A Randomized, Open-Label, Multicenter Phase III Study Evaluating Efficacy and Safety of Mosunetuzumab in Combination With Polatuzumab Vedotin in Comparison With Rituximab in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed or Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma
Phase: PHASE3
Conditions: Non-Hodgkin Lymphoma
Sponsor: Hoffmann-La Roche

 
Official Title: 
A Randomized, Open-Label, Multicenter Phase III Study Evaluating 
Efficacy and Safety of Mosunetuzumab in Combination with 
Polatuzumab Vedotin in Comparison with Rituximab in Combination 
with Gemcitabine Plus Oxaliplatin in Participants with Relapsed or 
Refractory Aggressive B-Cell Non-Hodgkin’s Lymphoma 
NCT Number: 
NCT05171647 
Document Date: 
Protocol Amendment Version 5: 05-Oct-2024 
 
 
 
 

CONFIDENTIAL 
This clinical study is being sponsored globally by F. Hoffmann-La Roche Ltd of Basel, 
Switzerland.  However, it may be implemented in individual countries by Roche's local affiliates, 
including Genentech, Inc. in the United States.  The information contained in this document, 
especially any unpublished data, is the property of F. Hoffmann-La Roche Ltd (or under its 
control) and therefore, is provided to you in confidence as an investigator, potential investigator, 
or consultant, for review by you, your staff, and an applicable Ethics Committee or Institutional 
Review Board.  It is understood that this information will not be disclosed to others without written 
authorization from Roche except to the extent necessary to obtain informed consent from persons 
to whom the drug may be administered. 
 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
Protocol GO43643, Version 5 
PROTOCOL 
PROTOCOL TITLE: 
A RANDOMIZED, OPEN-LABEL, MULTICENTER 
PHASE III STUDY EVALUATING EFFICACY AND 
SAFETY OF MOSUNETUZUMAB IN COMBINATION 
WITH POLATUZUMAB VEDOTIN IN COMPARISON 
WITH RITUXIMAB IN COMBINATION WITH 
GEMCITABINE PLUS OXALIPLATIN IN 
PARTICIPANTS WITH RELAPSED OR REFRACTORY 
AGGRESSIVE B-CELL NON-HODGKIN’S LYMPHOMA 
PROTOCOL NUMBER: 
GO43643 
STUDY NAME: 
SUNMO 
VERSION NUMBER: 
5 
TEST COMPOUND(S): 
Mosunetuzumab (RO7030816; BTCT4465A) 
Polatuzumab vedotin (RO5541077; DCDS4501S) 
Tocilizumab (RO4877533) 
STUDY PHASE: 
Phase III 
EUDRACT NUMBER: 
To be determined 
IND NUMBER: 
120651 
NCT NUMBER: 
NCT05171647 
MEDICAL MONITOR: 
 Ph.D. 
SPONSOR’S NAME 
AND LEGAL 
REGISTERED 
ADDRESS: 
F. Hoffmann-La Roche Ltd 
Grenzacherstrasse 124 
4070 Basel, Switzerland 
APPROVAL: 
See electronic signature and date stamp on the final page 
of this document 

Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
2/Protocol GO43643, Version 5  
PROTOCOL HISTORY 
Protocol 
Associated Country and/or Region-Specific Protocols 
Version 
Date Final 
Country and/or Region 
Version 
Date Final 
5 
See electronic 
date stamp on 
the final page of 
this document. 
 
 
 
4 
20 February 2024 
 
 
 
3 
04 October 2023 
US 
2 
23 May 2023 
2 
11 November 
2022 
US 
1 
17 January 2023 
1 
12 July 2021 
 
 
 
 

Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
3/Protocol GO43643, Version 5  
PROTOCOL AMENDMENT, VERSION 5: 
RATIONALE 
Protocol GO43643, Version 5 has been primarily amended for the following reasons: to 
include the required language updates to the identified risks of hemophagocytic 
lymphohistiocytosis (HLH) and neurologic toxicity including immune effector cell-
associated neurotoxicity syndrome (ICANS); to include updates from the recent protocol 
clarification letter (PCL) which provides clarification on post-treatment follow up visits 
after Month 30, and to include guidance for unscheduled additional survival follow-ups.  
Changes to the protocol, along with a rationale for each change are summarized below:  
 
The protocol has been updated to upgrade the potential risk of neurological adverse 
events to the identified risk of neurologic toxicity including ICANS.  The potential risk 
of HLH has also been updated to an identified risk.  This is following the Dear 
Investigator Letter issued on 28 June 2024.  Related changes include the following: 
– 
Text in the protocol referring to ‘neurologic adverse events’ has been replaced 
with "neurologic toxicity including ICANS" (Section 2.3, 4.3.2, A6-2.3.5, and 
Appendix 22). 
– 
The description of risks associated with mosunetuzumab has been updated to 
include neurologic toxicity including ICANS and HLH as identified risks 
(Appendix 6). 
– 
The management guidelines have been updated to include neurologic toxicity 
including ICANS (Table A6-10) (Appendix 6).  
– 
The management guidelines have also been updated with criteria for 
diagnosing HLH (Table A6-6) and with guidelines for managing suspected or 
confirmed HLH (Table A6-7).  
– 
The assessment of severity of adverse events has been updated to include a 
reference to Appendix 21 for the ASTCT ICANS consensus grading for adults 
and ICE assessment.  The assessment for severity for HLH events has been 
updated to include reference to a scale developed by the ASTCT working group 
(Table A6-8). 
– 
Additional guidance on the grading of ICANS and HLH have been updated.  
New cases of ICANS and HLH will continue to be graded using NCI CTCAE 
v5.0.  In addition, ASTCT grade for ICANS and HLH should be provided in the 
Additional Case Details section on the Adverse Events eCRF page (refer to 
Appendix 21, and Table A6-8) (Sections 4.1.1.4 and A3-3.2). 
 
Patients who remain in post-treatment follow-up without disease progression or new 
anti-lymphoma therapy through the Month 30 visit, will then move into the long-term 
survival follow-up phase in which they will be followed for survival status and new 
anti-lymphoma therapy via telephone calls, participant medical records, and/or clinic 
visits approximately every 3 months until death (unless the participant withdraws 
consent or the Sponsor terminates the study).  Guidelines for post-treatment follow-
up visits after Month 30 have been updated in Section 1.3 (Tables 1 and 2, 
footnotes c and d) and Section 7.1.  

Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
4/Protocol GO43643, Version 5  
 
Guidance on unscheduled additional survival follow-ups have been included in 
Tables 1 and 2, footnote d.  
 
Additional minor changes have been made to improve clarity and consistency.  
Substantive new information appears in italics.  This amendment represents cumulative 
changes to the original protocol. 

Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
5/Protocol GO43643, Version 5  
 
TABLE OF CONTENTS 
1. 
PROTOCOL SUMMARY ............................................................... 16 
1.1 
Synopsis .................................................................................. 16 
1.2 
Study Schema ......................................................................... 21 
1.3 
Schedule of Activities and Sample Collection Schedule .......... 22 
2. 
INTRODUCTION ........................................................................... 41 
2.1 
Study Rationale ....................................................................... 41 
2.2 
Background.............................................................................. 41 
2.3 
Benefit-Risk Assessment ......................................................... 42 
2.3.1 
COVID-19 Benefit-Risk Assessment ....................................... 43 
3. 
OBJECTIVES AND ENDPOINTS ................................................. 44 
4. 
STUDY DESIGN ........................................................................... 48 
4.1 
Overall Design ......................................................................... 48 
4.1.1 
Overview of Study Design........................................................ 48 
4.1.1.1 
Randomization ......................................................................... 48 
4.1.1.2 
Arm A Treatment (Mosunetuzumab  Polatuzumab 
Vedotin) ................................................................................... 48 
4.1.1.3 
Arm B Treatment (Rituximab, Gemcitabine, Oxaliplatin) ......... 49 
4.1.1.4 
Assessment During the Study .................................................. 50 
4.1.1.5 
Continued Treatment of Non-Hodgkin Lymphoma in Arm A 
After Suspected Disease Progression ..................................... 51 
4.1.2 
Independent Review Facility .................................................... 51 
4.1.3 
Independent Data Monitoring Committee ................................ 52 
4.2 
Rationale for Study Design ...................................................... 53 
4.2.1 
Rationale for Study Population ................................................ 53 
4.2.2 
Rationale for Control Group ..................................................... 55 
4.2.3 
Rationale for Randomization Ratio .......................................... 55 
4.2.4 
Rationale for Biomarker Assessments ..................................... 55 
4.2.5 
Rationale for Pharmacokinetic and Anti-Drug Antibody 
Sampling Schedule .................................................................. 57 
....................... 57 
4.3 
Justification for Dose and Schedule ......................................... 58 

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4.3.1 
Rationale for Polatuzumab Vedotin Dose and Schedule ......... 58 
...... 58 
...... 58 
...... 64 
...... 66 
4.4 
End of Study Definition ............................................................ 67 
4.5 
Duration of Participation .......................................................... 67 
5. 
STUDY POPULATION .................................................................. 67 
5.1 
Inclusion Criteria ...................................................................... 68 
5.2 
Exclusion Criteria ..................................................................... 71 
5.3 
Lifestyle Considerations ........................................................... 75 
5.3.1 
Meals and Dietary Restrictions ................................................ 75 
5.3.2 
Caffeine, Alcohol, and Tobacco ............................................... 75 
5.3.3 
Activity ..................................................................................... 75 
5.3.4 
Contraception Requirements ................................................... 75 
5.4 
Screen Failures ........................................................................ 75 
5.5 
Criteria for Temporarily Delaying Randomization or 
Administration of Study Intervention ........................................ 75 
6. 
STUDY TREATMENTS AND CONCOMITANT THERAPY ........... 75 
6.1 
Study Treatments Administered ............................................... 76 
6.1.1 
Polatuzumab Vedotin ............................................................... 77 
6.1.2 
Mosunetuzumab ...................................................................... 78 
6.1.3 
Tocilizumab.............................................................................. 79 
6.1.4 
Rituximab ................................................................................. 80 
6.1.5 
Gemcitabine ............................................................................. 81 
6.1.6 
Oxaliplatin ................................................................................ 81 
6.2 
Preparation, Handling, Storage, and Accountability ................. 81 
6.3 
Treatment Assignment ............................................................. 82 
6.4 
Study Treatment Compliance .................................................. 82 

Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
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6.5 
Dose Modification .................................................................... 82 
6.6 
Continued Access to Study Treatment after the End of the 
Study ....................................................................................... 82 
6.7 
Treatment of Overdose ............................................................ 83 
6.8 
Concomitant Therapy .............................................................. 83 
6.8.1 
Permitted Therapy ................................................................... 83 
6.8.1.1 
COVID-19 Vaccines ................................................................. 84 
6.8.2 
Cautionary Therapy ................................................................. 85 
6.8.2.1 
Medications Given with Precaution due to Effects Related 
to CYP Enzymes and P-glycoprotein Inhibitors ....................... 85 
6.8.2.2 
Herbal Therapies ..................................................................... 86 
6.8.3 
Prohibited Therapy .................................................................. 86 
7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION OR WITHDRAWAL ............ 87 
7.1 
Discontinuation of Study Treatment ......................................... 87 
7.2 
Participant Discontinuation or Withdrawal from the Study ....... 88 
7.3 
Participants Lost to Follow-Up ................................................. 88 
8. 
STUDY ASSESSMENTS AND PROCEDURES ........................... 89 
8.1 
Efficacy Assessments .............................................................. 90 
8.1.1 
Tumor and Response Evaluations ........................................... 90 
8.1.1.1 
Radiographic Assessments ..................................................... 90 
8.1.1.2 
Bone Marrow Examinations ..................................................... 91 
8.1.1.3 
Response Evaluation ............................................................... 91 
8.2 
Safety Assessments ................................................................ 91 
8.2.1 
Physical Examinations ............................................................. 91 
8.2.2 
Vital Signs ................................................................................ 92 
8.2.3 
Electrocardiograms .................................................................. 92 
8.2.4 
Clinical Safety Laboratory Assessments .................................. 93 
8.2.5 
Pregnancy Testing ................................................................... 94 
............................. 94 
............................. 94 
............................. 94 
............................. 94 

Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
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.............................. 95 
8.3 
Adverse Events, Serious Adverse Events, and Other 
Safety Reporting ...................................................................... 95 
8.3.1 
Time Period and Frequency for Collecting Adverse Event 
and Serious Adverse Event Information .................................. 95 
8.3.2 
Method of Detecting Adverse Events and Serious Adverse 
Events ...................................................................................... 96 
8.3.3 
Follow-Up of Adverse Events and Serious Adverse Events .... 96 
8.3.4 
Regulatory Reporting Requirements for Serious Adverse 
Events ...................................................................................... 97 
8.3.5 
Pregnancy................................................................................ 97 
8.3.6 
Death Events ........................................................................... 98 
8.3.7 
Anticipated Events Not Qualifying for Expedited Reporting ..... 98 
8.3.8 
Adverse Events of Special Interest .......................................... 98 
8.3.8.1 
Adverse Events of Special Interest Specific to 
Mosunetuzumab ...................................................................... 99 
8.3.8.2 
Adverse Events of Special Interest Specific to 
Polatuzumab Vedotin ............................................................... 99 
8.3.9 
Medical Monitors and Emergency Medical Contacts ............... 99 
8.4 
Pharmacokinetics .................................................................. 100 
8.5 
Pharmacodynamics ............................................................... 100 
8.6 
Genetics ................................................................................ 100 
8.7 
Biomarker Assessments ........................................................ 101 
8.8 
Immunogenicity Assessments ............................................... 102 
8.9 
Health Economics and Medical Resource Utilization ............. 103 
8.10 
Clinical Outcome Assessments ............................................. 103 
8.10.1 
Data Collection Methods for Clinical Outcome 
Assessments ......................................................................... 103 
8.10.2 
Description of Clinical Outcome Assessment Instruments ..... 104 
8.10.2.1 
EORTC QLQ-C30 .................................................................. 104 
........................................................................... 104 
8.10.2.3 
FACT-Lym and LymS Subscale ............................................. 105 
8.10.2.4 
FACT/GOG-Ntx ..................................................................... 105 
8.11 
Additional Assessments and Procedures 
Requiring Separate Consent or Performed 
Only at Participating Sites ...................................................... 105 

Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
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8.11.1 
Blood Samples for Whole-Genome Sequencing or 
Whole-Exome Sequencing (Participants at Participating 
Sites) ..................................................................................... 105 
8.11.2 
Optional Tumor Biopsies (Participants Providing Separate 
Consent) ................................................................................ 106 
8.11.3 
Samples for Research Biosample Repository 
(Participants Providing Separate Consent at Participating 
Sites) ..................................................................................... 107 
8.11.3.1 
Overview of the Research Biosample Repository .................. 107 
8.11.3.2 
Approval by the Institutional Review Board or 
Ethics Committee ................................................................... 107 
8.11.3.3 
Sample Collection .................................................................. 108 
8.11.4 
Confidentiality ........................................................................ 108 
8.11.5 
Consent to Participate in the Research Biosample 
Repository.............................................................................. 109 
8.11.6 
Withdrawal from the Research Biosample Repository ........... 109 
8.11.7 
Monitoring and Oversight ....................................................... 110 
9. 
STATISTICAL CONSIDERATIONS ............................................ 110 
9.1 
Statistical Hypotheses ........................................................... 110 
9.2 
Sample Size Determination ................................................... 110 
9.2.1 
Type I Error Control ............................................................... 111 
9.2.2 
Dual Primary Endpoint:  Objective Response Rate in 
Interim Analysis Population (IAP) .......................................... 113 
9.2.3 
Dual Primary Endpoint:  Progression-Free Survival in ITT .... 113 
9.2.4 
Key Secondary Endpoint:  Overall Survival in ITT ................. 114 
9.3 
Analysis Sets ......................................................................... 117 
9.4 
Statistical Analyses ................................................................ 117 
9.4.1 
General Considerations ......................................................... 117 
9.4.2 
Dual Primary Endpoints ......................................................... 118 
9.4.2.1 
ORR by IRF ........................................................................... 118 
9.4.2.2 
PFS by IRF ............................................................................ 119 
9.4.3 
Secondary Endpoints ............................................................. 120 
9.4.4 
Exploratory Endpoints ............................................................ 122 
9.4.5 
Other Safety Analyses ........................................................... 123 
9.4.6 
Other Analyses ...................................................................... 123 

Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
10/Protocol GO43643, Version 5  
9.4.6.1 
Summaries of Conduct of Study ............................................ 123 
9.4.6.2 
Summaries of Treatment Group 
Comparability/Demographics and Baseline Characteristics .. 123 
9.4.6.3 
Pharmacokinetic Analyses ..................................................... 123 
9.4.6.4 
Immunogenicity Analyses ...................................................... 124 
9.4.6.5 
Clinical Outcome Assessment Analyses ................................ 124 
9.4.6.6 
Simplified Geriatric Assessment Endpoints ........................... 125 
9.4.6.7 
Health Status Utility Analyses ................................................ 125 
9.5 
Interim Analysis ..................................................................... 125 
..... 125 
..... 125 
..... 125 
9.6 
Asian Subpopulation Analyses .............................................. 126 
9.7 
Independent Data Monitoring Committee .............................. 126 
10. 
REFERENCES............................................................................ 127 
 
 
LIST OF TABLES 
Table 1 
Schedule of Activities:  Arm A ..................................................... 22 
Table 2 
Schedule of Activities:  Arm B ..................................................... 29 
Table 3 
Schedule of Pharmacokinetic, Immunogenicity, and 
Biomarker Samples (Arm A) ....................................................... 35 
Table 4 
Schedule of Pharmacokinetic, Immunogenicity, and 
Biomarker Samples (Arm B) ....................................................... 38 
Table 5 
Schedule for Tocilizumab Treatment of Cytokine Release 
Syndrome.................................................................................... 39 
Table 6 
Objectives and Corresponding Endpoints ................................... 45 
Table 7 
Study GO40516 Arm L:  Demographics and Disease 
Characteristics for Participants with R/R Aggressive NHL 
Treated with Mosunetuzumab SC in Combination with 
Polatuzumab Vedotin .................................................................. 59 
Table 8 
 Study GO40516 Arm J and Arm L:  Overview of Adverse 
Events ......................................................................................... 62 
Table 9 
Study GO40516 Arm J and Arm L:  Summary of Efficacy in 
Participants with R/R Agressive NHL .......................................... 64 
Table 10 
Study Treatment Description (Arm A) ......................................... 76 
Table 11 
Study Treatment Description (Arm B) ......................................... 77 
Table 12 
Administration of Rituximab ........................................................ 80 

Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
11/Protocol GO43643, Version 5  
Table 13 
Analysis Timing and Stopping Boundaries for Overall 
Survival ..................................................................................... 116 
 
 
LIST OF FIGURES 
Figure 1 
Study Schema ............................................................................. 21 
....... 49 
Figure 3 
Arm B (Rituximab, Gemcitabine, Oxaliplatin) Dose and 
Schedule 
... 50 
... 63 
... 65 
... 66 
. 112 
 
LIST OF APPENDICES 
Appendix 1 
Regulatory, Ethical, and Study Oversight Considerations ......... 132 
A1–1 
Regulatory and Ethical Considerations ..................................... 133 
A1–2 
Financial Disclosure .................................................................. 133 
A1–3 
Informed Consent Process........................................................ 134 
A1–4 
Data Protection ......................................................................... 134 
A1–5 
Administrative Structure ............................................................ 135 
A1–6 
Dissemination of Clinical Study Data ........................................ 135 
A1–7 
Data Quality Assurance ............................................................ 136 
A1–8 
Source Documents ................................................................... 137 
A1–9 
Study and Site Closure ............................................................. 137 
A1–10 
Publication Policy ...................................................................... 138 
A1–11 
Protocol Deviations ................................................................... 138 
Appendix 2 
Clinical Safety Laboratory Tests ............................................... 139 
Appendix 3 
Adverse Events:  Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting ....................................... 141 
A3–1 
Definition of Adverse Event ....................................................... 142 
A3–2 
Definition of Serious Adverse Event .......................................... 143 

Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
12/Protocol GO43643, Version 5  
A3–3 
Recording and Follow-Up of Adverse Events and Serious 
Adverse Events ......................................................................... 144 
A3–3.1 
Adverse Event and Serious Adverse Event Recording ............. 144 
A3–3.2 
Assessment of Severity ............................................................ 145 
A3–3.3 
Assessment of Causality ........................................................... 146 
A3–3.4 
Follow-up of Adverse Events and Serious Adverse Events ...... 147 
A3–3.4.1 
Investigator Follow-Up .............................................................. 147 
A3–3.4.2 
Sponsor Follow-Up ................................................................... 148 
A3–4 
Reporting of Serious Adverse Events ....................................... 148 
A3–4.1 
Serious Adverse Event Reporting to The Sponsor via an 
Electronic Collection Tool.......................................................... 148 
A3–4.2 
Serious Adverse Event Reporting to The Sponsor via Paper 
CRF .......................................................................................... 148 
A3–5 
Reporting Requirements for Serious Adverse Events and 
Adverse Events of Special Interest ........................................... 149 
A3–5.1 
Events That Occur Prior to Study Treatment Initiation .............. 149 
A3–5.2 
Events That Occur After Study Treatment Initiation .................. 149 
A3–6 
Reporting Adverse Events That Occur after the Adverse 
Event Reporting Period ............................................................. 149 
A3–7 
Procedures for Recording Adverse Events ............................... 150 
A3–7.1 
Cytokine Release Syndrome/Injection-Related Reactions 
Attributed to Monsunetuzumab ................................................. 150 
A3–7.2 
Infusion-Related Reactions ....................................................... 151 
A3–7.3 
Diagnosis Versus Signs And Symptoms ................................... 151 
A3–7.4 
Adverse Events that are Secondary to Other Events ................ 151 
A3–7.5 
Persistent or Recurrent Adverse Events ................................... 152 
A3–7.6 
Abnormal Laboratory Values..................................................... 152 
A3–7.7 
Abnormal Vital Sign Values....................................................... 153 
A3–7.8 
Abnormal Liver Function Tests ................................................. 154 
A3–7.9 
Deaths ...................................................................................... 154 
A3–7.10 
Preexisting Medical Conditions ................................................. 155 
A3–7.11 
Lack of Efficacy or Worsening of Lymphoma ............................ 155 
A3–7.12 
Hospitalization or Prolonged Hospitalization ............................. 155 
A3–7.13 
Cases of Accidental Overdose or Medication Error .................. 156 
A3–7.14 
Participant-Reported Outcome Data ......................................... 157 
Appendix 4 
Contraceptive and Barrier Guidance ......................................... 158 
A4–1 
Pregnancies in Female Participants .......................................... 159 
A4–2 
Pregnancies in Female Partners of Male Participants .............. 159 
A4–3 
Abortions ................................................................................... 160 
A4–4 
Abnormal Pregnancy Outcomes ............................................... 160 
Appendix 5 
Genetics:  Use and Analysis of DNA ......................................... 162 
Appendix 6 
Safety Plan:  Management of Identified and Potential Risks ..... 163 
A6–1 
Risks Associated with the Study Drugs ..................................... 165 
A6–1.1 
Risks Associated with Mosunetuzumab .................................... 165 
A6–1.1.1 
Known Risks Associated with Mosunetuzumab ........................ 165 
A6–1.1.1.1 
Cytokine Release Syndrome ..................................................... 166 
A6–1.1.1.2 
Neutropenia .............................................................................. 167 

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A6–1.1.1.3 
Infections................................................................................... 167 
A6–1.1.1.4 
Tumor Flare .............................................................................. 168 
A6–1.1.1.5 
Tumor Lysis Syndrome ............................................................. 168 
A6–1.1.1.6 
Injection-Site Reactions ............................................................ 169 
A6–1.1.1.7 
Neurologic Toxicity Including ICANS ..................................... 169 
A6–1.1.1.8 
Hemophagocytic Lymphohistiocytosis ...................................... 170 
A6–1.1.2 
Potential Risks Associated with Mosunetuzumab ..................... 170 
A6–1.1.2.1 
Thrombocytopenia .................................................................... 171 
A6–1.1.2.2 
Elevated Liver Enzymes ........................................................... 171 
A6–1.1.2.3 
Immunogenicity (Anti-Drug Antibodies) ..................................... 171 
A6–1.2 
Risks Associated With Polatuzumab Vedotin............................ 172 
A6–1.2.1 
Known Risks Associated with Polatuzumab Vedotin ................ 172 
A6–1.2.1.1 
Myelosuppression:  Consolidation of Neutropenia 
(Including Febrile Neutropenia), Thrombocytopenia, and 
Anemia ...................................................................................... 172 
A6–1.2.1.2 
Peripheral Neuropathy (Sensory and/or Motor) ........................ 172 
A6–1.2.1.3 
Infections................................................................................... 172 
A6–1.2.1.4 
Infusion-Related Reactions ....................................................... 173 
A6–1.2.1.5 
Gastrointestinal Toxicity (Diarrhea, Nausea, Vomiting, 
Constipation) ............................................................................. 173 
A6–1.2.2 
Potential Risks Associated with Polatuzumab Vedotin ............. 173 
A6–1.2.2.1 
Progressive Multifocal Leukoencephalopathy ........................... 173 
A6–1.2.2.2 
Immunogenicity (Anti-Drug Antibodies) ..................................... 174 
A6–1.2.2.3 
Hepatotoxicity (Hyperbilirubinemia, Transaminase (ALT 
and/or AST Elevations) ............................................................. 174 
A6–1.2.2.4 
Reproductive Toxicity ................................................................ 174 
A6–1.2.2.5 
Fatigue and Asthenia ................................................................ 174 
A6–1.2.2.6 
Hyperglycemia .......................................................................... 174 
A6–1.2.2.7 
Renal Toxicity (Increased Serum Creatinine)............................ 175 
A6–1.2.2.8 
Pulmonary Toxicity (Interstitial Lung Disease) .......................... 175 
A6–1.2.2.9 
Joint Pain, Arthralgia, Skeletal Pain .......................................... 175 
A6–1.2.2.10 
Alopecia .................................................................................... 175 
A6–1.2.2.11 
Cardiac Arrhythmias ................................................................. 175 
A6–1.2.2.12 
Ocular Toxicity .......................................................................... 175 
A6–1.2.2.13 
Dysgeusia ................................................................................. 175 
A6–1.2.2.14 
Tumor Lysis Syndrome ............................................................. 175 
A6–1.2.2.15 
Genotoxicity/Carcinogenicity (Myelodysplastic Syndrome) ....... 176 
A6–1.2.2.16 
Drug-Drug Interaction (DDI) ...................................................... 176 
A6–1.3 
Risks of Overlapping Toxicities with Mosunetuzumab and 
Polatuzumab Vedotin ................................................................ 176 
A6–1.4 
Risks Associated with Rituximab .............................................. 176 
A6–1.5 
Risks Associated with Gemcitabine and Oxaliplatin .................. 176 
A6–2 
Management of Participants Who Experience Adverse 
Events ....................................................................................... 176 
A6–2.1 
Dose Modifications .................................................................... 176 
A6–2.2 
Treatment Interruption .............................................................. 177 
A6–2.3 
Management Guidelines ........................................................... 184 

