Clinical trial NCT03488251
Conditions: Non-hodgkin Lymphoma,B Cell Refractory Diffuse Large B-Cell Lymphoma Relapsed Diffuse Large B-Cell Lymphoma
Sponsor: Molecular Templates, Inc.
Start date: 2018-08-20; Completion date: 2021-03-12
Enrollment: 8 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The purpose of this study is to evaluate the safety and tolerability of MT-3724 in combination with gemcitabine and oxaliplatin (GEMOX) 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 GEMOX in relapsed or refractory B-cell Lymphoma patients.

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

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 GEMOX. In addition, the PK, PD, immunogenicity and tumor response at the MTD of MT-3724 in combination with GEMOX will be more thoroughly evaluated in Part 2.

In original protocol and amendment 2, participants will be administered intravenous (IV) MT-3724 over 1 hour on Days 1, 3, 5, 8, 10 and 12 in Cycles 1 and 2 (each 28-day cycle) and on Days 1, 8, 15, and 22 in Cycles 3 and 4 (each 28-day cycle). Participants will also be administered Gemcitabine 1000 milligrams per meter square (mg/m\^2) as 30-minute IV infusion and Oxaliplatin 100 mg/m\^2 as 2-hour IV infusion on Days 2 and 16 in Cycles 1, 2, 3 and 4 (each 28-day cycle). Per amendment 2, participants will be administered MT-3724 on Days 1, 3, 5, 8, 10, 12, 15, 22, 29, and 36 in Cycle 1 (42-day cycle). In Cycles 2, 3 and 4, MT-3724 will be administered weekly on Days 1, 8, 15, and 22 of each 28-day cycle. Gemcitabine and oxaliplatin will be administered on Days 16 and 30 of Cycle 1 and on Days 2 and 16 in Cycles 2, 3 and 4 (42-day cycle for Cycle 1 and 28-day cycle for Cycle 2, Cycle 3 and Cycle 4).

Continued Treatment with MT-3724 in combination with GEMOX will continue for four cycles of until death, disease progression, unacceptable toxicity, withdrawal of consent or another reason for withdrawal.

After four cycles, the participants who experience clinical benefit can continue MT-3724 treatment with additional cycles of 28 days each (either alone or in combination with GEMOX) if supported by the investigator's assessment of the benefit-risk ratio, after consultation with sponsor and Medical Monitor

Arms: arm 1: In original protocol and amendment 2, participants will be administered intravenous (IV) MT-3724 10 micrograms per kilograms (mcg/kg) over 1 hour on Days 1, 3, 5, 8, 10 and 12 in Cycles 1 and 2 (each 28-day cycle) and on Days 1, 8, 15, and 22 in Cycles 3 and 4 (each 28-day cycle). Participants will also be administered Gemcitabine 1000 milligrams per meter square (mg/m\^2) as 30-minute IV infusion and Oxaliplatin 100 mg/m\^2 as 2-hour IV infusion on Days 2 and 16 in Cycles 1, 2, 3 and 4 (each 28-day cycle). Per amendment 2, participants will be administered MT-3724 10 mcg/kg on Days 1, 3, 5, 8, 10, 12, 15, 22, 29, and 36 in Cycle 1 (42-day cycle). In Cycles 2, 3 and 4, MT-3724 10 mcg/kg will be administered weekly on Days 1, 8, 15, and 22 of each 28-day cycle. Gemcitabine and oxaliplatin will be administered on Days 16 and 30 of Cycle 1 and on Days 2 and 16 in Cycles 2, 3 and 4 (42-day cycle for Cycle 1 and 28-day cycle for Cycle 2, Cycle 3 and Cycle 4). arm 2: In original protocol and amendment 2, participants will be planned to administer IV MT-3724 25 mcg/kg over 1 hour on Days 1, 3, 5, 8, 10 and 12 in Cycles 1 and 2 (each 28-day cycle) and on Days 1, 8, 15, and 22 in Cycles 3 and 4 (each 28-day cycle). Participants will also be planned to administer Gemcitabine 1000 mg/m\^2 as 30-minute IV infusion and Oxaliplatin 100 mg/m\^2 as 2-hour IV infusion on Days 2 and 16 in Cycles 1, 2, 3 and 4 (each 28-day cycle). Per amendment 2, participants will be planned to administer MT-3724 25 mcg/kg on Days 1, 3, 5, 8, 10, 12, 15, 22, 29, and 36 in Cycle 1 (42-day cycle). In Cycles 2, 3 and 4, MT-3724 25 mcg/kg will be planned to administer weekly on Days 1, 8, 15, and 22 of each 28-day cycle. Gemcitabine and oxaliplatin will be planned to administer on Days 16 and 30 of Cycle 1 and on Days 2 and 16 in Cycles 2, 3 and 4 (42-day cycle for Cycle 1 and 28-day cycle for Cycle 2, Cycle 3 and Cycle 4). arm 3: In original protocol and amendment 2, participants will be planned to administer IV MT-3724 50 mcg/kg over 1 hour on Days 1, 3, 5, 8, 10 and 12 in Cycles 1 and 2 (each 28-day cycle) and on Days 1, 8, 15, and 22 in Cycles 3 and 4 (each 28-day cycle). Participants will also be planned to administer Gemcitabine 1000 mg/m\^2 as 30-minute IV infusion and Oxaliplatin 100 mg/m\^2 as 2-hour IV infusion on Days 2 and 16 in Cycles 1, 2, 3 and 4 (each 28-day cycle). Per amendment 2, participants will be planned to administer MT-3724 50 mcg/kg on Days 1, 3, 5, 8, 10, 12, 15, 22, 29, and 36 in Cycle 1 (42-day cycle). In Cycles 2, 3 and 4, MT-3724 50 mcg/kg will be planned to administer weekly on Days 1, 8, 15, and 22 of each 28-day cycle. Gemcitabine and oxaliplatin will be planned to administer on Days 16 and 30 of Cycle 1 and on Days 2 and 16 in Cycles 2, 3 and 4 (42-day cycle for Cycle 1 and 28-day cycle for Cycle 2, Cycle 3 and Cycle 4). arm 4: Participants will be planned to administer Maximum tolerated dose (MTD) of MT-3724 in combination with Gemcitabine and Oxaliplatin (GEMOX).
Interventions: intervention 1: MT-3724 intervention 2: Gemcitabine intervention 3: Oxaliplatin
Intervention descriptions: intervention 1: MT-3724 will be administered. intervention 2: Gemcitabine will be administered. intervention 3: Oxaliplatin will be administered.

Protocol documents:
Prot_000.pdf: 
Molecular Templates, Inc. 
MT-3724_NHL_002 
MT-3724 
Version.2.0, 14 January 2019
CLINICAL STUDY PROTOCOL 
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 Gemcitabine and Oxaliplatin in Subjects with Relapsed or Refractory B-
Cell Non-Hodgkin Lymphoma 
Protocol Number: 
MT-3724_NHL_002 
EudraCT no. 
Not applicable 
IND Number: 
121918 
Development Phase: 
2a 
Study Sponsor: 
Molecular Templates, Inc. 
9301 Amberglen Blvd., Suite 100 Austin, TX 78729 
United States 
Current Protocol Version: 
Amendment 1, Version 2.0 
Version Date: 
14-JAN-2019
Previous Version: 
Version 1.0 18-JUL-2018 
-CONFIDENTIAL- 
This document and its contents are the property of and confidential to Molecular Template, Inc. 
Any unauthorized copying or use of this document is prohibited. 
'tern 
MOLECULAR TEMPLATES 
NCT Number: NCT03488251 
This NCT number has been applied to the document
for the purposes of posting on clinicaltrials.gov


Molecular Templates, Inc. 
Protocol MT-3724_NHL_002, Version.2.0, 14 January 2019
Page 2 of 152 
FINAL PROTOCOL V2.0
AMENDMENT 1, VERSION 2.0 (JAN 2019) 
Amendment rationale: 
A complete list of changes can be found in APPENDIX I.– SUMMARY OF CHANGES, 14 
JAN 2019, VERSION 2.0 REPLACES VERSION 1.0  


Molecular Templates, Inc. 
Protocol MT-3724 NHL 002, Vcrsion.2.0, 14 Janumy 2019 
S APPROVAL 
 
, MD, PhD 
Acting Chief Medical Officer 
Molecular Templates, Inc. 
 
SVP Operation 
Molecular Templates, Inc. 
, PhD 
Senior Director Clinical Science 
Molecular Templates, Inc. 
, PhannD 
Director Clinical Operations 
Molecular Templates, Inc. 
FINAL PROTOCOL V2.0 
Page3of15l 
Date 
Date 


Molecular Templates, Inc. 
Protocol MT-3724_NHL_002, Version.2.0, 14 January 2019
Page 4 of 152 
FINAL PROTOCOL V2.0
INVESTIGATOR PROTOCOL AGREEMENT PAGE 
As the Investigator on the study MT-3724_NHL_002, I agree: 
•
To assume responsibility for the proper conduct of the study at this site.
•
To conduct the study in compliance with this protocol, any future amendments, and with
any other study conduct procedures provided by the Sponsor.
•
Not to implement any changes to the protocol without written agreement from the
Sponsor, and prior review and written approval from the Independent Ethics Committee
(IEC) or Institutional Review Board (IRB) except where necessary to eliminate an
immediate hazard to study subjects.
•
That I am thoroughly familiar with the appropriate use of the study drug, as described in
this protocol and any other information provided by the Sponsor, including, but not
limited to, the current Investigator’s Brochure (IB) for MT-3724.
•
That I am aware of, and will comply with, good clinical practices (GCP) and all
applicable regulatory requirements.
•
To ensure that all persons assisting me with the study are adequately informed about the
Sponsor, study drug and of their study-related duties and functions as described in the
protocol.
Signature: 
Date: 
Name 
(print): 
Site Name: 


Molecular Templates, Inc. 
 
Protocol MT-3724_NHL_002, Version.2.0, 14 January 2019 
Page 5 of 152 
 
FINAL PROTOCOL V2.0 
 
LIST OF CONTACTS 
 
Sponsor’s Physician Responsible: 
 
 
, MD, PhD 
Acting Chief Medical Officer 
Molecular Templates, Inc. 
Mobile:
 
External Medical Monitor: 
 
, MD 
CTI 
Mobile:
 
 
Pharmacovigilance and SAE reporting: 
CTI 
SAE Reports Fax: 1-866-561-3914 
SAE Reports Hotline: 1-877-755-0742 
General Safety: ctisafety@ctifacts.com 
 
Clinical Operations: 
 
, PharmD 
Director, Clinical Operations 
Molecular Templates, Inc. 
Mobile:
 


Molecular Templates, Inc. 
 
Protocol MT-3724_NHL_002, Version.2.0, 14 January 2019 
Page 6 of 152 
 
FINAL PROTOCOL V2.0 
 
 
SYNOPSIS  
Title 
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 Gemcitabine and Oxaliplatin in Subjects with Relapsed or 
Refractory B-Cell Non-Hodgkin Lymphoma 
Sponsor 
Molecular Templates, Inc. 
Development Phase 2a 
Primary Objective 
Determine the safety and tolerability [including the maximum 
tolerated dose (MTD)] of MT-3724 in combination with gemcitabine 
and oxaliplatin in subjects with relapsed or refractory B-Cell Non-
Hodgkin Lymphoma (NHL) 
Secondary 
Objectives 
• Characterize the pharmacokinetics (PK) of MT-3724 in 
combination with gemcitabine and oxaliplatin in subjects with 
relapsed or refractory B-Cell NHL 
• Assess the pharmacodynamics (PD) of MT-3724 in combination 
with gemcitabine and oxaliplatin in subjects with relapsed or 
refractory B-Cell NHL 
• Assess the immunogenicity of MT-3724 in combination with 
gemcitabine and oxaliplatin in subjects with relapsed or 
refractory B-Cell NHL 
• Assess the tumor response to MT-3724 in combination with 
gemcitabine and oxaliplatin in subjects with relapsed or 
refractory B-Cell NHL 
Exploratory 
Objectives 
Not applicable 
Study Design 
This will be an open-label dose escalation study of MT-3724 in 
combination with gemcitabine and oxaliplatin (GEMOX) 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. 


Molecular Templates, Inc. 
 
Protocol MT-3724_NHL_002, Version.2.0, 14 January 2019 
Page 7 of 152 
 
FINAL PROTOCOL V2.0 
 
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. 
Screening Period 
The screening procedures should be performed up to 28 days before 
Day 1 C1D1. The screening procedures will be identical in Part 1 and 
Part 2. 
Treatment Period 
Each subject may be treated only in one part of the study. The 
treatment procedures will be identical in Part 1 and Part 2. 
Treatment with MT-3724 in combination with GEMOX will continue 
for two cycles of 28-days each or until death, disease progression, 
unacceptable toxicity, withdrawal of consent or another reason for 
withdrawal (see 4.3.1).  
After two cycles, the MT-3724 treatment (either alone or in 
combination with GEMOX) can be continued for another two 28-day 
cycles if supported by the investigator’s assessment of the benefit-risk 
ratio, after consultation with sponsor and Medical Monitor. 
In all cycles, MT-3724 will be administered as intravenous (IV) 
infusion over 1 hour. In C1 and C2, MT-3724 infusion should be 
administered on Day 1, 3, 5, 8, 10 and 12. If MT-3724 treatment is 
continued to C3 and C4, then MT-3724 should be administered 
weekly (Day 1, 8, 15 and 22) of each 28-day cycle. MT-3724 cannot 
be administered between D22-D28 in C1-C2 or between D24-D28 in 
C3-C4. 
Gemcitabine (Gemzar®) 1000 mg/m2 will be administered as 30-
minute IV infusion on Day 2 and Day 16 of each 28-day cycle (i.e., 
every 14 days). Oxaliplatin (Eloxatin®) 100 mg/m2 will be 
administered as 2-hour IV infusion after gemcitabine on Day 2 and 
Day 16 of each 28-day cycle (i.e., every 14 days). Oxaliplatin 
infusion will start one hour after the start of gemcitabine infusion 
(unless a delay is warranted at the investigator’s discretion). 


Molecular Templates, Inc. 
 
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Treatment with GEMOX will continue for two cycles of 28-days each 
or until death, disease progression, unacceptable toxicity, withdrawal 
of consent or another reason for withdrawal (see 4.3.1). After two 
cycles, the GEMOX treatment may be continued for another two 28-
day cycles if supported by the investigator’s assessment of the 
benefit-risk ratio, after consultation with sponsor and Medical 
Monitor.   
End of Treatment 
The End of Treatment (EoT) Visit will be performed at the end of the 
treatment period in each subject in Part 1 and Part 2. EoT Visit should 
occur at the time of discontinuation (except for subjects who died, 
withdrew consent and objected to further data collection, or were lost 
to follow up) or ≥ 7 days and ≤ 14 days after the last dose of MT-
3724, gemcitabine or oxaliplatin for those that complete the study.  
The EoT Visit should be performed during the clinic visit. 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.  The 
EoT visit will be followed by a safety follow-up (SFU) phone call at 
least 30 days after last dose of MT-3724 or gemcitabine or 
oxaliplatin.  
Part 1 (MT-3724 Dose Escalation) 
Part 1 will include MT-3724 dose escalation according to the 
modified 3+3 design to identify the maximum tolerated dose (MTD) 
of MT-3724 in combination with standard doses of gemcitabine and 
oxaliplatin. If permitted by the safety results, the MT-3724 dose 
escalation is planned to proceed in three sequential dose cohorts 
(Cohorts 1-3).  
In all dose cohorts, MT-3724 will be administered in combination 
with starting doses of gemcitabine 1000 mg/m2 and oxaliplatin 100 
mg/m2.  The starting dose can be decreased per investigators 
discretion based on the known safety profile of gemcitabine and/or 
oxaliplatin and the patient status.  


Molecular Templates, Inc. 
 
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Table 1:  MT-3724 Dose Cohorts and Corresponding Dose Levels 
of MT-3724, gemcitabine and oxaliplatin 
Planned 
MT-3724 
Dose 
Cohorts 
Interim 
MT-3724   
Dose 
Cohortsa 
Starting 
MT-3724     
Dose 
(µg/kg/dose) 
Starting 
Gemcitabine 
Dose 
(mg/m2) 
Starting 
Oxaliplatin 
Dose 
(mg/m2) 
1 
 
10 
1000 
100 
 
-1 
(optional) ≤ 5b 
1000 
100 
2 
 
25 
1000 
100 
 
-2 
(optional) ≤ 17.5b 
1000 
100 
3 
 
50 
1000 
100 
 
-3 
(optional) ≤ 37.5b 
1000 
100 
a. To be evaluated only if warranted by the safety results in the 
previous planned cohorts 
b. The 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, all investigators 
and Medical Monitor 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 dose-limiting toxicity (DLT). See Section 5.4. 
for conduct of dose escalation and for dose decisions in Part 1. 


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MTD definition: The highest MT-3724 dose that can be given in 
combination with GEMOX 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 GEMOX and complete C1 or 
experience a DLT.  
The maximum dose of MT-3724 that will be given in this study is 50 
ug/kg/ dose (with a maximum total dose of 6000 µg), which is the 
MTD of MT-3724 as monotherapy. The MT-3724 dose escalation 
will not proceed above the 50 ug/kg/dose even if no more than 1 of 6 
subjects in Cohort 3 experience a DLT. 
The sponsor will make the decision on the MTD after consultation 
with all investigators and Medical Monitor. 
Up to 24 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 GEMOX. Subjects in Part 1 will be 
enrolled through competitive enrollment at multiple study centers in 
North America and Europe. 
 
Part 2 (MTD Expansion Cohort) 
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 GEMOX. In 
addition, the PK, PD, immunogenicity and tumor response at the 
MTD of MT-3724 in combination with GEMOX will be more 
thoroughly evaluated in Part 2. 
Part 2 can start only after the MTD of MT-3724 in combination with 
GEMOX 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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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 study centers in North America and Europe.  
Long-Term Follow Up 
Subjects will be followed every 6 months for 24 months for PFS and 
DOR until progressive disease, death or lost to follow up. 
Study Population  
Eligible subjects will have histologically confirmed, relapsed or 
refractory B-cell NHL that, in the investigator’s opinion, could 
benefit from MT-3724+GEMOX therapy. All subtypes of B-cell 
NHL may be considered for Part 1 (MT-3724 dose escalation). Only 
Diffuse Large B-Cell Lymphoma (DLBCL) may be considered for 
Part 2 (MTD Expansion Cohort). 
Sample Size 
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 GEMOX in Part 1. 
 
Eligibility 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 B-cell NHL that, in the 
investigator’s opinion, could benefit from MT-3724+GEMOX 
therapy. At least one histologically documented relapse of 
NHL, by: 
a. Bone marrow biopsy (FNA is not acceptable) or  


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b. Excisional lymph node biopsy or 
c. Core biopsy of any involved organ (FNA not 
acceptable)  
d. CD20-positive histology must have been confirmed at 
any time during NHL disease course and documented 
in the medical history 
e. If no histology is available after any relapse the 
investigator can consult the medical monitor to discuss 
if the patient can be included  
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 (expansion cohort). 
5. Have received all approved therapies for NHL that are 
applicable for the patient in the opinion of the treating 
physician. 
a. Patients refractory to treatment are eligible. 
b. Patient who have progressed following CAR T-cell 
therapy are also eligible. 
6. Have measurable disease by Lugano Classification for NHL 
(APPENDIX D) 
a. >1.5 cm longest diameter (LDi) for lymph nodes  
b. >1 cm LDi for extranodal disease 
7. Have ECOG performance score of ≤2 (APPENDIX G). 
8. Have adequate bone marrow function, as determined by: 
a. Absolute neutrophil count (ANC) ≥1,000/mm3 and 
b. Platelet count ≥50,000 mm³  
9. Have adequate kidney function, assessed by the estimated 
glomerular filtration rate (eGFR) ≥60 mL/min calculated by 
the CPK-EPI equation (APPENDIX F). 


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a. At the investigator’s discretion, the eGFR result <60 
mL/min may be verified by measurement of creatinine 
clearance (CLcr) based on the 24-hour urine 
collection. Subjects with CLcr ≥60 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 ≤3 x ULN for subjects 
with Gilbert's Syndrome and  
b. Aspartate aminotransferase (AST) ≤3 x ULN  (or ≤ 5.0 
xULN if liver involvement)  and 
c. Alanine aminotransferase (ALT) ≤3 x ULN  (or ≤ 5.0 
xULN if liver involvement).  
11. Have adequate coagulation, as determined by: 
a. INR or PT ≤1.5 x ULN  
b. aPTT ≤1.5 x ULN  
12. Have adequate serum albumin, as determined by: 
a. Albumin ≥ 3.0 g/dL  
13. Women of reproductive potential must have a negative 
pregnancy test during the screening period within 72 hours 
before the start of treatment. Women not of reproductive 
potential are female subjects who are postmenopausal or 
permanently sterilized (e.g., tubal occlusion, hysterectomy, 
bilateral salpingectomy).  
14. Subjects of reproductive potential and their partners must 
agree to either to abstain continuously from heterosexual 
intercourse or to use a reliable birth control method between 
signing the informed consent until  6 months following the 
last dose of MT-3724 or GEMOX .  The investigator or a 
designated associate should advise the subject how to achieve 
adequate contraception. The following birth control methods 
may be considered as adequate: 


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a. Condoms (male or female) with or without a 
spermicidal agent;  
b. Diaphragm or cervical cap with spermicide;  
c. Intrauterine device;  
d. Hormone-based contraception: Established use of oral, 
injected, or implanted hormonal methods of 
contraception; 
e. True abstinence; 
f. Vasectomy is an acceptable method for a male subject 
or male partner of a female subject. 
Exclusion Criteria 
Subjects who meet ANY of the following criteria will not be eligible 
for the study. 
Medical and surgical history 
15. History or current evidence of neoplastic disease that is 
histologically distinct from NHL except cervical carcinoma in 
situ, superficial noninvasive bladder tumors, curatively treated 
Stage I-II non-melanoma skin cancer, or any other previous 
cancer curatively treated >2 years before the start of treatment. 
16. 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  
b. Have no neurological symptoms (except Grade ≤2 
neuropathy)? 
c. Have stable brain or spinal disease on the CT or MRI 
scan within 1 month of enrollment and 
d. Do not require chronic steroid therapy 


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17. History of allogeneic hematopoietic stem cell transplant 
within 180 days before the start of treatment. 
18. Current evidence of acute or chronic Graft versus Host 
Disease. 
19. Current evidence of CTCAE Grade >1 toxicity (except for 
hair loss, and those toxicities listed as permitted in other 
eligibility criteria) before the start of treatment. 
20. Current evidence of incomplete recovery from surgery before 
the start of treatment, or planned surgery at any time during 
the study until the EoT Visit, except minor elective 
interventions deemed acceptable by the investigator.  
21. History or current evidence of significant (CTCAE Grade ≥2) 
infection or wound within 4 weeks before the start of 
treatment. 
22. History or current evidence of significant cardiovascular 
disease including, but not limited to the following conditions: 
a. Unstable angina (symptoms of angina at rest) or new-
onset angina within ≤3 months before the start of 
treatment. 
b. Arterial thrombosis or pulmonary embolism within 
≤3 months before the start of treatment. 
c. Myocardial infarction or stroke within ≤3 months 
before the start of treatment. 
d. 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 H) at screening  or LVEF <45%, 
assessed by Echo or MUGA scan within 1 month 
before starting study treatment. (Echo or MUGA scan 


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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). 
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 if the dose has 
been stable for ≥2 weeks before the start of treatment. 
Subjects with sinus arrhythmia and infrequent 
premature ventricular contractions are eligible at the 
investigator’s discretion. 
23. QTcF (Fridericia) >480 ms, determined as the average from 
three QTcF values on the triplicate ECG obtained at screening 
24. Current evidence of seropositive status for HIV, hepatitis B 
(positive for HBsAg or anti-HBsAg and anti-HBcAg 
antibodies) or hepatitis C (positive for anti-HCV antibody or 
HCV-RCV-RNA quantitation) at screening.   
a. Serology testing may be omitted at the investigator’s 
discretion if seronegativity is documented in the 
medical history and there are no clinical signs 
suggestive of HIV or hepatitis infection. 
b. Subjects with positive HBV serology are eligible if 
quantitative PCR for plasma HBV-DNA is negative 
and the subject will be receiving prophylaxis for 
potential HBV reactivation. 
c. Subjects with positive HCV serology are eligible if 
quantitative PCR for plasma HCV RNA is negative. 
25. Women who are pregnant or breastfeeding. 
26. History of hypersensitivity to any of the study drugs, or 
current evidence of hypersensitivity requiring systemic 
steroids at doses >20 mg/day prednisone equivalent. 


