quantitative data will be described by the following summary statistics: arithmetic mean, 
standard deviation, median, minimum, and maximum. Where appropriate, descriptive 
summary statistics will be tabulated for the absolute values and changes from baseline. 
Graphical illustrations will be provided where appropriate. Qualitative data will be presented 
in the frequency tables. 
The assessment obtained at the most recent time before the start of MT-3724 treatment will 
be the baseline for all post-baseline assessments. The value obtained before MT-3724 Dose 1 
on C1D1 (if available) will serve as the baseline; if not available, then the value obtained 
earlier at screening will serve as the baseline. 
Further details about the statistical analyses will be provided in the SAP. Any changes in the 
statistical methods described herein compared to the final SAP will be documented in the 
integrated clinical study report. 
7.3 
Sample size justification 
Approximately 64 subjects (i.e., 24 subjects in Part 1 and approximately 40 subjects in Part 
2), as well as the appropriate number of replacements (if needed), will be enrolled and treated 
in this study. The actual number will depend on the number of dose cohorts needed to 
identify the MTD of MT-3724 in combination with LEN in Part 1. 
No formal power calculation and sample size justification will be performed for this 
descriptive non-pivotal Phase 2a study. The proposed sample size is deemed sufficient for the 
adequate characterization of the study objectives and would be typical of the sample sizes of 
exploratory Phase 1b/2a studies with novel anti-cancer agents. 
7.4 
Analysis sets  
7.4.1 
Safety population 
The safety population is defined as all subjects who receive at least one dose of MT-3724 or 
LEN. The safety population will be used for the primary statistical analysis of safety and 
efficacy endpoints. 


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7.4.2 
Efficacy analysis population 
All subjects who received at least one dose of any study drug (either MT-3724 or LEN), and 
have the baseline tumor assessment as well as at least one post-baseline tumor assessment.  
7.4.3 
Pharmacokinetic population 
The PK population will include all subjects who received at least one dose of MT-3724 and 
have at least one post-baseline PK assessment. The PK population will be used for the PK 
analyses.  
Subjects who received only LEN but haven’t received MT-3724 will be excluded from the 
PK analyses. 
7.4.4 
Immunogenicity population 
All subjects who received at least one dose of MT-3724 and have at least one post-baseline 
immunogenicity assessment will be included in the analyses of ADA and NA. Subjects who 
received only LEN but haven’t received MT-3724 will be excluded from the immunogenicity 
analyses. 
7.4.5 
Pharmacodynamic analysis population 
All subjects who received at least one dose of MT-3724 and have at least one post-baseline 
PD assessment will be included in the analyses of B-cell count and immunophenotype (flow 
cytometry). Subjects who received only LEN but haven’t received MT-3724 will be excluded 
from the PD analyses.  
7.5 
Subject disposition and termination status 
The number and percentage of enrolled (signed consent), screened, screen-failed and treated 
subjects will be summarized by treatment group/cohort. Reasons for screen failure will be 
listed and reasons for treatment discontinuation will be tabulated. Safety assessments among 
subjects will be listed and summarized by treatment group and reason for discontinuations 
(grouped as due to AEs, disease progression, and other). 
7.6 
Handling missing data 
Missing data will not be imputed in this study. For summary statistics and concentration-time 
profiles, all values that are below the limit of quantitation will be set to zero. 
7.7 
Baseline and demographic characteristics 
Subject baseline characteristics; including demographics, medical history, physical 
examination, ECG, and vital signs will be summarized descriptively. The descriptive 
statistics, including n (number of observations or sample size), mean, standard deviation 
and/or standard error, median, range (minimum-maximum), geometric means and geometric 


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coefficient of variance (where applicable) for numerical variables, and frequency and 
percentages for categorical variables, will be presented. 
7.8 
Safety analyses  
The primary analysis of safety will be a comprehensive evaluation of AEs and/or toxicity, 
presented by dose, regimen and tumor type cohort and overall, based on: 
 The type, incidence, severity, timing, seriousness, and relatedness of adverse events.  
 Incidence of DLT and TEAEs that led to treatment modification 
 Recording of IRR, CRS and CLS 
 Results of monitoring vital signs (BP, HR, RR and body temperature) 
 Results of clinical chemistry, hematology, thyroid function, coagulation, and urine 
analysis tests 
 ECG results 
 Changes in physical examination 
 Results of immunogenicity assessments ADA and NAb 
 Need for concomitant medications 
All safety analyses will be descriptively summarized based on the safety population. 
AEs/SAEs will be coded and tabulated using the current version of MedDRA. Each AE will 
be classified by system organ class and preferred term. All AEs along with the coded terms 
will be listed. 
7.8.1 
Safety data handling 
Adverse events 
All AEs will be coded according to MedDRA and graded for severity using the CTCAE 
v.5.0. 
Treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events 
(TESAEs) are defined as those AEs/SAEs that occurred or worsened at or after the start of 
the first infusion of the first study drug. The occurrence of TEAEs and TESAEs will be 
reported up until the STFU Visit.  
Only TEAEs and TESAEs will be summarized. The incidence of TEAEs will be presented 
using the number and percent of subjects who experienced the AE using MedDRA (overall 
incidence, System Organ Class and preferred term) and the worst CTCAE grade. The 
incidence of the following TEAEs and drug-related TEAEs will be summarized by treatment 
group / cohort: Overall, TEAEs leading to dose interruption, dose delay, dose reduction, 
permanent discontinuation, IRR, CRS, and CLS. The TESAEs will be summarized similarly. 
Individual listings of DLTs will be presented by MT-3724 dose cohort in Part 1, with the AE 
term, MedDRA terms, treatment cycle of onset, serious or non-serious and severity grade 
(CTCAE v.5.0) provided for each DLT. 


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The pre-treatment AEs include those AEs that occurred due to study-related procedures. 
These AEs will be assessed by verbal probes and from medical history. The pre-treatment 
AEs will be listed by subject but not summarized. 
Laboratory safety tests 
Laboratory results will be summarized by treatment group/cohort using absolute values and 
change from baseline; or presented as per-subject listings. The incidence of laboratory data 
outside the reference range (L, H) will be summarized in frequency tables by treatment 
group/cohort. Further details will be provided in the SAP. 
Physical examination 
The overall results of the physical examination (‘normal’, ‘abnormal, NCS’, or ‘abnormal, 
CS’) will be summarized by treatment group/cohort and listed per subject. Comments for 
abnormal CS results will be listed. 
Other safety variables 
Quantitative data for other safety variables will be summarized by the following descriptive 
statistics: arithmetic mean, standard deviation, median, minimum, and maximum. These 
summary statistics will be presented by the treatment group/cohort for the absolute values 
and changes from baseline. Frequency tables will be provided for qualitative data. 
Results of VS (body temperature, systolic blood pressure, diastolic blood pressure, 
respiratory rate, and heart rate) will be summarized by the descriptive statistics listed above.  
ECG results (HR, PR, QRS, RR interval, QT, QTcF, and the results of the overall ECG 
review by the investigator) will be summarized by the descriptive statistics listed above. 
Comments for abnormal CS results of the ECG will be listed. 
All prior and concomitant medications will be assigned a generic name and a drug class 
based on the World Health Organization Dictionary. Prior and concomitant medications will 
be listed and summarized by treatment group/cohort and (if appropriate) by drug class.  
7.9 
Efficacy analyses 
The statistical analysis of efficacy variables will be performed on the safety population.  
Tumor assessment will be performed by the FDG-PET-CT scan in subjects with FDG-avid 
NHL histology along with CT or MRI to capture measurements, wherever possible, and by 
the CT or MRI scan in subjects with low or variable FDG avidity. The investigator at each 
site will determine the ORR at each time point based on the radiologist’s measurement of all 
evaluable lesions.  
The investigator at each site will determine the objective tumor response (OR) using the 5PS 
per the Lugano Classification for Lymphoma (Cheson 2014) adjusted according to LYRIC 
(lymphoma response to immunomodulatory therapy criteria) (Cheson 2016). An overview of 
LYRIC is presented in Appendix 3. The BORR of all time points will be reported. Subjects 


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who experience disease progression before undergoing the first tumor assessment will be 
added to the disease progression stratum. The BORR will be descriptively summarized by the 
treatment group/cohort; the exact 95% confidence intervals will also be produced. 
The ORR representing clinically significant clinical benefit in this study will comprise the 
Lugano Score 1, 2 or 3, or the CR or PR. All subjects achieving clinically significant clinical 
benefit according to both response criteria will be included in the analysis of the DOR. DOR 
is defined as the time from the first documented complete or partial response to the actual 
date of disease progression or death before progression. The PFS will be defined as the time 
from the start of treatment with MT-3724 on C1D1 to the date of disease progression or 
death from any cause. Subjects who have not progressed or died at the time of data base lock 
will be censored at the date of their last tumor assessment. The DOR will be descriptively 
summarized by the treatment group/cohort; the exact 95% confidence intervals will also be 
produced. 
The DCR will be defined as the percent of subjects with objective response of CR, PR or 
stable disease (SD, defined as SD for 6 months or longer). The DCR will be analyzed using 
similar methods as the ORR. Further details will be provided in the SAP. 
A detailed description of analysis methods will be provided in the SAP to be completed 
before the EoT Visit in the last subject. 
7.10 Pharmacokinetic analyses 
MT-3724 serum concentration time data from all eligible subjects will be subjected to non-
compartmental assessment using the software package Phoenix WinNonlin (Certera, 
Princeton NJ). Parameters will be stratified by dose group and summary statistics will be 
generated.  
In addition, the concentration time data may be evaluated using nonlinear mixed effects 
modeling using Nonmem (Icon PLC, Dublin Ireland). 
7.11 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, while the data for the NAb against MT-3724 
will be obtained as the positive or negative. 
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 immunogenicity results will be listed by time point for each subject by 
treatment group/cohort.  
Details of the immunogenicity analyses will be provided in a separate analysis plan for this 
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7.12 Pharmacodynamic analyses 
B-cell count and immunophenotype data by flow cytometry will be presented as absolute 
values and percentage change from pre- to post-dose time points. The summary statistics by 
time point and graphs of summary statistics over time will be presented by treatment group 
and overall.  
Details of the PD analyses will be provided in a separate analysis plan for this study 
objective. 
7.13 Interim analysis 
No formal interim statistical analysis is planned during either part of this study. A formal 
interim statistical analysis may be performed only pursuant to a health authority request. 
Informal (preliminary) statistical analyses may be performed at sponsor’s discretion at any 
time during the study. These analyses would be performed without the interim data base lock 
for the purposes of the IB update, safety reports to the health authorities (e.g., data safety 
update report), meetings with health authorities or for internal decisions. 
In addition, data from individual subjects and cohorts will be reviewed without formal 
statistical analysis on an ongoing basis during the study (e.g. to support the dose escalation 
decisions in Part 1). 
7.14 Protocol deviations 
Protocol deviations are defined as deviations from the procedures outlined in the protocol. 
Major protocol deviations are those deviations that could have an impact on subject’s safety 
or on the ability to interpret the study results.  
Deviations from the protocol should not occur. If a deviation occurs, the investigator must 
immediately inform the monitor, and the implications of the deviation must be reviewed and 
discussed with the sponsor. Deviations should be reported to the IRB/EC per local 
requirements.   
The impact of the protocol deviations on data quality and integrity will be re-assessed after 
the completion of the study conduct (last visit by the last subject) and before the data base 
lock. All decisions regarding the type of deviations (major or minor) will be made prior to 
commencing the final analysis on the final locked database. Major protocol deviations may 
lead to exclusion of data from analysis. A listing of all major protocol violations will be 
presented in the final study report. 