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A6–2.3.1 
Management of Cytokine Release Syndrome (Arm A) ............. 185 
A6–2.3.2 
Management of Hemophagocytic Lymphohistiocytosis (Arm 
A) .............................................................................................. 192 
A6–2.3.3 
Injection-Site Reactions After Mosunetuzumab SC (Arm A) ..... 196 
A6–2.3.4 
Tumor Lysis Syndrome (Arm A and B) ..................................... 197 
A6–2.3.5 
Neurologic Toxicity Including ICANS (Arm A) ........................ 198 
A6–2.3.6 
Elevated Liver Enzymes and Hepatotoxicity (Arm A) ................ 201 
A6–2.4 
Management of Adverse Events (Arm B) .................................. 202 
Appendix 7 
Anaphylaxis Precautions ........................................................... 207 
Appendix 8 
European Organisation for Research and Treatment of 
Cancer Quality of Life−Core 30 Questionnaire (EORTC QLQ-
C30) .......................................................................................... 208 
Appendix 9 
 .................................................................... 210 
Appendix 10 
Lugano Response Criteria for Malignant Lymphoma  
(Cheson et al. 2014) ................................................................. 212 
Appendix 11 
American Society for Transplantation and Cellular Therapy 
(ASTCT) Consensus Grading Criteria for Cytokine Release 
Syndrome.................................................................................. 217 
Appendix 12 
Eastern Cooperative Oncology Group (ECOG) Performance 
Status Scale .............................................................................. 218 
Appendix 13 
Functional Assessment of Cancer Therapy−Lymphoma 
Lymphoma Subscale ................................................................ 219 
Appendix 14 
Functional Assessment of Cancer Treatment/Gynecologic 
Oncology Group−Neurotoxicity ................................................. 220 
Appendix 15 
Calculation of Creatinine Clearance With Use of the 
Cockcroft−Gault Formula .......................................................... 221 
.. 222 
.. 227 
.. 229 
.. 230 
Appendix 20 
Sample List of Cautionary Medications ..................................... 232 
Appendix 21 
ASTCT ICANS Consensus Grading for Adults and 
ICE Assessment ....................................................................... 233 
Appendix 22 
Neurologic Toxicity Including ICANS that May Affect 
Driving ....................................................................................... 235 
Appendix 23 
Protocol Amendment History .................................................... 236 
Appendix 24 
Abbreviations ............................................................................ 245 
 

Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
15/Protocol GO43643, Version 5  
PROTOCOL AMENDMENT ACCEPTANCE FORM 
PROTOCOL TITLE: 
A RANDOMIZED, OPEN-LABEL, MULTICENTER 
PHASE III STUDY EVALUATING EFFICACY AND 
SAFETY OF MOSUNETUZUMAB IN COMBINATION 
WITH POLATUZUMAB VEDOTIN IN COMPARISON 
WITH RITUXIMAB IN COMBINATION WITH 
GEMCITABINE PLUS OXALIPLATIN IN 
PARTICIPANTS WITH RELAPSED OR 
REFRACTORY AGGRESSIVE B-CELL 
NON-HODGKIN’S LYMPHOMA 
PROTOCOL NUMBER: GO43643 
STUDY NAME: 
SUNMO 
VERSION NUMBER: 
5 
TEST COMPOUND(S): Mosunetuzumab (RO7030816; BTCT4465A) 
Polatuzumab vedotin (RO5541077; DCDS4501S) 
Tocilizumab (RO4877533) 
MEDICAL MONITOR: 
 Ph.D. 
SPONSOR NAME: 
F. Hoffmann-La Roche Ltd 
 
I agree to conduct the study in accordance with the current protocol. 
 
 
 
Principal Investigator's Name (print) 
 
 
 
 
 