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27. 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 
28. Received any amount of anti-CD20 MAb therapy within the 
following periods before the start of treatment 
a. Rituximab (Rituxan®): 84 days; if a subject received 
rituximab within 37 weeks before the start of 
treatment, then a serum rituximab level must be 
negative (<500 ng/mL) at screening. 
b. Obinutuzumab (Gazyva®): 184 days 
c. Ofatumumab (Arzerra®): 88 days 
29. Received therapy for NHL (excluding the anti-CD20 MAbs 
listed above) within 4 weeks of the agent before the start of 
treatment. 
30. 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. 
31. Received radiotherapy to tumor lesion(s) that would be chosen 
as target lesions (measurable disease) within 4 weeks before 
the start of treatment, unless the lesion(s) exhibited objective 
progression between the radiotherapy and the screening 
according to the Lugano classification for NHL.  
a. Palliative radiotherapy to non-target lesions is allowed 
at the investigator’s discretion. 
32. Received any vaccines within 28 days of the start of 
treatment, or likely to require vaccines at any time from the 
start of treatment until 28 days after the last dose of MT-3724. 


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Injectable flu vaccine (inactivated or recombinant) is 
permitted at the investigator’s discretion. 
33. Received systemic immune modulators within 2 weeks before 
the start of treatment.   
a. Systemic immune modulators include, but are not 
limited to, systemic corticosteroids at doses >20 
mg/day of prednisone equivalent (except for 
premedication), cyclosporine and tacrolimus.  
b. The use of non-steroidal anti-inflammatory drugs 
(NSAIDs) is permitted. 
Treatments 
MT-3724 Investigational Medical Product (IMP) 
MT-3724 will be administered as intravenous (IV) infusion over 1 
hour.  
In C1 and C2, MT-3724 infusion should be administered on Day 1, 3, 
5, 8, 10 and 12 of each 28-day cycle. If the treatment with MT-3724 
is continued to Cycle 3 (C3) and Cycle 4 (C4), then MT-3724 will be 
administered weekly (Day 1, 8, 15 and 22) of each 28-day cycle.  
Different dosing days within ±2 days from scheduled weekly doses 
may be selected at investigator’s discretion. In C1-C2, 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 
(more than five half-lives of MT-3724 in plasma) must elapse 
between the start of the two infusions. 
MT-3724 cannot be administered between D22-D28 in C1-C2 or 
between D24-D28 in C≥3. 
 
In Part 1 (MT-3724 dose escalation), the starting MT-3724 doses in 
each of the planned cohorts will be: 
• 10 µg/kg/dose in Cohort 1 
• 25 µg/kg/dose in Cohort 2 
• 50 µg/kg/dose in Cohort 3 


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If MT-3724 is not tolerated in any of the planned cohort, then 
additional MT-3724 dose may be evaluated in the interim cohorts at 
the sponsor’s discretion in consultation with the investigator and 
Medical Monitor (Table 1).  
In Part 2 (Expansion Cohort), the starting MT-3724 dose will be the 
MTD (or a maximum dose of 50µg/kg) of MT-3724 from Part 1 in 
combination with GEMOX. 
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 presented in Section 5.4. 
Premedication 
Premedication should be given within 60 minutes before the start of 
each MT-3724 infusion in every cycle in Part 1 and Part 2. The agents 
from the following 3 drug classes are recommended for 
premedication: 
• Oral anti-inflammatory agent (e.g. acetaminophen not to 
exceed 1000 mg PO) 
• H1 histamine receptor antagonist (e.g. diphenhydramine not to 
exceed 100 mg IV) 
• Corticosteroid agent (e.g. methylprednisolone not to exceed 
1000 mg IV)  
Note: The specific premedication agents in each class and their doses 
should be selected at investigator’s discretion or according to the 
institutional guideline. The investigator may adjust the dosage 
and/or avoid using certain premedication agents during the 
treatment, if warranted by the investigator’s assessment of the 
risk from infusion-related reaction or other hypersensitivity 
events.   
See Section 5 for details about the IMP properties and dosing 
schedule. 


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Gemcitabine and Oxaliplatin (GEMOX) 
In all cohorts in Part 1 and Part 2, the starting doses of gemcitabine 
and oxaliplatin will be as follows: 
Gemcitabine 1000 mg/m2 will be administered as 30-minute IV 
infusion on Day 2 and Day 16 of each 28-day cycle.  
Oxaliplatin 100 mg/m2 will be administered as 2-hour IV infusion 
after gemcitabine on Day 2 and Day 16 of each 28-day cycle.  
Oxaliplatin infusion will start one hour after the start of gemcitabine 
infusion (unless a delay is warranted at the investigator’s discretion). 
Modification of starting dose of gemcitabine or oxaliplatin treatments 
or modification during treatment will be guided by the respective 
reference prescribing information, as interpreted by the investigator 
after consultation with sponsor and Medical Monitor. 
If gemcitabine or oxaliplatin dose has been reduced due to a TEAE, 
the intra-subject escalation of the respective drug’s dose is permitted 
if continued treatment is supported by the investigator’s assessment 
of the benefit-risk ratio after consultation with sponsor and Medical 
Monitor. In such cases, the gemcitabine or oxaliplatin dose may be 
increased only up to the level before the most recent dose reduction. 
Treatment Duration 
Treatment with MT-3724 in combination with GEMOX will continue 
for 2 cycles of 28-days each or until death, disease progression, 
unacceptable toxicity, withdrawal of consent or another reason for 
withdrawal, or study discontinuation.  
If supported by the investigator’s assessment of the benefit-risk ratio 
after consultation with sponsor and Medical Monitor, the treatment 
with MT-3724 in combination with GEMOX may continue for 2 
additional cycles of 28-days each (up to the total of 4 cycles), or until 
death, disease progression, unacceptable toxicity, withdrawal of 
consent or another reason for withdrawal, or study discontinuation. 
If the subject exhibits SD, CR or PR after the end of Cycle 4 and the 
investigator determines that the benefit-risk ratio is favorable, then 


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the treatment with MT-3724 may be continued after discussion with 
the sponsor. Continuation of GEMOX is at investigators discretion.  
Withdrawal Criteria Subjects must be withdrawn from the study at their own request or at 
the request of their legally acceptable representative. The subject has 
the right to withdraw from the study at any time for any reason, 
without the need to justify his/her withdrawal. The subject will not 
suffer any disadvantage because of the withdrawal. Subjects must 
also be withdrawn if the β-HCG pregnancy test indicates that they are 
pregnant. 
The subject may be withdrawn from the study at the discretion of the 
investigator due to: 
• Safety concerns  
• Lack of clinical benefit (disease progression is not 
documented but the investigator determines that the subject 
requires alternative anticancer treatment) 
• Non-compliance with study procedures to the extent that 
precludes the assessment of study objectives 
The sponsor also has the right to discontinue the study for any reason, 
in which case the treatment in all subjects must be permanently 
discontinued. 
Discontinuation of the study drug(s) for documented disease 
progression will be considered as the study completion and not as 
premature withdrawal from the study. 
Subject 
Characteristics and 
Safety Assessments 
The subject’s characteristics will include:  
• Demography 
• Height, body weight, BMI, BSA 
• NHL assessment (at initial diagnosis, relapse and/or current / 
baseline), including the NHL type, tumor histology, grading, 
staging (Ann Arbor-Cotswold Modification) and IPI for NHL 
or FLIPI (APPENDIX C). 
• Serum beta-2 microglobulin 


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• Medical history 
• Prior systemic NHL therapy 
• Prior radiotherapy for NHL 
• Prior and concomitant medications (except for NHL) 
• Serology for rituximab level (if applicable) 
• Serology for HIV, HBV and HCV (if applicable) 
The safety assessments will include: 
• Adverse events:  
• Physical examination (PE) 
• Blood pressure and heart rate (HR) 
• Body temperature 
• LVEF (MUGA or Echocardiogram)  
• New York Heart Association (NYHA) 
• ECOG 
• 12-lead ECG  
• Hematology  
• Blood chemistry and eGFR (CPK-EPI) 
• HbA1c 
• Coagulation (PT or INR, aPTT) 
• Thyroid function (TSH, FT4) 
• Urinalysis (Dipstix); urine microsediment may be ordered at 
the investigator’s discretion.  
• Cytokines 
• Complement, histamine 
• Immunoglobulins  
• Pregnancy test (urine or serum), if applicable 


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Unscheduled assessments may be performed at any time at the 
investigator’s discretion. Please see the Section 6. and APPENDIX A 
for further details. 
Efficacy 
Assessments 
Efficacy (tumor response) will be evaluated according to the revised 
Lugano Classification for Lymphoma (22) adjusted according to 
LYRIC (lymphoma response to immunomodulatory therapy criteria) 
(21). Positron emission tomography-computed tomography (PET-CT) 
should be used for response assessment in subjects with 
fluorodeoxyglucose (FDG)-avid tumor histology (using the 5-point 
scale [5PS]). Computer tomography (CT) or magnetic resonance 
imaging (MRI) should be used in subjects with tumor histology of 
low or variable FDG avidity.  
FDG-PET-CT or CT scan of all anatomic regions involved with the 
measurable disease will be performed at screening (baseline), within 
7 days before the start of MT-3724 infusion on C3D1 (end of C2) and 
at the EoT VISIT (only if the previous tumor scan has been 
performed >4 weeks before the EoT VISIT). 
Unscheduled tumor response assessment by FDG-PET-CT (or CT / 
MRI, where applicable) may be ordered at the investigator’s 
discretion. Please see Section 6 and APPENDIX A for further details. 
PK Assessments 
Blood samples will be collected 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, selected 
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 will be collected at prespecified time points on C1-4 
in Part 1 and Part 2. 
The PK of gemcitabine and oxaliplatin will not be assessed in this 
study. 
Please see Section 6.6 and APPENDIX A for further details. 


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Immunogenicity 
Assessments 
Serial blood samples for the assessment of immunogenicity of MT-
3724 [anti-drug antibody (ADA) titer and neutralizing antibody (NA)] 
will be collected at the prespecified time points in Part 1 and Part 2 
(See Section6.8. and APPENDIX A). 
Unscheduled assessments may be performed at any time at the 
investigator’s discretion. 
PD Assessments 
PD marker in this study will be the B-cell count and 
immunophenotype in peripheral blood, as determined by flow 
cytometry. Blood samples for the assessment of PD markers will be 
collected at the prespecified time points in Part 1 and Part 2 (See 
Section 6.9 and APPENDIX A). 
In Part 2 of the study an optional FNA biopsy will be obtained at EoT 
in patients who consented for this procedure and exhibit PD and have 
accessible peripheral lymph node(s). The purpose of biopsy is to 
assess the CD20 status of DLBCL by IHC staining of the fine needle 
aspirate and determine if the B-cell lymphoma cells have lost CD20 
positive status. 
Unscheduled assessments may be performed at any time at the 
investigator’s discretion. 
Statistical Methods 
All subjects who received at least one dose of MT-3724, gemcitabine 
or oxaliplatin will be included in the safety analysis set, which will be 
used for the statistical analyses of safety and efficacy data.  
All subjects who received at least one dose of MT-3724 and have at 
least one post-treatment PK and immunogenicity assessment will be 
included in the analysis set for the PK and immunogenicity analyses, 
respectively. Subjects who received only gemcitabine or oxaliplatin 
(haven’t received MT-3724) will be excluded from the PK and 
immunogenicity analyses. 
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 v.5.0. The AEs and SAEs are 


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treatment-emergent if they have started or worsened after the first 
dose of MT-3724. Only TEAEs and SAEs will be summarized, while 
the AEs and SAEs (if any) reported before the start of treatment will 
be listed. 
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 (20) adjusted according 
to LYRIC (lymphoma response to immunomodulatory therapy 
criteria) (21) (see APPENDIX D). 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 BORR will 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 complete or partial response 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. 
A detailed description of analysis methods will be provided in the 
statistical analysis plan (SAP) to be completed before the EoT Visit in 
the last subject. 


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PK Analyses 
MT 3724 serum concentration time data from all eligible subjects will 
be subjected to non-compartmental analysis (NCA) using the 
software package Phoenix WinNonlin (Certara, Princeton NJ). PK 
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 anti-drug antibody (ADA) against MT-3724 will be 
obtained as titer  for ADA samples confirmed as a positive result, 
while the data for the neutralizing antibodies (NA) 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 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. 
PD 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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TABLE OF CONTENTS 
AMENDMENT 1, version 2.0 (JAN 2019) ...................................................................... 2 
LIST OF CONTACTS ...................................................................................................... 5 
SYNOPSIS 
6 
TABLE OF CONTENTS ................................................................................................ 27 
LIST OF ABBREVIATIONS ........................................................................................... 35 
1. 
INTRODUCTION .................................................................................. 39 
1.1. 
Non-Hodgkin Lymphoma (NHL) ................................................................................. 39 
1.1.1. Anti-CD20 MAb Therapy for NHL .......................................................................... 39 
1.2. 
MT-3724 ....................................................................................................................... 40 
1.2.1. Clinical Experience with MT-3724 .......................................................................... 41 
1.3. 
Gemcitabine .................................................................................................................. 42 
1.4. 
Oxaliplatin..................................................................................................................... 43 
1.5. 
R-GEMOX .................................................................................................................... 43 
2. 
Study objectives ................................................................................. 45 
2.1. 
Primary Objective ......................................................................................................... 45 
2.2. 
Secondary Objectives.................................................................................................... 45 
3. 
Investigational plan ............................................................................ 46 
3.1. 
Description of Overall Study Design and Plan ............................................................. 46 
3.2. 
Screening Period ........................................................................................................... 46 
3.3. 
Treatment Period ........................................................................................................... 46 
3.3.1. MT-3724 ................................................................................................................... 46 
3.3.2. GEMOX .................................................................................................................... 47 
3.4. 
End of Treatment Visit and Safety Follow-up phone call ............................................ 47 


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3.5. 
Long-term Follow up Visit ........................................................................................... 48 
3.6. 
Part 1 (MT-3724 dose escalation) ................................................................................. 48 
3.6.1. Subject Evaluable for Dose Decisions ...................................................................... 50 
3.6.2. DLT Criteria.............................................................................................................. 51 
3.6.3. MTD Definition ........................................................................................................ 51 
3.6.4. MTD Communication Plan ....................................................................................... 51 
3.7. 
Part 2 (MTD Expansion Cohort)................................................................................... 52 
3.8. 
Rationale for the Study Design ..................................................................................... 52 
3.9. 
Guidance to the investigator ......................................................................................... 52 
3.10. Benefit/Risk Ratio ......................................................................................................... 53 
4. 
Study Population ................................................................................ 55 
4.1. 
Inclusion Criteria .......................................................................................................... 55 
4.2. 
Exclusion Criteria ......................................................................................................... 57 
4.3. 
Subject Withdrawal, Replacement and Study Discontinuation .................................... 60 
4.3.1. Subject Withdrawal ................................................................................................... 60 
4.3.2. Subject Replacement ................................................................................................. 60 
4.3.2.1. Part 1 (MT-3724 Dose Escalation) ................................................................... 60 
4.3.2.2. Part 2 (MTD Expansion) ................................................................................... 61 
4.3.3. Study Discontinuation ............................................................................................... 61 
5. 
Treatments ........................................................................................ 62 
5.1. 
MT-3724 ....................................................................................................................... 62 
5.1.1. MT-3724 Drug Product............................................................................................. 62 
5.1.2. MT-3724 Dose Selection .......................................................................................... 63 
5.1.2.1. Part 1 (MT-3724 Dose Escalation) ................................................................... 63 
5.1.2.2. Part 2 (MTD Expansion Cohort)....................................................................... 63 
5.1.3. MT-3724 Dosing Schedule ....................................................................................... 64 


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5.1.3.1. Time Windows for MT-3724 Dosing ............................................................... 64 
5.1.4. Premedication Before MT-3724 infusion ................................................................. 64 
5.2. 
Gemcitabine .................................................................................................................. 65 
5.2.1. Gemcitabine Dose Selection ..................................................................................... 65 
5.2.2. Gemcitabine Dosing Schedule .................................................................................. 65 
5.3. 
Oxaliplatin..................................................................................................................... 65 
5.3.1. Oxaliplatin Dose Selection ....................................................................................... 65 
5.3.2. Oxaliplatin Dosing Schedule .................................................................................... 66 
5.4. 
Intra-subject Dose Escalation ....................................................................................... 66 
5.5. 
Treatment Modification ................................................................................................ 66 
5.5.1. MT-3724 Treatment Modification ............................................................................ 66 
5.5.2. Gemcitabine Treatment Modification ....................................................................... 67 
5.5.3. Oxaliplatin Treatment Modification ......................................................................... 68 
5.5.4. Treatment Modification Due to IRR or Other Hypersensitivity Event ..................... 69 
5.5.5. Treatment Modification Due to Neutropenia or Thrombocytopenia ........................ 70 
5.5.6. Treatment Modification Due to Increased AST, ALT and/or Bilirubin Levels ....... 71 
5.6. 
Treatment Assignment .................................................................................................. 72 
5.7. 
Blinding......................................................................................................................... 72 
5.8. 
Treatment Compliance .................................................................................................. 73 
5.9. 
Treatment Duration ....................................................................................................... 73 
5.10. Prohibited Treatment .................................................................................................... 73 
5.11. Permitted Medication .................................................................................................... 74 
5.11.1. 
Reasons for caution ............................................................................................... 74 
6. 
Study assessments ............................................................................. 75 
6.1. 
General Subject Characteristics .................................................................................... 75 
6.1.1. Demographics ........................................................................................................... 75 


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6.1.2. Body Weight ............................................................................................................. 75 
6.1.3. Height, BMI and BSA............................................................................................... 75 
6.1.4. NHL Assessment ...................................................................................................... 75 
6.1.5. Prior Systemic Therapy............................................................................................. 76 
6.1.6. Prior Radiotherapy .................................................................................................... 76 
6.2. 
Safety Assessments ....................................................................................................... 76 
6.2.1. Medical History ........................................................................................................ 76 
6.2.2. Prior and Concomitant Medications ......................................................................... 76 
6.2.3. Physical Examination................................................................................................ 77 
6.2.3.1. Complete Physical Examination ....................................................................... 77 
6.2.3.2. Abbreviated Physical Examination ................................................................... 78 
6.2.4. Body Temperature .................................................................................................... 79 
6.2.5. Blood Pressure and Heart Rate ................................................................................. 79 
6.2.6. LVEF......................................................................................................................... 80 
6.2.7. Electrocardiograms, 12-lead ECG ............................................................................ 80 
6.3. 
Adverse Events ............................................................................................................. 81 
6.3.1. AE Reporting Period ................................................................................................. 82 
6.3.2. AE Terminology ....................................................................................................... 82 
6.3.3. Severity ..................................................................................................................... 82 
6.3.3.1. Causality / Relationship .................................................................................... 83 
6.3.4. Expected and unexpected adverse events and SUSARs ........................................... 84 
6.3.5. Serious adverse events .............................................................................................. 85 
6.3.5.1. SAE Reporting instructions .............................................................................. 85 
6.3.5.2. SUSAR .............................................................................................................. 86 
6.3.6. Clinical Laboratory Adverse Events ......................................................................... 86 
6.3.7. Action Taken with Study Treatment ......................................................................... 86 
6.3.8. Outcome .................................................................................................................... 87 


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6.4. 
Laboratory Tests ........................................................................................................... 87 
6.4.1. Hematology, Chemistry and Urinalysis .................................................................... 88 
6.4.2. eGFR ......................................................................................................................... 88 
6.4.3. Urinalysis .................................................................................................................. 88 
6.4.4. HbA1c ....................................................................................................................... 89 
6.4.5. Thyroid Function Assessment................................................................................... 89 
6.4.6. Coagulation ............................................................................................................... 89 
6.4.7. Cytokines, histamine, complement and Immunoglobulins ....................................... 90 
6.4.8. Beta-2 Microglobulin ................................................................................................ 90 
6.4.9. Rituximab concentration ........................................................................................... 90 
6.4.10. 
Serology – HIV, HBV and HCV .......................................................................... 90 
6.4.11. 
Pregnancy Test ...................................................................................................... 91 
6.5. 
Drug administration ...................................................................................................... 91 
6.6. 
Pharmacokinetic Assessments ...................................................................................... 91 
6.7. 
Efficacy Assessments.................................................................................................... 92 
6.7.1. Central Review of Efficacy Results .......................................................................... 93 
6.8. 
Immunogenicity Assessments ....................................................................................... 93 
6.9. 
Pharmacodynamic Assessments ................................................................................... 94 
6.9.1. Peripheral blood ........................................................................................................ 94 
6.10. Optional Tumor Tissue Biopsy ..................................................................................... 94 
7. 
Data management and statistical analysis .......................................... 95 
7.1. 
Data handling and electronic CRF ................................................................................ 95 
7.2. 
General statistical considerations .................................................................................. 95 
7.3. 
Sample Size Justification .............................................................................................. 96 
7.4. 
Analysis Sets ................................................................................................................. 96 
7.4.1. Safety Population ...................................................................................................... 96 


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7.4.2. Efficacy Population ................................................................................................... 96 
7.4.3. PK Population ........................................................................................................... 96 
7.4.4. Immunogenicity Population ...................................................................................... 96 
7.4.5. PD Population ........................................................................................................... 97 
7.5. 
Subject Disposition and termination Status .................................................................. 97 
7.6. 
Handling missing Data .................................................................................................. 97 
7.7. 
Baseline and demographic characteristics .................................................................... 97 
7.8. 
Safety analyses .............................................................................................................. 97 
7.8.1. Safety data handling .................................................................................................. 98 
7.8.1.1. Adverse events .................................................................................................. 98 
7.8.1.2. Laboratory safety tests ...................................................................................... 99 
7.8.1.3. Physical examination ........................................................................................ 99 
7.8.1.4. Other safety variables ....................................................................................... 99 
7.9. 
Efficacy analyses .......................................................................................................... 99 
7.10. PK analyses ................................................................................................................. 100 
7.11. Immunogenicity analyses............................................................................................ 100 
7.12. PD analyses ................................................................................................................. 101 
7.13. Interim analysis ........................................................................................................... 101 
7.14. Protocol deviations...................................................................................................... 101 
8. 
Study management .......................................................................... 103 
8.1. 
Approval and consent ................................................................................................. 103 
8.1.1. Regulatory Guidelines ............................................................................................ 103 
8.1.2. Independent ethics committee/Institutional Review Board .................................... 103 
8.1.3. Informed consent .................................................................................................... 103 
8.2. 
Protocol Amendments and Administrative Changes .................................................. 104 
8.3. 
Discontinuation of the Study by the Sponsor ............................................................. 105 