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8 STUDY MANAGEMENT 
8.1 
Approval and consent 
8.1.1 
Regulatory guidelines 
This study will be performed in accordance with the Standard Operating Procedures of the 
sponsor, the EU Clinical Trials Directive and the FDA CFR, the guidelines of the ICH 
(ICH 2016), and the most recent guidelines of the Declaration of Helsinki (World Medical 
Association 2013).  
8.1.2 
Independent ethics committee/Institutional Review Board 
Conduct of the study must be approved by an appropriately constituted IEC or IRB. 
Approval is required for the study protocol, IB, protocol amendments, informed consent 
forms, subject information sheets, and any advertising materials. No study drug will be 
shipped to the study site until written IEC or IRB authorization has been received by the 
sponsor or its representative. 
Study progress is to be reported to the IRB/IECs annually (or as required by the committee) 
by the investigator or sponsor, depending on local regulatory obligations. The investigator or 
sponsor will also submit, depending on local regulations, periodic reports and inform the 
IRB/IEC of any reportable adverse events per ICH guidelines and local IRB/IEC standards of 
practice.   
The IRB/IEC and regulatory authorities will be notified of the end of the trial per local 
requirements. A summary of the study outcome will be provided, where required. 
The investigator will be responsible for obtaining annual IRB approval or renewal throughout 
the duration of the study. Copies of the investigator’s reports and the IRB continuance of 
approval must be sent to Molecular Templates’ representative. 
8.1.3 
Informed consent 
Before any trial activities are performed, subjects must give written consent to participate 
after the nature, scope, and possible consequences of the study have been explained in a form 
understandable to them. 
If local SOC procedures or tests were performed prior to signing of the ICF but are still 
within 35 days, unless otherwise specified (e.g. LVEF), of initiation of dosing, then those 
results/data can be used for the intended protocol screening procedure. If various study 
parameters within a given procedure are missing from the SOC procedures, then only those 
missing parameters need to be collected. 
As part of written informed consent procedure, the principal investigator or one of his/her 
associates must explain orally and in writing the nature, duration, and purpose of the study, 
and the action of the study drug in such a manner that the subject is aware of the potential 
risks, inconveniences, or adverse effects that may occur. The document must be in a 


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language understandable to the subject. The subject will have sufficient time to read the 
document prior to being asked if there are any questions about the study procedures. A 
qualified, trained member of the study team must respond to these questions, (e.g., a study 
staff member who has been specifically trained on the protocol). They should be informed 
that the subject may withdraw from the study at any time. They will receive all information 
that is required by the 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 (e.g., 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. Where required by local law, the 
person who informs the subject must be a physician.  
If the ICF is obtained on the same date when screening procedures are performed, the trial 
file and the subject’s notes must document that the ICF was signed prior to the start of any 
screening procedure. 
The ICF and any other written information provided to subjects, or subject’s legal 
representatives or proxy consenters will be revised whenever important new information 
becomes available that may be relevant to the subject’s well-being on the study, or the 
amendment of the study protocol necessitates a change to the ICF content. Any revised 
written ICF must receive the IEC’s/IRB`s approval/favorable opinion in advance of use. 
After the IRB/IEC approval, the investigator will inform the subject, or subject’s legal 
representative or proxy consenter about the ICF changes in a timely manner and will ask the 
subject to confirm his/her participation in the study by signing the revised ICF. The signed 
revised ICF will be archived as described above for the original ICF. 
8.2 
Protocol amendments and other changes in study conduct 
Changes to this protocol that meet the criteria of a substantial amendment in accordance with 
European Guidance (2010/C 82/01) require a protocol amendment that must be approved by 
the sponsor, the investigator(s), IRB/IEC and regulatory authorities before implementation. A 
substantial amendment in the EU will be treated as a protocol amendment in the USA per 
FDA 21 CFR 312.30(b). 
The requirements for approval of the substantial changes should in no way prevent any 
immediate action from being taken by the investigator or by the sponsor in the interest of 
preserving the safety of all subjects included in the study. 
Changes representing only administrative aspects of the study that meet the criteria of a non-
substantial amendment in accordance with local regulatory requirements do not require 
formal protocol amendments or IEC/IRB approval. The IRB/IEC should be informed of each 
administrative change as they are implemented, and a log of such changes should be 


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maintained in the trial master file. The sponsor must be consulted and approve of such 
changes prior to their implementation. 
No changes in this protocol can be made without the sponsor’s written approval. 
8.3 
Discontinuation of the study by the sponsor 
The sponsor reserves the right to discontinue the study for safety or administrative reasons at 
any time. Should the study be terminated, and/or the site closed for whatever reason, all 
documentation and study medication pertaining to the study must be returned to the sponsor 
or its representative. 
8.4 
Confidentiality 
The contents of this protocol and any amendments and results obtained during the study 
should be kept confidential and not disclosed, in whole or in part to others, or used for any 
purpose other than reviewing or performing the study, without written consent of the 
sponsor. 
The investigator agrees to conduct the study according ICH GCP and comply with all 
applicable federal, state, and local laws and regulations relating to the privacy of subject 
health information, including, but not limited to, the EU Clinical Trials Directive or the FDA 
CFR. The investigator shall ensure that study subjects authorize the use and disclosure of 
protected health information in accordance with the EU Clinical Trials Directive, and EU 
Law or the FDA CFR and in a form satisfactory to the sponsor to allow for review and 
monitoring of the conduct of the study and to verify the accuracy of data by the sponsor, its 
representatives, IRBs/IECs, and regulatory authorities. 
The investigator will ensure that all persons assisting in the performance of the study 
preserve the confidentiality of the subjects’ data as set forth in the ICF and Clinical Trial 
Agreement. In eCRF or any other documents and biological samples submitted to the 
sponsor, the subjects will not be identified by their names. Each subject will be assigned an 
identification number to be used on any data or laboratory samples collected by the sponsor. 
Hence, subject name must be obliterated before a copy of the document is supplied to the 
sponsor. Documents not for submission to the sponsor, e.g., the signed ICFs and subject 
medical records, will be maintained by the investigator and made available for review and 
inspection as described above for as long as is required by local regulations. 
8.5 
Study monitoring, auditing and inspection 
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.  


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The study may be audited or inspected by the sponsor or by regulatory authorities, 
respectively. If an audit or inspection occurs, the investigator must agree to allow direct 
access to required subject records. By signing this protocol, the investigator grants 
permission to personnel from the sponsor, its representatives, regulatory authorities and 
IEC/IRBs for on-site monitoring of all appropriate study source documentation, as well as 
on-site review of the procedures employed in eCRF generation, where clinically appropriate. 
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 inspection, the sponsor must be 
notified within 24 hours of the investigator’s notification by the inspecting authority. 
8.6 
Source data  
Data will be recorded in an FDA CFR Part 11-compliant eCRF. 
All data in the eCRF must reflect the corresponding source data (Section 7.1). No data are to 
be recorded directly on the eCRFs (i.e. the CRF is not to be considered as source data).  
Data reported on the eCRF that are derived from source documents should be consistent with 
the source documents, or the discrepancies must be explained. 
The investigator should agree to have completed source documents and eCRFs available for 
inspection by the clinical monitor at the time of each scheduled monitoring visit. The 
investigator must sign the completed eCRF. 
A Clinical Research Associate 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/medical records that are used. Source documents may include but 
are not limited to all original documents, data, and records (e.g., 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, microfiches, 
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), subject study identification 
(e.g., 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 CRFs, 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 CRFs by trained and qualified study staff. 


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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 one or more screen procedures or withdraw 
consent following screening and never progress to receive study drug.  
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 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 at regular intervals by the investigator and signed by the 
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 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 will retain the final, complete electronic data base with all 
CRFs. The investigator will retain a copy of all CRF pages completed at their site. 
8.7 
Retention of records 
The investigator must arrange for retention of study records at the site. The nature of the 
records and the duration of the retention period must meet the requirements of the relevant 
health authority. In addition, because this may be an international study, the retention period 
must meet the most stringent requirements of any local health authority. The site should plan 
to retain study documents until directed by the sponsor that they are no longer required. The 
investigator should take measures to prevent accidental or premature destruction of these 
documents. 
8.8 
Subject insurance 
The sponsor will obtain clinical trial insurance to cover subjects participating in the study in 
accordance with all applicable laws and regulations. The terms of the insurance will be kept 
in the study files.   
8.9 
Financial Disclosure 
In accordance with the regulatory requirements in the involved countries Molecular 
Templates will request a statement attesting for any financial disclosure 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 


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spouses and dependent children of the investigators. Any changes to the disclosure statement 
must be submitted in writing to Molecular Templates.  
Disclosure is required for those financial interests other than the Clinical Study Agreement 
for this study.  
8.10 Study disclosure and publication 
The study will be posted on www.clinicaltrials.gov and other applicable public databases as 
required by local regulations. 
By signing the study protocol, the investigator agrees to the use of results of the study for the 
purposes of national and international regulatory filings and registration. If necessary, the 
authorities will be notified of the investigator’s name, address, qualifications, and extent of 
involvement. A final integrated study report covering clinical and biometric aspects of the 
study will be prepared by the sponsor or its representative and results of the trial will be 
disclosed to regulatory authorities and posted on public registries, as required. 
8.10.1 
Publications of study results 
The sponsor intends to publish the results of this study upon completion of the appropriate 
analyses during the study conduct and/or after the study completion. The sponsor reserves the 
right to name as authors members of staff at the investigational site if they have made 
qualifying contributions to the research. Order of authorship will generally be assigned in 
relation to the relative contribution of each author. Disagreements concerning authorship will 
be resolved by the sponsor. All authors will be required to review and agree upon the content 
of the draft publication prior to its submission to a peer-reviewed congress, journal or posting 
on the sponsor’s website. 
The detailed obligations regarding the publication of any data, material results, or other 
information generated or created in relation to the study shall be set out in the Clinical Trial 
Agreement between each investigator and the sponsor, as appropriate. 


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Witzig TE, Nowakowski GS, Habermann TM, Goy A, Hernandez-Ilizaliturri JF, Chiappella 
A, Vitolo U, Fowler N, Czuczman MS; A comprehensive review of lenalidomide therapy for 
B-cell non-Hodgkin lymphoma, Annals of Oncology, Volume 26, Issue 8, 1 August 2015, 
Pages 1667–1677. 
Witzig TE, Wiernik PH, Moore T, et al. Lenalidomide oral monotherapy produces durable 
responses in relapsed or refractory indolent non-Hodgkin’s lymphoma. J Clin Oncol 2009; 
27:5404-5409. 
Witzig TM, et al. Durable responses after lenalidomide oral monotherapy in patients with 
relapsed or refractory aggressive non-Hodgkin’s lymphoma: results from an international 
phase 2 study (CC-5013-NHL-003). ASH 2009, abstract no. 1676 
World Medical Association, 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.  
Zinzani PL, Pellegrini C, Derenzini E et al. Long-term efficacy of the combination of 
lenalidomide and rituximab in elderly relapsed/refractory diffuse large B-cell lymphoma 
patients. Hematol Oncol 2013; 31: 223–224. 
Zinzani PL, Pellegrini C, Gandolfi L et al. Combination of lenalidomide and rituximab in 
elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin 
Lymphoma Myeloma Leuk 2011; 11: 462–466. 
 
 
 


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APPENDIX 1. LABORATORY PANELS 
Table 10 
Laboratory Assays 
Hematology (central laboratory): 
WBC1 
hemoglobin 
platelet count 
hematocrit 
RBC and indices2 
Chemistry (central laboratory): 
albumin 
amylase 
lipase 
creatinine 
ALT 
AST 
CPK 
calcium 
chloride 
GGT 
LDH 
serum glucose3 
magnesium 
phosphorous 
potassium 
sodium 
bilirubin (total and 
direct) 
total protein 
BUN 
Uric acid 
eGFR4 
HbA1c 
β-2 microglobulin 
Coagulation (central laboratory) 
INR or PT 
aPTT 
Thyroid function (central laboratory) 
TSH 
free T4 
Urinalysis macroscopic6 (local laboratory): 
pH 
specific gravity 
glucose 
ketones 
leukocytes 
nitrites 
protein 
occult blood 
Urinalysis microscopic [optional] (local laboratory): 
RBC 
WBC 
bacteria 
casts 
epithelial cells 
mucous threads 
crystals 
Urinalysis or serum (local laboratory) 
β-HCG5 
Immunoglobulins (central laboratory) 
IgG 
IgA 
IgM 
Other assessments (central laboratory) 
cytokines 
complement 
ADA/NAb 
histamine 
B-cell count
rituximab 
PK (serum) 
PK (CSF) 
Other assessments (local laboratory) 
Viral loads (HIV, 
HBV, HCV) 
CD4+ T-cell counts 
β-HCG = beta human chorionic gonadotropin; ADA = anti-drug antibody; AST = aspartate aminotransferase; 
ALT = alanine aminotransferase; aPTT = Activated partial thromboplastin time; BUN = blood urea nitrogen; 
CPK = creatinine phosphokinase; CSF = cerebrospinal fluid; eGFR = Estimated glomerular filtration rate; freeT4 
= Free thyroxin; GGT = gamma-glutamyl transferase; 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 = pharmacokinetics; PT = 
Prothrombin time; RBC = Red Blood Cell; TSH = Thyroid-stimulating hormone; WBC = white blood cell. 
1WBC with differential (including neutrophils, basophils, eosinophils, lymphocytes, monocytes) reported as 
percentage and absolute values 
2Red cell indices (mean cell volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular 
hemoglobin concentration [MCHC]) and distribution widths (red cell and platelet) 
3If possible, the blood for chemistry assessments should be drawn after a subject has fasted for at least 2 hours, in 
order to facilitate a more reliable interpretation of the serum glucose result. The compliance with this 
recommendation (Yes / No) will be entered in the eCRF for every chemistry assessment. 
4eGFR, Cockcroft-Gault calculation, see Appendix 5. 
5β-HCG, only for women of childbearing potential 
6 Microscopic examination of sediment will be performed if the results of the urinalysis dipstick evaluation are 
positive at the investigator’s discretion 


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APPENDIX 2. STAGING OF NHL 
Ann Arbor Staging System with Cotswold Modification (Lister 1989) 
Ann Arbor stage is determined as outlined in Table 11, for calculation of the appropriate 
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 11:  Ann Arbor Staging System with Cotswold Modification 
Stage1 
Ann Arbor Staging System Features 
I 
Involvement of a single lymph node region or lymphoid structure (e.g., spleen, 
thymus, Waldeyer's ring) 
II 
Involvement of two or more lymph node regions on the same side of the 
diaphragm 
III2 
Involvement of lymph regions or structures on both sides of the diaphragm 
IV 
Involvement of extra nodal site(s) beyond that designated E 
 
Cotswold Modifications 
For all stages 
  
A 
No B symptoms 
 
B 
Fever (>38oC), drenching sweats, weight loss (10% body weight over 6 months) 
  
X 
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, extra nodal site contiguous or proximal to known nodal 
site 
1 The number of anatomic regions involved should be indicated by a subscript (e.g., II3).  
2 Stage III may be subdivided into: III1, with or without splenic, hilar, celiac, or portal nodes; III2, with para-aortic, 
iliac, mesenteric nodes. 
 