Principal Investigator's Signature 
 
Date 
Please retain the signed original of this form for your study files.  Please return a copy of 
the signed form as instructed by your local study monitor. 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
16/Protocol GO43643, Version 5  
1. 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS 
PROTOCOL TITLE: 
A RANDOMIZED, OPEN-LABEL, MULTICENTER PHASE III 
STUDY EVALUATING EFFICACY AND SAFETY OF 
MOSUNETUZUMAB IN COMBINATION WITH POLATUZUMAB 
VEDOTIN IN COMPARISON WITH RITUXIMAB IN COMBINATION 
WITH GEMCITABINE PLUS OXALIPLATIN IN PARTICIPANTS 
WITH RELAPSED OR REFRACTORY AGGRESSIVE B-CELL 
NON-HODGKIN’S LYMPHOMA 
BRIEF TITLE: 
An Open-Label Study Evaluating the Efficacy and Safety of 
Mosunetuzumab in Combination with Polatuzumab Vedotin in 
Participants with Aggressive B-Cell Non-Hodgkin’s Lymphoma 
Study Rationale 
The purpose of this study is to assess the efficacy and safety of mosunetuzumab in combination 
with polatuzumab vedotin (M  P) in participants with relapsed or refractory (R/R) diffuse-large 
B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, transformed follicular lymphoma (trFL) 
and follicular lymphoma (FL) Grade 3B (FL3B) in comparison with a commonly used regimen in 
this participant population, rituximab, gemcitabine and oxaliplatin (R-GemOx).  While there have 
been recent advances in treatments for patients with R/R DLBCL, including those with novel 
mechanisms of action, a high unmet medical need continues to exist particularly for those who 
are not eligible for autologous stem cell transplant (ASCT). 
Objectives and Endpoints 
This study will evaluate the efficacy and safety of M + P compared with R-GemOx in participants 
with R/R aggressive non-Hodgkin’s lymphoma (aNHL), including DLBCL, high-grade B-cell 
lymphoma, trFL, and FL3B, who received at least one prior systemic therapy and are not 
candidates for ASCT. 
Primary Objective 
Corresponding Dual Primary Endpoints 
● To evaluate the efficacy of M  P 
(Arm A) compared with R-GemOx 
(Arm B) 
● ORR, defined as the proportion of participants in 
whom an objective response (CR or PR) was 
observed at any time during the study as 
determined by IRF 
● PFS, defined as the time from randomization to the 
first occurrence of disease progression as 
determined by IRF, or death due to any cause, 
whichever occurs first 
 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
17/Protocol GO43643, Version 5  
Secondary Objective 
Corresponding Endpoints 
● To evaluate the efficacy of M + P 
compared with R-GemOx 
● ORR, defined as the proportion of participants in 
whom an objective response (CR or PR) was 
observed at any time during the study as 
determined by the investigator  
● DOR, defined as the time from the first occurrence 
of a documented objective response to disease 
progression, or death from any cause, whichever 
occurs first as determined by the investigator and 
IRF 
● OS, defined as the time from randomization to 
death from any cause 
● PFS, defined as the time from randomization to the 
first occurrence of disease progression as 
determined by the investigator, or death due to any 
cause, whichever occurs first 
● CRR, defined as the proportion of participants in 
whom CR was observed at any time during the 
study as determined by IRF and by the investigator 
● DOCR, defined as the time from the first 
occurrence of a documented CR to disease 
progression, or death from any cause, whichever 
occurs first.  This will be determined by IRF and by 
the investigator. 
● Time to deterioration in physical functioning and 
fatigue, as measured by the EORTC QLQ-C30 
● Time to deterioration in lymphoma symptoms, as 
measured by FACT-LymS 
Safety Objective 
Corresponding Endpoint 
● To evaluate the safety and tolerability 
of M + P compared with R-GemOx 
● Incidence and severity of adverse events, with 
severity determined according to the 
NCI CTCAE v5.0, including CRS, with severity 
determined according to the ASTCT CRS 
Consensus grading criteria 
● Change from baseline in targeted vital signs 
● Change from baseline in targeted clinical laboratory 
test results 
● Tolerability, as assessed by dose interruptions, 
dose reductions, and dose intensity, and study 
treatment discontinuation because of adverse 
events 
● Change from baseline in peripheral neuropathy, as 
measured by the FACT/GOG-Ntx 
 
 

 
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20/Protocol GO43643, Version 5  
Note: "Enrolled" means a participant's, or their legally acceptable representative’s, agreement to 
participate in a clinical study following completion of the informed consent process.  
Potential participants who are screened for the purpose of determining eligibility for the study, 
but do not participate in the study, are not considered enrolled, unless otherwise specified by 
the protocol. 
Study Treatment 
Polatuzumab Vedotin 
Polatuzumab vedotin will be administered at 1.8 mg/kg IV for 6 cycles, which is the approved 
dose based on previous clinical studies.  The total dose of polatuzumab vedotin for each 
participant will depend on the participant’s weight on Cycle 1, Day 1 (or within 96 hours before 
Cycle 1, Day 1).   
Mosunetuzumab 
In this study, mosunetuzumab will be administered SC in a 21-day cycle with corticosteroid 
premedication, and a Cycle 1 step-up-dosing regimen that was established in the ongoing 
first-in-human Phase I/II Study GO29781 to mitigate the risk of acute toxicities 
(e.g., cytokine release syndrome and tumor lysis syndrome).  With the Cycle 1 step-up-dosing 
regimen, mosunetuzumab is administered as 
mg on Day 1, 
mg on Day 8, and
mg on 
Day 15 (
 mg).  The target dose of 
mg will be administered on Day 1 of subsequent 
cycles every 3 weeks.  The
mg every 3 weeks (Q3W) dosing regimen is the 
recommended mosunetuzumab SC dosing regimen in monotherapy based on clinical data from 
Study GO29781. 
Tocilizumab 
Tocilizumab will be administered IV only to those participants who experience a CRS event for 
which tocilizumab is indicated.   
Tocilizumab should be administered at a dose of 8 mg/kg IV (not exceeding 800 mg per 
infusion).  The infusion should be administered IV over 60 minutes.  If no clinical improvement in 
the signs and symptoms of CRS occurs after the first dose, a second dose may be administered 
at least 8 hours apart (maximum 2 doses per CRS event).  Within each time-period of 6 weeks 
of mosunetuzumab treatment, the total number of tocilizumab doses should not exceed 3 
doses. 
Rituximab 
Rituximab will be administered at a dose of 375 mg/m2 by IV infusion on Day 1 of each 14-day 
cycle (Cycles 1−8).  The dose of rituximab should not be modified. 
Gemcitabine 
Gemcitabine will be administered at 1000 mg/m2 IV on Day 1 of each 14-day cycle 
(Cycles 1−8).  Gemcitabine should be administered before oxaliplatin on the same day.  
Gemcitabine should be administered in accordance with local institutional guidelines and 
prescribing information. 
Oxaliplatin 
Oxaliplatin will be administered at 100 mg/m2 IV on Day 1 of each 14-day cycle (Cycles 1−8).  
Oxaliplatin should be administered after gemcitabine on the same day.  Oxaliplatin should be 
administered in accordance with local institutional guidelines and prescribing information. 
Duration of Participation 
The total length of the study, from the screening of the first participant to the end of the study, is 
expected to be approximately 5 years. 
Independent Data Monitoring Committee 
An independent Data Monitoring Committee is being used. 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
21/Protocol GO43643, Version 5  
1.2 
STUDY SCHEMA 
Figure 1 Study Schema 