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8.4. 
Confidentiality ............................................................................................................ 105 
8.5. 
Study monitoring, Auditing and inspection ................................................................ 106 
8.6. 
Source data .................................................................................................................. 106 
8.7. 
Retention of Records................................................................................................... 108 
8.8. 
Subject insurance ........................................................................................................ 108 
8.9. 
Financial disclosure .................................................................................................... 108 
8.10. Study disclosures and publications ............................................................................. 108 
8.10.1. 
Publications of study results ............................................................................... 109 
9. 
References ....................................................................................... 110 
APPENDIX A. SCHEDULE OF ASSESSMENTS (SOA) .................................................. 113 
APPENDIX B. LABORATORY PANELS ...................................................................... 122 
APPENDIX C. Staging of NHL .................................................................................. 124 
APPENDIX D. REVISED LUGANO CLASSIFICATION OF RESPONSE ASSESSMENT IN 
LYMPHOMA ADJUSTED FOR LYRIC .......................................................................... 127 
APPENDIX E. DOSE LIMITING TOXICITY CRITERIA ................................................... 134 
APPENDIX F. CKD-EPI Creatinine Equation (2009) .................................................. 136 
APPENDIX G. ECOG PERFORMANCE STATUS .......................................................... 137 
APPENDIX H. NEW YORK HEART ASSOCIATION (NYHA) CLASSIFICATION ................ 138 
APPENDIX I. Summary Of Changes ....................................................................... 139 
LIST OF TABLES 
Table 1:  MT-3724 Dose Cohorts and Corresponding Dose Levels of MT-3724, gemcitabine and 
oxaliplatin ....................................................................................................................................... 9 
Table 2: Dose Adjustments in Response to Neutrophil and Platelet Nadir Counts ...................... 70 


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Table 3: Dose Adjustments in Response to the Worst Increase in AST, ALT or Bilirubin Levels
....................................................................................................................................................... 71 
Table 4:   Classification of Adverse Events by Severity Grade (CTCAE v.5.0) .......................... 83 
Table 5:  Classification of adverse events by causality / relationship to the study drug(s) .......... 84 
Table 6 :  Ann Arbor Staging System for NHL with Cotswolds Modification .......................... 124 
Table 7:  Revised Lugano Classification of Response Assessment in Lymphoma adjusted for 
LYRIC......................................................................................................................................... 127 
Table 8: Modified Lugano 5-point scale (5PS)........................................................................... 133 
Table 9:  ECOG Performance Status .......................................................................................... 137 
Table 10: NYHA Function Classification................................................................................... 138 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
5PS 
five-point scale 
ADA 
anti-drug antibody 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
AE 
adverse event 
ALT (SGPT) 
alanine aminotransferase (serum glutamic pyruvic transaminase) 
ANC 
Absolute neutrophil count 
ASCT 
autologous stem cell transplantation 
AST (SGOT) 
aspartate aminotransferase (serum glutamic oxaloacetic transaminase) 
BMI 
body mass index 
BORR 
best overall response rate 
BSA 
body surface area 
CD20 
protein on B-cell surface; target for MT-3724 binding 
CFR 
Code of Federal Regulations 
CL 
clearance 
CLcr 
creatinine clearance 
CLS 
capillary leak syndrome 
CRF 
case report form 
CR 
complete remission/response 
CRS 
cytokine release syndrome 
CRO 
contract research organization 
CS 
clinically significant 
CT  
computed tomography  
CTCAE 
Common Terminology Criteria for Adverse Events 
DLBCL 
Diffuse large B-cell lymphoma 


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DLT 
dose-limiting toxicity 
DOR 
duration of tumor response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic Case Report Form 
EDC 
electronic data capture 
eGFR 
estimated glomerular filtration rate 
EMA 
European Medicines Agency  
EoT 
End-of-Treatment 
EU 
European Union 
FDA 
Food and Drug Administration 
FDG 
fluorodeoxyglucose 
FNA 
fine needle aspiration 
FT4 
free thyroxin 
GCP 
Good Clinical Practice 
GEM 
Gemcitabine 
H 
hour 
HbA1c 
glycated hemoglobin 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IHC 
immunohistochemistry 


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IMP 
investigational medicinal product 
INR 
international normalized ratio 
IPI 
international prognostic index 
IRB 
Institutional Review Board 
IRR 
Infusion-related reaction 
IV 
intravenous 
kDa 
kiloDalton 
LDi 
longest diameter 
LVEF 
left ventricular ejection fraction 
LYRIC 
lymphoma response to immunomodulatory therapy criteria 
MAb 
mononuclear antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NA 
neutralizing antibody 
NCI 
National Cancer Institute 
NCS 
not clinically significant 
NHL 
Non-Hodgkin lymphoma 
NSAID 
non-steroidal anti-inflammatory drug 
NYHA 
New York Heart Association 
ORR 
objective tumor response rate 
OX 
oxaliplatin  
PD 
‘progressive disease’ or ‘pharmacodynamic(s)’  
PDNF 
Protocol Deviation Notification Form 
PE 
physical exam  
PET 
positron emission tomography 


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pH 
potential of hydrogen 
PK 
pharmacokinetic(s) 
PR 
partial response 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
QRS 
interval between Q and S wave on ECG 
QT 
interval between Q and T wave on ECG 
QTcF 
interval between Q and T wave on ECG corrected for the heart rate by 
Fridericia’s formula 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS 
Statistical Analysis System 
scFv 
single chain variable fragment 
SD 
stable disease 
SFU 
Safety follow-up  
SOC 
‘system organ class’ or ‘standard of care’ 
SOP 
standard operating procedure 
SUSAR 
suspected unexpected (related) serious adverse reaction 
TEAE 
treatment-emergent adverse event 
TMF 
Trial Master File 
TSH 
thyroid-stimulating hormone 
ULN 
upper limit of normal 
WHO 
World Health Organization 


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1. 
 INTRODUCTION 
1.1. 
Non-Hodgkin Lymphoma (NHL) 
CD20 is a B-cell specific differentiation antigen with four transmembrane domains (1). 
The CD20 protein plays a critical role in normal B-cell development and is expressed on 90% 
of B-cell Non-Hodgkin Lymphomas (NHL) (2). 
According to National Cancer Institute (NCI), the number of new NHL cases in the United 
States between 2010 and 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 (3). The NCI estimates that in 2017 
there will 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 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 (3) and varies by ethnicity, with 
Caucasians having higher rates than African Americans, Asians, or Native Americans.  
DLBCL 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 
percent) proliferation fraction. The immunophenotype of DLBCL can be confirmed by 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 subject depends on many host or tumor 
characteristics including tumor histology, tumor bulk burden and stage of tumor, subject’s 
age and performance status. According to Friedberg et al. (4), one third of subjects (33%) 
with newly diagnosed DLBCL will be refractory to first line therapy (e.g. R-CHOP). 
Although 16% of all newly diagnosed will be eligible for high-dose chemotherapy followed 
by autologous stem-cell transplantation (HD-ASCT), only 3.3% will be cured by ASCT.   
Thus, approximately 30% of all newly diagnosed DLBCL subjects will have either the 
refractory or relapsed DLBCL and represent a population with unmet need for new 
therapeutic strategies to achieve or regain disease remission. 
1.1.1. 
Anti-CD20 MAb Therapy for NHL 
Anti-CD20 monoclonal antibody (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 (rituximab and ofatumumab) induce 
redistribution of CD20 into large lipid rafts in the plasma membrane and have strong 
complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated 


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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 rituximab, 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 (5). 
Of those subjects with indolent NHL who relapse >6 months after initial response to 
rituximab, only 40% will respond again when retreated with rituximab (6). The multicenter 
Phase 2 CORAL (Collaborative Trial in Relapsed Aggressive Lymphoma) study showed that 
subjects who had previously responded to a rituximab containing treatment regimen had a 
worse outcome following rituximab containing salvage immunochemotherapy. (7). 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 (8). It has also been shown that anti-CD20 MAbs induce internalization 
of CD20 by malignant cells, where the degree of internalization is higher with type I anti-
CD20 MAbs (9). The internalization requires the binding of the Fc tail of the MAb to the Fcγ 
receptor IIb (FcγRIIb) on the malignant B cell. Differential FcγRIIb expression has been 
correlated with resistance to anti-CD20 therapy in different types of B-cell malignancies (10). 
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 (11). Further, due to their relatively large size, 
typically, less than 0.01% of the injected dose of an anti-CD20 MAb localizes to NHL tumors 
in human subjects (12).  
1.2. 
MT-3724 
MT-3724 is a recombinant homodimeric fusion protein, where each monomer consists of a 
single chain variable fragment (scFv) with affinity for human CD20 cell surface protein, and 
this fragment is fused to the enzymatically active A1 subunit of Shiga-like Toxin 1 (SLT-I 
A1). The theoretical molecular weight of the MT-3724 homodimer is ~ 110.4 kDa. MT-3724 
has been shown to specifically bind and kill CD20-expressing malignant B-cells (13).  
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 


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CDC to induce cell death. The scFv in MT-3724 should not be adversely impacted by 
reduction of CD20 B-cell expression via internalization or trogocytosis. Thus, MT-3724 
could avoid, mitigate or delay the emergence of resistance to anti-CD20 MAb therapy and 
offer potential benefit in unmet medical need. 
1.2.1. 
Clinical Experience with MT-3724 
The clinical experience with MT-3724 as monotherapy is derived from the ongoing study 
MT-3724-NHL-001. This is a first-in-human open-label, dose escalation Phase 1 study in 
subjects with NHL who had relapsed after having previously responded to anti-CD20 
monoclonal antibodies. MT-3724 is administered as 6 intravenous infusions over 2 hours in 
the first 12 days of each cycle for up to 5 cycles; Cycle 1 is 28 days and Cycles 2-5 are 21 
days. As of 15JUN2018, 24 subjects with relapsed NHL have received at least one dose of 
MT-3724 in the study MT-3724-NHL-001; of these, 54% were female, with the mean age of 
66 years (range 34-78) and ≥4 prior NHL therapies in 67% subjects. The median number of 
prior therapies in the study to date is 4.5 and the median age is 69. 
Part 1 of this study (dose escalation according to the 3+3 design) has been completed, with 
the total of 21 subjects treated in the following 6 sequential dose cohorts: 5 µg/kg/dose, 10 
µg/kg/dose, 20 µg/kg/dose, 50 µg/kg/dose, 100 µg/kg/dose and 75 µg/kg/dose. MT-3724 was 
generally well tolerated at dose levels ≤75 µg/kg/dose in Part 1. All of the 21 subjects had at 
least one non-serious adverse event (59 Grade≥3 events, of whom 13 were related to MT-
3724), and 15 (63%) subjects had 33 serious adverse events (23 Grade ≥3 of which 4 were 
related). The most common adverse events in Part 1 were peripheral edema (67%), fatigue 
(43%), diarrhea (38%), myalgia (38%) and cough (33%). The first 2 subjects treated at 100 
µg/kg/dose had one DLT each (Grade 2 pneumonia and Grade 2 ileus); in addition, one of 
these subjects had Grade 3 muscle weakness related to MT-3724 and multiple adverse events 
indicative of systemic inflammatory response in the first cycle of treatment. The Data 
Monitoring Committee determined that 100 µg/kg/dose is a non-tolerable dose level. None of 
the 19 subjects treated at dose levels ≤75 µg/kg/dose had a DLT, including the 6 subjects 
treated at 75 µg/kg/dose. Therefore, 75 µg/kg/dose was declared to be the MTD for MT-3724 
as monotherapy in subjects with relapsed NHL in Part 1. Neutropenia, leukopenia, myalgia, 
pneumonia, infection, muscle weakness, acute kidney failure and vascular leak were reported 
as adverse events related to MT-3724 and identified in the Investigator’s Brochure (16) as 
potential risks for subjects receiving MT-3724 therapy. 
In Part 2 of this study (MTD expansion), a total of 3 subjects have received MT-3724 at 75 
µg/kg/dose so far. Two had a Grade 2 capillary leak syndrome (CLS) in Cycle 1, with a 
typical cluster of adverse events comprising hypotension, hypoalbuminemia, weight gain due 
to fluid retention, headache, myalgia and arthralgia of varying levels of severity (Grade 1 to 
3). All adverse events were fully reversible. The CLS occurred in obese subjects (96 and 154 


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kg) who received a high total MT-3724 dose of 7208 and 11572 µg/infusion, respectively); 
however, both events required extended dose delay and dose reduction. In light of the 
frequent and dose-limiting CLS, the MTD of MT-3724 was reduced to 50 µg/kg/dose and 
capped at the total dose of 6000 µg per infusion; the safety and efficacy of the revised MTD 
is being evaluated in the Part 2 of the study as of 15JUN2018.  
In the first-in-human study, MT-3724 has exhibited clinical benefit at doses between 5-
100µg/kg/dose in patients who had negative serum rituximab levels at baseline (<500 
ng/mL). In this group, 3 of 16 patients had PR (ORR of 19%) and 5 subjects had SD (DCR 
50%); 2 subjects with SD had large tumor reduction (47% and 49%) near the threshold for 
PR by the Cheson criteria (24). All 3 subjects with PR had DLBCL. Tumor response data 
were available in 10 DLBCL patients with negative serum rituximab level at baseline, so the 
ORR in this clinically relevant subset was 33% and the DCR was 70%. Because MT-3724 
binds the same epitope as rituximab, no subjects who had positive serum level of rituximab at 
baseline (≥500 ng.mL) had clinical benefit in this study (16) . 
In summary, MT-3724 showed clinical anti-tumor activity in heavily pre-treated subjects 
with relapsed B-cell NHL. The assessment of the safety and efficacy of MT-3724 at the 
reduced MTD of 50 µg/kg/dose is ongoing in DLBCL subjects with undetectable screening 
RTX level in Part 2 of the study MT-3724-NHL-001. 
Please refer to the Investigator’s Brochure (16) for comprehensive information available for 
MT-3724 to date.  
1.3. 
Gemcitabine 
Gemcitabine (Gemzar®) is a nucleoside analog anticancer agent which blocks new DNA 
synthesis leading to cell death. Gemcitabine is approved for the treatment of i) advanced 
ovarian cancer that has relapsed at least 6 months after completion of platinum- based therapy 
when given in combination with carboplatin, ii) first-line treatment of metastatic breast 
cancer after failure of prior anthracycline-containing adjuvant chemotherapy, when given in 
combination with paclitaxel, iii) non-small cell lung cancer when given in combination with 
cisplatin and iv) pancreatic cancer as a single agent.  
The most common adverse reactions (incidence ≥20%) for gemcitabine as the single agent 
are nausea/vomiting, anemia, neutropenia, thrombocytopenia, increase in transaminases and 
alkaline phosphatase, proteinuria, fever, hematuria, rash, dyspnea, and peripheral edema.  
In clinical studies of gemcitabine including 979 subjects with various cancers who received 
gemcitabine as a single agent, no differences in the safety profile were observed between 
older (≥65 years) and younger subjects, except for a higher rate of Grade 3 or Grade 4 
thrombocytopenia in older subjects (15). In a randomized trial in women with ovarian cancer, 
175 women received gemcitabine plus carboplatin, of which 29% were ≥65 years of age. This 


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data set is relevant for the current study because like carboplatin, oxaliplatin is a platinum-
based therapeutic agent (15).  Similar anti-tumor efficacy was observed between older and 
younger women. There was significantly higher incidence of Grade 3 or Grade 4 neutropenia 
in women ≥65 years of age. The renal clearance of gemcitabine is affected by age, however 
there are no recommended dose adjustments based on subject’s age. Please see the reference 
prescribing information on gemcitabine for additional details (14). 
1.4. 
Oxaliplatin 
Oxaliplatin (Eloxatin®) is a platinum-based anticancer agent that causes DNA crosslinking 
causing inhibition of DNA synthesis and/or repair as well as inhibition of DNA replication 
and transcription, leading to cell death. Oxaliplatin is approved for i) the adjuvant treatment 
of stage III colon cancer in combination with 5-fluorouracil /leucovorin, and ii) the treatment 
of advanced colorectal cancer.  
The most common adverse reactions (incidence ≥40%) were peripheral sensory neuropathy, 
neutropenia, thrombocytopenia, anemia, nausea, increase in transaminases and alkaline 
phosphatase, diarrhea, emesis, fatigue and stomatitis. Anaphylactic reactions to oxaliplatin 
have been reported and may occur within minutes of administration (16).  Please see the 
reference prescribing information on oxaliplatin for additional details (16).  
1.5. 
R-GEMOX 
R-GEMOX (rituximab 375 mg/m2 in combination with gemcitabine 1000 mg/m2 and 
oxaliplatin 100 mg/m2) represents one of several standard treatments for patients with 
relapsed or refractory DLBCL (17, 18). R-GEMOX is used to achieve maximum tumor 
burden cytoreduction in preparation for HD-ASCT, or as salvage (palliative) therapy in NHL 
subjects ineligible for HD-ASCT.  
El Gnaoui et al. (17) reported on 46 subjects with R/R NHL (72% DLBCL) who received R-
GEMOX (rituximab 375 mg/m2 on Day 1 and gemcitabine 1000 mg/m2 together with 
oxaliplatin 100 mg/m2 on Day 2 of a 2-week cycle) after first (26%) or second/multiple 
relapse (61%) or in the primary refractory setting (13%) for up to 8 cycles. After the first 4 
cycles (induction), the overall response rate (ORR) was 83% with 50% of all NHL subjects 
and 58% of DLBCL subjects having a confirmed or unconfirmed complete response 
(CR/CRu). These responders continued on R-GEMOX for the second 4 cycles 
(consolidation), resulting in the ORR of 74%, with 72% of all NHL subjects and 73% of 
DLBCL subjects having a CR/CRu. R-GEMOX achieved better ORR and CR/Cru rates in 
rituximab-naive subjects than in those who relapsed after prior rituximab (ORR 95% vs. 73% 
and CR/CRu 85% vs. 65%, respectively). The subjects who were refractory to their last 
treatment or had a previous response for <1 year had lower ORR than those subjects who had 
a previous response for >1 year (53% vs. 97%, respectively). At last follow-up (median 


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duration of 28 months) of 38 subjects who responded, 11 had relapsed, translating to a 2-year 
progression free survival (PFS) of 62%. Notably, the 2-year PFS was only 37% in responders 
to R-GEMOX previously treated with rituximab, as compared to 81% in responders who 
were not previously treated with rituximab. These results are consistent with previous 
observations that NHL can become refractory to rituximab. R-GEMOX was generally well 
tolerated in this study, with Grade 3 and 4 neutropenia in 27% and 17% of cycles, 
respectively, Grade 3 and 4 thrombocytopenia in 19% and 4% of cycles, respectively and 
febrile neutropenia in 4% of cycles. There were no fatal toxicities and no Grade 3 and 4 non-
hematological toxicities. 
Mounier et al. (18) reported on 49 subjects with R/R DLBCL who received R-GEMOX 
(rituximab 375 mg/m2 on Day 1 and gemcitabine 1000 mg/m2 together with oxaliplatin 100 
mg/m2 on Day 2 of a 2-week cycle) for up to 8 cycles.  The ORR after the first 4 cycles was 
61%, with 21 (44%) subjects achieving CR/CRu and 8 (17%) a partial response (PR).  These 
responders continued on R-GEMOX for the second 4 cycles, whereupon 18 of the 21 (86%) 
subjects remained in CR/CRu and 4 of 8 (50%) subjects remained in PR. The ORR at the end 
of consolidation treatment was 46% and the overall CR/CRu rate was 38%, with the median 
duration of response of 10 months. As in the Gnaoui study (17), the ORR was negatively 
impacted by refractory disease/relapse <1 year (18% vs. 69%) and also by prior rituximab 
treatment (32% vs. 71%). R-GEMOX was generally well tolerated in this study, 73% with 
Grade 3 and 4 neutropenia in 31% and 42% of cycles, respectively, Grade 3 and 4 
thrombocytopenia in 23% and 21% of cycles, respectively and febrile neutropenia in 4% of 
cycles. There were no fatal toxicities; the most common non-hematological toxicities were 
Grade 3 or 4 infectious episodes in 22% of the cycles, while the Grade 3 neurotoxicity and 
Grade 3 renal toxicity were infrequent (8% and 2%, respectively). 
The efficacy of R-GEMOX in NHL/DLBCL was negatively impacted by the refractory 
disease status or the near-term relapse (within <1 year) after the prior anti-CD20 NHL 
therapy, which commonly included rituximab (17, 18). The limited responsiveness to R-
GEMOX in refractory or relapsed NHL/DLBCL could be driven by the acquired resistance of 
malignant B-cells to rituximab (see Section 1.1.1). 
 
 


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2. 
STUDY OBJECTIVES  
2.1. 
Primary Objective 
The primary objective of this study is to determine the safety and tolerability [including the 
maximum tolerated dose (MTD)] of MT-3724 in combination with gemcitabine and 
oxaliplatin in subjects with relapsed or refractory B-Cell Non-Hodgkin Lymphoma (NHL). 
2.2. 
Secondary Objectives 
The secondary objectives of this study are to: 
1. Characterize the pharmacokinetics (PK) of MT-3724 in combination with 
gemcitabine and oxaliplatin in subjects with relapsed or refractory B-Cell NHL 
2. Assess the pharmacodynamics (PD) of MT-3724 in combination with gemcitabine 
and oxaliplatin in subjects with relapsed or refractory B-Cell NHL 
3. Assess the immunogenicity of MT-3724 in combination with gemcitabine and 
oxaliplatin in subjects with relapsed or refractory B-Cell NHL 
4. Assess the tumor response to MT-3724 in combination with gemcitabine and 
oxaliplatin in subjects with relapsed or refractory B-Cell NHL 
 
 


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3. 
INVESTIGATIONAL PLAN  
3.1. 
Description of Overall Study Design and Plan  
This will be a multi-center, open-label, dose escalation phase 2a study of MT-3724 in 
combination with gemcitabine and oxaliplatin (GEMOX) 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. 
There are two sequential parts to this study. Part 1 is an evaluation of doses of MT-3724 in 
combination with GEMOX 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 GEMOX. For Long-Term Follow Up, subjects from both parts of 
the study will be followed for 24 months for PFS and DOR until progressive disease, death or 
lost to follow up. 
In both parts of the study, the subject’s participation in the study will comprise of 3 periods: 
screening, treatment and safety follow-up: 
3.2. 
Screening Period 
Screening procedures will be performed within 28 days before the start of treatment on 
C1D1. A signed written 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 (see Section 
4.1 and Section 4.2.) the Medical Monitor on behalf of the sponsor should review the 
screening results and acknowledge that the subject may enter the treatment phase of the 
study. 
3.3. 
Treatment Period  
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 intravenous (IV) infusion over 1 hour. 
Treatment with MT-3724 will be administered for two cycles of 28-days each or until death, 
disease progression, unacceptable toxicity, withdrawal of consent or another reason for 
withdrawal, or until study discontinuation  
In C1 and C2, MT-3724 infusion should be administered on Day 1, 3, 5, 8, 10 and 12. 
Different dosing days up to D21 may be selected at investigator’s discretion. MT-3724 


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cannot be administered between D22-D28 in C1-C2 (or in the 7 days following the last dose 
of the cycle in cases where the treatment was delayed) 
No more than two MT-3724 doses can be administered on consecutive days in C1-C2. If MT-
3724 is administered on 2 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. 
After two cycles, the treatment with MT-3724 may be continued for another two cycles of 28 
days each if supported by the investigator’s assessment of the benefit-risk ratio after 
consultation with sponsor and Medical Monitor.  
In C3-C4, MT-3724 will be administered weekly, i.e. on Day 1, 8, 15 and 22 of each 28-day 
cycle. Different dosing days within ±2 days from scheduled weekly doses may be selected at 
investigator’s discretion.  
MT-3724 cannot be administered between D24-D28 in C3-C4. 
If the subject exhibits SD, CR or PR after the end of Cycle 4 and the investigator determines 
that the benefit-risk ratio is favorable, then the treatment with MT-3724 may be continued 
after discussion with the sponsor. Continuation of GEMOX is at investigators discretion. 
3.3.2. 
GEMOX 
Gemcitabine (Gemzar®) 1000 mg/m2 will be administered as 30-minute IV infusion on Day 
2 and Day 16 of each 28-day cycle (i.e., every 14 days). Different dosing days within ±2 days 
from scheduled weekly doses may be selected at investigator’s discretion.  
Oxaliplatin (Eloxatin®) 100 mg/m2 will be administered as 2-hour IV infusion after 
gemcitabine on Day 2 and Day 16 of each 28-day cycle (i.e., every 14 days). Different dosing 
days within ±2 days from scheduled weekly doses may be selected at investigator’s 
discretion. Oxaliplatin infusion will start one hour after the start of gemcitabine infusion 
(unless a delay is warranted at the investigator’s discretion) to facilitate easier compliance 
with the post-dose sampling schedule. 
Treatment with GEMOX will continue for two cycles of 28-days each or until death, disease 
progression, unacceptable toxicity, withdrawal of consent or another reason for withdrawal, 
or until study discontinuation. After two cycles, the GEMOX treatment could be continued 
for another two cycles of 28 days each if supported by the investigator’s assessment of the 
benefit-risk ratio after consultation with sponsor and Medical Monitor.  
3.4. 
End of Treatment Visit and Safety Follow-up phone call 
The End of Treatment (EoT) Visit will be performed at the end of the treatment period in 
each subject in Part 1 and Part 2. EoT VISIT should occur, at the time of discontinuation 
(except for subjects who died, withdrew consent and objected to further data collection, or 


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were lost to follow up) or ≥ 7 days and ≤ 14 days after the last dose of MT-3724, gemcitabine 
or oxaliplatin for those that complete the study.  
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 
The Safety Follow-up (SFU) phone call will take place at least 30 days (+7 days) after the 
last dose of MT-3724, gemcitabine or oxaliplatin, whichever is last (except for subjects who 
died, withdrew consent and objected to further data collection, or were lost to follow up). 
3.5. 
Long-term Follow up Visit  
Long-term Follow-up (LTFU) Visits should occur every 6 months (±14 days) for up to 24 
months after the last dose of MT-3724, gemcitabine or oxaliplatin.  Subjects will be followed 
for 24 months for PFS and DOR until progressive disease, death or lost to follow up or until 
progressive disease, death or loss to follow up. 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.  
 