 


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International Prognostic Index for Aggressive Non-Hodgkin's Lymphoma (NHL Project 
1993) 
The International Prognostic Index (IPI) for Aggressive NHL is used to assess the prognostic 
score of patients at diagnosis with aggressive NHL. In this study, this index should apply to 
subjects who have been diagnosed with DLBCL, mantle cell lymphoma, sporadic (non-endemic, 
non-immune deficiency associated) Burkitt’s lymphoma (BL), small noncleaved non-Burkitt's 
(Burkitt’s–like) lymphoma (SNC-NB), DLBCL transformed FL [excluding unclassifiable, 
blastoid and lymphoblastic subsets], and transformed (Helicobacter pylori negative) mucosa-
associated lymphoid tissue (or extra nodal marginal zone B-cell) lymphoma (MALTL) and, if 
available, should be recorded as part of the Medical History in the appropriate CRF. (n.b. 
Relapse-free and OS rates at 5 years are 75% for 0-1 factors; 50% for 2-3 factors and 25% for 
4 - 5 factors.) 
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 LDH ≥450 IU/L  
4. ECOG performance status of 2, 3, or 4  
5. Extra-nodal sites ≥2 
Subjects will be documented to be in one of four risk groups:  
Low Risk 
0-1 risk factors 
5-year survival of 73% 
Low-intermediate risk (2 points) 
2 risk factors 
5-year survival of 51% 
High-intermediate risk (3 points) 
3 risk factors 
5-year survival of 43% 
High risk (4-5 points) 
4-5 risk factors 
5-year survival of 26% 
 
Follicular Lymphoma International Prognostic Index (FLIPI) [Solal-Céligny 2004] 
The FLIPI is used to assess the prognostic score of subjects with indolent Follicular NHL at 
diagnosis and, if available, should be recorded as part of the Medical History in the appropriate 
CRF. The FLIPI score is calculated on the basis of 5 adverse prognostic factors.  
One point is assigned for each of these adverse prognostic factors:  
1. Age >60 years  
2. Ann Arbor Stage III or IV disease 
3. Involved lymph node groups >4  
4. Serum hemoglobin <12 g/dL 
5. Serum LDH >450 IU/l 
Subjects will be documented to be in one of three risk groups: 
Low Risk 
0-1 risk factors 
Intermediate Risk 
2 risk factors 
Poor Risk 
3-5 risk factors 


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APPENDIX 3. REVISED LUGANO CLASSIFICATION FOR RESPONSE 
ASSESSMENT IN LYMPHOMA WITH LYRIC MODIFICATION  
Tumor response will be evaluated according to the revised Lugano Classification for Lymphoma 
(Table 12) adjusted according to LYRIC (lymphoma response to immunomodulatory therapy 
criteria).  
Table 12:  Revised Lugano Classification of Response Assessment in Lymphoma adjusted 
for LYRIC 
Response and Site 
PET-CT-Based Response 
CT/MRI-Based Response 
Complete 
Complete metabolic response 
Complete radiologic response (all of the 
following) 
Lymph nodes and  
extralymphatic sites  
5PS score of 1, 2, or 31 with or 
without residual mass.  
It is recognized that in Waldeyer’s 
ring or extranodal sites with high 
physiologic uptake or with activation 
within spleen or marrow (e.g., with 
chemotherapy or myeloid colony-
stimulating factors), uptake may be 
greater than normal mediastinum 
and/or liver. In this circumstance, 
complete metabolic response 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 (Table 13) 
with reduced uptake compared with 
baseline and residual mass(es) of any 
size. 
At interim, these findings suggest 
responding disease. 
At end of treatment, 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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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 end of treatment 
<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 
Extranodal lesions 
Score 4 or 5 with an increase in 
intensity of uptake from baseline 
and/or  
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 ≥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 (e.g., 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 (e.g., 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 
Bone Marrow 
New or recurrent FDG-avid foci 
New or recurrent involvement 
LYRIC Indeterminate 
response (IR)2 
Increase in FDG uptake without a 
concomitant increase in lesion size 
meeting criteria for PD 
>50% increase in SPD in first 12 weeks 
<50% increase in SPD with 
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b. ≥50% increase in PPD of a lesion or set of 
lesions at any time during treatment (in the 
context of the lack of overall progression, a 
biopsy is encouraged)>50% increase in SPD 
in first 12 weeks 
 <50% increase in SPD with 
a. New lesion(s), or  
b. ≥50% increase in PPD of a lesion or set of 
lesions at any time during treatment 
(in the context of the lack of overall 
progression, a biopsy is encouraged) 
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. 
1A score of 3 in many subjects 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 six of the largest 
dominant nodes, nodal masses, and extranodal lesions selected to be clearly measurable in two 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 (e.g., liver, spleen, kidneys, lungs), 
gastrointestinal 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 (e.g., gastrointestinal 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 (e.g., with marrow activation as a result of chemotherapy or 
myeloid growth factors). 
2See original paper (Cheson 2014, Cheson 2016) for more detailed information on immune related response. 
 
 


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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 (i.e., metabolically 
intense) area of disease (across all index and non-index lesions), is assigned for each PET/CT 
scan in the study, see Table 13. 
Table 13: 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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APPENDIX 4. DLT CRITERIA 
GENERAL PRINCIPLES 
A 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 of Part 1.  
a. If a TEAE that fulfills a DLT criterion is observed in cycle ≥2 of Part 1, 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). 
Note: TEAEs related to LEN will not be declared a DLT unless they exceed in severity the worst 
grade described or are not mentioned in the reference prescribing information. If a Grade ≥3 
TEAE related to LEN is more severe than the worst grade described in the reference prescribing 
information or has not been reported in the reference prescribing information, then the sponsor 
may declare this event a DLT 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 TEAEs: Any TEAE listed below may represent a DLT for 
MT-3724 in this study. 
Hematological TEAEs 
 Grade ≥3 febrile neutropenia (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 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 clinically significant bleeding 
(i.e., bleeding requiring platelet transfusion) 
 Grade 4 thrombocytopenia (<25,000/μl) with or without bleeding 
 Grade 4 anemia 
Nonhematological TEAEs 
 Grade ≥2 Cytokine Release Syndrome 
 Grade ≥3 Capillary Leak Syndrome 
 Grade ≥3 acute kidney injury 
 AST and/or ALT increase 5.0 times ULN (>8.0 times for those with liver involvement)  
 AST and/or ALT increase 3.0 times ULN with concomitant increase in total bilirubin 
≥2.5 times ULN  
 Total bilirubin 4.0 times ULN   


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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 x ULN (depending on 
laboratory values as specified above), could be interpreted as non-DLT in light of the elevated 
baseline value (see CTCAE v5.0) 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 
o 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 (e.g., 
long-lasting fatigue or anorexia).  
 
 


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APPENDIX 5. COCKCROFT-GAULT (2009) 
Creatinine clearance should be calculated using the Cockcroft-Gault Formula 
(Cockcroft DW 1979), which is given below:  
 
CLcr = {((140–age) x weight) / (72 x SCr)} x 0.85 (if female) 
Abbreviations/Units: CLcr (creatinine clearance) = mL/minute; Age = years; sCR (serum 
creatinine) = mol/L  
 
 


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APPENDIX 6. ECOG PERFORMANCE STATUS 
ECOG will be recorded per the investigator’s assessment of subject’s 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 (e.g., 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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APPENDIX 7. NEW YORK HEART ASSOCIATION (NYHA) FUNCTIONAL 
CLASSIFICATION 
The stages of heart failure will be assessed according to the NYHA functional classification 
system. This system relates symptoms to everyday activities and the subject’s quality of life. 
NYHA classification 
Class 
Subject 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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APPENDIX 8. ABBREVIATIONS 
Abbreviation 
Definition 
5PS 
five-point scale 
ACVBP 
adriamycin, cyclophosphamide, vindesine, bleomycin and prednisone 
ADA 
anti-drug antibodies 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
ADR 
adverse drug reaction 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count  
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
-HCG 
Beta-human chorionic gonadotropin 
BIW 
twice weekly 
BMI 
body mass index 
BORR 
best overall response rate 
BP 
blood pressure 
°C 
Celsius 
C 
cycle 
C1D1 
cycle 1 day 1 
CDC 
complement-dependent cytotoxicity  
CFR 
Code of Federal Regulations 
CHOP 
cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine (Oncovin), and 
prednisone 
CLcr 
creatinine clearance 
CLS 
capillary leak syndrome 
Cm 
centimeter 
CNS 
central nervous system 
CR 
complete response 
CRF 
case report form 
CRO 
contract research organization 
CRS 
cytokine release syndrome 
CS 
clinically significant 
CT 
computer tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 


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Abbreviation 
Definition 
DCR 
disease control rate 
DHAP 
dexamethasone, cytosine arabinoside, cisplatin 
DLBCL 
diffuse large B-cell lymphoma 
DLT 
d-dose-limiting toxicity 
DOR 
duration of tumor response 
ECG 
electrocardiogram 
ECHO 
echocardiography 
ECOG 
Eastern Cooperative Oncology Group  
eCRF 
electronic CRF 
EDC 
electronic data capture 
EoI 
end of infusion 
EoT 
end of treatment 
EPOCH 
etoposide, prednisolone, vincristine, cyclophosphamide and doxorubicin 
°F 
Fahrenheit 
FDA 
Food and Drug Administration 
FDG 
fluordeoxyglucose 
FL 
follicular lymphoma 
FLIPI 
Follicular Lymphoma International Prognostic Index 
FNA 
fine needle aspirate 
GCP 
Good Clinical Practice 
GDP 
gemcitabine, dexamethasone and cisplatin 
G-CSF 
granulocyte-colony stimulating factor  
HbsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HSCT 
hematopoietic stem cell transplantation 
HR 
heart rate 
IB 
Investigator’s Brochure 
ICE 
ifosfamide, carboplatin and etoposide 
ICF 
informed consent form  
ICH 
International Conference on Harmonisation  
IEC 
Independent Ethic Committee 
Ig 
immunoglobulin 


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Abbreviation 
Definition 
IHC 
immunohistochemistry 
INR 
international normalized ratio 
IPI 
International Prognostic Index  
IRB 
Institutional Review Board 
IRR 
infusion-related reactions  
IV 
intravenous  
Kg 
kilogram 
L 
liter 
LDi 
longest diameter 
LDH 
lactic dehydrogenase 
LEN 
Lenalidomide 
LTFU 
Long-Term Follow Up 
LVEF 
left ventricular ejection fraction 
LYRIC 
Lymphoma Response to Immunomodulatory Therapy Criteria  
mAb 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
Mg 
milligram 
Ml 
milliliter 
mM 
millimolar 
MM 
multiple myeloma 
mmHg 
millimeter of mercury 
mm3 
cubic millimeter 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
MUGA 
multiple-gated acquisition 
NAb 
neutralizing antibody  
NCS 
not clinically significant 
NHL 
non-Hodgkin’s lymphoma 
NSAIDS 
non-steroidal anti-inflammatory drugs 
NYHA 
New York Heart Association 
OR 
objective tumor response 
ORR 
objective tumor response rate 
OS 
overall survival 
OTC 
over the counter 


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Abbreviation 
Definition 
PCR 
polymerase chain reaction 
PD 
pharmacodynamics 
PE 
physical examination  
PET 
positron emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetics 
PO 
orally 
PR 
partial response 
PRBC 
packed red blood cells 
PT 
prothrombin time  
PTT 
partial thromboplastin time 
Qd 
once daily 
QTcF 
QT interval corrected according to Fridericia’s formula 
R2 
lenalidomide plus rituximab 
RBC 
red blood cell (count) 
R-CHOP 
rituximab-CHOP 
REMS 
Risk Evaluation and Mitigation Strategy 
RNA 
ribonucleic acid 
RR 
respiratory rate 
R/R 
relapsed or refractory 
RTX 
rituximab 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
scFv 
single chain variable fragment 
SCT 
stem cell transplantation 
SD 
stable disease 
STFU 
Short-Term Follow-Up 
SOC 
standard of care 
SUSAR 
suspected, unexpected serious adverse reaction 
TEAE 
treatment emergent adverse event 
TESAE 
treatment-emergent serious adverse events 
TIW 
three times a week 
TSH 
thyroid-stimulating hormone 
µg 
microgram 


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Abbreviation 
Definition 
ULN 
upper limit normal  
WBC 
white blood cell (count) 
 
 
 