Table 1 
Schedule of Activities:  Arm A (cont.) 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
25/Protocol GO43643, Version 5  
ADA  anti-drug antibody;
BSA  body surface area;
CMV  cytomegalovirus; CR  complete response; CT  computed tomography (scan); ctDNA  circulating tumor DNA: D  Day; EBV  Epstein-Barr virus; 
ECOG PS  Eastern Cooperative Oncology Group Performance Status; eCRF  electronic Case Report Form; FFPE  formalin-fixed, paraffin-embedded; 
GGT  gamma-glutamyl transferase; HBcAb  hepatitis B core antibody; HBsAb  hepatitis B surface antibody; HBsAg  hepatitis B surface antigen; 
HBV  hepatitis B virus; HCV = hepatitis C virus;
M = mosunetuzumab;
 P  polatuzumab vedotin; PBMC  peripheral blood mononuclear cell; PCR  polymerase chain reaction; PD  progressive disease; 
PET   positron emission tomography (scan); PK  pharmacokinetic; PRO   participant-reported outcome; Q3M  every 3 months  1 month; Q6M  every 
6 months; RBR  Research Biosample Repository; SARS-CoV-2  severe acute respiratory syndrome coronavirus 2. 
Note:  Assessments are to be taken prior to study drug infusion/injection, unless otherwise specified.  Pre-administration laboratory samples should be drawn 
0−48 hours prior to study treatment infusion/injection. 
For any dose delay resulting in a treatment-free interval of 6 weeks or longer, step-up dosing of mosunetuzumab is required with 
mg administered on Day 1 
of the first cycle after the dose delay (in combination with polatuzumab vedotin, if applicable), followed by the next planned dose on Day 8.  The local 
assessments on the two dosing days should follow the Cycle 1, Day 1 and Cycle 1, Day 8 schedule, respectively. 
In the event that a participant has a toxicity necessitating mosunetuzumab interruption for  7 days prior to the Cycle 1, Day 8 dose, the participant is required 
to repeat the
mg mosunetuzumab (without polatuzumab vedotin) prior to resuming the planned treatment schedule (7 days after re-administration of the  
mg dose).  The local assessments on the two dosing days should follow the Cycle 1, Day 1 and Cycle 1, Day 8 schedule, respectively. 
Please see Table 3 for additional instructions on central laboratory assessments.  
a Screening and pretreatment tests and evaluations will be performed within 14 days preceding the first dose of study treatment.  Fresh pretreatment biopsy, 
radiographic tumor assessment, quantitative PCR for detection of EBV and CMV, and bone marrow aspirate and biopsy (if applicable) may be performed 
up to 28 days preceding the first dose of study drug, providing no anti-tumor therapy was administered in this period.  In addition, a serum pregnancy test 
should be performed within 7 days preceding the first dose of study treatment.  Results of standard of care tests, radiographic tumor assessment or 
examinations performed prior to obtaining informed consent and within the screening window specified above may be used; these tests do not need to be 
repeated for screening.  Archival tumor samples do not need to be within the 28 days screening window and are preferably obtained after the last anti-
lymphoma treatment.  
b Participants who complete the treatment period will return to the clinic for a treatment completion visit within 30 ( 7) days after the last dose of study drug.  
Participants who discontinue study drug prematurely will return to the clinic for a treatment discontinuation visit within 30 ( 7) days after the last dose of 
study drug.  The visit at which response assessment shows PD may be used as the treatment discontinuation visit. 
c Schedule corresponds to visit timepoints only for participants who complete or discontinue the study treatment but remain on the study without disease 
progression or new anti-lymphoma therapy.  Perform assessments until disease progression, start of new anti-lymphoma therapy, withdrawal from study 
participation, or until the Month 30 tumor assessment visit is completed, whichever occurs first.  Continue to follow participants on this schedule timed 
from the end of treatment/early termination visit (within 30 days after the last dose of mosunetuzumab administered; with the exception for tumor 
assessment, which is timed from Cycle 1, Day 1).  Visits should occur within  1 month from the scheduled date.  Other assessments/procedures can be 
performed at an earlier timepoint to align with the schedule of tumor assessment visit. 
d When discontinued from treatment or post-treatment follow-up due to disease progression, start of new anti-lymphoma therapy, or after completing the 
Month 30 tumor assessment visit, participants should be followed for survival status and new anti-lymphoma therapy via telephone calls, 
participant medical records, and/or clinic visits approximately every 3 months   1 month until death (unless the participant withdraws consent or the 

Table 1 
Schedule of Activities:  Arm A (cont.) 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
26/Protocol GO43643, Version 5  
Sponsor terminates the study).  All participants may be contacted periodically for additional survival and/or new anti-lymphoma therapy information 
unless the participant requests to be withdrawn from the study.  If the participant withdraws from the study, the site’s staff may use a public information 
source (e.g., county records) to obtain information about survival status only. 
e Informed consent must be documented before any study-specific screening procedure is performed. 
f 
Medication (e.g., prescription drugs, over-the-counter drugs, vaccines, herbal or homeopathic remedies, nutritional supplements) used by a participant in 
addition to protocol-mandated treatment from 7 days prior to initiation of study drug until 90 days after the last dose of study treatment or the initiation of 
next anti-lymphoma therapy, whichever is earlier.  After this period, concomitant medications should be collected if they were used to manage serious 
adverse events that are believed to be related to prior study treatment.   
g After informed consent has been obtained but prior to initiation of study drug, only serious adverse events caused by a protocol-mandated intervention 
should be reported.  After initiation of study drug, all adverse events will be reported until 90 days after the last dose of study treatment or the initiation of 
next anti-lymphoma therapy, whichever is earlier.  After this period, the Sponsor should be notified if the investigator becomes aware of any serious 
adverse event (if believed to be related to prior study drug treatment) that occurs after the end of the adverse event reporting period.  The investigator 
should follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the 
participant is lost to follow-up, or the participant withdraws consent.  Every effort should be made to follow all serious adverse events considered to be 
related to study drug or trial-related procedures until a final outcome can be reported. 
h Includes systolic and diastolic blood pressure, respiratory rate, pulse oximetry, pulse rate, and body temperature while the participant is in a sitting or 
semi-supine position.  Record abnormalities observed at baseline on the General Medical History and Baseline Conditions eCRF.  At subsequent visits, 
record new or worsened clinically significant abnormalities on the Adverse Event eCRF. 
i 
Height and BSA are required at screening only.  After initiation of the study if there has been a  10% change in body weight since the last BSA 
assessment, BSA should be recalculated and documented in the eCRF. 
j 
Complete physical examination includes an evaluation of the head, eyes, ears, nose, and throat, and the cardiovascular, dermatologic, musculoskeletal, 
respiratory, gastrointestinal, and neurologic systems.  Record abnormalities observed at baseline on the General Medical History and Baseline Conditions 
eCRF.  As part of the complete physical examination, the presence and degree of enlarged lymph nodes, hepatomegaly, and splenomegaly will be recorded
the appropriate Tumor Assessment eCRF.  At subsequent visits, record new or worsened clinically significant abnormalities on the Adverse Event eCRF. 
k Targeted physical examinations should be limited to systems of primary relevance (i.e., cardiovascular, respiratory, neurologic, and any system that might 
be associated with tumor assessment [e.g., lymph nodes, liver, and spleen and those systems associated with symptoms], or potential drug-related toxicity 
[e.g., clinical assessment for peripheral neuropathy in participants receiving polatuzumab vedotin]).  Record new or worsened clinically significant 
abnormalities on the Adverse Event eCRF.  For pre-infusion timepoints, targeted physical examinations may be performed within 96 hours preceding study 
treatment administration unless otherwise specified. 
l Assess response with use of image-based evaluation, using standard Lugano 2014 criteria.  Positron emission tomography and diagnostic-quality CT 
scans are required at screening and at the interim response assessment at 8, 16 and 24 weeks ( 1 weeks).  Subsequent follow-up imaging studies should 
be performed every 3 months ( 1 month) for the first two years on study, then at month 30 (   2 months) after Cycle 1 Day 1, until disease progression, 
start of new anti-lymphoma therapy, or study discontinuation, whichever is earlier.  For participants who are in CR at 24 weeks, a CT scan with or without 
PET scan will be acceptable for subsequent scans.  For participants who are not in CR at 24 weeks, continue imaging studies with PET and diagnostic-
quality CT scans until CR or PD.  A full tumor assessment, including radiographic assessment, must be performed any time disease progression or relapse 
is suspected.  Scans should be performed according to the guidelines in the imaging manual provided to all sites.  
m Submission of pretreatment biopsy tissue is mandatory.  For China participants (if China participates in the study), collection of tissue samples should be in 