3.6. 
Part 1 (MT-3724 dose escalation) 
Part 1 will include MT-3724 dose escalation according to the modified 3+3 design to identify 
the maximum tolerated dose (MTD) of MT-3724 in combination with standard doses of 
gemcitabine and oxaliplatin (GEMOX).  
Up to 24 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 GEMOX. 
If permitted by the safety results, the MT-3724 dose escalation is planned to proceed in three 
sequential dose cohorts (Cohorts 1-3). The starting MT-3724 doses will be 10 µg/kg/dose in 
Cohort 1, 25 µg/kg/dose in Cohort 2 and 50 µg/kg/dose in Cohort 3. Interim MT-3724 doses 
may be evaluated in additional cohorts at the sponsor’s discretion in consultation with the 
investigator and Medical Monitor.  
In all dose cohorts, MT-3724 will be administered in combination with gemcitabine 1000 
mg/m2 and oxaliplatin 100 mg/m2 (Table 1).  
 
 


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Table 1:  MT-3724 Dose Cohorts and Corresponding Dose Levels of MT-3724, gemcitabine 
and oxaliplatin 
Planned 
MT-3724 
Dose Cohorts 
Interim 
MT-3724          
Dose 
Cohortsa 
Starting 
MT-3724 
Dose 
(µg/kg/dose) 
Starting 
Gemcitabine 
Dose 
(mg/m2) 
Starting 
Oxaliplatin 
Dose 
(mg/m2) 
1 
 
10 
1000 
100 
 
-1 (optional) 
≤5b 
1000 
100 
2 
 
25 
1000 
100 
 
-2 (optional) 
≤17.5b 
1000 
100 
3 
 
50 
1000 
100 
 
-3 (optional) 
≤37.5b 
1000 
100 
a. To be evaluated only if warranted by the safety results in the planned cohorts 
b. The 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, all available investigators and Medical 
Monitor will review all available data in the current dose cohort.  The sponsor, all available 
investigators and Medical Monitor will have a safety review meeting (teleconference) to 
discuss the data in the current dose cohort. All 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 relevant study manuals. 
Cohort management and dose escalation decisions (including the MTD) will be based on the 
incidence of treatment-emergent adverse events (TEAEs) that fulfill the criteria for a dose-
limiting toxicity (DLT), as follows. 
• The first dose escalation decision in the current MT-3724 dose cohort will be made 
after at least 3 subjects complete C1 or experience a DLT. Up to 6 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. 
• The first three subjects in each MT-3724 dose cohort should be treated at least one 
week apart, starting from the administration of MT-3724 in the previous subject, to 
allow for adequate safety monitoring. Prospective subjects for all 3 treatment slots 


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may be consented and screened in parallel with the treatment of previous subjects in 
the same cohort.  
• 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. 
• 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.  
• 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.  
• 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, then the dose escalation will stop, 
and the current MT-3724 dose level will be declared as the non-tolerable dose. In this 
case, one of the following 2 steps may be undertaken at the sponsor’s discretion after 
consultation with investigator and Medical Monitor: 
o If not previously done, up to 6 subjects may be treated at the planned MT-
3724 dose level immediately below the non-tolerable dose. 
o Alternatively, up to 4 subjects may be initially treated at the ‘interim’ MT-
3724 dose level 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 1; however, the 
actual MT-3724 doses for ‘interim’ cohorts will be recommended by the 
sponsor after consultation with all investigators and Medical Monitor.  
• 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 irrespective of the number of MT-3724, gemcitabine and oxaliplatin 
doses received in C1; or 


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• In the absence of DLT, have received at least 4 of 6 (83%) doses of MT-3724 and 
both doses of gemcitabine and oxaliplatin in C1 
Subjects in the current cohort who are not evaluable for dose decisions will be replaced.  
3.6.2. 
DLT Criteria 
A treatment-emergent adverse event (TEAE) will be declared as DLT if both of the following 
criteria are met:  
1. The TEAE occurred after the start of infusion in C1 of Part 1.  
a. If a TEAE that fulfills a DLT criterion is observed in C ≥2 of Part 1, then the 
sponsor may declare this event a DLT after consultation with the investigator and 
Medical Monitor. 
2. The TEAE is at least possibly related to MT-3724 (i.e., not reasonably related to 
another etiology), as determined by the sponsor after consultation with investigator 
and Medical Monitor. 
Note: If a Grade ≥3 TEAE related to gemcitabine or oxaliplatin 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 and Medical Monitor. 
The severity of TEAEs potentially fulfilling the DLT criteria will be graded according to the 
CTCAE v.5.0.  
See APPENDIX E 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 GEMOX 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 GEMOX and complete C1 or experience a DLT. The maximum dose of 
MT-3724 that will be given in this study is 50 ug/kg/dose with a maximum total dose of 
6000 µg, which is the MTD of MT-3724 as monotherapy. The MT-3724 dose escalation 
will not proceed above the 50 ug/kg/dose even if no more than 1 of 6 subjects in Cohort 3 
experience a DLT. 
The MTD decision will be made by the sponsor after consultation with all investigators and 
Medical Monitor. 
3.6.4. 
MTD Communication Plan 


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The investigator, Medical Monitor and sponsor 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 and sponsor become aware that the MTD may be 
declared in the current dose cohort (e.g. based on the occurrence of qualifying AE/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 relevant study manuals.  
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 the dose declared as MTD of MT-3724 in Part 1 would be given in 
combination with GEMOX. In addition, the PK, PD, immunogenicity and tumor response of 
MT-3724 in combination with GEMOX 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 study centers in North America 
and Europe. 
Part 2 can start only after the MTD of MT-3724 in combination with GEMOX 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. 
See Section 4.3.2. for the principles of subject replacement in Part 2 of the study. 
3.8. 
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 standard 
of care 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. The MT-3724 dose will not exceed 50 ug/kg/dose, as this is 
the MTD for MT-3724 given as monotherapy.  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.  
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. 
3.9. 
Guidance to the investigator 


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Preclinical studies and the ongoing first-in-man clinical trial MT-3724-NHL-001 have 
indicated several adverse events pertaining to patient safety.  These adverse events should be 
kept in mind prior to treatment of any patient in this study as well as the precautions as 
indicated in the gemcitabine and oxaliplatin SmPC.  
• The most common adverse events in the previous monotherapy study (in % of patients) 
were peripheral edema (62%), fatigue (46%), diarrhea (46%), myalgia (46%), insomnia 
(33%) nausea (29%), cough (29%), pyrexia (25%) and headache (25%).  
• DLTs in this trial were symptoms indicative of systemic inflammatory response/cytokine 
release syndrome (CRS) at 100µg/kg (2 patients) and signs of capillary leak syndrome 
grade 2 at 75µg/kg (2 patients). All DLTs occurred in patients who received a high total 
MT-3724 dose of 8500; 10730; 7208 and 11572 µg/infusion.  
• Patients should be closely monitored for signs of CLS/CRS.  
• This includes monitoring of vital signs (temperature, heart rate, blood 
pressure, weight and respiration rate) 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 and liver function and cytokines in case of clinical symptoms 
indicative of CRS/CLS.  
3.10. 
Benefit/Risk Ratio 
Most patients with CD20-positive B-cell NHL will eventually become resistant to available 
anti-CD20 therapy, including R-GEMOX. 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 (see Section 1.1.1). 
The current study aims to address this unmet medical need by replacing rituximab in the R-
GEMOX regimen with MT-3724, while keeping the dose and schedule of gemcitabine and 
oxaliplatin the same.  
In vitro, MT-3724 was tested in combination with gemcitabine or cisplatin to assess additive, 
synergistic or antagonistic cytotoxic effects against 4 different CD20-positive cell lines (16). 
In all cell lines, MT-3724 with gemcitabine yielded synergistic or predominantly synergistic 
effects, and MT-3724 with cisplatin yielded synergistic or predominantly synergistic effects 
in 2 of 4 cell lines and a mixed effect in the other 2. This in vitro data justifies further 
exploring the potential benefit of MT-3724 in combination with gemcitabine and oxaliplatin 
in the treatment of relapsed or refractory NHL/DLBCL in the Phase 2a study MT-3724-NHL-
002. 


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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 (50 µg/kg/dose), and the safety 
profile of MT-3724 so far has been similar to that of rituximab in the R-GEMOX regimen. 
MT-3724 achieved objective tumor response at the lowest dose potentially used in the current 
study (5 µg/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 ASCT 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 gemcitabine and oxaliplatin in this 
population. Thus, the benefit-risk ratio in the current study is acceptable. 
 
 


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4. 
STUDY POPULATION  
Eligible subjects will have histologically confirmed, relapsed or refractory B-cell NHL that, 
in the investigator’s opinion, could benefit from MT-3724+GEMOX therapy.  
All subtypes of B-cell NHL may be considered for Part 1 (MT-3724 dose escalation). Only 
DLBCL may be considered for Part 2 (MTD Expansion Cohort). 
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 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 B-cell NHL that, in the investigator’s opinion, could benefit 
from MT-3724+GEMOX therapy. At least one histologically documented relapse of NHL 
by: 
a. Bone marrow biopsy (FNA is not acceptable) or  
b. Excisional lymph node biopsy (FNA not acceptable) or 
c. Core biopsy of any involved organ  
d. CD20-positive histology must have been confirmed at any time during NHL 
disease course and documented in medical history. 
e. If no histology is available after any relapse the investigator can consult the 
medical monitor to discuss if the patient can be included.  
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 (expansion cohort). 
5. Have received all approved therapies for NHL that are applicable for the patient in the 
opinion of the treating physician. 
a. Patients refractory to treatment are eligible. 
b. Patient who have progressed following CAR T-cell therapy are also eligible. 
6. Have measurable disease by Lugano Classification for NHL (APPENDIX D). 
a. >1.5 cm longest diameter (LDi) for lymph nodes  
b. >1 cm LDi for extranodal disease 


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7. Have ECOG performance score of ≤2 (APPENDIX G). 
8. Have adequate bone marrow function, as determined by: 
a. Absolute neutrophil count (ANC) ≥1,000/mm3 (CTCAE Grade ≤2) and 
b. Platelet count ≥50,000 mm³ (CTCAE Grade ≤2)  
9. Have adequate kidney function, assessed by the estimated glomerular filtration rate 
(eGFR) ≥60 mL/min calculated by the CPK-EPI equation (APPENDIX F). 
a. At the investigator’s discretion, the eGFR result <60 mL/min may be verified by 
measurement of creatinine clearance (CLcr) based on the 24-hour urine collection. 
Subjects with CLcr ≥60 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 ≤3 x ULN for subjects with Gilbert's Syndrome and  
b. Aspartate aminotransferase (AST)  ≤3 x ULN (or ≤ 5.0 xULN if liver involvement) 
(and 
c. Alanine aminotransferase (ALT) ≤3 x ULN (or ≤ 5.0 xULN if liver involvement)  
11. Have adequate coagulation, as determined by: 
a. INR or PT ≤1.5 x ULN  
b. PTT ≤1.5 x ULN  
12. Have adequate serum albumin, as determined by:  
a. Albumin ≥ 3.0 g/dL  
13. Women of reproductive potential must have a negative pregnancy test during the 
screening period within 72 hours before the start of treatment. Women not of reproductive 
potential are female subjects who are postmenopausal or permanently sterilized (e.g., 
tubal occlusion, hysterectomy, bilateral salpingectomy).  
14. Subjects of reproductive potential and their partners must agree to either to abstain 
continuously from heterosexual intercourse or to use a reliable birth control method 
between signing the informed consent until 6 months following the last dose of MT-3724 
or GEMOX.  The investigator or a designated associate should advise the subject how to 
achieve adequate contraception. The following birth control methods may be considered 
as adequate: 
a. Condoms (male or female) with or without a spermicidal agent;  
b. Diaphragm or cervical cap with spermicide;  
c. Intrauterine device;  


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d. Hormone-based contraception: Established use of oral, injected, or implanted 
hormonal methods of contraception; 
e. True abstinence; 
f. Vasectomy is an acceptable method for a male subject or male partner of a female 
subject. 
4.2. 
Exclusion Criteria 
Subjects who meet ANY of the following criteria will not be eligible for 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, or any other previous cancer curatively 
treated >2 years before the start of treatment. 
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  
b. Have no neurological symptoms (excluding Grade ≤2 neuropathy) 
c. Have stable brain or spinal disease on the CT or MRI scan within 1 month of 
enrollment and 
d. Do not require chronic steroid therapy 
3. History of allogeneic hematopoietic stem cell transplant within 180 days before the start 
of treatment. 
4. Current evidence of acute or chronic Graft versus Host Disease. 
5. Current evidence of CTCAE Grade >1 toxicity (except for hair loss, and those toxicities 
listed as permitted in other eligibility criteria) before the start of treatment. 
6. Current evidence of incomplete recovery from surgery before the start of treatment, or 
planned surgery at any time until the EoT Visit, except minor elective interventions 
deemed acceptable by the investigator.  
7. History or current evidence of significant (CTCAE Grade ≥2) infection or wound within 
4 weeks before the start of treatment. 
8. History or current evidence of significant cardiovascular disease including, but not 
limited to the following conditions: 


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a. Unstable angina (symptoms of angina at rest) or new-onset angina within 
≤3 months before the start of treatment. 
b. Arterial thrombosis or pulmonary embolism within ≤3 months before the start 
of treatment. 
c. Myocardial infarction or stroke within ≤3 months before the start of treatment. 
d. Pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade ≥2), 
non-malignant pleural effusion (CTCAE Grade ≥2) or malignant pleural 
effusion (CTCAE Grade ≥3) within ≤3 months before the start of treatment 
with MT-3724.  
e. Congestive heart failure (NYHA Class III or IV) at screening or LVEF <45%, 
assessed by Echo or MUGA scan within 1 month before starting study 
treatment. (ECHO or MUGA performed within 6 months before screening and 
at least 28 days after the last cancer therapy is acceptable provided the subject 
has not received any potentially cardiotoxic agents). 
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 if the dose has been stable for ≥2 weeks 
before the start of treatment. Subjects with sinus arrhythmia and infrequent 
premature ventricular contractions are eligible at the investigator’s discretion. 
9. QTcF (Fridericia) >480 ms, determined as the average from three QTcF values on the 
triplicate ECG obtained at screening. 
10. Current evidence of seropositive status for HIV, hepatitis B virus (positive for HBsAg or 
anti-HBsAg and anti-HBcAg antibodies) or hepatitis C virus (positive for anti-HCV 
antibody or HCV-RCV-RNA quantitation) at screening.   
a. Serology testing may be omitted at the investigator’s discretion if 
seronegativity is documented in the medical history and there are no clinical 
signs suggestive of HIV or hepatitis infection. 
b. Subjects with positive HBV serology are eligible if quantitative PCR for 
plasma HBV-DNA is negative and the subject will be receiving prophylaxis 
for potential HBV reactivation. 
c. Subjects with positive HCV serology are eligible if quantitative PCR for 
plasma HCV RNA is negative. 
11. Women who are pregnant or breastfeeding. 


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12. History of hypersensitivity to any of the study drugs, or current evidence of 
hypersensitivity requiring systemic steroids at doses >20 mg/day prednisone equivalent. 
13. 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 
14. Received any amount of anti-CD20 MAb therapy within the following periods before the 
start of treatment 
a. Rituximab (Rituxan®): 84 days; if a subject received rituximab within 37 
weeks before the start of treatment, then a serum rituximab level must be 
negative (<500 ng/mL) at screening. 
b. Obinutuzumab (Gazyva®): 184 days 
c. Ofatumumab (Arzerra®): 88 days 
15. Received therapy for NHL (other than the anti-CD20 MAbs listed above) within 4 weeks 
before the start of treatment.  
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 lesion(s) that would be chosen as target lesions 
(measurable disease) within 4 weeks before the start of treatment, unless the lesion(s) 
exhibited objective progression between the radiotherapy and the screening according to 
the Lugano Classification for NHL.  
d. Palliative radiotherapy to non-target lesions is allowed at the investigator’s 
discretion. 
18. Received any vaccines within 28 days of the start of treatment, or likely to require 
vaccines at any time from the start of treatment until 28 days after the last dose of MT-
3724. Injectable flu vaccine (inactivated or recombinant) is permitted at the investigator’s 
discretion. 
19. Received systemic immune modulators within 2 weeks before the start of treatment.   
e. Systemic immune modulators include, but are not limited to, systemic 
corticosteroids at doses >20 mg/day of prednisone equivalent (except for 
premedication), cyclosporine and tacrolimus.  
f. The use of NSAIDs is permitted. 


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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 if the β-HCG pregnancy test indicates that they are 
pregnant at any time between the consent and the EoT Visit. Subjects who are identified to 
have become pregnant after the EoT Visit will not be withdrawn from the Long-term Follow-
up.  
The subject may be withdrawn from the study at the discretion of the investigator due to: 
• Safety concerns  
• Lack of clinical benefit (disease progression is not documented but the investigator 
determines that the subject requires alternative anticancer treatment) 
• Non-compliance with study procedures to the extent that precludes the assessment of 
study objectives 
Discontinuation of the study drug(s) for documented disease progression is considered study 
completion and not as premature withdrawal from the study. 
Depending on the time point of withdrawal, a withdrawn subject is referred to as either a 
screening failure (withdrawn before the start of treatment) or a dropout (withdrawn after 
receiving the first dose of a study drug). 
All subjects who permanently discontinue study treatment for any reason should have an EoT 
Visit and a SFU phone call performed as described in the Schedule of Assessments 
(APPENDIX A) before discontinuation.  
The reason for any discontinuation from the study will be documented in the subject’s 
medical record and recorded on the appropriate 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. 
4.3.2.1. 
Part 1 (MT-3724 Dose Escalation) 
Subjects who discontinue in C1 and are not evaluable for dose decisions (see Section 4.3.3.) 
must be replaced in the current dose cohort to ensure that sufficient number of subjects is 


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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 sponsor and 
Medical Monitor. 
Subjects who discontinue for any reason after C1 will not be replaced. 
4.3.2.2. 
Part 2 (MTD Expansion) 
Subjects in Part 2 of the study who have insufficient safety or PK, PD or immunogenicity 
data in C1 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. In this case, the ongoing 
subjects may continue treatment for up to 4 cycles if supported by the investigator’s 
assessment of the benefit-risk ratio after consultation with sponsor and Medical Monitor. 


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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 a single chain variable fragment 
(scFv) with affinity for human CD20 cell surface protein, fused to the enzymatically active 
A1 subunit of Shiga-like Toxin 1.   
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 
2.0 ml of MT-3724 (0.5 mg/ml or 1000 µg per vial) in a formulation buffer comprised of 
Sorbitol (200 mM), Sodium Citrate (20 mM) 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 (D5W) or normal saline for intravenous (IV) administration. All doses should be 
administered over 1 hour through an IV line (peripheral cannula or PICC catheter). See 
Pharmacy Manual for detailed instructions and worksheets regarding study drug preparation 
and administration. 
Thawed vials with intact stoppers can be stored at 2 - 8°C for up to 1 month. After 1 month of 
storage at 2 - 8°C, unused drug vials should be destroyed by the pharmacist according to local 
institutional standard procedures.  
The investigator is responsible for the accountability of the drug product and related supplies 
at the site. Records of the receipt and disposition of IMP must be maintained at the site. 
Records and drug supplies must be available for inspection by the study monitor. 
 
 


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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 the purpose of 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) and before the 
first dose of MT-3724 in Cycle 2-4. If the body weight has changed by >10% from the 
baseline value, this may require re-calculation of MT-3724 dose at investigator’s discretion.  
The maximum dose of MT-3724 that will be given in this study is 50 ug/kg/dose, which 
is the MTD of MT-3724 as monotherapy. 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 5.5. 
5.1.2.1. 
Part 1 (MT-3724 Dose Escalation) 
The starting dose of MT-3724 in Part 1 in each planned cohort will be: 
1. Cohort 1: 10 µg/kg/dose  
2. Cohort 2: 25 µg/kg/dose  
3. Cohort 3: 50 µg/kg/dose  
If MT-3724 is not tolerated in any planned cohort, then additional MT-3724 dose may be 
evaluated in the interim cohort at the sponsor’s discretion in consultation with the 
investigator and Medical Monitor.  
The hypothetical doses of MT-3724 in the interim cohorts are:  
1. Cohort -1: 5 µg/kg/dose (if MT-3724 10 µg/kg/dose is not tolerated in Cohort 1)  
2. Cohort -2: 17.5 µg/kg/dose (if MT-3724 25 µg/kg/dose is not tolerated in Cohort 2) 
3. Cohort -3: 37.5 µg/kg/dose (if MT-3724 50 µg/kg/dose is not tolerated in Cohort 3)  
The actual MT-3724 doses in the interim cohorts will be recommended by the sponsor after 
consultation with the investigators and Medical Monitor.  The actual MT-3724 dose in the 
interim Cohort -1 should not be <5 µg/kg/dose, as this was the lowest dose evaluated in the 
clinic so far.   
5.1.2.2. 
Part 2 (MTD Expansion Cohort) 
The starting dose of MT-3724 in Part 2 will be the MTD (or a maximum dose of 50 µg/kg) of 
MT-3724 from Part 1. The total administered dose of MT-3724 for subjects will be capped at 
6000 µg per infusion. 