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APPENDIX 9. SUMMARY OF CHANGES  
Version 3.0 (14 April 2020) replaces version 2.0 (10 December 2018) and is applicable to all 
investigators participating in this protocol. 
Rationale for changes: 
1. A modification of the dosing schedule has been implemented in this amendment to 
address the occurrence of dose-limiting toxicities in two subjects treated with MT-3724 at 
25µg/kg/dose (Cohort 2).  The starting dose for Cohort 3 was subsequently reduced to 20 
µg/kg/dose while maintaining the 3 weekly dosing schedule for the first 2 cycles. MT-
3724 will be administered at a reduced dosing frequency from twice rather than three 
times weekly starting with Cohort 4; the lenalidomide (LEN) schedule is unchanged.  
2. The CTC Grade 2 events occurred in subjects treated at a dose lower than the MTD of 
50µg/kg/dose with monotherapy. While the two trials cannot be directly compared 
because of confounding factors (MT-3724 in combination with LEN versus monotherapy 
and differences in investigator discretion vis-a-vis pre-dose medication), and since the 
dose-response relationship is still being evaluated, a new dosing schedule is being 
implemented to evaluate if dosing of MT-3724 at a reduced frequency when combined 
with LEN will be more tolerable while still allowing for higher doses on a µg/kg basis to 
maximize response potential. 
3. The dose-limiting toxicity (DLT) criterion regarding capillary leak syndrome (CLS) has 
been updated from Grade 2 to Grade 3 based upon available safety data. Across the 
MT-3724 trials, to date, treatment-emergent adverse events (TEAEs) have been 
manageable. Capillary leak syndrome as the most common DLT did not exceed Grade 2, 
resolved within days in most cases, except for those dosed at 75µg/kg when resolution 
occurred over 2-4 weeks, and did not prevent subjects from resuming treatment. 
4. Pre-dose medication requirements have been updated to clarify that subjects must receive 
pre-dose medications with all doses in cycle 1, rather than allowing pre-dose medications 
at the investigator’s discretion which may reduce the incidence and/or severity of innate 
immune responses typically observed early in cycle 1. 
5. 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. 
6. 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. The current safety data do not indicate a heightened 
risk for study subjects to have new or reactivated infectious diseases.  Also, a reduced 
washout period (consistent with the relevant half-life for subjects whose last treatment 
include small molecules, as opposed to monoclonal antibodies) is implemented.  


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7. 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 as long as there is a 
favorable risk-benefit ratio in the opinion of the investigator. 
8. The screening period has been increased from 28 days to 35 days to allow for central 
laboratory processing of screening samples 
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. Vast majority of changes made were to provide clarifications to existing language. 


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High-level summary of changes made:  
 
 
Section 
Change 
Rationale 
1.  
Global changes 
Change patient to subject 
Changed from MT-3724 concentration in plasma to serum 
Sponsor and investigator are not capitalized 
No space between value and unit (e.g. 50g/kg/day) 
No space between slash (e.g. D1/D2) 
Removed reference to CRO (since medical monitor is from 
the sponsor, have maintained only medical monitor when 
both sponsor and medical monitor were cited) 
Abbreviations updated as necessary 
Relocated sections of protocol for better readability (eg 
SOA after synopsis, TOC before synopsis) 
Administrative 
2.  
Investigator protocol agreement 
Changed to reflect prior protocol language 
Consistency with previous protocol 
3.  
List of contacts 
Updated to reflect different contacts 
Administrative 
4.  
Amendment rationale 
Added to protocol amendment 
Explanatory 
5.  
Synopsis 
Updated synopsis to reflect all the changes made to body of 
protocol and reformatted (matched objectives to endpoints 
for clarification) 
Clarification and – for consistency with updated 
protocol 
6.  
Synopsis 
Deleted Table (p15-18) 
Redundant and information not required in 
synopsis 
7.  
Synopsis 
Added “in both parts” and “either part of” for clarity in 
Study Treatment and Duration section 
For clarity and consistency with previous protocol 
8.  
Section 1.1 
Updated language for NHL 
For clarity and consistency with previous protocol 
9.  
Section 1.2.1 
Update clinical experience with MT-3724 based on IB v5, 
2019 
updating and clarification 
10. Section 2.1 Study Objectives 
1 
Reformatted to match objectives to endpoints 
2 
 
1 
Administrative 
2 
 
11. Figure 1 
Revised Figure 1: Study Design for MT-3724_NHL-003 
For clarity and consistency with changes in 
protocol 
12. Section 3.2 Screening 
Updated screening window from 28 days to 35 days 
To allow for flexibility should there be a delay in 
receipt of RTX results 
PPD
PPD


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13. Section 3.3.1 MT-724 
(1) Simplified to reduce redundancy with content in Section 
5.1.3 and add period of LTFU as mention of it was 
previously missing; (2) removed “Every subsequent cycle 
should be started on D28+1, except if prevented by ongoing 
AEs.” 
(1) Clarification / administrative; (2) removed 
because it’s not required per safety – this avoids 
unnecessary protocol deviations 
14. Section 3.4 End of Treatment visit 
and Short-Term Follow-up phone 
call 
For EoT visit, removed “for those that complete the study” 
for clarification 
Clarification 
15. Section 3.5 Long-term Follow up 
visit 
Updated frequency of contact (from every 6 to every 3 
months), duration (from 24 months after last dose to 18 
months after first dose), and endpoints 
To decrease the number of subjects lost to follow-
up and increase precision with which DOR and 
survival will be captured 
16. Section 3.6 Part 1 (MT-3724 dose 
escalation) 
Updated section to allow for dose re-escalation at reduced 
dose frequency and added evaluation criteria, clarify 
number of subjects in Part 1 
Clarification 
17. Section 3.6.3 MTD Definition 
Removed “in Cohort 3” since the dose in Cohort 3 may not 
be 50mcg/kg and also removed “The dose of MT-3724 that 
will be given in this study is 50µg/kg/dose with a maximum 
total dose of 6000µg, which is the MTD of MT-3724 as 
monotherapy. The MT-3724 dose escalation will not 
proceed above the 50µg/kg/dose even if no more than 1 of 6 
subjects in Cohort 3 experiences a DLT” 
Remove since the dose in Cohort 3 may not be 
50g/kg 
18. Section 3.7 Part 2 (MTD expansion 
cohort) 
Removed “(or at a maximum dose of 50µg/kg)” 
Clarification 
19. Section 3.8 Rationale for the study 
design 
Updated LTFU from how and what will be collected to why 
it’s being conducted  
Clarification since this section is on rationale and 
not methodology. Also this section moved to 1.4 
20. Section 3.9 Guidance to the 
investigator 
Updated most common AE from latest version of IB (v 5) 
and also incorporated guidance to the investigator for CLS 
Update with most recent data from IB v5. Section 
moved to 1.6  
21. Section 3.10 Benefit/Risk Ratio 
Updated to reflect MoA, in vitro and clinical data 
Update with most recent data from IB v5. Section 
moved to 1.5 
22. Section 4 Study population 
Added language that requires eligibility needs to be 
reconfirmed prior to C1D1 
Clarification 
23. Section 4.1 inclusion criterion #3 
Reorganized for clarification and added that B-cell NHL 
should be CD20 positive 
Clarification 
24. Section 4.1 inclusion criterion #3 
1. Added criterion on SCT to inclusion criterion #5 (and 
removed it from exclusion criteria) 
2. Added that sponsor approval is required when 
considering enrolling patients who did not receive all 
available therapies for NHL 
3. Added language for proof of CD20 positive NHL 
1. Clarification because easier to understand 
hematologic recovery when worded as an 
inclusion criterion 
2. To ensure sponsor oversight 


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25. Section 4.1 inclusion criterion #5 
Added criterion for eligibility regarding CAR-T and SCT 
Clarification to ensure compliance and expand 
eligibility 
26. Section 4.1 inclusion criterion #6 
Added “bi-dimensionally” for clarification and deleted 
reference to “Table 7” 
Clarification 
27. Section 4.1 inclusion criterion #8 
Added requirement on hemoglobin 
To ensure adequate bone marrow function 
28. Section 4.1 Inclusion criterion #9 
Updated CLcr criteria from at least 60 to at least 50 and 
changed method from CPK-EPI for Cockcroft-Gault 
To be in alignment with data generated for 
MT-3724 using the Cockcroft-Gault formula with 
the cutoff of ≥50 mL/min. 
29. Section 4.1 inclusion criteria #10, 
#11  
Updated for consistency across MT-3724 protocols  - 
changed requirement for total bilirubin to be <2 instead of 
1.5 (and info for subjects with Gilbert’s syndrome); for 
AST and ALT, changed requirement from ≤3 to 2.5 and 
added (or ≤ 5 x ULN if liver involvement); for coagulation 
added that requirement is not necessary for those on 
therapeutic anticoagulants 
Allow flexibility for subjects with liver 
involvement and those taking anticoagulants 
30. Section 4.1 inclusion criterion #13 
Added definition for postmenopausal 
Clarification 
31. Section 4.1 inclusion criterion #16 
Added criteria on life-expectancy  
To reduce likelihood of enrolling moribund 
subjects 
32. Section 4.2 exclusion criterion #1 
Reworded for clarification 
Clarification 
33. Section 4.2 exclusion criterion #2 
Updated to add stipulation around autologous SCT and 
additional criteria added “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 of signing the ICF 
and compared with prior imaging results 
d. Do not require chronic steroid therapy (or, if 
applicable, have been stable on steroid dose of no more than 
prednisone 20 mg/day or equivalent by C1D1)” 
Update to allow for subjects with autologous SCT 
and clarify additional criteria 
34. Section 4.2 exclusion criterion #3 
Relocated to inclusion criterion #5 (previously regarding 
SCT) and therefore all subsequent exclusion criterion were 
renumbered 
clarification 
35. Section 4.2 exclusion criterion #4 
Added “that are related to prior anti-cancer therapy” 
clarification 
36. Section 4.2 exclusion criterion #5 
Added “or radiotherapy”  
To ensure subjects with AE from radiotherapy 
recovered before study enrollment  
37. Section 4.2 exclusion criterion #6 
Added requirement regarding Grade 2 infection  
To allow for more flexibility for subjects with 
Grade 2 infection with respect to eligibility 
38. Section 4.2 exclusion criterion #7e 
Added option to allow for subjects with LVEF between 40-
45% possible enrollment per sponsor approval 
To allow for subjects with LVEF between 40-45 
possibility for enrollment to trial 


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39. Section 4.2 exclusion criterion #9 
Updated to allow subjects with HIV/HBV/HCV to have 
undetectable viral load and for HIV, minimum CD4+ T-cell 
count of 50cells/uL, provided prophylaxis therapy for 
opportunistic infections given and appropriate anti-viral 
prophylaxis, per institutional guidelines 
To allow for subjects with well controlled-
HIV/HBV to participate in the trial 
40. Section 4.2 exclusion criterion #13  
Added “Prior treatment with MT-3724” 
To ensure subjects are naïve to MT-3724 
41. Section 4.2 exclusion criterion #15 
Added requirement on washout for radioimmunoconjugates 
and added that for small molecules,  
To ensure appropriate washout period for subjects  
who received radioimmunoconjugates and small 
molecules for NHL  
42. Section 4.2 exclusion criterion #17 
Added more details regarding palliative radiation therapy 
Relaxed requirement given patient population and 
MT-3724 MoA 
43. Section 4.2 exclusion criterion #18 
Updated requirement regarding vaccinations 
Relaxed requirement given patient population and 
MT-3724 MoA 
44. Section 4.2 exclusion criterion #19 
Updated requirement regarding steroid use 
Relaxed requirement given patient population and 
MT-3724 MoA 
45. Section 4.3.1 Subject withdrawal 
Updated from “discontinued from study” to “discontinued 
from treatment period”  
in order to make it clear that it’s expected the 
subject will remain in follow-up 
46. Section 4.3.1 Subject withdrawal 
Deleted paragraph defining withdrawn subjects as either 
screen failures or dropouts 
Clarification 
47. Section 4.3.3 Study discontinuation 
Removed last sentence 
Clarification  
48. Section 5.1.1., 5.1.2, 5.1.3 MT-
3724 dosing schedule 
1 
Updated to add window (including that doses must be 
administered at least 48 hours apart in cycles 1 and 2) 
2 
Updated to add new dosing schedule 
3 
Added maximum break permitted between cycles (14 
days) 
4 
Removed mention of max dose administration will be 
50mcg/kg  
1 
To allow for flexibility, and to ensure 
adequate time between dosing for tolerability, 
based on the DLTs that occurred in cohort 2. 
2 
To reduce the probability of DLTs in the first 
2 cycles and broaden the therapeutic window. 
3 
To ensure subjects are not off treatment for 
extended duration 
4 
Removed max dose because of dosing 
schedule differences between this amendment 
and the monotherapy dose escalation study 
49. Section 5.2 Lenalidomide 
Changed Lenalidomide will be “supplied” to “available” 
Clarification  
50. Section 5.1.1 MT-3724 Drug 
Product 
Changed handling requirements 
Clarification for compliance 
51. Section 5.1.2 MT-3724 dose 
selection  
Changed “may” to “will” regarding requirement for body 
weight adjustment for MT-3724 dose 
Revised dosing guidance to Table 1 
Updated dosing schedules for Cohorts greater than 3 
Added “MT-3724 must be administered at least 48 hours 
apart” 
Clarification for safety, compliance 