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5.1.3. 
MT-3724 Dosing Schedule 
In C1 and C2, MT-3724 should be administered as 1-hour IV infusion on Day 1, 3, 5, 8, 10 
and 12 of each 28-day cycle.  
MT-3724 may be continued in C3-C4 (with or without GEMOX) if supported by the 
investigator’s assessment of the benefit-risk ratio. In C3-C4 (and subsequent cycles, if 
applicable), MT-3724 should be administered as 1-hour IV infusion weekly (Day 1, 8, 15 and 
22 of each 28-day cycle).  
MT-3724 administration on the same day as gemcitabine and oxaliplatin should be avoided, 
unless deemed acceptable by the investigator based on the careful assessment of all available 
data in the individual subject. 
5.1.3.1. 
Time Windows for 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. 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. 
Cycles 3-4 (if applicable) 
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.  
5.1.4. 
Premedication Before MT-3724 infusion 
One premedication agent from each of the following 3 therapeutic classes should be 
considered within 60 minutes before the start of MT-3724 infusion in each cycle in both parts 
of the study:  
• Oral anti-inflammatory agent (e.g. acetaminophen not to exceed 1000 mg PO) 
• Intravenous H1 histamine receptor antagonist (e.g. diphenhydramine not to exceed 
100 mg IV) 
• Intravenous corticosteroid agent with a shorter biological half-life (e.g. 
methylprednisolone not to exceed 1000 mg IV)  
The specific drugs in each class and their doses should be selected at investigator’s 
discretion or according to the institutional guideline. The investigator may adjust the 


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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. 
Gemcitabine    
Gemcitabine (Gemzar®) is a nucleoside analog anticancer agent which blocks new DNA 
synthesis leading to cell death. 
Gemcitabine drug product will be supplied by the local pharmacy at the study site. It will be 
prepared, administered and stored according to the reference prescribing information.  
Premedication is permitted at the investigator’s discretion according to site protocols. 
5.2.1. 
Gemcitabine Dose Selection 
In all cohorts in Part 1 and Part 2, the starting dose of gemcitabine will be 1000 mg/m2. This 
is the standard dose of gemcitabine as part of the R-GEMOX regimen in the treatment of 
patients with relapsed or refractory DLBCL (17,18). The gemcitabine starting dose can be 
decreased per investigators discretion based on the known safety profile of gemcitabine and 
patient status.  
See Section 5.5. for guidance about the gemcitabine treatment modification. In addition, the 
modification of gemcitabine treatment in this study should be guided by the reference 
prescribing information, as interpreted by the investigator. 
5.2.2. 
Gemcitabine Dosing Schedule 
Gemcitabine will be administered as 30-minute IV infusion on Day 2 and Day 16 of each 28-
day cycle (i.e., every 14 days).  
5.3. 
Oxaliplatin 
Oxaliplatin (Eloxatin®) is a platinum-based anticancer agent that causes DNA crosslinking 
causing inhibition of DNA synthesis and/or repair as well as inhibition of DNA replication 
and transcription, leading to cell death. 
Oxaliplatin drug product will be supplied by the local pharmacy at the study site. It will be 
prepared, administered and stored according to the reference prescribing information.  
Premedication is permitted at the investigator’s discretion according to site protocols. 
5.3.1. 
Oxaliplatin Dose Selection 
In all cohorts in Part 1 and Part 2, the starting dose of oxaliplatin will be 100 mg/m2. This is 
the standard dose of oxaliplatin as part of the R-GEMOX regimen in the treatment of patients 
with relapsed or refractory DLBCL (17, 18). The oxaliplatin starting dose can be decreased 
per investigators discretion based on the known safety profile of oxaliplatin and patient 
status.  


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See Section 5.5. for guidance about the oxaliplatin treatment modification. In addition, the 
modification of oxaliplatin treatment in this study should be guided by the reference 
prescribing information, as interpreted by the investigator. 
5.3.2. 
Oxaliplatin Dosing Schedule 
Oxaliplatin will be administered as 2-hour IV infusion after gemcitabine on Day 2 and Day 
16 of each 28-day cycle (i.e., every 14 days).  Oxaliplatin infusion will start one hour after 
the start of gemcitabine infusion (unless a delay is warranted at the investigator’s discretion) 
to facilitate easier compliance with the post-dose assessment schedule. 
5.4. 
Intra-subject Dose Escalation 
Intra-subject escalation of MT-3724 dose is not allowed in either part of the study.  
Intra-subject escalation of gemcitabine or oxaliplatin dose up to the most recent level is 
allowed in both parts of the study, if supported by the investigator’s assessment of the 
benefit-risk ratio after consultation with the sponsor and Medical Monitor. 
5.5. 
Treatment Modification 
Treatment modification due to a TEAE (dose interruption/delay, dose reduction, or 
permanent discontinuation) can be done in an individual subject at the investigator’s 
discretion after consultation with sponsor and 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). 
The severity of TEAEs requiring treatment modification will be graded according to the 
CTCAE v.5.0. 
5.5.1. 
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 Medical Monitor and sponsor. 
• Any TEAE irrespective of the time of onset that would otherwise fulfill the DLT 
criteria (APPENDIX E) 
• 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 sponsor and Medical Monitor. This may be Grade 1 or Grade 2 
toxicity that notably limits the activities of daily life (e.g. long-lasting fatigue or 
anorexia), making a dose reduction necessary to ensure the subject’s compliance. 


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The following actions are recommended after any of the above TEAEs occur. 
• The Investigator should notify the Medical Monitor and sponsor 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 C1 that is related to MT-3724 and qualifies as 
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 the ≥25% reduced dose of 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 central laboratory. 
• MT-3724 dose may be reduced by ≥25% at the investigator’s discretion after 
consultation with sponsor and Medical Monitor. The number of dose reductions per 
subject is not limited, except that the reduced dose cannot be <5 mcg/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 did not 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 sponsor and Medical Monitor.  
5.5.2. 
Gemcitabine Treatment Modification 
Any TEAE irrespective of the time of onset, which would otherwise fulfill the DLT criteria 
(APPENDIX E), may trigger gemcitabine (GEM) treatment modification, if deemed at least 
possibly related to GEM by the investigator. 
In addition, the modification of GEM treatment in this study will be guided by the reference 
prescribing information, as interpreted by the investigator. 
The following actions are recommended after any of the above TEAEs occur. 
• The Investigator should notify the Medical Monitor and sponsor about the TEAE 
within 24 hours of the awareness. 


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• The Investigator should monitor the subject and if necessary, perform diagnostic 
procedures and therapeutic interventions. 
• 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. 
• GEM dose may be reduced by ≥25% at the investigator’s discretion after consultation 
with sponsor and Medical Monitor. The number of dose reductions per subject is not 
limited.  
• Intra-subject escalation of gemcitabine dose up to the most recent level is allowed 
(see Section 5.4.) 
GEM treatment should be permanently discontinued after the onset of any of the following 
TEAEs in any treatment cycle, if deemed at least possibly related to GEM by the investigator 
after consultation with Medical Monitor and sponsor: 
• Grade ≥3 dyspnea or other Grade 3 pulmonary toxicity that cannot be attributed to the 
underlying NHL or comorbidity 
• Grade ≥3 hemolytic-uremic syndrome  
• Grade ≥3 acute kidney injury (acute kidney injury (serum creatinine increase ≥2 times 
above baseline in the absence of dehydration or bleeding) 
• Grade ≥2 capillary leak syndrome (CLS) 
• Grade ≥3 posterior reversible encephalopathy syndrome 
GEM treatment should also be permanently discontinued if any TEAE that previously led 
to dose interruption/delay or reduction did not 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 sponsor and Medical Monitor. 
5.5.3. 
Oxaliplatin Treatment Modification 
Any TEAE irrespective of the time of onset, which would otherwise fulfill the DLT criteria 
(APPENDIX E), may trigger oxaliplatin (OX) treatment modification, if deemed at least 
possibly related to OX by the investigator after consultation with Medical Monitor and 
sponsor. 
In addition, the modification of OX treatment in this study will be guided by the reference 
prescribing information, as interpreted by the investigator. 
The following actions are recommended after any of the above TEAEs occur. 


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• The Investigator should notify the Medical Monitor and sponsor 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 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. 
• OX dose may be reduced by ≥25% at the investigator’s discretion after consultation 
with sponsor and Medical Monitor. The number of dose reductions per subject is not 
limited. 
• Intra-subject escalation of oxaliplatin dose up to the most recent level is allowed (see 
Section 5.4.).  
OX dose should be reduced after the onset of Grade ≥2 peripheral neuropathy. Further, OX 
treatment should be permanently discontinued if Grade ≥2 peripheral neuropathy persists 
within 4 weeks after dose reduction. 
OX treatment should be temporarily discontinued after the onset of pulmonary toxicity 
indicative of interstitial pneumonitis or pulmonary fibrosis (e.g. cough, dyspnea not 
attributable to the underlying NHL or comorbidity). If interstitial pneumonitis or pulmonary 
fibrosis are confirmed, OX treatment should be permanently discontinued. 
OX treatment should also be permanently discontinued if any TEAE that previously led to 
dose interruption/delay or reduction did not 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 sponsor and Medical Monitor. 
5.5.4. 
Treatment Modification Due to IRR or Other Hypersensitivity Event 
This guidance is applicable to any among the 3 study drugs that, in the investigator’s opinion, 
is at least possibly related to infusion-related reactions (IRR) or other hypersensitivity event. 
If a subject experienced a Grade ≥2 IRR or other Grade ≥2 hypersensitivity reaction, the 
infusion must be immediately and permanently interrupted for that day. 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 after consultation with the sponsor and 
Medical Monitor  


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o If continued treatment is indicated, then  
 it must occur after the appropriate delay (re-treatment on the same day 
is not allowed)  
 it may represent the completion of the interrupted dose or the next dose 
per protocol.  
 for the next dose of the study drug causally related to IRR, the infusion 
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. 
5.5.5. 
Treatment Modification Due to Neutropenia or Thrombocytopenia 
This guidance is applicable to any case of treatment-emergent neutropenia and/or 
thrombocytopenia that, in the investigator’s opinion, is at least possibly related to the study 
drug(s). 
If treatment modification of the study drug is warranted due to treatment-emergent 
neutropenia and/or thrombocytopenia, and the continuation of treatment is appropriate at 
investigator’s discretion after consultation with sponsor and Medical Monitor, then the dose 
will be adjusted as described in Table 2. 
Table 2: Dose Adjustments in Response to Neutrophil and Platelet Nadir Counts 
Absolute neutrophil nadir count 
 
Platelet nadir count 
MT-3724 and/or 
gemcitabine and/or 
oxaliplatin dose 
modification a 
>500/μl or <500/μl for ≤5 days 
and 
≥25,000/μl 
No change 
<500/μl for >5 days 
and / 
or 
<25,000/μl with or without 
active bleeding, OR 
<50,000/μl with clinically 
significant bleeding b 
 Decrease by ≥25% (MT-
3724); or according to 
reference prescribing 
information (GEM and/or 
OX) 


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Febrile neutropenia c 
and / 
or 
<25,000/μl with or without 
active bleeding, OR 
<50,000/μl with clinically 
significant bleeding b 
Decrease by ≥25% (MT-
3724); or according to 
reference prescribing 
information (GEM and/or 
OX) 
a. The actual amount(s) will be determined by the investigator after consultation with sponsor 
and Medical Monitor. Repeated dose reductions are permitted if continued treatment is 
supported by the investigator’s assessment of the benefit-risk ratio. 
b. Clinically significant bleeding is that which requires platelet transfusion. 
c. Febrile neutropenia is defined as ANC <1000/μl and fever (a single body temperature 
reading of >38.3°C [101°F] or a sustained body temperature of ≥38.0°C [100.4°F] for more 
than one hour). 
Repeated dose reductions are permitted if continued treatment is supported by the 
investigator’s assessment of the benefit-risk ratio. 
5.5.6. 
Treatment Modification Due to Increased AST, ALT and/or Bilirubin Levels 
This guidance is applicable to any case of treatment-emergent increased serum AST, ALT 
and/or bilirubin levels that, in the investigator’s opinion, is at least possibly related to the 
study drug(s). 
If treatment modification of the study drug is warranted due to treatment-emergent increased 
AST, ALT and/or bilirubin levels, and the continuation of treatment is appropriate at 
investigator’s discretion after consultation with sponsor and Medical Monitor, then the dose 
will be adjusted as described in Table 3 
Table 3: Dose Adjustments in Response to the Worst Increase in AST, ALT or Bilirubin 
Levels 
Worst AST and / or ALT 
increase 
 
Worst bilirubin increase MT-3724 and/or gemcitabine 
and/or oxaliplatin dose 
modification a 
≤3.0 x ULN (isolated) 
or 
≤1.5 x ULN (isolated) 
No change in treatment 
Monitor subject 
≤3.0 x ULN 
and 
≤1.5 x ULN 
Temporarily discontinue 
treatment 
Monitor subject 
May continue at same dose after 
abnormal values resolve to ULN 


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>3.0 x ULN – 5.0 x ULN 
and / 
or 
>1.5 x ULN – 3.0 x ULN 
Temporarily discontinue 
treatment  
After abnormal values resolve to 
Grade ≤1, may continue at dose 
reduced by ≥25% (MT-3724) or 
according to reference prescribing 
information (GEM and/or OX) 
>5.0 x ULN – 10.0 x ULN 
or 
>3.0 x ULN – 10.0 x ULN Temporarily discontinue 
treatment  
May continue at dose reduced by 
≥25% (MT-3724) or according to 
reference prescribing information 
after abnormal values resolve to 
Grade ≤1 
>10.0 x ULN 
or 
>10.0 x ULN 
Permanently discontinue 
a. The actual amount(s) will be determined by the investigator after consultation with 
sponsor and Medical Monitor. Repeated dose reductions are permitted if continued 
treatment is supported by the investigator’s assessment of the benefit-risk ratio. 
Repeated dose reductions are permitted if continued treatment is supported by the 
investigator’s assessment of the benefit-risk ratio. 
5.6. 
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 
eligible and the Medical Monitor in consultation with the sponsor reviews the screening 
results and acknowledge the investigator’s eligibility decision.  
All subjects in all cohorts will receive the same standard doses of gemcitabine (Section 5.2.1) 
and oxaliplatin (Section 5.3.1). 
Assignment of screening slots and treatment slots will be done on basis of competitive 
enrollment (i.e. “first-come first-served”). The details will be described in a separate study 
manual. 
5.7. 
Blinding 
Not applicable for this open-label study. 


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5.8. 
Treatment Compliance 
All study drugs will be administered by investigational site staff during the site visit. 
Treatment compliance for each study drug will be monitored through the eCRF and source 
documents (patient notes and pharmacy records) and clinical observations during study drug 
infusion. Actual dose administered vs. planned dose will be used to assess compliance for 
each study drug. Details will be provided in the standalone Pharmacy Manual. 
5.9. 
Treatment Duration 
The following guidance for treatment duration applies to both parts of the study. 
Treatment with MT-3724 in combination with GEMOX will continue for 2 cycles of 28-days 
each or until death, disease progression, unacceptable toxicity, withdrawal of consent or 
another reason for subject withdrawal, or until discontinuation of the study.  
If supported by the investigator’s assessment of the benefit-risk ratio after consultation with 
sponsor and Medical Monitor, the treatment with MT-3724 in combination with GEMOX 
may continue for 2 additional cycles of 28-days each (up to the total of 4 cycles), or until 
death, disease progression, unacceptable toxicity, withdrawal of consent or another reason for 
withdrawal, or until discontinuation of the study. 
If any of the 3 study drugs is permanently discontinued, the treatment with the remaining 
study drug(s) may continue for up to 4 cycles if supported by the investigator’s assessment of 
the benefit-risk ratio after consultation with sponsor and Medical Monitor.  
If the subject exhibits SD, CR or PR after the end of Cycle 4 and the investigator determines 
that the benefit-risk ratio is favorable, then the treatment with MT-3724 may be continued 
after discussion with the sponsor. Continuation of GEMOX is at investigators discretion. 
5.10. 
Prohibited Treatment 
The following treatments are not permitted during the specified periods: 
• Rituximab (Rituxan®) from 84 days before the start of treatment until the EoT Visit. 
If a subject had received rituximab within 37 weeks before the start of treatment, then 
a serum rituximab level must be documented to be negative (<500 ng/mL) during the 
screening period 
• Obinutuzumab (Gazyva®) from 184 days before the start of treatment until the EoT 
Visit 
• Ofatumumab (Arzerra®) from 88 days before the start of treatment until the EoT 
Visit 


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• Therapy for NHL (other than the anti-CD20 MAbs listed above) from 3 weeks or 5 
half-lives of the agent before the start of treatment, whichever is longer, until the EoT 
Visit 
• 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 according to the Lugano Classification for NHL (2014) between 
the radiotherapy and the screening.  
o Palliative radiotherapy to non-target lesions is allowed at the investigator’s 
discretion after consultation with the Medical Monitor and sponsor 
• Systemic immune modulators from 2 weeks before the start of treatment until the EoT 
Visit.  The immune modulators include, but are not limited to, systemic 
corticosteroids at doses >20 mg/day of prednisone equivalent (except for 
premedication), cyclosporine and tacrolimus. The use of NSAIDs is permitted 
• 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 
• Subjects must not have received any vaccines from 28 days before the start of 
treatment until 28 days after the last dose of MT-3724. The single exception to this 
exclusion is for the injectable flu vaccine (inactivated or recombinant), which may be 
administered at the investigator’s discretion at any time during the above period 
5.11. 
Permitted Medication 
Except for prohibited treatments (see above), the use of any other concomitant medications is 
permitted during the treatment period at the investigator’s discretion. 
The injectable flu vaccine may be administered at the investigator’s discretion from 28 days 
before the start of treatment until 28 days after the last dose of MT-3724, and at any time 
thereafter. If the investigator allows the flu vaccine, they should carefully assess if it is 
appropriate to administer the flu vaccine before all study-related laboratory abnormalities or 
AEs have resolved. The subjects treated with B-cell depleting MAbs have been shown to 
have impaired humoral immune responses to neo-antigens for variable periods of time 
following the B-cell depleting treatment. 
5.11.1. 
Reasons for caution 
No results are available about the potential for drug-drug interactions between MT-3724 and 
oxaliplatin or gemcitabine, or between MT-3724 and other drugs. Therefore, investigator 
should use caution when prescribing concomitant medications. 
 
 


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6. 
STUDY ASSESSMENTS 
Please refer to the schedule of assessments (APPENDIX A) for details of all assessments and 
procedures to be performed at each visit during the study.  
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  
Demographic parameters will be assessed at screening.  
This will include date of birth, sex, race/ethnicity, history of smoking and alcohol 
consumption. 
6.1.2. 
Body Weight 
Body weight [in kilograms (kg)] will be measured at the following time points: 
• At screening 
• At any time before each MT-3724 infusion in each cycle.  
• At the EoT Visit 
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. 
The body weight measured before the MT-3724 dose on Day 1 of Cycle 1 will be the 
baseline for all subsequent measurements. If the body weight has changed by >10% from the 
baseline value, this may require re-calculation of MT-3724 dose at investigator’s discretion. 
6.1.3. 
Height, BMI and BSA  
Height [in meters (m)], body mass index (BMI) and body surface area (BSA) will be 
measured/calculated 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 has been last confirmed, the disease status at the initial diagnosis 
and the current status. The following information will be documented:  
• NHL histology confirmation by biopsy (bone marrow, lymph node, organ) 


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• NHL assessment (status at initial diagnosis and after relapse): NHL type, histology, 
staging (Ann Arbor Classification-Cotswold Modification), grading (low, 
intermediate or high) 
• NHL assessment (current status): same as for the status at initial diagnosis plus the 
mutational status (eg MYC and/or BCL2 and/or BCL6 rearrangement/overexpression; 
del 9p32. TP53, MLL2 mutations).  
The prognostic assessment instruments (Ann Arbor Classification with Cotswold 
Modification and (follicular lymphoma) International Prognostic Index) are described in 
APPENDIX C. 
6.1.5. 
Prior Systemic Therapy  
Prior systemic therapy for NHL (including SCT) administered at any time before the start of 
treatment will be assessed at screening. This should be documented by itemizing each 
regimen (line of treatment) and the individual agents within each regimen. 
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 
The following other clinical safety assessments will be performed in this study. Note that the 
adverse events are described in the Section 6.3, and the laboratory safety tests are described 
together with all laboratory tests in the Section 6.4. 
6.2.1. 
Medical History  
Medical history will be recorded at screening. This will include prior surgery, prior and 
concomitant medications, prior and concomitant illnesses and allergy history. The prior 
antitumor chemotherapy and radiotherapy will be collected as separate categories. 
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 medical history and the start of treatment 
should be reported as pre-treatment adverse events. 
6.2.2. 
Prior and Concomitant Medications 


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Any medication (either prescription and over-the-counter [OTC] medications and 
supplements) used within 4 weeks prior to the start of treatment until the EoT Visit will be 
recorded in the eCRF, together with the main reason for its prescription. 
The medications taken before the start of treatment will be regarded as prior medications 
(prior NHL therapy should be captured separately). The prior medications will be captured at 
the following time points: 
• At screening 
• Before the start of treatment on C1D1. 
The medications taken after the start of treatment will be regarded as concomitant 
medications. Concomitant medications will be captured at every clinic visit and telephone 
contact from the start of treatment until the EoT Visit  
6.2.3. 
Physical Examination 
The physical examination (PE) will be performed by a physician or a qualified delegate at the 
investigating site. For each element of the PE (see below), the result will be documented as 
normal, or abnormal, not clinically significant (NCS), or abnormal, clinically significant 
(CS). The pathological findings will be captured in the comment field only for the abnormal 
CS results. 
6.2.3.1. 
Complete Physical Examination 
The complete physical examination (PE) will be performed at the following time points:  
• At screening 
• At the EoT Visit 
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) 


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• 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 (awareness of self and environment) 
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 
• ECOG performance status (APPENDIX G) 
• NYHA classification (APPENDIX H) 
Other aspects / body parts or organ systems may be assessed at the investigator’s discretion. 
The investigator or delegate at the site will perform the PE and evaluate the results. The 
overall PE result will be categorized as ‘normal’, ‘abnormal, not clinically significant 
(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 AE in the 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. 
6.2.3.2. 
Abbreviated Physical Examination 
Abbreviated physical examination will be performed at the following time points:  
• At any time before MT-3724 infusion on D1 of each cycle 
• At any time before gemcitabine infusion on D16 of each cycle 
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) 


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• Lungs 
• Heart 
• Abdomen (pain, tenderness, peristaltic, ascites, organomegaly) 
• Lymph nodes 
• Extremities (petechial bleedings, ulcers, signs of thrombosis), hands and feet (signs of 
hand-foot syndrome / palmar-plantar erythrodysesthesia) 
• Abbreviated neurological examination to include the following assessments: 
o Oculomotor testing, pupil accommodation, double images  
o Motor system: muscle strength of arms 
o Sensory system: pain and touch sensation of thighs 
o Mental Status (awareness of self and environment) 
o Posture 
o Coordination: finger-to-nose and heel-to-shin test 
• ECOG performance status (APPENDIX G) 
Other aspects / body parts or organ systems may be assessed at the investigator’s discretion. 
6.2.4. 
Body Temperature 
Body temperature (in Fahrenheit or Celsius) will be measured at the following time points: 
• At screening 
• At any time before the start of MT-3724 infusion on D1 of each cycle 
• At any time before the start of gemcitabine infusion on D16 of each cycle 
• At the EoT Visit 
6.2.5. 
Blood Pressure and Heart Rate 
Blood pressure and heart rate will be measured after 5-10 minutes of quiet rest in a sitting or 
semi-recumbent position. The use using an automatic blood pressure measuring device is 
recommended, but a manual device is permitted.  
Blood pressure and heart rate will be assessed at the following time points:  
• At screening 
• At any time before the start of MT-3724 infusion in each cycle  
• At 0.5h, 1h and 2h (±10 min each) after the start of MT-3724 infusion in each cycle 


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• At 3h and 4h (±10 min allowed at each time point) after the start of MT-3724 infusion 
on C1D1  
• At any time before the start of gemcitabine infusion in each cycle  
• At 3 h (±10 min) after the start of oxaliplatin infusion in each cycle 
• At the EoT Visit 
Unscheduled blood pressure and heart rate measurements may be performed at investigator’s 
discretion in each cycle. 
When PK, ECG and blood pressure assessments are scheduled to occur at the same time 
point, then the PK sample collection should be performed at the protocolled time and the 
ECG and blood pressure / heart rate should be done in that order at least 10 minutes before or 
10 minutes after the PK sampling. In this case, the blood pressure / heart rate measurement 
may begin immediately after ECG recording (no need for additional 5-10 minutes’ rest).   
Any clinically significant abnormality in the blood pressure or heart rate, as determined at the 
investigator’s discretion, 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. 
6.2.6. 
LVEF 
The left ventricular ejection fraction (LVEF) will be measured by multigated acquisition 
(MUGA) scan or echocardiography. Either MUGA or echocardiography may be performed at 
investigator’s discretion or according to institutional standards, but the method for each 
subject should not change during the study. 
LVEF will be assessed at the following time points:  
• At screening (if not available within 3 months before the start of treatment) 
• At the EoT Visit (only if the subject has received MT-3724 in all 4 cycles)  
6.2.7. 
Electrocardiograms, 12-lead ECG  
Standard resting 12-lead ECG assessments will be performed after the subject had rested 
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).  
• At any time before the start of MT-3724 infusion on D1 of each cycle (single ECG) 
• At the EoT Visit (single ECG) 


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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 blood pressure assessments are scheduled to occur at the same time 
point, then the PK sample collection should be performed at the protocolled time and the 
ECG and blood pressure / heart rate should be done in that order at least 10 minutes before or 
10 minutes after the PK sampling.  
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 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. 
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, vital 
signs 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). 


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Adverse events (AEs) 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 SFU phone call. 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 Sponsor Medical Monitor or 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 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 patient’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 because of disease progression or deterioration of the 
patient’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. 
6.3.1. 
AE Reporting Period 
The adverse event (AE) reporting period will be from the time of signing the informed 
consent form until the SFU.  
Grade ≥2 AEs related to MT-3724 and /or GEMOX that were ongoing at the EoT Visit 
should be followed by the investigator until the all events have resolved to grade ≤1. 
Those AEs that occur after the start of treatment 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 GEMOX. 
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. 
6.3.2. 
AE Terminology 
All AE terms 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, intensity, 
association with the study medication, assessment of possible causes, actions taken, and 
outcome, using choices given on the eCRF.  
6.3.3. 
Severity 


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Severity will be classified according to the criteria provided by the Common Toxicity Criteria 
guidelines from the National Cancer Institute (CTCAE) v5.0. 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 
Table 4 will be assigned to the investigator’s AE term. 
Table 4:   Classification of Adverse Events by Severity Grade (CTCAE v.5.0) 
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. 
Every effort should be made to find the appropriate AE term and definitions of severity in the 
modified CTCAE v. 5.0. 
6.3.3.1. 
Causality / Relationship 
Causality should be assessed separately for each study drug (MT-3724, gemcitabine and 
oxaliplatin) 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 study treatment. 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 
Table 5.  
Table 5:  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”.   
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 adverse event that is not identified by type, severity grade, or 
frequency in the Reference Safety Information (RSI) section of the Investigator’s Brochure 
for MT-3724 or in the MT-3724 safety reports to the health authorities (e.g. DSUR) and for 


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gemcitabine or oxaliplatin any ADR that is not described in the respective SmPCs of each 
drug. 
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 
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 
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. 
6.3.5.1. 
SAE Reporting instructions 
If an SAE occurs at any time from the time of signing the informed consent form until the 
SFU phone call, it must be reported to the CTI Safety Department and the Medical Monitor 
on behalf of the sponsor (contact details on page 5). The investigator must report any SAE 


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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 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 photocopies of hospital case 
reports, consultant reports, autopsy reports, and other documents when requested and 
applicable. All photocopies 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. 
Comprehensive SAE reporting instructions will be provided in the CTI Safety Management 
Plan for this study. 
6.3.5.2. 
SUSAR  
An unexpected SAE that is at least possibly related to the study drug will be considered a 
suspected unexpected serious adverse drug reaction (SUSAR). Please see Section 6.3.2. for 
the definition of the unexpected event. 
The sponsor will determine if a reported SAE meets the criteria for SUSAR and confirm the 
decision with the Medical Monitor and sponsor. The CTI Safety Department will then notify 
the institutional review boards (IRBs) / independent ethics committees (IECs), health 
authorities and ail investigators about the SUSAR according to the applicable regulations.  
6.3.6. 
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. 
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.  
6.3.7. 
Action Taken with Study Treatment 


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Any action with any of the study treatments to manage the AE should be documented using 
the categories as described in the eCRF completion guidelines. The study treatment action 
should be recorded separately for MT-3724, gemcitabine and oxaliplatin as detailed in the 
eCRF. 
6.3.8. 
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 (see APPENDIX A and APPENDIX B). 
The following tests will be performed by the central laboratory:  
• Hematology 
• Chemistry (with eGFR) 
• HbA1c 
• Coagulation (activated partial thromboplastin time (aPTT) and either INR or PT) 
• Thyroid function (TSH and FT4) 
• Beta-2 microglobulin 
• Serum cytokines 
• Complement 
• Immunoglobulins 
• Histamine 
• B-cell count and immunophenotype (flow cytometry) 
• Immunogenicity of MT-3724; Anti-drug antibodies [anti-drug antibody (ADA) and 
neutralizing antibody (NA)]  
• Serology for rituximab concentration (if applicable) 
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) 
The same laboratory should analyze all scheduled laboratory tests throughout the study.  


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A standalone Laboratory Manual will provide complete instructions for the collection, 
handling, storage and shipment of samples for the laboratory tests. 
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 should be considered as an AE and documented accordingly in the 
eCRF. 
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 
• In C1 and C2:  
o On D1 and D8 (at any time before the start of MT-3724 infusion) 
o On D16 (at any time before the start of gemcitabine infusion) 
o On D22 (at any time before the start of MT-3724 infusion) 
• In C3 and C4 (if applicable):  
o On D1, D8, D15 and D22 (at any time before the start of MT-3724 infusion) 
• 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. 
6.4.2. 
eGFR 
The estimated glomerular filtration rate (eGFR) will be assessed as a measure of renal 
function.  The central laboratory will calculate eGFR using the CPK-EPI equation 
(APPENDIX F) (19) and the serum creatinine values from the blood chemistry assessment at 
the same time point.   
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 creatinine clearance 
(CLcr) based on the 24-hour urine collection.  Furthermore, if warranted by the eGFR result 
at any other time point, the investigator may order creatinine clearance (measured from the 
24-hour urine) as unscheduled assessment. 
6.4.3. 
Urinalysis 


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A standard Dipstix urinalysis will be initially performed at the following time points: 
• At screening 
• In C1 and C2:  
o On D1 and D8 (at any time before MT-3724 infusion) 
o On D16 (at any time before gemcitabine infusion) 
o On D22 (at any time before MT-3724 infusion) 
• In C3 and C4 (if applicable):  
o On D1, D8, D15 and D22 (at any time before MT-3724 infusion) 
o On D16 (at any time before MT-3724 infusion) 
• At the EoT Visit 
The analysis of the urine microsediment is not part of the initial urinalysis, unless warranted 
as unscheduled test at the investigator’s discretion. 
Any clinically significant abnormality in Dipstix 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 AE in the eCRF. 
6.4.4. 
HbA1c 
Glycated hemoglobin in plasma (HbA1c) will be assessed at the following time points as a 
measure of glycemic control: 
• At screening  
• At the EoT Visit 
6.4.5. 
Thyroid Function Assessment 
The thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in serum will be assessed 
at the following time points as a measure of thyroid function: 
• At screening  
• At the EoT Visit 
6.4.6. 
Coagulation 
The coagulation parameters (INR or PT, and aPTT) will be assessed at the following time 
points: 
• At screening 
• At any time before the start of MT-3724 infusion on D1 of each cycle 


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• At the EoT Visit 
6.4.7. 
Cytokines, histamine, complement and Immunoglobulins 
The cytokine panel, histamine, complement and immunoglobulins will be assessed at the 
following time points: 
• At screening 
• Before the start of MT-3724 infusion (±10 min) 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. 
6.4.8. 
Beta-2 Microglobulin 
A serum sample for the collection of beta-2 microglobulin will be collected at the following 
time points: 
• At screening 
6.4.9. 
Rituximab concentration 
Serum rituximab (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 undetectable (i.e., below the lower limit of quantification for 
the assay of 500 ng/mL). 
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).  After 37 weeks, serum RTX will be assessed for exploratory purposes.  The 
results after 37 weeks will not impact eligibility. The serology for RTX concentration should 
not be assessed for subjects who never received RTX. 
RTX concentration in serum should be obtained prior to performing any other screening 
procedure, unless the investigator has determined that the subject must obtain access to anti-
cancer therapy as soon as possible. 
6.4.10. 
Serology – HIV, HBV and HCV 
The serology for individual viruses may be omitted at screening at the investigator’s 
discretion if seronegativity has been previously documented and there are no signs of the 
corresponding viral infection. 


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If applicable, viral serology assessments will include the following parameters: 
Human immunodeficiency virus (HIV) 
• Anti-HIV-1 antibody 
• Anti-HIV-2 antibody  
Hepatitis B virus (HBV) 
• HBsAg 
• Anti-HBsAg antibody 
• Anti-HBcAg antibody 
Hepatitis C Virus (HCV) 
• HCV-RCV-RNA quantitation 
• Anti-HCV antibody 
6.4.11. 
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 72 hours before the start of treatment) 
• Within 72 h before the start of treatment in each cycle 
• At the EoT Visit 
6.5. 
Drug administration 
Drug administration schedule and study’s specific handling instructions are described in 
Section 5. 
6.6. 
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 pre-specified time 
points listed below. 
Cycle 1 
• Dose 1 (Day 1):  


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o Within 4 h before the start of MT-3724 infusion (SOI) 
o Within 10 minutes before the end of infusion (EOI) 
o At the following times after the EOI:  
 5 minutes (±1 min) 
 0.5 h, 1 h, 2 h (±5 min) 
 3 h and 4 h (±10 min) 
• Dose 3 (Day 5): 
o Within 4 h before the start of MT-3724 infusion (SOI) 
o Within 10 minutes before the end of infusion (EOI) 
o At the following times after the EOI:  
 5 minutes (±1 min) 
 2 h (±5 min) 
• Dose 6 (Day 12): 
o Within 4 h before the start of MT-3724 infusion (SOI) 
o  Within 10 minutes before the end of infusion (EOI) 
o At the following times after the EOI:  
 5 minutes (±1 min) 
 2 h (±5 min) 
Cycles 2-4 
• Dose 1 (Day 1): 
o Within 4 h before the start of MT-3724 infusion (SOI) 
o Within 10 minutes before the end of infusion (EOI) 
o At 5 minutes (±1 min) after the EOI 
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. 
The PK of gemcitabine and oxaliplatin will not be assessed in this study. 
6.7. 
Efficacy Assessments 
The tumor response assessment should be performed at the following time points. 


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• At screening (except if an existing scan of the same lesion(s) obtained within 28 days 
before the start of treatment is available) 
o The investigator is encouraged to obtain the screening tumor scan as close as 
possible to the start of treatment, as the advanced, R/R DLBCL is commonly 
aggressive and grows rapidly. 
• Within 7 days before the start of treatment on C3D1 (end of C2) 
• Between D23 and D28 of C4 (end of C4, if applicable) and each even numbered cycle 
thereafter in cases where treatment was continued past C4. 
• Within 7 days of the EoT Visit (only if the previous tumor scan has been performed 
>4 weeks before the EoT Visit) 
Unscheduled tumor response assessment by FDG-PET-CT (of CT / MRI, where applicable) 
may be ordered at the investigator’s discretion.  
Efficacy (tumor response) will be assessed by the scan of all anatomic regions involved with 
the measurable disease.  Positron emission tomography-computed tomography (PET-CT) 
should be used in subjects with fluorodeoxyglucose (FDG)-avid tumor histology. Computed 
tomography (CT) or magnetic resonance imaging (MRI) should be used in subjects with 
tumor histology of low or variable FDG avidity.  
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 (20) adjusted 
according to LYRIC (lymphoma response to immunomodulatory therapy criteria) (21).  An 
overview of NHL response criteria in subjects with FDG avid NHL is presented in 
APPENDIX D. 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). 
6.7.1. 
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.  
6.8. 
Immunogenicity Assessments 


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Blood samples will be collected at pre-specified time points for the assessment of 
immunogenicity of MT-3724 [anti-drug antibody (ADA) titer and neutralizing antibody 
(NA)]. 
The immunogenicity samples will be collected at pre-specified time points listed below. 
• At screening 
• Day 1 of each cycle (at any time before the start of MT-3724 infusion)  
• At the EoT Visit 
Please also see the Schedule of Assessments table (APPENDIX A). Unscheduled assessments 
may be performed at any time at the investigator’s discretion. 
6.9. 
Pharmacodynamic Assessments 
6.9.1. 
Peripheral blood 
The pharmacodynamics (PD) markers in this study will be the B-cell count 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 
• Day 1 in each cycle (at any time before the start of MT-3724 infusion on the dosing 
day) 
• Day 12 of C1-C2 (at any time before the start of MT-3724 infusion on the dosing day) 
• Day 15 of C3-C4 (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. 
6.10. 
Optional Tumor Tissue Biopsy 
In Part 2 of the study an optional FNA biopsy will be obtained at EoT in patients who 
consented for this procedure and exhibit PD and have accessible peripheral lymph node(s). 
The purpose of biopsy is to assess the CD20 status of DLBCL by IHC staining of the fine 
needle aspirate and determine if the B-cell lymphoma cells have lost CD20 positive status. 


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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 a FDA 21 CFR Part 11 compliant electronic case report form 
(eCRF), also known as the electronic data capture (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. 
7.2. 
General statistical considerations 
Statistical analysis will be performed using the Statistical Analysis System (SAS); the SAS 
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. 


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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 
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 GEMOX in Part 1. 
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. 
7.4. 
Analysis Sets 
7.4.1. 
Safety Population 
All subjects who received at least one dose of any study drug (either MT-3724, or 
gemcitabine or oxaliplatin) will be included in the safety population. The safety population 
will be used for the primary statistical analysis of safety and efficacy endpoints. 
7.4.2. 
Efficacy Population 
All subjects who received at least one dose of any study drug (either MT-3724 or 
gemcitabine or oxaliplatin) and have the baseline tumor assessment as well as at least one 
post-baseline tumor assessment.  
7.4.3. 
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 gemcitabine or oxaliplatin but haven’t received MT-3724 will be 
excluded from the PK analyses. 
7.4.4. 
Immunogenicity Population 


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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 gemcitabine or oxaliplatin but haven’t received MT-3724 will be excluded 
from the immunogenicity analyses. 
7.4.5. 
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 gemcitabine or oxaliplatin 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. 
Early withdrawals (i.e., subjects who did not complete 4 cycles of MT-3724+GEMOX) and 
the reason for withdrawal will be tabulated. The number and percentage of subjects who 
complete the study (i.e., complete 4 treatment cycles of MT-3724+GEMOX), and dropouts 
(i.e., subjects who withdraw consent, are discontinued from the study or die) will be 
tabulated. If dropouts are numerous or concentrated in specific cohort(s), safety assessments 
among dropouts 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 (BLQ) 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 
CV (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 SAEs, 
presented by treatment group / cohort and overall, based on: 


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• The type, incidence, severity, timing, seriousness, relatedness and outcome of adverse 
events. In particular, the following AE categories will be evaluated: 
• Incidence of DLT and TEAEs that led to treatment modification 
• Recording of Infusion-related reactions (IRR), cytokine release syndrome (CRS) and 
capillary leak syndrome (CLS) 
• Results of vital sign assessment (blood pressure, heart rate and body temperature) 
• Results of ECG assessment 
• Results of clinical chemistry, hematology, thyroid function, coagulation, and 
urinalysis tests 
• Changes in physical examination 
• Results of immunogenicity assessments ADA and NA 
• Need for concomitant medications 
All safety variables will be descriptively summarized by cohort 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 
7.8.1.1. 
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 SFU phone call.  
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 (SOC) 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. 


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Individual listings of DLTs will be presented by MT-3724 dose cohort in Part 1, with the AE 
term, MedDRA terms (SOC and PT), treatment cycle of onset, serious or non-serious and 
severity grade (CTCAE v.5.0) provided for each DLT. 
The pre-treatment AEs include those AEs 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. 
7.8.1.2. 
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. 
7.8.1.3. 
Physical examination 
The overall results of the physical examination (‘normal’, ‘abnormal, not clinically 
significant’, or ‘abnormal, clinically significant’) will be summarized by treatment group / 
cohort and listed per subject. Comments for abnormal CS results will be listed. 
7.8.1.4. 
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 vital signs (body temperature, systolic blood pressure, diastolic blood pressure, and 
heart rate) will be summarized by the descriptive statistics listed above.  
ECG results [heart rate, PR, QRS, RR interval, QT, QT interval corrected according to 
Fridericia’s formula (QTcF), and the results of the overall ECG review by the investigator or 
delegate] 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 (WHO) 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.  


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Tumor assessment will be performed by the FDG-PET-CT scan in subjects with FDG-avid 
NHL histology, and by the CT or MRI scan in subjects with low or variable FDG avidity. 
The investigator at each site will determine the objective tumor response rate (ORR) at each 
time point based on the rediologist’s measurement of all evaluable lesions.  
The investigator at each site will determine the objective tumor response rate (ORR) using 
the five-point scale (5PS) per the Lugano Classification for Lymphoma (20) adjusted 
according to LYRIC (lymphoma response to immunomodulatory therapy criteria) (21). An 
overview of LYRIC is presented in APPENDIX D (0). The best objective tumor 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 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 duration of 
tumor response (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 
DOR will be descriptively summarized by the treatment group / cohort; the exact 95% 
confidence intervals will also be produced. 
7.10. 
PK analyses 
MT-3724 serum concentration time data from all eligible subjects will be subjected to non-
compartmental 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.  
In addition, the MT-3724 serum concentration time data may be evaluated using nonlinear 
mixed effects modeling using Nonmem (Icon PLC, Dublin Ireland). 
7.11. 
Immunogenicity analyses 
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 NA 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 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.   


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Details of the immunogenicity analyses will be provided in a separate analysis plan for this 
study objective. 
7.12. 
PD 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 immunogenicity 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. DSUR), 
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 major deviation occurs, the Investigator 
must immediately inform the monitor, and the implications of the major deviation must be 
reviewed and discussed with the sponsor. Major deviations must be documented on the 
applicable Protocol Deviation Notification Form (PDNF), stating the date and description of 
the deviation as well as the action taken and the impact on the subject’s safety and/or the 
study results. The PDNF must be kept in the trial master file at the site. Major 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 


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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 (or designee), the EU Clinical Trials Directive and the FDA Code of Federal 
Regulations, the guidelines of the ICH (22), and the most recent guidelines of the Declaration 
of Helsinki (21).  
8.1.2. 
Independent ethics committee/Institutional Review Board 
Conduct of the study must be approved by an appropriately constituted Institutional Review 
Board (IRB) or Independent Ethics Committee (IEC). Approval is required for the study 
protocol, Investigator’s Brochure, protocol amendments, informed consent form, subject 
information sheets, patient diaries and other non-CRF data collection documents, and any 
advertising materials. No study drug will be shipped to the study site until the site has 
received written IRB or IEC authorization. 
The investigator should inform the IRB/IECs about the study progress annually (or as 
required by the IRB/IEC). The CTI Safety Department (contact details on page 4) will also 
submit to IRB/IEC periodic reports of any reportable adverse events per ICH guidelines and 
local requirements.   
The IRB/IEC and Competent Authorities will be notified of the end of the trial per local 
requirements.  Where required, a summary of the study outcome will be provided to the 
IRB/IEC. 
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 standard of care procedures or tests were performed prior to signing of the ICF but 
are still within 28 days 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 language 


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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 Administrative Changes  
Changes to this protocol that would require a substantial amendment according to the EU 
Guidance (2010/C 82/01) will be implemented via a protocol amendment. A substantial 
amendment in the EU will be treated as a protocol amendment in the USA per 21 CFR 
312.30(b). The sponsor, investigator(s), IRB/IEC and health authorities must approve the 
protocol amendment before implementation.   
The requirements for approval of the substantial changes should not prevent any immediate 
action from being taken by the investigator or by the sponsor to preserve the safety of study 
subject(s). 


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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 
maintained in the TMF. 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 and/or close the site for safety or 
administrative reasons at any time. Should the sponsor terminate the study and/or close the 
site for whatever reason, all documentation and study medication pertaining to the study must 
be returned to the sponsor or its representative, or discarded as instructed by the sponsor or 
according to institutional guidelines. 
8.4. 
Confidentiality 
The contents of this protocol and any amendments and results obtained during the study 
should be kept confidential. These documents and/or results should not be disclosed 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 to Good Clinical Practice (GCP) and 
comply with all applicable federal, state, and local laws and regulations regarding the privacy 
of subject health information. The investigator shall ensure that study subjects authorize the 
use and disclosure of protected health information in accordance with the Code of Federal 
Regulations, EU Clinical Trials Directive, and EU Law, 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/ECs, 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 Subject Informed Consent 
Form and Clinical Trial Agreement. Study subjects will not be identified by their names on 
eCRF or any other documents and biological samples submitted to the sponsor or other 
parties. Each subject will be assigned an identification number to be used on any data or 
laboratory samples collected by the sponsor. Documents not for submission to the sponsor 
(e.g. the signed informed consent forms), 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. If the subject’s medical records are shared with the sponsor and/or Medical 
Monitor (e.g. for the purpose of eligibility review), they must be redacted of all information 
revealing the subject’s identity. 


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8.5. 
Study monitoring, Auditing and inspection 
CRO personnel will monitor the conduct of this study on behalf of the sponsor. Monitoring 
will include personal 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.  
The study may be audited by the sponsor, its designee or by regulatory authorities. According 
to the GCP, 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, and appropriate regulatory authorities for on-site monitoring of all 
appropriate study documentation, as well as on-site review of the procedures employed in 
CRF 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, see 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. 
The Sponsor/CRO will provide the following: 
• Backup SAE Forms 
• Backup Pregnancy Forms 
• Infusion Bag Preparation Sheet (from Pharmacy Manual) 
The Central laboratory will provide the following:  
• Laboratory Report Correction Request Forms 
• Laboratory Requisition Forms 
• Laboratory Way Bills 


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A Clinical Research Associate (CRA) will perform source document verification as per the 
monitoring plan so 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. A Screen Procedure CRF 
will be provided. This will be completed beginning at the Screening Visit. It will be the only 
CRF for subjects who fail one or more screen procedures and never progress to receive study 
drug. Local laboratory data will be entered into the CRFs by trained and qualified study staff. 
Monitors and auditors must have direct 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. If the source document contains a subject’s address and 
phone number, it must be obliterated before it is included as a study document and the 
subject’s name will be obliterated except for the first letters of the first, middle (if present), 
and last names. 
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. 