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52. Section 5.1.4 Premedication 
Changed “should” to “must” 
Clarification for safety 
53. Section 5.2.1 Len dose 
For Parts 1 and 2, starting with cycle 2 (after completion of 
the DLT assessment period for Part 1), the investigator may 
increase the LEN dose to 25mg qd, if clinically indicated, 
with sponsor approval. 
Clarification of dosing of LEN 
54. Section 5.2.2 Lenalidomide dosing 
selection 
Section added to state starting dose of LEN and language 
regarding increasing LEN dose to 25mg 
Clarification for investigator 
55. Section 5.2.3 
Removed reference to “up to 6 additional cycles” 
Added language regarding monotherapy with MT-3724 
 
Removed since treatment is permitted beyond 
cycle 6 
Clarification for discontinuation of LEN 
 
56. Section 5.3 Intra-subject dose 
escalation  
Starting with cycle 2 (after the DLT assessment period for 
subjects in Part 1), the dose of LEN may be increased to 25 
mg qd, as described in Section 5.2.1 
Clarification of LEN dosing 
57. Section 5.4.5  Treatment 
modification for MT-3724 and 
LEN due to increased AST, ALT 
and/or bilirubin levels 
Updated table 3 in section 5.4.5 
Updated table to better reflect possible clinical 
scenarios 
58. Section 5.8 Treatment duration 
Updated duration from up to 12 cycles to allowing 
treatment until disease progression withdrawal of consent or 
any other reason 
To allow for extended treatment in subjects who 
benefit 
59. Section 5.9 Prohibited Treatments 
Updated radiotherapy to be allowed during screening, 
relaxed vaccination prohibitions, steroid use, vaccines, and 
added washout for radioimmunoconjugates 
Relaxed requirement given patient population and 
MT-3724 MoA 
60. Section 5.10 Permitted medication  
Added clarification that palliative therapy is allowed, Also 
added requirement for use of G-CSF for G3 neutropenia. 
Also added caution statement in 5.10.1 
clarification 
61. Section 6.1.2 body weight 
Added clarification that recalculation of study drug dose 
based on body weight changes can also be per institutional 
policy 
Clarification 
62. Section 6.1.4 NHL assessment 
Added additional criteria for NHL assessment 
clarification 
63. Section 6.1.5 Prior systemic 
therapy 
Includes CAR-T and clarification of recordation 
clarification 
64. Section 6.2.3 Physical Examination 
Change that physical exam can be done from up to 72 hours 
to up to 24 hours before dosing 
To unify that predose assessments can be done up 
to 24 hours predose 
65. Section 6.2.2. Prior and 
concomitant medications 
Changed from “at screening” to “during the screening 
period” to clarify that meds are to be collected during the 
screening period and not just at the screening visit 
Clarification 


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66. Section 6.2.3 Physical Exam 
(1) Changed from up to 72 hours before to up to 24 hours 
before dosing; (2) removed repeated information 
(1) To unify with other predose assessments that 
can be done up to 24 hours predose; (2) 
administrative 
67. Section 6.2.3.1 
Changed heading to remove “including ECOG and NYHA” 
since these two topics are covered elsewhere 
Administrative 
68. Section 6.2.5 New York Heart 
Association 
Added clarification that NYHA need only be assessed for 
subjects with heart failure 
Clarification 
69. Section 6.2.6 Vital signs 
(1) Added respiratory rate and body temperature whenever 
BP and HR are assessed (and thereby removed separate 
section on vital signs (previously section 6.2.7), therefore 
section numbers were updated) 
(2) And changed order of assessments 
(1) Inadvertently left-off RR and body 
temperature 
(2)  To allow more flexibility with site procedures 
70. Section 6.2.7 Left ventricular 
ejection fraction 
Updating requirements 
Clarification 
71. Section 6.2.8 Electrocardiograms 
Added language that when assessments are due at the same 
time; the order is ECG and VS first then PK  
To allow for more flexibility with site procedures 
72. Section 6.3.1 AE reporting period 
(1) Updated AE reporting to start at start of treatment, 
unless related to study screening procedure, and until STFU 
or start of new cancer therapy, (2) added that symptoms of 
CLS/CRS/SIRS/IRR should be reported in CRF on separate 
eCRF pages 
(1) To avoid collection of AEs that are not due to 
MT-3724 treatment, (2) administrative to add 
guidance for reporting expectations 
73. Section 6.3.5 Serious Adverse 
Events 
Removed erroneous example of SAE which stated that 
hospitalization for diagnostic procedure should be reported 
as SAE 
Administrative  
74. Section 6.4 Laboratory tests 
(1) Added Virology; for local labs, (2) removed “at the site”  (1) Added virology in order to capture data 
confirming viral load is undetectable for subjects 
with HBV/HIV; (2) administrative 
75. Section 6.4.2 eGFR 
Revised calculation to Cockcroft-Gault 
Consistency with previous protocol 
76. Section 6.4.1 Hematology, 
Chemistry, Urinalysis 
a) Added that local labs should be done to evaluate status 
if needed;  
b) Added that that these will be collected with continued 
dosing (replaced C3-C6 with cycle 3 and beyond); 
c) Updated that eGFR will be assessed by Cockcroft-
Gault rather than CPK-EPI 
a) Clarification 
b) To provide flexibility in obtaining pre-dose 
assessments 
c) To address continuation of assessments given 
allowance of continued dosing 
d) Updated for consistency throughout MT-3724 
program 
77. Section 6.4.4 HbA1c 
Updated frequency to assess at every odd cycle after cycle 3 
to account for continued dosing 
Clarification to assess for HbA1c to account for 
continued dosing 
78. Section 6.4.5. Thyroid function 
Updated frequency to assess at every odd cycle after cycle 3 
to account for continued dosing 
Clarification to assess for thyroid to account for 
continued dosing 


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79. Section 6.4.6 Coagulation 
Updated frequency to assess at every odd cycle after cycle 3 
to account for continued dosing 
Clarification to assess for coagulation to account 
for continued dosing 
80. Section 6.4.10 Rituximab 
concentration 
Added language that RTX doesn’t need to be re-evaluated 
once deemed “negative” in cases of re-screening  
Clarification 
81. Section 6.4.11 Serology/Virology 
Added Virology for HBV and HIV and CD4+ T-cell counts 
for HIV 
Added for consistency with updated exclusion 
criterion 
82. Section 6.4.12 Pregnancy test 
Updated language regarding at-home pregnancy tests “For 
pregnancy tests scheduled to occur when there is no 
corresponding on-site visit, the subject should use a 
commercial pregnancy test kit on their own and contact the 
site to report the test result.” 
Clarification: previous text only referred to at-
home pregnancy testing for cycle 1, while this is 
also expected to occur for cycle 2.  
83. Section 6.5 Drug Administration 
 Deleted because it’s redundant with section 5 
Administrative 
84. Section 6.5 Pharmacokinetic 
assessments 
Added PK timepoint in Table 3  
Clarification 
85. Section 6.6. Efficacy Assessment: 
Radiological Assessment of Tumor 
Response 
1. Updated to conduct efficacy assessment at every other 
cycle 
2. added that CT is encouraged at baseline for everyone 
3. updated title to include “radiological assessment”  
4. Added that the original schedule needs to be maintained 
even if there is a delay is dosing 
1. To provide guidance on continuation of 
efficacy assessment given continued dosing  
2. To obtain accurate measurements of tumor 
lesions for all subjects at baseline 
3. Administrative 
4. Clarification 
86. Section 6.8.1 Peripheral blood 
Update from change “C3-C6” to “cycle 3 and beyond” 
To provide guidance on continuation of peripheral 
blood collection for pharmacodynamics given 
continued dosing 
87. Section 6.9 Tumor Tissue 
Add, “Subjects may also have a biopsy to confirm CR, in 
the absence of PET/CT scans.” 
Clarification – part of Lugano criteria, added 
explicitly to protocol to clarify 
88. Section 6.10 Exploratory 
assessments 
 
 
 
89. Section 7.5 Subject disposition and 
termination status 
Removed language around tabulation of subjects and 
dropouts 
Clarification 
90. Section 7.9 Efficacy analysis 
Updated to add PFS and DCR definitions; and that CT/MRI 
to be done even for subjects with FDG-avid lymphoma 
Clarification 
91. Section 7.14 Protocol deviations 
Updated language to remove language that was not 
applicable per Molecular Templates SOPs 
Administrative  
92. Section 8.1.3 Informed consent 
Updated timing of screening from 28 days predose to 35 
days predose, with the exception of safety labs and 
radiographic assessments which are to be done within 28 
days of dosing 
Administrative/consistency 
93. Section 8.5 Study monitoring, 
auditing and inspection 
Changed “personal” to “on-site” 
Administrative 
PPD


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94. Section 8.6 Source Data 
(1) removed “direct access”; (2) removed requirement of 
redaction of materials reviewed on-site; (3) removed 
reference to screen procedure CRF (4) removed mention of 
specific documents being provided  
(1) to allow for remove monitoring; (2) to reflect 
current monitoring practices; (3) removed as not 
part of this study (administrative); (4) 
administrative 
95. References 
Updated IB reference to current version (v5 2019) and new 
references added 
Update with most recent version 
96. Appendix 1 SOA for screening 
(1) Added virology for HBV/HIV; (2) removed reference to 
visits in Table 7 header; (3) Table 8 added for PK 
timepoints  
(1) Added for consistency with updated exclusion 
criterion; (2) administrative (3) clarification 
97. Appendix 2 
Virology added, PK (serum and CSF for MT-3724 
measurement) added 
Clarification 
98. Appendix 4 
Updated table to match Cheson 2014 publication  
Administrative 
99. Appendix 5 
(1) Updated grade of CLS from Grade 2 to Grade 3 for 
DLT; deleted information that is repeated in section 3.6.2; 
(2) corrected definition for febrile neutropenia (per CTCAE 
v5) 
(1) CLS G2 does not constitute a major medical 
management challenge, and has thus far not 
stopped subjects from continuing treatment with 
study drug; (2) administrative 
 
 
 

SAP_001.pdf: 
A Phase 2a Open-label Study to Investigate Safety and Tolerability (including the MTD), 
Efficacy, Pharmacokinetics, Pharmacodynamics and Immunogenicity of MT-3724 in 
Combination with Lenalidomide in Subjects with Relapsed or Refractory B-cell Non-Hodgkin 
Lymphoma 
Protocol Number:  MT-3724_NHL_003 
Protocol Version: 2.0 
Protocol Date: 10DEC2018 
STATISTICAL ANALYSIS PLAN 
Version 1.0 
NCT Number: NCT03645395
This NCT number has been applied to the document
for the purposes of posting on clinicaltrials.gov


Molecular Templates MT-3724_NHL_002 SAP (version 1.0)
CONFIDENTIAL 
Page 2 of 23 
A Phase 2a Open-label Study to Investigate Safety and Tolerability (including the MTD), 
Efficacy, Pharmacokinetics, Pharmacodynamics and Immunogenicity of MT-3724 in 
Combination with Lenalidomide in Subjects with Relapsed or Refractory B-cell Non-
Hodgkin Lymphoma 
STATISTICAL ANALYSIS PLAN 
Version 1.0 
Author: 
  
Date 
Biostatistician, CTI 
CTI Biostatistics 
Reviewer: 
 
 
Date 
Senior Biostatistician, CTI 
Sponsor Approval: 
 
Date 
Senior Clinical Director 
Molecular Templates, Inc.  
 
Date 
CMO 
Molecular Templates, Inc. 


 
Molecular Templates MT-3724_NHL_002 SAP (version 1.0) 
 
CONFIDENTIAL  
 
Page 3 of 23 
Table of Contents 
SAP REVISIONS (EXAMPLE, IF NECESSARY) ................................. ERROR! BOOKMARK NOT DEFINED. 
1. 
INTRODUCTION .............................................................................................................................................. 5 
2. 
OBJECTIVES AND ENDPOINTS ................................................................................................................... 5 
2.1 
OBJECTIVES .................................................................................................................................................. 5 
2.1.1 
Primary Objective .................................................................................................................................... 5 
2.1.2 
Secondary Objectives ............................................................................................................................... 5 
2.2 
ENDPOINTS ........................................................................................... ERROR! BOOKMARK NOT DEFINED. 
2.2.1 
Primary Endpoint .................................................................................... Error! Bookmark not defined. 
2.2.2 
Secondary Endpoints ............................................................................... Error! Bookmark not defined. 
3. 
INVESTIGATIONAL PLAN............................................................................................................................. 5 
3.1 
STUDY DESIGN ............................................................................................................................................. 5 
3.2 
TREATMENT .................................................................................................................................................. 6 
3.2.1 
Randomization Scheme and Treatment Arm Assignment ......................... Error! Bookmark not defined. 
3.2.2 
Blinding ................................................................................................... Error! Bookmark not defined. 
3.2.3 
Dosing Schedule ...................................................................................................................................... 6 
3.2.4 
Patient Compliance.................................................................................. Error! Bookmark not defined. 
4. 
GENERAL CONSIDERATIONS FOR DATA ANALYSIS ........................................................................... 7 
4.1 
DATA QUALITY ASSURANCE ................................................................ ERROR! BOOKMARK NOT DEFINED. 
4.2 
ANALYSIS SETS ............................................................................................................................................. 7 
4.3 
ASSESSMENT WINDOWS ............................................................................................................................... 9 
4.4 
HANDLING OF DROPOUTS OR MISSING DATA ............................................................................................... 9 
4.5 
MULTIPLE COMPARISONS ........................................................................................................................... 10 
4.6 
DATA DERIVATIONS AND TRANSFORMATIONS ........................................................................................... 10 
5. 
STUDY PATIENTS .......................................................................................................................................... 10 
5.1 
DISPOSITION OF PATIENTS .................................................................... ERROR! BOOKMARK NOT DEFINED. 
5.2 
PROTOCOL DEVIATIONS ........................................................................ ERROR! BOOKMARK NOT DEFINED. 
5.3 
DEMOGRAPHIC CHARACTERISTICS ....................................................... ERROR! BOOKMARK NOT DEFINED. 
5.4 
BASELINE CHARACTERISTICS ............................................................... ERROR! BOOKMARK NOT DEFINED. 
5.5 
MEDICAL HISTORY ............................................................................... ERROR! BOOKMARK NOT DEFINED. 
5.6 
PRIOR AND CONCOMITANT MEDICATIONS ............................................ ERROR! BOOKMARK NOT DEFINED. 
5.6.1 
Non-Immunosuppressant Medications ..................................................... Error! Bookmark not defined. 
5.6.2 
Immunosuppressant Medications ............................................................. Error! Bookmark not defined. 
6. 
EFFICACY ANALYSIS ................................................................................................................................... 10 
6.1 
PRIMARY EFFICACY ENDPOINT AND ANALYSIS .................................... ERROR! BOOKMARK NOT DEFINED. 
6.2 
SECONDARY EFFICACY ENDPOINTS AND ANALYSES ............................ ERROR! BOOKMARK NOT DEFINED. 
6.3 
TERTIARY EFFICACY ENDPOINTS AND ANALYSES ................................ ERROR! BOOKMARK NOT DEFINED. 
6.4 
PROGNOSTIC FACTORS AND SUBGROUP ANALYSES .............................. ERROR! BOOKMARK NOT DEFINED. 
6.5 
PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSES .................. ERROR! BOOKMARK NOT DEFINED. 
7. 
SAFETY ANALYSIS........................................................................................................................................ 11 
7.1 
EXTENT OF EXPOSURE .......................................................................... ERROR! BOOKMARK NOT DEFINED. 
7.2 
ADVERSE EVENTS ................................................................................. ERROR! BOOKMARK NOT DEFINED. 


 
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7.2.1 
Treatment-emergent Adverse Events ....................................................... Error! Bookmark not defined. 
7.2.2 
Adverse Event Severity ............................................................................. Error! Bookmark not defined. 
7.2.3 
Adverse Event Relationship to Study Medication .................................... Error! Bookmark not defined. 
7.2.4 
Serious Adverse Events ............................................................................ Error! Bookmark not defined. 
7.2.5 
Adverse Event Summaries ........................................................................ Error! Bookmark not defined. 
7.3 
CLINICAL LABORATORY ASSESSMENTS ................................................ ERROR! BOOKMARK NOT DEFINED. 
7.4 
VITAL SIGNS ......................................................................................... ERROR! BOOKMARK NOT DEFINED. 
7.5 
ECG...................................................................................................... ERROR! BOOKMARK NOT DEFINED. 
7.6 
PHYSICAL EXAMINATION ...................................................................... ERROR! BOOKMARK NOT DEFINED. 
7.7 
OTHER SAFETY MEASURES ................................................................... ERROR! BOOKMARK NOT DEFINED. 
8. 
INTERIM ANALYSIS ..................................................................................................................................... 13 
9. 
SAMPLE SIZE AND POWER CALCULATIONS ........................ ERROR! BOOKMARK NOT DEFINED. 
10. 
REFERENCES ............................................................................................................................................. 19 
11. 
APPENDICES .............................................................................................................................................. 21 
11.1 
APPENDIX A: SCHEDULE OF ASSESSMENTS ................................................................................................ 21 
11.2 
APPENDIX B: EXAMPLE HLA MISMATCH CALCULATIONS ......................................................................... 22 
 
 


 
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1. 
INTRODUCTION 
This statistical analysis plan (SAP) is based on Molecular Templates’ Protocol # MT-
3724_NHL_003, titled “A Phase 2a Open-label Study to Investigate Safety and Tolerability 
(including the MTD), Efficacy, Pharmacokinetics, Pharmacodynamics and Immunogenicity of 
MT-3724 in Combination with Lenalidomide in Subjects with Relapsed or Refractory B-cell Non-
Hodgkin Lymphoma”. See the study Protocol for details on study rationale, conduct and endpoints. 
The purpose of this SAP is to provide details of the statistical analyses specified in the study 
protocol. The SAP summarizes key aspects of the study to provide context for statistical methods 
and presents details of the planned statistical methods following the completion of the trial.  
This study will be conducted in compliance with the study protocol and ICH guideline E9 
(Statistical Principles for Clinical Trials 1998). 
2. 
OBJECTIVES AND ENDPOINTS 
2.1 
Objectives 
2.1.1 
Primary Objective 
The primary objective of the study is to determine the safety and tolerability (including the MTD) 
of MT-3724 in combination with lenalidomide in subjects with relapsed or refractory B-Cell NHL 
2.1.2 
Secondary Objectives 
The secondary objectives of the study are to: 
• Characterize the PK of MT-3724 in combination with lenalidomide in subjects with 
relapsed or refractory B-cell NHL 
• Assess the PD of MT-3724 in combination with lenalidomide in subjects with relapsed or 
refractory B-cell NHL 
• Assess the immunogenicity of MT-3724 in combination with lenalidomide in subjects with 
relapsed or refractory B-cell NHL 
• Assess the tumor response to MT-3724 in combination with lenalidomide in subjects with 
relapsed or refractory B-cell NHL 
3. 
INVESTIGATIONAL PLAN 
3.1 
Study Design 
This is a multi-center, open-label, multiple-dose Phase 2a, dose-escalation study of MT-3724 in 
combination with LEN in subjects with relapsed or refractory B-Cell NHL. Eligible subjects will 
be identified and treated through competitive enrollment at multiple study centers in North 
America and Europe.  
The study will be conducted in two sequential parts (Part 1 and Part 2); in both parts of the study, 
the subject’s participation in the study will comprise 2 periods: screening and treatment. 


 
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Part 1 will include MT-3724 dose escalation according to the modified 3+3 design to identify the 
MTD of MT-3724 in combination with fixed standard doses of LEN. If permitted by the safety 
results, the MT-3724 dose escalation is planned to proceed in three sequential dose cohorts 
(Cohorts 1-3). 
The purpose of Part 2 is to confirm the safety and tolerability of the MTD of MT-3724 from Part 
1 in the MTD Expansion Cohort, where MT-3724 will be given at the MTD in combination with 
LEN. In addition, the PK, PD, immunogenicity and tumor response at the MTD of MT-3724 in 
combination with LEN will be more thoroughly evaluated in Part 2. 
See the study protocol for full study design details.    
3.2 
Treatment 
MT-3724 will be administered as intravenous (IV) infusion over 1 hour. 
In Part 1 (MT-3724 dose escalation), the starting MT-3724 doses in each of the planned cohorts 
will be: 
1. 10 µg/kg/dose in Cohort 1 
2. 25 µg/kg/dose in Cohort 2 
3. 50 µg/kg/dose in Cohort 3 
Additional interim dose cohorts may be evaluated only if warranted by the safety results in the 
previous planned cohorts.  The maximum dose of MT-3724 that will be given in this study is 50 
ug/kg/dose. 
In Part 2 (Expansion Cohort), the starting MT-3724 dose will be the MTD of MT-3724 from Part 
1. 
The administered dose of MT-3724 for subjects will be capped at 6000 µg per infusion.  Intra-
subject escalation of MT-3724 dose is not permitted in this study. The guidance for treatment 
modification (dose interruption / delay, dose reduction or treatment discontinuation) is outlined in 
the study protocol. 
3.2.1 
Dosing Schedule 
MT-3724 Dosing Schedule 
Cycles 1-2 
In Cycle 1 and Cycle 2, MT-3724 should be administered as 1-hour IV infusion on Day 1, 3, 5, 8, 
10 and 12 of each 28-day cycle.  
Any of the scheduled MT-3724 doses may be administered on different dosing days at 
investigator’s discretion up to D21. However, no more than two MT-3724 doses can be 
administered on consecutive days.  
If MT-3724 is administered on consecutive days, then at least 20 hours (approximately five half-
lives of MT-3724 in plasma) must elapse between the start of the 2 infusions. 
The “catch up” on missed MT-3724 doses in the current cycle is allowed at the investigator’s 
discretion up to D21. MT-3724 should not be administered between D21-D28 in C1-C2. 


 
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MT-3724 may be continued in C3-C4 (with or without LEN) if supported by the investigator’s 
assessment of the benefit-risk ratio. 
Cycles 3-4 (if applicable or beyond) 
If treatment is continued, then dosing in C3-C4, MT-3724 should be administered as 1-hour IV 
infusion weekly (Day 1, 8, 15 and 22 of each 28-day cycle). Any of the scheduled weekly MT-
3724 doses may be administered within ±2 days at investigator’s discretion. MT-3724 should not 
be administered between D24-D28 in C3-C4. 
Lenalidomide Dosing Schedule 
In both parts of the current study, subjects will self-administer LEN qd PO with or without food, 
around the same time each day, on the first 21 consecutive days (Day 1-Day 21) of each 28-day 
cycle. LEN cannot be administered between D22-D28 in any cycle. 
4. CHANGES TO PLANNED ANALYSIS 
The statistical methods described in this SAP take precedence over the protocol. Additional 
exploratory efficacy endpoints have been added. 
• 
 
 
• 
 
  
5. 
GENERAL CONSIDERATIONS FOR DATA ANALYSIS 
Quantitative data will be described by the following summary statistics: arithmetic mean, 
standard deviation, median, minimum, and maximum. Where appropriate, descriptive summary 
statistics will be tabulated for the absolute values and changes from baseline. Graphical 
illustrations will be provided where appropriate. Qualitative data will be presented in the 
frequency tables. 
Analyses will be performed using SAS for Windows statistical software, version 9.2 or higher 
(SAS, Cary, NC), except where other software may be deemed more appropriate.  
CTI Clinical Trial and Consulting Services (Cincinnati, OH) will perform all efficacy and safety 
statistical analyses.   
Subject data will be listed, sorted by cohort and subject number. Dose escalation cohorts and MTD 
expansion cohort will be reported separately and combined at the recommended phase 2 dose. 
5.1 
Data Quality Assurance 
Molecular Templates, or its designated representative, will conduct a pre-study visit for each study 
site to verify the qualifications of the investigator, inspect study site facilities, become familiarized 
with site staff assigned to the study, and inform the investigator of responsibilities and procedures 
for ensuring correct study documentation. 
A study coordinator at the investigative site will enter subject data into a remote data capture 
PPD
PPD


 
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database (RDC) by completing electronic case report forms (eCRFs).  All information recorded in 
the eCRFs for this study must be consistent with the investigator’s source documentation for the 
study participants.  The investigative site will make available source documents to CTI personnel 
monitoring the study.  The study monitor will verify consent of all subjects to participate in the 
study and will perform 100% source document verification of the eCRF data. 
A CTI Clinical Data Associate (CDA) will review the data for discrepancies via programmed 
electronic consistency checks, data listings, or manually.  Any discrepancies discovered via the 
data review process will be issued as queries in the RDC system to the investigative site for 
resolution.  Once all the source verification is complete, all queries are resolved, and the database 
has been updated appropriately, the database will be locked and made available to CTI Biostatistics 
for analysis. 
Data may be pulled by CTI Biostatistics for interim analysis at a time when source verification 
and query resolution is ongoing. No interim statistical analysis is planned during either part of this 
study. An interim statistical analysis may be performed only pursuant to a health authority request. 
All SAS programs used to create analysis datasets and output will be validated by ensuring that 
the “.log” files are void of all errors, warnings and notes indicative of problems.  Additionally, 
each program will be checked to ensure that it performs according to the program specification. 
All programs are developed and validated by separate members of the CTI Biostatistics 
Department.  
At the time of analysis, a quality control (QC) review of database values listed in SAS output will 
be compared to the database.  The sample size of fields to undergo QC review will be determined 
by utilizing American National Standards Institute (ANSI) sampling procedures1.  Sampling 
procedures are conducted using “normal” inspection criteria (Inspection Level II, Single, and 
Normal) and an Acceptable Quality Level (AQL) of 0.010%.  The following shows the sampling 
criteria: 
Single Normal sampling procedure for Acceptable Quality Level (AQL) 0.010% 
Number of Fields 
Sample 
Size 
Accept/Reject 
Criteria 
2-8 
2 
0/1 
9-15 
3 
0/1 
16-25 
5 
0/1 
26-50 
8 
0/1 
51-90 
13 
0/1 
91-150 
20 
0/1 
151-280 
32 
0/1 
281-500 
50 
0/1 
501-1,200 
80 
0/1 
1,201-3,200 
125 
0/1 
3,201-10,000 
200 
0/1 
10,001-35,000 
315 
0/1 
35,001-150,000 
500 
0/1 
150,001-500,000 
800 
0/1 