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The eCRFs must be reviewed at regular intervals by the Principal Investigator and signed by 
the Principal Investigator named in the clinical study protocol at the end of the study. Any 
changes to the eCRF after retrieval using data clarification forms or queries must also be 
authorized/signed by the Principal Investigator and/or the study coordinator and/or the data 
entry coordinator. (Note: Study Coordinators and Data Entry Coordinators are sometimes 
allowed to sign Data Clarification Forms.) The Sponsor or CRO acting as an agent of the 
Sponsor will retain the final, complete electronic data base with all 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 sponsor’s TMF. 
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 
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 disclosures and publications 
This study will be posted on www.clinicaltrials.gov and other public databases as required by 
local regulations. 
By signing the study protocol, the investigator agrees to the sponsor’s use of the study results 
for the national and global regulatory filings of the study drug for marketing approval. If 
necessary, the authorities will be notified of the investigator’s name, address, qualifications, 


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and extent of involvement. The sponsor will prepare a final integrated study report covering 
clinical and biometric aspects of the study 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/CRO, as appropriate. 


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9. 
REFERENCES 
1. Kuijpers TW et al. CD20 deficiency in humans results in impaired T cell-independent antibody 
responses.  J Clin Invest. 2010; 1:214-222. 
2. Tedder TF et al. Isolation and structure of a cDNA encoding the B1 (CD20) cell-surface 
antigen of human B lymphocytes. Proc Natl Acad Sci USA 1988; 85: 208-212. 
3. SEER Cancer Stat Facts: Non-Hodgkin Lymphoma. National Cancer Institute. Bethesda, 
MD, 44T44T44Thttp://seer.cancer.gov/statfacts/html/nhl.html 
4. Friedberg JW. Relapsed/Refractory Diffuse Large B-Cell Lymphoma. Hematology Am Soc 
Hematol Educ Program. 2011; 2011: 498-505. 
5. Maloney DG. Anti-CD20 antibody therapy for B-cell lymphomas. N Engl J Med. 2012; 24: 
2008-2016. 
6. Davis TA et al. Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin's 
lymphoma: safety and efficacy of re-treatment. J Clin Oncol. 2000; 17: 3135–3143. 
7.  Gisselbrecht C et al. Salvage regimens with autologous transplantation for relapsed large B-
cell lymphoma in the rituximab era. J Clin Oncol. 2010; 28: 4184-4190. 
8. Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. 
Oncogene 2003; 22:  7359-7368. 
9. Beers SA et al. Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications 
for antibody selection. Blood 2010; 115: 5191–5201. 
10. Lim SH et al. Fc gamma receptor IIb on target B cells promotes rituximab internalization and 
reduces clinical efficacy. Blood 2011; 118: 2530-2540. 
11. Beum PV et al. Loss of CD20 and bound CD20 antibody from opsonized B cells occurs more 
rapidly because of trogocytosis mediated by Fc receptor-expressing effector cells than direct 
internalization by the B cells. J Immunol 2011; 187: 3438-3447. 
12. Levey et al. A New Equation to Estimate Glomerular Filtration Rate. Ann Intern Med. 
2009;150:604-612. 
13. Milenic DE et al. Construction, Binding Properties, Metabolism, and Tumor Targeting of a 
Single-Chain Fv Derived from the Pancarcinoma Monoclonal Antibody CC49. Cancer 
Research 1991; 51: 6363-6371. 


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14. Rajagopalan S et al. CD20-Specific Engineered Toxin Body Demonstrates Direct Cell Kill of 
Multiple B-Cell Non-Hodgkin's Lymphoma Types. Blood 2013; 122: 5152. 
15. US Food and Drug Administration. Prescribing Information for Gemzar® (gemcitabine). 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020509s077lbl.pdf   
16. US Food and Drug Administration.  Prescribing Information for Eloxatin® (oxaliplatin). 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021492s011,021759s009lbl.pdf 
17. Investigator’s Brochure: MT-3724, Version 4.0, effective date: 16NOV2018 
18. El Gnaoui T et al, Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for 
subjects with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. 
Ann Oncol. 2007;18: 1363-1368. 
19. Mounier N et al; Rituximab plus gemcitabine and oxaliplatin in subjects with 
refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose 
therapy. A phase II Lymphoma Study Association trial. Haematologica. 2013; 98: 1726–1731. 
20. National Institutes of Health National Cancer Institute; published Nov 27, 2017, updated 
Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Available from: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm  
21. 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. 
22. ICH, Integrated addendum of ICH E6(R1): Guideline for Good Clinical Practice E6 (R2). 2016 
23. Cheson BD. et al. Recommendations for initial evaluation, staging and response assessment of 
Hodgkin and Non-Hodgkin Lymphoma. The Lugano Classification. J Clin Oncol 2014; 32: 
3059-3067. 
24. Cheson BD et al. Refinement of the Lugano Classification lymphoma response criteria in the 
era of immunomodulatory therapy. Blood 2016; 128: 2489-2496. 
25. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and 
Response Criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982: 5: 
649-655. 
26. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for 
Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & 
Co; 1994; 352: 15. 


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24. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model 
for aggressive non-Hodgkin's lymphoma. N Engl J Med 1993; 329(14):987-994. 
25. Lister TA et al. Report of a committee convened to discuss the evaluation and staging of 
patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 1989; 7: 1630-1636. 
 
 


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APPENDIX A. 
SCHEDULE OF ASSESSMENTS (SOA) 
SOA FOR SCREENING PERIOD 
 
The schedule of assessments for the screening period will be the same in Part 1 and Part 2, as 
outlined below. Unscheduled assessments may be performed at any time at the investigator’s 
discretion. 
Assessments and Procedures 
Within 28 days 
of dosing on 
C1D1 
Within 72 h of 
dosing on C1D1 
Informed consent 
X 
 
Demographics 
X 
 
Height 
X 
 
Body weight 
X 
X 
BMI 
X 
 
BSA 
X 
 
Medical history1,2 
X 
 
NHL disease status (at initial diagnosis and after 
relapse)3 
X 
 
NHL disease status (current)4 
X 
 
Prior Medications5 
X 
X 
Prior systemic NHL therapy6 
X 
 
Prior NHL radiotherapy7 
X 
 
Complete physical exam (with NYHA and ECOG) 
X 
 
Abbreviated physical exam (with ECOG) 
 
X 
Body temperature  
X 
X 
Blood pressure and heart rate8,10 
X 
X 
12-lead ECG (triplicate)9,10 
X 
 
LVEF (MUGA or Echocardiogram)11 
X 
 


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Radiological tumor assessment (PET-CT or 
CT/MRI)12,13 
X 
 
CENTRAL LABORATORY 
Serum rituximab level (if applicable)14,15 
X 
 
Hematology 
X 
 
Chemistry (with eGFR16) 
X 
 
HbA1c 
X 
 
Coagulation (PT or INR, aPTT) 
X 
 
Thyroid function (TSH, FT4) 
X 
 
Beta-2 microglobulin 
X 
 
Cytokines 
X 
 
MT-3724 Immunogenicity (ADA/NA) 
X 
 
B-cell count and immunophenotype (flow 
cytometry) 
X 
 
Complement 
X 
 
Histamine 
X 
 
Immunoglobulins 
X 
 
LOCAL LABORATORY 
Urinalysis (Dipstix)17 
X 
 
Serology for HIV, HBV and HCV18,19 
X 
 
Pregnancy (serum or urine) 
 
X 
Check of new or worsening illnesses20 
 
X 
Check of all inclusion/exclusion criteria 
X 
X 
Abbreviations: ADA – Anti-drug antibodies; aPTT – Activated partial thromboplastin time; C – 
Cycle; CT – Computed tomography; D – Day in cycle; ECG – Electrocardiogram; ECOG – 
Eastern Cooperative Group of Oncology; eGFR – Estimated glomerular filtration rate; FT4 – Free 
thyroxine; HbA1c – Glycated hemoglobin; HBV – Hepatitis B  virus; HCV – Hepatitis C virus; 


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HIV – Human immunodeficiency virus; INR – International normalized ratio; LVEF – Left 
Ventricular Ejection Fraction; NA – Neutralizing antibodies; MRI – Magnetic resonance imaging; 
MUGA – Multigated acquisition; NYHA – New York Heart Association; PET – positron-
emission tomography; PT – Prothrombin time; TSH – Thyroid-stimulating hormone. 
Footnotes: 
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. 
2. Illnesses that are active at the time of informed consent should be captured in the medical history as concomitant 
illnesses.  
3. 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). 
4. NHL disease status (current) will include the same as for the status at initial diagnosis plus the mutational status. 
5. Prior medication is any medication (either prescription and OTC) used within 4 weeks prior to the start of 
treatment. Prior therapy for NHL should be captured separately from prior medications. 
6. Prior systemic therapy for NHL 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. 
7. Prior radiotherapy for NHL administered at any time before the start of treatment. 
8. Blood pressure (systolic and diastolic) and heart rate should be measured after 5-10 minutes of quiet rest in a 
sitting or semi-recumbent position. 
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. When ECG and blood pressure assessments are scheduled to occur at the same time point, then the ECG should be 
performed first (occurring after 5-10 quiet rest in supine or semi-recumbent position) and the blood pressure / 
heart rate measurement may begin immediately after ECG recording (without additional 5-10 minutes’ rest). 
11. If prior LVEF is not available within 3 months before the start of treatment 
12. A scan of all anatomic regions involved with the measurable disease by PET-CT (in subjects with FDG-avid 
tumor histology) or CT or MRI (in subjects with tumor histology of low or variable FDG avidity).  
13. Screening tumor assessment may be omitted at the investigator’s discretion if a scan of the same lesion(s) 
obtained within 28 days before the start of treatment is already available. The investigator is encouraged to obtain 


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the screening tumor scan as close as possible to the start of treatment, as the advanced R/R DLBCL is often 
aggressive and grows rapidly 
14. Serum rituximab (RTX) level should be assessed in all subjects who received RTX within 37 weeks before the 
start of treatment. 
15. Serum RTX level (where indicated) should be determined prior to performing any other screening procedure, 
unless the investigator has determined that the subject must obtain access to anti-cancer therapy as soon as 
possible.  
16. Calculated by the central laboratory using CPK-EPI formula and the serum creatinine from the corresponding 
chemistry panel 
17. Analysis of urine microsediment may be performed at the investigator’s discretion. 
18. 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. 
19. If applicable, serology should include anti-HIV1 and anti-HIV2 antibodies, HBsAg, anti-HBsAg and anti-HBcAg 
antibodies, HCV-RCV-RNA quantitation and anti-HCV antibody. 
20. New illnesses and/or worsening of concomitant illnesses detected by verbal probes or subject’s spontaneous 
reports between the screening medical history and the start of treatment should be reported as pre-treatment 
adverse events 


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SOA FOR TREATMENT AND FOLLOW-UP PERIODS 
The schedule of assessments for the treatment and long-term follow-up periods will be the same in Part 1 and Part 2, as outlined 
below. Unscheduled assessments may be performed at any time at the investigator’s discretion. 
Visit / Day 
Treatment Period (1 cycle = 28 Days) 
 
Day 1–Day 22 
Day 22–Day 
28 
End of 
Treatment 
(EoT) 
Visit 
Safety 
Follow-up 
phone call 
(SFU) 
1 
(D1) 
2 
(D2
) 
3 
(D3
) 
4 
(D5
) 
5 
(D8
) 
6 
(D1
0) 
7 
(D1
2) 
8 
(D1
5) 
9 
(D1
6) 
10 
(D2
2) 
11 
12 
13 
TREATMENTS IN CYCLES 1-2 
 
Premedication for MT-
37241 
X 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
MT-37242,3 
X 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
Gemcitabine4 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
Oxaliplatin5,6 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
TREATMENTS IN CYCLES 3-4 (AND FURTHER IF APPLICABLE)7 
 
Premedication for MT-
37241 
X 
 
 
 
X 
 
 
X 
 
X 
 
 
 
MT-37248 
X 
 
 
 
X 
 
 
X 
 
X 
 
 
 
Gemcitabine4 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
Oxaliplatin5,6 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
STUDY PROCEDURES IN CYCLES 1-4 
 


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Blood pressure and heart 
rate9,10,16 
X 
 
X 
 
Body temperature11 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
Complete PE (with NYHA 
and ECOG) 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Abbreviated PE (with 
ECOG)12 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
Body weight13.14 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
12-Lead ECG (single)15,16 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
LVEF (MUGA or 
Echocardiography) 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Radiological tumor 
assessment (PET-CT or 
CT/MRI)17,18, 
 
 
 
 
 
 
 
 
 
 
X 
(X)18 
 
Concomitant medications19 
X 
X 
X 
X 
AEs19 
X 
X 
X 
X 
LOCAL LAB 
ANALYSES 
 
 
Urinalysis (Dipstix)20 
X 
 
 
 
X 
 
 
X 
X 
X 
 
X 
 
Pregnancy21 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
CENTRAL LAB ANALYSES 
 
Hematology 
X 
 
 
 
X 
 
 
X 
X 
X 
 
X 
 
Chemistry (incl. 
eGFR22) 
X 
 
 
 
X 
 
 
X 
X 
X 
 
X 
 


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Coagulation (PT or 
INR, aPTT) 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
HbA1c 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Thyroid function (TSH, 
FT4) 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Complement23,24 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
Histamine23,24 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
Immunoglobulins23 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
Cytokines23,24 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
B-cell count and 
immunophenotype 
(flow cytometry)25 
X 
 
 
 
 
 
X26 
X27 
 
 
 
X 
 
MT-3724 
Immunogenicity 
(ADA/NA)28 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
MT-3724 PK29 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
FNA biopsy (optional, 
part 2)30 
 
 
 
 
 
 
 
 
 
 
 
X 
 
ADA – Anti-drug antibodies; aPTT – Activated partial thromboplastin time; C – Cycle; CT – Computed tomography; D – Day in 
cycle; ECG – Electrocardiogram; ECOG – Eastern Cooperative Group of Oncology; eGFR – Estimated glomerular filtration rate; 
FT4 – Free thyroxine; HbA1c – Glycated hemoglobin; INR – International normalized ratio; LVEF – Left Ventricular Ejection 
Fraction; NA – Neutralizing antibodies; MRI – Magnetic resonance imaging; MUGA – Multigated acquisition; NYHA – New York 
Heart Association; PET – positron-emission tomography; PK – Pharmacokinetics; PT – Prothrombin time; TSH – Thyroid-
stimulating hormone. 
Footnotes: 
1. Premedication should be administered within 60 minutes before the start of MT-3724 infusion in each cycle in both parts of the study. See Section 5.1.4 


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2. In C1 and C2, MT-3724 should be administered as 1-hour IV infusion on Day 1, 3, 5, 8, 10 and 12 of each 28-day cycle. At the investigator’s discretion, MT-
3724 may be administered on different days up to D21. MT-3724 should not be administered between D22-D28. 
3. No more than two MT-3724 doses can be administered on consecutive days. If MT-3724 is administered on 2 consecutive days in C1 and C2, then at least 20 
hours must elapse between the start of the 2 infusions. 
4. In all cycles, gemcitabine 1000 mg/m2 should be administered as 30-minute IV infusion on Day 2 and Day 16 of each 28-day cycle. At the investigator’s 
discretion, gemcitabine may be administered within ±2 days from scheduled dosing days. Gemcitabine should not be administered between D24-D28. 
5. In all cycles, oxaliplatin (Eloxatin®) 100 mg/m2 should be administered as 2-hour IV infusion after gemcitabine on Day 2 and Day 16 in each 28-day cycle. 
At the investigator’s discretion, oxaliplatin may be administered within ±2 days from scheduled dosing days. Oxaliplatin should not be administered between 
D24-D28. 
6. Oxaliplatin infusion will start one hour after the start of gemcitabine infusion (unless a delay is warranted at the investigator’s discretion). 
7. After C2, treatment with MT-3724 and/or GEMOX may be continued for another 2 (or more) cycles of 28 days each, if supported by the investigator’s 
assessment of the benefit-risk ratio after consultation with sponsor and Medical Monitor 
8. In C3 and C4 (and thereafter), MT-3724 should be administered as 1-hour IV infusion weekly, i.e. on Day 1, 8, 15 and 22 of each 28-day cycle. At the 
investigator’s discretion, MT-3724 may be administered within ±2 days from scheduled dosing days in C3 and C4. MT-3724 should not be administered 
between D24-D28.   
9. Blood pressure (systolic and diastolic) and heart rate should be performed at the following times on each dosing day in each cycle: at any time before the start 
of MT-3724 infusion; at 0.5 h, 1 h, 2 h and 3 h after the start of each MT-3724 infusion in each cycle (±10 min allowed at each time point); at any time before 
the start of gemcitabine infusion; at 3 h (±10 min) after the start of oxaliplatin infusion in each cycle; at the EoT Visit 
10. Blood pressure and heart rate should be measured after 5-10 minutes of quiet rest in a sitting or semi-recumbent position. 
11. Body temperature assessment should be performed at any time before the start of MT-3724 infusion on D1 of each cycle, at any time before the start of 
gemcitabine infusion on D16 of each cycle, and at the EoT Visit 
12. Abbreviated physical exam. should be performed at any time before the start of MT-3724 infusion on D1 of each cycle (within 72 h before the start of MT-
3724 infusion on C1D1 is allowed), and at any time before the start of gemcitabine infusion on D16 of each cycle.  
13. Body weight assessment will be performed at any time before the start of MT-3724 infusion on each dosing day in each cycle, and at the EoT Visit.  
14. Body weight measured before the first dose of MT-3724 in each cycle will be used to calculate all MT-3724 doses in that cycle. 
15. Single 12-lead ECG should be obtained after the subject has rested quietly in supine or semi-recumbent position for 5-10 minutes before the procedure. 
16. When PK, ECG and blood pressure assessments are scheduled to occur at the same time point, then the PK sample collection should be performed at the 
protocolled time and the ECG and blood pressure / heart rate should be done in that order at least 10 minutes before or 10 minutes after the PK sampling. In 
this case, the blood pressure / heart rate measurement may begin immediately after ECG recording (without additional 5-10 minutes’ rest). 
17. 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). 
18. Radiological assessment of tumor response should be performed within 7 days before the start of treatment on C3D1 (end of C2); between D23 and D28 of 
C4 (and end of each even cycle thereafter, if applicable); within 7 days of the EoT Visit (only if the previous tumor scan has been performed >4 weeks before 
the EoT Visit). 
19. Concomitant medications and treatment-emergent adverse events will be reported by verbal probes at every visit to the clinic; in addition, subject’s 
spontaneous reports will be captured. 
20. Analysis of urine microsediment may be performed at the investigator’s discretion. 
21. Pregnancy test (serum or urine) should be performed within 72 h before the first dose of the first study drug in each cycle and at the EoT Visit. 
22. Estimated by the central laboratory using CPK-EPI equation and the serum creatinine from the corresponding chemistry panel 


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23. Cytokines, histamine, complement and immunoglobulins should be assessed before the start of MT-3724 infusion (±10 min) on D1 of each cycle and at 3 h 
after the start of MT-3724 infusion (±10 min) on D1 of each cycle. 
24. 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. 
25. B-cell count and immunophenotype by flow cytometry should be performed on D1 of each cycle (at any time before the start of MT-3724 infusion) and at the 
EoT Visit in all cycles 
26. B-cell count and immunophenotype by flow cytometry should be performed on D12 of C1 and C2 only (at any time before the start of MT-3724 infusion). 
27. B-cell count and immunophenotype by flow cytometry should be performed on D15 of C3 and C4 only (at any time before the start of MT-3724 infusion). 
28. Immunogenicity of MT-3724 (ADA and NA) should be performed at any time before the start of MT-3724 infusion on D1 of each cycle 
29. PK assessments should be made at the following time points: 
• 
C1D1 (MT-3724 Dose 1) 
o 
Within 4 h before the start of infusion (SOI)  
o 
Within 10 minutes before the end of infusion (EOI) 
o 
At the following times after the EOI: 5 minutes (±1 min); 0.5 h, 1 h, 2 h (±5 min each); 3 h and 4 h (±10 min each) 
 
• 
C1D5 (MT-3724 Dose 3) 
o 
Within 4 h before the SOI 
o 
Within 10 minutes before the EOI 
o 
At the following times after the EOI: 5 minutes (±1 min) and 2 h (±5 min) 
 
• 
C1D12 (MT-3724 Dose 6) 
o 
Within 4 h before the SOI  
o 
Within 10 minutes before the end of infusion (EOI) 
o 
At the following times after the EOI: 5 minutes (±1 min); 2 h (±5 min) 
 
• 
Day 1 of Cycles 2-4 (MT-3724 Dose 1) 
o 
Within 4 h before the SOI  
o 
Within 10 minutes before the EOI 
o 
At 5 minutes (±1 min) after the EOI 
30. Optional FNA biopsy at EoT for patients in Part 2, who had consented for this procedure, exhibit PD and have accessible peripheral lymph node(s).


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APPENDIX B. 
LABORATORY PANELS 
Hematology (central laboratory): 
WBC1  
hemoglobin 
platelet count 
hematocrit 
RBC and indices2 
Chemistry (central laboratory): 
albumin 
amylase 
lipase 
creatinine 
ALT [SGPT] 
AST [SGOT] 
CPK 
calcium 
chloride 
GGT 
LDH 
serum glucose3 
magnesium 
phosphorous 
potassium 
sodium 
bilirubin (total and 
direct) 
total protein 
BUN 
Uric acid 
eGFR4  
β-HCG5 
histamine 
HbA1c 
β-2microglobulin 
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 
NA 
B-cell count 
Abbreviations: 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; 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; NA – Neutralizing antibodies; PT – Prothrombin time; RBC – Red Blood Cell; 


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SGOT - serum glutamic-oxaloacetic transaminase; SGPT - serum glutamic-pyruvic transaminase; 
TSH – Thyroid-stimulating hormone; WBC – white blood cell. 
Footnotes: 
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, CKD-EPI calculation, see APPENDIX F 
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 C. 
Staging of NHL  
The Ann Arbor stage of NHL with Cotswolds modification (25) is determined as outlined in 
Table 6, 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 6 :  Ann Arbor Staging System for NHL with Cotswolds Modification 
Stagea  
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  
IIIb  
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 Ann Arbor stages  
A  
No symptoms  
B  
Fever (>38oC), drenching sweats, weight loss (10% body weight over 
6 months)  
For Ann Arbor Stages I to III  
E  
Involvement of a single, extra nodal site contiguous or proximal to 
known nodal site  
X  
Massive mediastinal disease has been defined by the Cotswold meeting 
as a thoracic ratio of maximum transverse mass diameter greater than 
or equal to 33% of the internal transverse thoracic diameter measured 
at the T5/6 intervertebral disc level on chest radiography.  
a. The number of anatomic regions involved should be indicated by a subscript (e.g., II3). Staging should be 
identified as clinical stage (CS) or pathologic stage (PS).  
b. Stage III may be subdivided into: III1, with or without splenic, hilar, celiac, or portal nodes; III, with para-aortic, 
iliac, mesenteric nodes. 