 
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Number of Fields 
Sample 
Size 
Accept/Reject 
Criteria 
500,001-up 
1,250 
0/1 
 
5.2 
Analysis Sets 
The following analysis populations are defined for this study: 
Safety Population 
All subjects who received at least one dose of any study drug (either MT-3724, or lenalidomide) 
will be included in the safety population. The safety population will be used for the primary 
statistical analysis of safety and efficacy endpoints. 
Efficacy Evaluable Population 
The efficacy evaluable population will include patients who have at least one post-baseline 
radiographic evaluation or those that were discontinued for clinical progression. 
PK Population 
The PK population will include all subjects who received at least one dose of MT-3724 and have 
at least one post-baseline PK assessment. The PK population will be used for the PK analyses.  
Subjects who received only lenalidomide but haven’t received MT-3724 will be excluded from 
the PK analyses. 
Immunogenicity Population 
All subjects who received at least one dose of MT-3724 and have at least one post-baseline 
immunogenicity assessment will be included in the analyses of anti-drug antibody (ADA) and 
NA. Subjects who received only lenalidomide but haven’t received MT-3724 will be excluded 
from the immunogenicity analyses. 
PD Population 
All subjects who received at least one dose of MT-3724 and have at least one post-baseline PD 
assessment will be included in the analyses of B-cell count and immunophenotype (flow 
cytometry). Subjects who received only lenalidomide but haven’t received MT-3724 will be 
excluded from the PD analyses.  
5.3 
Assessment Windows 
Data will be summarized based on the CRF (Study Visit) in which it was collected even if the 
assessment is outside of the specified visit window.  In data listings, the relative day of all dates 
will be presented.  Such days will be measured relative to Day 1, the day in which the first dose of 
study drug is received.   
The last post-baseline visit where data were collected will be flagged for each subject. These visits 
will be combined for analysis of laboratory and vital sign results.  
The assessment obtained at the most recent time before the start of MT-3724 treatment will be the 
baseline for all post-baseline assessments. The value obtained before MT-3724 Dose 1 on C1D1 
(if available) will serve as the baseline; if not available, then the value obtained earlier at screening 


 
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will serve as the baseline. Screening procedures should be performed up to 28 days before Day 1 
C1D1. 
If a repeat laboratory sample was drawn for a visit, the values from the repeat sample will be used 
for summary and analysis purposes.  In this case, only the repeat sample values will be listed. 
5.4 
Handling of Dropouts or Missing Data 
In both parts of the study, the sponsor will determine if a subject should be replaced. All subject 
data collected will be analyzed in the Safety Analysis set. The additional subject(s) included to 
replace non-evaluable subjects will be given new unique subject IDs. 
Subjects in Part 1 will be evaluable for dose decisions if they satisfy one of the following 
criteria:  
• Have had a DLT irrespective of the number of MT-3724, lenalidomide doses received in 
C1; or 
• In the absence of DLT, have received at least 4 of 6 (83%) doses of MT-3724 and both 
doses of lenalidomide in C1 
Subjects in the current cohort who are not evaluable for dose decisions will be replaced. 
For summary statistics and concentration-time profiles, all values that are below the limit of 
quantitation (BLQ) will be set to zero. Missing data will not be imputed in this study. 
5.5 
Multiple Comparisons 
There are no multiple comparisons. 
5.6 
Data Derivations and Transformations 
Not applicable. 
6. 
STUDY PATIENTS 
6.1 
Disposition of Subjects 
A table of counts of all safety subjects will be provided. Reasons for not completing study 
medication as planned and reasons for premature withdrawal will be tabulated by dose level. 
6.2 
Protocol Deviations 
Distribution for the types of protocol deviations and the number of subjects that deviate from the 
protocol will be tabulated for the dose levels. 
6.3 
Demographic Characteristics 
Descriptive statistics will be used to summarize the demographic characteristics (age, gender, race, 
ethnicity, weight, and height) for the safety analysis set. 


 
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6.4 
Baseline Characteristics 
Subject baseline characteristics; including demographics, medical history, physical examination, 
ECG, and vital signs will be summarized descriptively.  
6.5 
Medical History 
All medical conditions and surgical procedures will be classified by system organ class (SOC) and 
preferred term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA). Medical 
history will be categorized into either non-cancer related or cancer related. Summaries and listings 
of each category will be presented separately. 
6.6 
Prior and Concomitant Medications 
Prior medications within 30 days of consent and inter-current concomitant medications will be 
coded using World Health Organization (WHO) drug classifications. The number and percent of 
safety subjects using concomitant medications will be tabulated by Anatomical, Therapeutic, and 
Chemical (ATC) class and by preferred name.  
All prior and concomitant medication data will be listed, sorted by dose level, investigative site 
and subject number, start and stop date. Information listed will include medication, indication, 
dose, and route of administration. 
7. 
EFFICACY ANALYSIS 
7.1 
Primary Efficacy Endpoint and Analysis 
The primary endpoints of this study are safety related and therefore there are no primary efficacy 
endpoints. 
7.2 
Secondary Analysis 
A secondary analysis of efficacy to evaluate response to MT-3724 in combination with 
lenalidomide will be performed in this trial. The efficacy parameters of interest are objective 
response rate (ORR), best objective response rate (BORR), and duration of response (DOR). All 
efficacy summaries will be based on the safety population. 
6.1.1 Objective Response Rate 
The ORR measures the proportion of subjects with a reduction in tumor size (Partial Response or 
Complete Response) using the five-point scale (5PS) per the Lugano Classification for  
Lymphoma (2) adjusted according to LYRIC (lymphoma response to immunomodulatory 
therapy criteria) (3). An overview of LYRIC is presented in the protocol. The proportion of 
subjects with a Partial Response or Complete Response will be summarized and presented at 
each scheduled visit. The ORR representing clinically significant clinical benefit in this study 
will comprise the Lugano Score 1, 2 or 3, or the CR, CRu or PR. The number and percentage of 
subjects with clinically significant results will be presented. 


 
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6.1.2 Best Objective Response Rate 
The best ORR (BORR) at all time points will be reported. Subjects who experience disease 
progression before undergoing the first tumor assessment will be added to the disease 
progression stratum. The BORR will be descriptively summarized by the treatment group / 
cohort; the exact 95% confidence intervals will also be produced. 
6.1.3 Duration of Response 
All subjects achieving clinically significant clinical benefit according to the response criteria 
(CR, CRu, PR, or stable disease for at least 3 months) will be included in the analysis of the 
duration of tumor response (DOR).  
 
DoR is defined as the time interval (days) from date of the first objective response (CR, CRu, or 
PR; achieved after the date of exposure to MT-3724) to the date of disease progression.   
Duration of Response (days) =  
Date of Progression after 1st Objective Response − Date of 1st Objective Response +1 
• If the subject does not have a response of CR, CRu, or PR the Duration of Response will 
be set to missing.  
• Subjects not meeting the criteria for progression or death by the analysis cutoff date will 
be censored at their last evaluable disease assessment date and their first response will be 
noted as ongoing.   
• For death or PD after more than 1 missed evaluation, the duration will be censored at the 
last visit. 
The DOR will be descriptively summarized by the treatment group / cohort; the exact 95% 
confidence intervals will also be produced. 
6.1.4 Progression-free Survival 
Progression-free survival (PFS) is the time from study drug administration until disease 
progression or death. The disease assessment by the RECIST V1.1 criteria occurs at Screening, 
months 1, 3, 6, 9, 12, 18 and 24. 
PFS is defined as the interval between the date of first infusion of and the date of PD or death, 
whichever is first reported.  
PFS (days) =  
Date of Progression − Date of 1st Infusion + 1 
The following Kaplan-Meier (KM) estimates will be provided: 
• 25th, 50th (i.e., median) and 75th KM percentiles with 95% CIs 
• Number and percent of subjects censored/not censored 
KM estimates of the proportion of subjects event-free at: 3, 6, 12, 18, and 24 months (note: not all 
estimates may be provided for interim analyses) 


 
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7.3 
Pharmacokinetic and Pharmacodynamic Analyses 
MT-3724 serum concentration/time data from all eligible subjects will be subjected to 
noncompartmental analysis (NCA) using the software package Phoenix WinNonlin (Certera, 
Princeton NJ). PK parameters will be stratified by MT-3724 dose group and summary statistics 
will be generated. Exploratory analyses between PK and PD results as well as clinical responders 
will be conducted, as appropriate.  Details will be provided in a separate analysis plan for this 
study objective. 
7.4 
Immunogenicity Analyses 
Data for the ADA against MT-3724 will be obtained as titer, if the screening and confirmation 
assays are positive, while the data for the neutralizing antibodies (NA) against MT-3724 will be 
obtained as either positive or negative. The number and percent of subjects with a detectable 
ADA titer, and separately with a positive NA result, will be summarized by time point for each 
treatment group/cohort. The individual subject’s immunogenicity results will be listed by time 
point for each subject by treatment group/cohort. Details of the immunogenicity analyses will be 
provided in a separate analysis plan for this study objective.  
8. 
SAFETY ANALYSIS 
All safety summaries will be conducted using the safety analysis set. No formal hypothesis 
testing will be performed to compare differences between dose levels. 
8.1 
Extent of Exposure 
The total number of doses received, the expected total dose, the actual dose administered, and 
outcome of infusion will be summarized and presented. Information in the listing will include 
total dose of MT-3724 administered, start and stop times, outcome of infusion, and duration of 
interruption (if applicable). 
8.2 
Adverse Events  
An adverse event (AE) is any untoward medical occurrence in a subject or clinical investigation 
subject who is administered study drug, whether or not the event is considered related to the 
investigational product. An AE is therefore any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated 
with the use of the study drug. Examples of AEs include but are not limited to: 
• Abnormal test findings 
• Clinically significant symptoms and signs 
• Changes in PE 
• Hypersensitivity 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
investigational product or a concurrent medication 
Any AE or SAE occurring after the subject provides informed consent and prior to receiving 
investigational product that is considered by the Investigator to be related to study procedures, 
will be reported. 


 
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8.2.1 
Pre-treatment-emergent Adverse Events 
Pre-treatment AEs include those aspects of the patient’s medical history that were ongoing at 
consent, as well as the new or worsening AEs reported between the screening medical history 
and the start of treatment. These AEs will be assessed by verbal probes and from medical history. 
The pre-treatment AEs will be listed by subject but not summarized. 
8.2.2 
Treatment-emergent Adverse Events 
A treatment-emergent adverse event (TEAE) is defined as any event not present prior to 
exposure of study drug or an event already present that worsens in either severity or frequency 
following exposure. 
8.2.3 
Adverse Event Severity 
The CTCAE v.5.0 will be used for grading the severity of AEs. Every effort should be made to 
find the appropriate AE term and definition of severity in the CTCAE v.5.0. If the AE term 
chosen by the investigator is not listed in the CTCAE v.5.0, then the highest severity level on the 
scale in the following table will be assigned to the investigator’s AE term. 
 
Classification of Adverse Events by Severity Grade (CTCAE v.5.0) 
Grade 
Description 
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. 
8.2.4 
Adverse Event Relationship to Study Medication 
Causality should be assessed separately for each study drug (MT-3724, lenalidomide) as detailed 
in the eCRF. If the investigator feels that the event cannot be firmly attributed to one of the study 
treatments, then the same assessment should be documented for each of the study treatments. 
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. 
 