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International prognostic index for aggressive NHL  
At screening, the prospective subjects will be classified in to one of the 4 risk groups according 
to the International Prognostic Index (IPI) for aggressive NHL (24). The classification will be 
determined in 2 steps, as follows. 
1. One point is assigned for each of the following risk factors: 
a. Age greater than 60 years 
b. Stage III or IV disease according to the Ann Arbor staging with Cottswolds 
modification (25) 
c. Elevated serum LDH 
d. ECOG/Zubrod performance status of 2, 3, or 4 
e. More than 1 extranodal site 
2. The sum of the points allotted correlates with the following risk groups: 
a. Low risk (0-1 points) - 5-year survival of 73% 
b. Low-intermediate risk (2 points) - 5-year survival of 51% 
c. High-intermediate risk (3 points) - 5-year survival of 43% 
d. High risk (4-5 points) - 5-year survival of 26% 
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% 
 
 
 


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Follicular Lymphoma International Prognostic Index (FLIPI) [Solal-Céligny 2004] 
The FLIPI is used to assess the prognostic score of patients 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 D. 
REVISED LUGANO CLASSIFICATION OF RESPONSE 
ASSESSMENT IN LYMPHOMA ADJUSTED FOR LYRIC  
Tumor response will be evaluated according to the revised Lugano Classification for Lymphoma 
(20) adjusted according to LYRIC (lymphoma response to immunomodulatory therapy criteria) 
(21). Positron emission tomography-computed tomography (PET-CT) should be used for 
response assessment in subjects with fluorodeoxyglucose (FDG)-avid tumor histology (using the 
5-point scale [5PS]); computer tomography (CT) or magnetic resonance imaging (MRI) is 
preferred in subjects with tumor histology of low or variable FDG avidity. 
Overview of response criteria for FDG avid and non-avid NHL is presented in Table 7. 
Table 7:  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 3* 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 
Target nodes/nodal masses must 
regress to ≤1.5 cm in LDi 
No extralymphatic sites of disease 


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normal tissue even if the tissue 
has high physiologic uptake 
Nonmeasured lesion Not applicable 
Absent 
Organ enlargement Not applicable 
Regress to normal 
New lesion(s) None 
None 
Bone Marrow No evidence of FDG-avid 
disease in marrow 
Normal by morphology; if 
indeterminate, IHC negative 
Partial 
Partial metabolic response 
Partial remission (all of the 
following) 
Lymph nodes and  
extralymphatic sites  
Score 4 or 5 on the 5PS (see 
Table 10) 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 or MRI, 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 
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Individual target 
nodes/nodal masses  
Score 4 or 5 with an increase in 
intensity of uptake from 
baseline and/or 
PPD progression 
Extranodal lesions New FDG-avid foci consistent 
with lymphoma at interim or 
end-of-treatment assessment 
An individual node/lesion must be 
abnormal with: 
LDi >1.5 cm and 
Increase by ≥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 
Regrowth of previously resolved 
lesions 
A new node >1.5 cm in any axis 


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another etiology (e.g., infection, 
inflammation). If 
uncertain regarding etiology of 
new lesions, biopsy or 
interval scan may be considered 
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)** 
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 
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)>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) 


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Abbreviations:  
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. 
Footnotes: 
*A score of 3 in many patients indicates a good prognosis with standard treatment, especially 
if at the time of an interim scan. However, in trials involving PET where de-escalation is 
investigated, it may be preferable to consider a score of 3 as inadequate response (to avoid 
undertreatment). Measured dominant lesions: Up to 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), GI involvement, cutaneous lesions, or those noted on palpation. 
Nonmeasured lesions: Any disease not selected as measured, dominant disease and truly 
assessable disease should be considered not measured. These sites include any nodes, nodal 
masses, and extranodal sites not selected as dominant or measurable or that do not meet the 
requirements for measurability but are still considered abnormal, as well as truly assessable 
disease, which is any site of suspected disease that would be difficult to follow quantitatively 
with measurement, including pleural effusions, ascites, bone lesions, leptomeningeal disease, 
abdominal masses, and other lesions that cannot be confirmed and followed by imaging. In 
Waldeyer’s ring or in extranodal sites (e.g., GI tract, liver, bone marrow), FDG uptake may be 
greater than in the mediastinum with complete metabolic response, but should be no higher 
than surrounding normal physiologic uptake (e.g., with marrow activation as a result of 
chemotherapy or myeloid growth factors). 
** See original paper (Cheson BD. et al. J Clin Oncol 2014; 32: 3059-3067) for more detailed 
information on immune related response. 
 
 
 
Lugano 5PS scale (21) 


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The Lugano 5-point scale (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) see Table 8. 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.  
Table 8: 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 E. 
DOSE LIMITING TOXICITY CRITERIA 
 
General Principles 
A treatment-emergent adverse event (TEAE) will be declared as DLT if both of the following 
criteria are met:  
1. The TEAE occurred after the start of infusion in C1 of Part 1.  
a. If a TEAE that fulfills a DLT criterion is observed in C ≥2 of Part 1, then the sponsor 
may declare this event a DLT after consultation with the investigator and Medical 
Monitor. 
2. TEAE is at least possibly related to MT-3724 (i.e., not reasonably related to another 
etiology), as determined by the sponsor after consultation with investigator and Medical 
Monitor. 
Note: If a Grade ≥3 TEAE related to gemcitabine or oxaliplatin is more severe than the worst 
grade described in the reference prescribing information, or hasn’t been reported in the reference 
prescribing information, then the sponsor may declare this event a DLT after consultation with 
the investigator and Medical Monitor. 
The severity of TEAEs potentially fulfilling the DLT criteria will be graded according to the 
CTCAE v.5.0.  
TEAEs potentially qualifying as DLT 
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 
Non-hematological TEAEs 
• Grade ≥2 Cytokine Release Syndrome 
• Grade ≥2 Capillary Leak Syndrome 


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• Grade ≥2 acute kidney injury (serum creatinine increase ≥2 times above baseline in the 
absence of dehydration or bleeding) 
• AST and / or ALT increase >5.0 times ULN (CTCAE Grade ≥3) 
• AST and / or ALT increase >3.0 times ULN (CTCAE Grade ≥2) with concomitant 
increase in total bilirubin >1.5 times ULN (CTCAE Grade ≥2) 
• Total bilirubin >3.0 times ULN (CTCAE Grade ≥3) 
• 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. The exception is allowed for isolated Grade 3 
or 4 electrolyte abnormalities without a clinical correlate that don’t 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 Medical Monitor 
and investigator. 
• 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 and Medical Monitor, 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 F. 
CKD-EPI Creatinine Equation (2009) 
Expressed as a single equation: 
eGFR = 141 x min(SCr/κ, 1)α x max(SCr /κ, 1)-1.209 x 0.993Age  
x 1.018 [if female] x 1.159 [if Black] 
Abbreviations / Units 
eGFR (estimated glomerular filtration rate) = mL/min/1.73 m2 
SCr (standardized serum creatinine) = mg/dL 
κ = 0.7 (females) or 0.9 (males) 
α = -0.329 (females) or -0.411 (males) 
min = indicates the minimum of SCr/κ or 1 
max = indicates the maximum of SCr/κ or 1 
age = years 
Assays 
Creatinine is assayed using methods that are traceable to IDMS assigned NIST certified reference 
materials. To learn more, go to nkdep.nih.gov. 
Clinical Use 
Recommended method for estimating GFR in adults. 
Designed for use with laboratory creatinine values that are standardized to IDMS. 
Estimates GFR from serum creatinine, age, sex, and race. 
More accurate than the MDRD Study equation, particularly in people with higher levels of GFR. 
Based on the same four variables as the MDRD Study equation, but uses a 2-slope “spline” to 
model the relationship between estimated GFR and serum creatinine, and a different relationship 
for age, sex and race. 
Some clinical laboratories are still reporting GFR estimates using the MDRD Study equation. The 
National Kidney Foundation has recommended that clinical laboratories should begin using the 
CKD-EPI equation to report estimated GFR in adults. 
Developed in 2009 by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI 2009]. 


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APPENDIX G. 
ECOG PERFORMANCE STATUS 
 
The ECOG performance status (22) will be assessed as part of the complete and abbreviated 
physical examinations during the screening, treatment and long-term follow-up periods (see 
Section 6.2.3 and APPENDIX A). 
The criteria for the assessment of the ECOG performance status (22) are presented in Table 9 
 
 
Table 9:  ECOG Performance Status 
Grade 
ECOG performance status scale 
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 house work, office work) 
2 
Ambulatory and capable of all self-care but unable to carry out any work 
activities; up and about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of 
waking hours 
4 
Completely disabled; cannot carry on any self-care; totally confined to bed or 
chair 
5 
Dead 
ECOG = Eastern Cooperative Oncology Group 
 


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APPENDIX H. 
NEW YORK HEART ASSOCIATION (NYHA) 
CLASSIFICATION 
 
The status of heart function will be assessed according to the NYHA classification (23) as part of 
the complete physical examination at screening and the EoT Visit (see  Section 6.2.3 and 
APPENDIX A). 
The NYHA classes are presented in Table 10. 
 
Table 10: NYHA Function Classification 
NYHA class 
Symptoms 
I 
No symptoms and no limitation in ordinary physical activity (e.g., shortness 
of breath when walking or climbing stairs) 
II 
Mild symptoms (mild shortness of breath and / or angina) and slight 
limitation during ordinary activity 
III 
Marked limitation in activity because of symptoms, even during less-than-
ordinary activity, e.g., walking short distances (20 - 100 m); comfortable 
only at rest 
IV 
Severe limitations; experiences symptoms even while at rest; mostly 
bedbound patients 
NYHA = New York Heart Association  
 
 
 
 


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APPENDIX I. 
Summary Of Changes 
List of Changes and Rationale: Amendment 1.0 
 Topic 
Change 
Rationale 
1.  Protocol Title 
Removed “CD20” from protocol title 
To be in alignment with study population description 
2.  Protocol Version 
Changed from Version 1.0 to Amendment 1, Version 2.0 
To account for the amendment 
3.  Signature Page/List 
of Contacts 
Changed medical representative name 
To account for change in MTEM study management 
4.  Objectives/Study 
Design 
Removed “CD20” from protocol title 
To be in alignment with study population description 
5.  End of Treatment 
Visit 
EoT VISIT should occur ≥ 14 days and ≤ 21 days after the last dose 
of MT-3724, gemcitabine or oxaliplatin, whichever is last, at the time 
of discontinuation (except for subjects who died, withdrew consent 
and objected to further data collection, or were lost to follow up).) or 
≥ 7 days and ≤ 14 days after the last dose of MT-3724, gemcitabine 
or oxaliplatin for those that complete the study. 
Edits to clarify when visit takes place 


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6.  Safety Follow-Up 
Changed the safety follow-up (SFU) phone call: approximately at 
least 30 days after last dose of MT-3724 or GEMOX 
To stipulate that a minimum of 30 days must elapse 
before the follow-up 
7.  Gemcitabine and 
Oxaliplatin Dose 
Changed from requiring a fixed starting and ongoing doses of 
gemcitabine and oxaliplatin to add allowance for the doses to be 
decreased per investigators discretion based prescribing information 
and patient status. 
To allow flexibility for the dosing based on 
investigator and site practices 
8.  Long-Term Follow 
Up 
Revised to add subjects will be followed for 24 months for PFS and 
DOR until progressive disease, death or lost to follow up. 
Long-term follow up has been revised to clarify 
information to be collected. 
9.  Patient Population 
Reference to CD20-positive histology removed in the description of 
the patient population and throughout the document and added as 
inclusion criterion 3.d. 
Inclusion criterion 3.d. provides a more detailed 
description of the requirement for CD20 histology. 
10.  Inclusion Criteria 
Criterion 3:  Changed  
3. 
Have histologically confirmed, relapsed or refractory CD20-
positive B-cell NHL that, in the investigator’s opinion, could benefit 
from MT-3724 + GEMOX therapy. 
NHL histology must be determined at any time after the most recent 
At least one histologically documented relapse of NHL by: 
a. Bone marrow biopsy (FNA not acceptable) or 
Changes made to allow more flexibility in timing of 
required histology and allowance of mixed DLBCL 
histology in Part 2 


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b. Excisional lymph node biopsy (FNA or other procedure not 
acceptable) or 
c. Core biopsy of any involved organ (FNA not acceptable)   
d. CD20-positive histology must have been confirmed at any 
time during NHL disease course and documented in medical 
history. 
e. If no histology is available after any relapse the investigator 
can consult the medical monitor to discuss if the patient can 
be included. 
11.  Inclusion Criteria 
Inclusion criterion 4 
Added “mixed histology” in the description of NHL subtypes 
To clarify that DLBCL mixed histology will be 
accepted in Part 2 of the study 
12.  Inclusion Criteria 
Removed IPI and Ann Arbor staging requirements 
Since the patient population is relapsed/refractory, 
prognostic scoring is not needed 
13.  Inclusion Criteria 
Removed CTCAE grading 
redundant 
14. Inclusion Criteria 
Inclusion Criterion 8:  Changed calculation to be used for kidney 
function from Cockcroft and Gault’s to CPK-EPI 
The updated formula is SOC 
15. Inclusion Criteria 
Inclusion Criterion 9b and c:   
To include patients with liver involvement 


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Added allowance for ≤ 5.0 x ULN if liver involvement    
16. Inclusion Criteria 
Inclusion Criterion 11 added:   
12. 
Have adequate serum albumin, as determined by: 
a. 
Albumin ≥ 3.0 g/dL 
For added safety 
17. Exclusion Criteria 
8e. added additional detail to criterion for congestive heart failure: 
e. Congestive heart failure (NYHA Class III or IV;APPENDIX 
H) at screening  or LVEF <45%, assessed by Echo or 
MUGA scan within 1 month before starting study treatment. 
(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). 
For greater flexibility in assessing heart failure 
18. Exclusion Criteria 
Prior Treatments:  10 – added b. and c. 
b. Subjects with positive HBV serology are eligible if 
quantitative PCR for plasma HBV-DNA is negative 
and the subject will be receiving prophylaxis for 
potential HBV reactivation. 
To provide additional detail on viral test results and 
related actions 


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c. Subjects with positive HCV serology are eligible if 
quantitative PCR for plasma HCV RNA is negative. 
19. Exclusion Criteria 
Prior Treatments:  14 
Reduced the required rituximab washout from 110 days to 84 days 
and reduced the required testing period from 365 days to 37 weeks.   
Note:  All enrolled subjects will be tested for serum rituximab, but 
only the result out to 37 wks will be used for exclusion.  
Updated based on most recent MTEM clinical data  
20. Exclusion Criteria 
Prior Treatments:   
15. 
Received therapy for NHL (excluding the anti-CD20 MAbs 
listed above) or any investigational treatment within 3 4 weeks or 5 
half-lives of the agent before the start of treatment, whichever is 
longer. 
Added exclusion 16 for any investigational treatments 
21. Exclusion Criteria 
Prior Treatments:   
Added criterion 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.”  
To exclude patients that may be on other investigation 
treatments not already listed 
22. Exclusion Criteria 
Exclusion Criterion 17 
For added clarity 


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Added “according to Lugano Classification for NHL” 
23. Exclusion Criteria 
Exclusion Criterion 18 
Removed the need for consultation with medical monitor 
Not required 
24. Treatments 
Oxaliplatin 100 mg/m2 will be administered as 2-hour IV infusion 
after gemcitabine on Day 2 and Day 16 of each 28-day cycle.  
Oxaliplatin infusion will start exactly one hour after the start of 
gemcitabine infusion (unless a delay is warranted at the 
investigator’s discretion). 
To allow for reasonable flexibility in timing of dosing 
25. Treatment Duration 
(section 5.9)  
Added: 
“If the subject exhibits SD, CR or PR after the end of Cycle 4 and the 
investigator determines that the benefit-risk ratio is favorable, then 
the treatment with MT-3724 may be continued after discussion with 
the sponsor. Continuation of GEMOX is at investigators discretion.” 
To allow for continued dosing with up to 6 additional 
cycles of MT-3724 for subjects who respond 
 
26. Clinical Experience 
(section 1.2.1) 
Removed “Hypertension” and added updated clinical data 
To be in alignment with updated IB 
27. MTD Definition 
(section 3.6.3) 
Added “with a maximum total dose of 6000 µg” to the MTD 
definition 
To further clarify the definition 


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28. MTD 
Communication 
Plan (section 3.6.4) 
Added “If the Medical Monitor and sponsor become aware that the 
MTD may be declared in the current dose cohort (e.g. based on the 
occurrence of qualifying AE/SAE in ≥2 subjects), then they will 
inform the investigators that recruitment should be suspended 
pending the safety review meeting.” 
To provide additional detail within the protocol 
29. Guidance to the 
Investigator 
Section 3.9 Guidance to the Investigator added 
For safety guidance in alignment with updated IB 
30. Treatments (Section 
5) 
Removed the requirement for assisted ventilation in the treatment 
area and added requirement to have access to emergency facilities 
through an emergency call. 
To allow some flexibility with the requirements for 
treatment areas 
31. Table 2 & Table 3:  
Dose Adjustments 
Changed from Dose-level decreases to % decreases and adjusted the 
number of days to trigger a dose adjustment.  Added statement 
allowing for repeated dose reductions. 
More accurate and consistent  
32. Prohibited 
Medication (section 
5.10) 
Reduced the required rituximab washout from 110 days to 84 days 
and reduced the required testing period from 365 days to 37 weeks.   
Note:  All enrolled subjects will be tested for serum rituximab, but 
only the result out to 37 wks will be used for exclusion. 
Updated based on most recent MTEM clinical data 


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33. Prohibited 
Medication (section 
5.10) 
Added: 
“Subjects must not have received any vaccines from 28 days before 
the start of treatment until 28 days after the last dose of MT-3724. 
The single exception to this exclusion is for the injectable flu vaccine 
(inactivated or recombinant), which may be administered at the 
investigator’s discretion at any time during the above period” 
To be in alignment with inclusion/exclusion criteria 
34. Permitted 
Medication (section 
5.11) 
Added: 
“The injectable flu vaccine may be administered at the investigator’s 
discretion from 28 days before the start of treatment until 28 days 
after the last dose of MT-3724, and at any time thereafter. If the 
investigator allows the flu vaccine, they should carefully assess if it 
is appropriate to administer the flu vaccine before all study-related 
laboratory abnormalities or AEs have resolved. The subjects treated 
with B-cell depleting MAbs have been shown to have impaired 
humoral immune responses to neo-antigens for variable periods of 
time following the B-cell depleting treatment.” 
To be in alignment with inclusion/exclusion criteria 
35. Study Assessments 
(section 6.1.2) 
Removed: 
“Body weight measurement before the first dose of MT-3724 in each 
cycle will be used to calculate all MT-3724 doses in that cycle” 
More accurate description of how body weight is to be 
used for dose calculation is provided below in the same 
section. 


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36. Study Assessments 
(section 6.1.4) 
Added the collection of available data on mutational status at 
screening 
To further characterize the assessment of NHL at 
screening 
37. Study Assessments 
- Complete physical 
examination 
(section 6.2.3.1) 
Removed requirement for eye examination/fundoscopy 
Not standard of care and not required for this study 
38. Study Assessments 
– Blood 
Pressure/Heart Rate 
(section 6.2.5) 
Removed the 3hr assessment after start of MT-3724 infusion in each 
cycle. 
Added 3h and 4h assessment after start of MT-3724 infusion on 
C1D1. 
Lessen burned on subjects since a 3h assessment for 
each cycle would require >2h additional time after 
every infusion.  Instead, added additional assessments 
only on C1D1 – where there is already an extended 
visit due to PK sampling. 
39. Adverse Events 
(section 6.3) 
Re-worded 
For simplification and clarification of reporting 
40. Adverse Events 
(section 6.3) 
Added  
“Natural disease progression of the malignancy or deterioration of 
the patient’s condition under study (including new sites of metastasis 
and death due to disease progression) will be recorded as part of the 
To provide clarity on how certain events should be 
characterized and reported 


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efficacy evaluation and should not be reported as an AE or as an 
SAE. 
Discontinuation from the study because of disease progression or 
deterioration of the patient’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.” 
41. Action Taken with 
Study Treatment 
(section 6.3.7) and 
Outcome (section 
6.3.8) 
Removed list of specific categories and changed to refer to eCRF 
guidelines for specifics on selections for documentation 
For simplification 
42. Laboratory Tests 
(section 6.4) 
Added Histamine, Immunogenicity of MT-3724; Anti-drug 
antibodies [anti-drug antibody (ADA) and neutralizing antibody 
(NA)] 
 
43. Laboratory Tests 
(section 6.4.7) 
Added histamine 
 
44. Glucose Testing 
Change from Plasma to Serum 
To be in better alignment with lab practices 


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45. Laboratory Testing 
beta-2 
microglobulin 
(section 6.4.8) 
Removed all samples taken after screening 
Not needed for the study 
46. Rituximab 
concentration 
(section 6.4.9) 
Clarified washout period, testing period for eligibility and that testing 
is to be performed on all eligible subjects such that all enrolled 
subjects will be tested for serum rituximab, but only the result out to 
37 wks will be used for exclusion.  
Updated based on most recent MTEM clinical data and 
so that additional data can be collected for exploratory 
purposes after week 37. 
47. Pharmacokinetic 
assessments 
(section 6.6) 
Added: 
“The PK of gemcitabine and oxaliplatin will not be assessed in this 
study. 
These tests are not needed for the study 
48. Efficacy 
assessments 
(section 6.7) 
Between D23 and D28 of C4 (end of C4, if applicable) and each even 
numbered cycle thereafter in cases where treatment was continued 
past C4. 
 
49. Efficacy 
assessments 
(section 6.7) 
Added 
“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 
To clarify scanning technique for consistency  


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whenever possible. Scans must meet the SOC for imaging of lesions 
in the respective organ system(s).” 
50. Pharmacodynamic 
Assessments 
(section 6.10) 
Added: 
In Part 2 of the study an optional FNA biopsy will be obtained at 
EoT in patients who consented for this procedure and exhibit PD and 
have accessible peripheral lymph node(s). The purpose of biopsy is 
to assess the CD20 status of DLBCL by IHC staining of the fine 
needle aspirate and determine if the B-cell lymphoma cells have lost 
CD20 positive status. 
The optional biopsy was added to collect additional, 
exploratory data to determine CD20-positive status in 
subjects that progressed 
51. Data Management 
and Statistical 
Analysis (section 7) 
Re-worded 
For simplification and clarification 
52. Efficacy Population 
(section 7.4.2) 
Added: 
All subjects who received at least one dose of any study drug (either 
MT-3724 or gemcitabine or oxaliplatin) and have the baseline tumor 
assessment as well as at least one post-baseline tumor assessment.  
 
To define efficacy population 


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53. Safety Analyses 
(section 7.8) 
Added thyroid function and changes in physical exam 
To align with assessments taken 
54. Informed Consent 
(section 8.1.3) 
Re-worded 
For better clarity 
55. Study monitoring, 
Auditing and 
inspection (section 
8.5) 
Added 
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. 
Standard practice for regulatory compliance 
56. Source Data 
(section 8.6) and 
Financial 
Disclosure (section 
8.9) 
Added entire sections 
Standard practices for regulatory compliance 


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57. APPENDIX C 
(formerly Appendix 
3) 
Added Follicular Lymphoma International Prognostic Index (FLIPI) 
For the assessment of follicular lymphoma in Part 1 
58. APPENDIX F 
(formerly Appendix 
6) 
Changed from Cockcroft-Gault to CKD-EPI 
To be in alignment with eligibility criterion for kidney 
function 
 

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04/01/2021 15:50:54 UTC
(Signer)
SignNow e-signature ID: c247772993...
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(Signer)
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NCT Number: NCT03488251 
This NCT number has been applied to the document
for the purposes of posting on clinicaltrials.gov


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MT-3724 GEMOX MES20001 Statistical Analysis Plan v1.0
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