 
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The investigator and separately, the Medical Monitor on behalf of the sponsor, will determine the 
causal relationship / relatedness to the study drug(s) according to the classification in the 
following table: 
 
Classification of adverse events by causality / relationship to the study drug(s) 
Causal Relationship 
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. 
At least 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, DLT assignment and treatment modification, the 
causality assessment of “at least probably”, “possibly” or “definitely” will be treated as 
“related”, while the causality assessment of “unlikely” and not related” will be treated as 
“unrelated”. 
8.2.5 
Serious Adverse Events 
A serious adverse event (SAE) is any AE that meets one 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-subject 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 patient or subject or may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 


 
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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. For example, an overnight 
hospitalization for a diagnostic procedure must be reported as an SAE even though the 
occurrence is not medically serious. 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 adverse event 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. 
8.2.6 
Adverse Event Summaries 
All AEs (serious and non serious) occurring after completion of the informed consent process and 
before the end of study, regardless of relationship to study drug, will be included and classified by 
system organ class (SOC) and preferred term (PT) using the Medical Dictionary for Regulatory 
Activities (MedDRA).     
For treatment-emergent AEs (TEAEs), the following will be summarized and presented for the 
safety analysis set: 
i. 
An overall summary of TEAEs, which includes:   
a. the number and percentage of subjects experiencing a TEAE 
b. the number and percentage of subjects experiencing a TEAE by relationship to 
study medication (for each study medication) 
c. the number and percentage of subjects experiencing a TEAE by greatest grade 
d. the number and percentage of subjects experiencing a TEAE leading to study dose 
interruption  
e. the number and percentage of subjects experiencing a TEAE leading to dose delay  
f. the number and percentage of subjects experiencing a TEAE leading to dose 
reduction  
g. the number and percentage of subjects experiencing a TEAE leading to study 
withdrawal  
h. the number and percentage of subjects experiencing a TEAE of special interest 
(IRR, CRS, and CLS) 
i. the number and percentage of subjects experiencing a treatment emergent SAE 
(TESAE) 
ii. 
the number and percentage of subjects experiencing a TEAE by SOC, PT 
iii. 
the number and percentage of subjects experiencing a TEAE by SOC, PT and 
relationship to study medication (for each study medication) 
iv. 
the number and percentage of subjects experiencing a TEAE by SOC, PT and greatest 
grade 


 
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v. 
the number and percentage of subjects experiencing a TEAE leading to dose 
interruption by SOC and PT 
vi. 
the number and percentage of subjects experiencing a TEAE leading to dose delay by 
SOC and PT 
vii. 
the number and percentage of subjects experiencing a TEAE leading to dose reduction 
by SOC and PT 
viii. 
the number and percentage of subjects experiencing a TEAE leading to study 
withdrawal by SOC and PT 
ix. 
the number and percentage of subjects experiencing a TEAE of special interest by SOC 
and PT 
x. 
the number and percentage of subjects experiencing a TESAE leading to dose 
interruption by SOC and PT 
xi. 
the number and percentage of subjects experiencing a TESAE leading to dose delay by 
SOC and PT 
xii. 
the number and percentage of subjects experiencing a TESAE leading to dose reduction 
by SOC and PT 
xiii. 
the number and percentage of subjects experiencing a TESAE leading to study 
withdrawal by SOC and PT 
xiv. 
the number and percentage of subjects experiencing a TESAE of special interest by 
SOC and PT 
In the overall summary of TEAEs table (i), besides tabulating the number and percentage of 
subjects, the total number of TEAE episodes will also be provided. If a subject has repeated 
episodes of a particular TEAE, all episodes will be counted in the summary table.   
In the remaining summary tables, the incidence of TEAEs will be calculated by dividing the 
number of subjects who have experienced the event by the total number of subjects in the safety 
analysis set.  Thus, the incidence of TEAEs is shown in terms of the total number of subjects and 
not in terms of the total number of episodes.  If a subject has repeated episodes of a particular 
TEAE, only the most severe episode, or the episode with the strongest causal relationship to study 
drug, will be counted in the summary tables.  
A subject with more than one type of TEAE in a particular SOC will be counted only once in the 
total of subjects experiencing TEAEs in that particular SOC.  Since a subject could have more than 
one type of TEAE within a particular SOC, the sum of subjects experiencing different TEAEs 
within the SOC could appear larger than the total number of subjects experiencing TEAEs in that 
SOC.  Similarly, a subject who has experienced a TEAE in more than one SOC will be counted 
only once in the total number of subjects experiencing AEs in all SOCs. 
All occurrences of all AEs will be listed for each subject, grouped by cohort.  The listing will 
contain the following information: treatment group, verbatim term, SOC, PT, severity, relationship 
to study medication, date and day of onset, date and day of resolution, treatment given to treat the 
adverse event, the outcome, whether the event was an SAE, whether it led to withdrawal and 
whether it is a TEAE.  Listings will be sorted by subject identification number, onset date, SOC, 
and PT. If the onset date is completely missing, then these events will be presented first. If the 


 
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onset date is missing a month or a day, then these events will be presented before any complete 
dates. 
8.2.7 
Dose Limiting Toxicity (DLT) 
The number and percentage of subjects experiencing a DLT will be summarized and presented by 
dose level. A listing of DLTs will also be presented. 
8.3 
Clinical Laboratory Assessments 
Laboratory assessments will be summarized by presenting descriptive statistics of raw data and 
change from baseline. Listings will include flags for values outside of the reference ranges, and 
clinical significance if a laboratory result is deemed abnormal. 
The following tests will be performed by the central laboratory:  
• Hematology 
• Chemistry (with eGFR) 
• HbA1c 
• Coagulation (aPTT and either INR or PT) 
• Thyroid function (TSH and FT4) 
• Serum cytokines 
• Histamine 
• Complement 
• Immunoglobulins 
• B-cell count and immunophenotype (flow cytometry) 
The following laboratory tests will be performed in the local laboratory at the site: 
• Urinalysis (Dipstix) 
• Pregnancy test (serum or urine) 
• Serology for HIV, HBV and HCV (if applicable) 
A shift table displaying baseline CTCAE grade to maximum post-baseline CTCAE grade will be 
presented for hematology and chemistry lab values. 
8.4 
Physical Examination 
The overall results of the physical examination (‘normal’, ‘abnormal, not clinically significant’, 
or ‘abnormal, clinically significant’) and ECOG performance status will be summarized by 
treatment group / cohort and listed per subject. Comments for abnormal CS results will be listed. 
8.5 
Vital Signs 
Vital sign data including weight, systolic blood pressure, diastolic blood pressure, heart rate, and 
temperature, will be summarized by presenting descriptive statistics of raw data and change from 
baseline values at each visit. 
 
A shift table displaying baseline to maximum post-baseline values and last post-baseline value 
will be presented. 


 
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8.6 
ECG Results 
The following ECG results will be summarized.  
• Heart rate 
• PR interval 
• QRS duration  
• RR interval 
• QT interval 
• 
QT interval corrected according to Fridericia’s formula (QTcF) 
 
The results of the overall ECG review by the investigator or delegate will also be summarized. 
Comments for abnormal CS results of the ECG will be listed.  
QTcF values will also be categorized according to their values as defined in ICH E14:  
• ≤ 450 ms 
• > 450 ms to ≤ 480 ms 
• > 480 ms to ≤ 500 ms 
• > 500 ms  
and categorized according to their change from baseline into the categories 
• ≤ 30 ms 
• > 30 ms to ≤ 60 ms  
• > 60 ms  
The categories described above will be summarized in frequency tables using number of patients 
(n) and percentages for each dose cohort. 
9. 
INTERIM ANALYSIS 
No interim statistical analysis is planned during either part of this study. An interim statistical 
analysis may be performed only pursuant to a health authority request. 
Informal (preliminary) statistical analyses may be performed at sponsor’s discretion at any time 
during the study. These analyses would be performed without the interim data base lock for the 
purposes of the IB update, safety reports to the health authorities (e.g. DSUR), and meetings with 
health authorities or for internal decisions. 
In addition, data from individual subjects and cohorts will be reviewed without formal statistical 
analysis on an ongoing basis during the study (e.g. to support the dose escalation decisions in Part 
1). 
10. SAMPLE SIZE AND POWER CALCULATIONS 
Up to 64 subjects (i.e., up to 24 subjects in Part 1 and up to 40 subjects in Part 2), as well as the 
appropriate number of replacements (if needed), will be enrolled and treated in this study. The 
actual number will depend on the number of dose cohorts needed to identify the MTD of MT-3724 
in combination with LEN in Part 1.  


 
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This is an exploratory Phase 2a study, so the formal power calculation is not deemed necessary to 
justify the sample size. The proposed sample size is deemed sufficient for the adequate 
characterization of the study objectives and would be typical of the sample sizes of exploratory 
Phase 1b / 2a studies with novel anti-cancer agents


11. 
REFERENCES 
1. American National Standards Institute.  Sampling Procedures and Tables for Inspection by 
Attributes, ANSI/ASQC Z1.4-1993 
12. 
APPENDICES 
12.1 
Appendix A: Schedule of Assessments 
Insert schedule of assessments from protocol. 
 
 
 


 
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12.2 
Appendix B: Example HLA Mismatch Calculations 
 
HLA: Mismatched Antigens 
 
 
 
 
 
 
 
 
           
               0 Antigen Mismatch 
 
 
 
 
          1 Antigen Mismatch 
 
 
  
  
  
   
 
 
  
2 
Antigen Mismatch 
 
 
 
 
          3 Antigen Mismatch 
 
 
 
 
 
 
 
 
 
 
  4 Antigen Mismatch 
 
 
 
 
          5 Antigen Mismatch 
 
 
 
 
 
 
 
 
 
 
  6 Antigen Mismatch 
 
 
 
 
 
 
 
 
 
D 
O 
N 
O 
R 
                         RECIPIENT 
 
A01 
A02 
B07 
B08 
DR13 
DR15 
A01 
 
 
 
 
 
 
A02 
 
 
 
 
 
 
B07 
 
 
 
 
 
 
B08 
 
 
 
 
 
 
DR13 
 
 
 
 
 
 
DR15 
 
 
 
 
 
 
 
 
D 
O 
N 
O 
R 
                         RECIPIENT 
 
A01 
A02 
B07 
B08 
DR13 
DR15 
A01 
 
 
 
 
 
 
A03 
 
 
 
 
 
 
B07 
 
 
 
 
 
 
B08 
 
 
 
 
 
 
DR13 
 
 
 
 
 
 
DR15 
 
 
 
 
 
 
 
 
D 
O 
N 
O 
R 
                         RECIPIENT 
 
A01 
A02 
B07 
B08 
DR13 
DR09 
A01 
 
 
 
 
 
 
A02 
 
 
 
 
 
 
B44 
 
 
 
 
 
 
B08 
 
 
 
 
 
 
DR13 
 
 
 
 
 
 
DR15 
 
 
 
 
 
 
 
 
D 
O 
N 
O 
R 
                         RECIPIENT 
 
A01 
A11 
B07 
B22 
DR08 
DR15 
A01 
 
 
 
 
 
 
A02 
 
 
 
 
 
 
B07 
 
 
 
 
 
 
B08 
 
 
 
 
 
 
DR13 
 
 
 
 
 
 
DR15 
 
 
 
 
 
 
 
 
D 
O 
N 
O 
R 
                         RECIPIENT 
 
A01 
A02 
B07 
B08 
DR13 
DR15 
A03 
 
 
 
 
 
 
A02 
 
 
 
 
 
 
B60 
 
 
 
 
 
 
B51 
 
 
 
 
 
 
DR13 
 
 
 
 
 
 
DR14 
 
 
 
 
 
 
 
 
D 
O 
N 
O 
R 
                         RECIPIENT 
 
A01 
A02 
B27 
B08 
DR11 
DR15 
A24 
 
 
 
 
 
 
A33 
 
 
 
 
 
 
B07 
 
 
 
 
 
 
B08 
 
 
 
 
 
 
DR13 
 
 
 
 
 
 
DR17 
 
 
 
 
 
 
 
 
D 
O 
N 
O 
R 
                         RECIPIENT 
 
A01 
A02 
B07 
B08 
DR13 
DR15 
A24 
 
 
 
 
 
 
A33 
 
 
 
 
 
 
B27 
 
 
 
 
 
 
B56 
 
 
 
 
 
 
DR17 
 
 
 
 
 
 
DR18 
 
 
 
 
 
 
MATCH 
MISMATCH 


 
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Homozygosity: Instances in which antigens are not defined are typically a result of homozygosity.  
Homozygosity is defined as the condition of having identical genes at one or more loci (A, B, DR).  
As HLA genes are inherited from the mother and the father, if the mother and father share an 
antigen or multiple antigens, it is possible for a child to inherit the same A and/or B and/or DR 
antigen from both parents.  When this occurs, antigens suspected to be duplicated are termed 
“blank”, and the results will appear as shown below. 
 
 
      
 
 
 
 
 
 
 
Example 1 
0 Antigen Mismatch 
(“blanks” on donor and recipient) 
No antigens differ between the recipient and donor.  
This combination would qualify as a 0 antigen 
mismatch. 
 
 
                   
 
Example 2 
0 Antigen Mismatch 
(“blanks” on donor only) 
Because the donor does not express any    antigens 
the recipient does not express, this combination 
would also qualify as a 0 antigen mismatch. 
                    
 
 
Example 3  
3 Antigen Mismatch 
(“blanks” on recipient only) 
If Example 2 is reversed and the donor expresses 
antigens that the recipient does not, these will 
qualify as mismatched antigens. The recipient 
immune system may now recognize the A02, B44, 
and DR 17 from the donor as foreign and mount an 
immune response. 
 
 
 
 
 
 
 
 
 
 
 
 
D 
O 
N 
O 
R 
                         RECIPIENT 
 
A01 
 
B03 
 
DR13 
 
A01 
 
 
 
 
 
 
 
 
 
 
 
 
 
B03 
 
 
 
 
 
 
 
 
 
 
 
 
 
DR13 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D 
O 
N 
O 
R 
                         RECIPIENT 
 
A01 
A02 
B03 
B44 
DR13 
DR17 
A01 
 
 
 
 
 
 
 
 
 
 
 
 
 
B03 
 
 
 
 
 
 
 
 
 
 
 
 
 
DR13 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D 
O 
N 
O 
R 
                         RECIPIENT 
 
A01 
 
B03 
 
DR13 
 
A01 
 
 
 
 
 
 
A02 
 
 
 
 
 
 
B03 
 
 
 
 
 
 
B44 
 
 
 
 
 
 
DR13 
 
 
 
 
 
 
DR17 
 
 
 
 
 
 
MATCH 
MISMATCH 
SUSPECTED 
MATCH