Table 1 
Schedule of Activities:  Arm A (cont.) 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
27/Protocol GO43643, Version 5  
accordance with local regulatory requirements.  Tumor tissue biopsies during the study are optional. 
n Pretreatment biopsy:  Fresh pretreatment biopsy is preferred but archival tissue obtained preferably after the last anti-lymphoma treatment is acceptable if 
the conditions for fresh biopsy cannot be met.  Biopsy tissues, whether fresh or archival, must be accompanied by the associated pathology report. 
Optional during study biopsy:  Obtain biopsy during the study between Cycle 1, Day 16 and Cycle 2, Day 8.  A blood sample (ctDNA and PBMC) is 
required when a tumor biopsy is collected during the study for biomarker analysis (see Table 3 for biomarker sample collection). 
Optional tumor biopsies:  Additional tumor biopsies are optional and may be performed at the investigator’s discretion (e.g., to confirm disease recurrence 
or progression or to confirm an alternate histologic diagnosis). 
Archival tissue samples must be accompanied by the associated pathology report.  Tumor tissue samples should consist of representative tumor 
specimens in FFPE blocks (preferred) or at least 10 slides (preferably 15) containing unstained, freshly cut, serial sections.  
o Not applicable for a site that has not been granted approval for RBR sampling.  Performed only for participants at participating sites who have provided 
written informed consent to participate.  Obtain prior to study treatment. 
p Questionnaires will be self-administered before the participant receives any information on disease status, prior to the performance of non-PRO 
assessments (with the only exception of laboratory blood collection which needs to be performed prior to PRO questionnaire completion due to logistic 
reasons), and prior to administration of study treatment, unless otherwise specified. 
q For polatuzumab vedotin infusions:  During the administration of polatuzumab vedotin, vital signs should be assessed within 30 minutes before the start of 
the infusion, every 15 ( 5) minutes during the infusion, within 10 minutes after the end of the infusion, and every 30 ( 10) minutes for 90 minutes 
following completion of dosing at Cycle 1 and 30 ( 10) minutes following completion of dosing in subsequent cycles.  For subsequent cycles, observation 
period can be 30 minutes.  The time between the end of polatuzumab vedotin infusion and the mosunetuzumab injection should be at least 60 minutes for 
all cycles. 
r For mosunetuzumab injections:  Observation and vital signs with mosunetuzumab injection for Cycle 1, Day 1, 8, 15 and Cycle 2, Day 1 (or later cycle if 
CRS occurred during the previous cycle):  check vital signs within 30 minutes pre-injection.  Observe participants at least 30 minutes after injection.  Check 
vital signs 30 ( 15) minutes after injection.  Subsequent mosunetuzumab injections in the absence of CRS after last injection:  check vital signs pre-
injection.  Observe participants at least 15 minutes.  Check vital signs at least once during observation period.  Participants with extended dose 
interruptions may need to repeat the step-up dosing when treatment is resumed.  Please see Section A6–2.2 for details on the repeated step-up dosing. 
s Details of protocol required safety laboratory assessments are listed in Table A2-1. 
t HBsAg, HBsAb, HBcAb, HCV antibody, and HIV antibody serology are required.  Participants with occult or prior hepatitis B infection (defined as positive 
total HBcAb and negative HBsAg) may be included if HBV DNA is undetectable at the time of screening.  These participants should be considered for 
prophylactic antivirals (e.g., entecavir) before and throughout the treatment, and must undergo monthly DNA testing while the patient is on treatment.  
During post treatment follow up, the HBV DNA testing will continue every 3 months ( 4 weeks) for 12 months after end of treatment visit.  Participants 
who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation.   
Participants who are positive for HIV may be eligible provided they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count   200/L, 
have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months.  Participants with a 
positive HIV result at screening should be monitored after receiving study treatment.  HIV viral load will be performed every 3 months (   4 weeks) until 
end of study treatment, and then every 6 months ( 4 weeks) during post treatment follow up for 12 months after end of treatment visit.  If the HIV viral 
load is detected (positive), the participant should be treated per local institutional standards, and the Medical Monitor should be notified.  Testing may be 
performed at the local institution.  If local laboratory assessments are not available for testing, local laboratory collections may be waived only if samples 
are collected for central laboratory assessments of viral infections. 

Table 1 
Schedule of Activities:  Arm A (cont.) 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
28/Protocol GO43643, Version 5  
u Quantitative PCR for detection of active EBV and CMV should be performed at screening, Cycle 2, Day 1, and when clinically indicated on a peripheral 
blood sample per local laboratory requirements.  If EBV or CMV DNA levels are detected (positive), contact the Medical Monitor for additional 
recommendations, and repeat quantitative PCR monitoring weekly until DNA levels decrease, and then continue to monitor by quantitative PCR at every 
cycle until two consecutive negative (undetectable) results. 
v SARS-CoV-2 testing by antigen or PCR is required within 7 days prior to enrollment. 
w Hematology includes CBC (including hemoglobin, hematocrit, RBC, WBC), platelet count, ANC, eosinophils, basophils, monocytes, absolute lymphocyte 
count, and other cells.   
x Chemistry panel (serum) includes sodium, potassium, chloride, bicarbonate (or total carbon dioxide if considered standard of care for the region; may be 
measured using blood gas test per institutional practice), glucose, BUN or urea, creatinine, calcium, magnesium, phosphorous, total and direct bilirubin, 
total protein, albumin, ALT, AST, ALP, GGT, LDH, and uric acid. 
y All women of childbearing potential will have a serum pregnancy test at screening.  Serum pregnancy should be performed within 7 days preceding the first 
dose of study treatment.  Urine or serum pregnancy tests will be performed at specified subsequent visits.  If a urine pregnancy test is positive, it must be 
confirmed by a serum pregnancy test. 
z  Total IgA, IgG, IgM should be collected at least Q3M including during post-treatment follow-up period. 
 

Table 2 
Schedule of Activities:  Arm B (cont.) 
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32/Protocol GO43643, Version 5  
c Schedule corresponds to visit timepoints only for participants who complete or discontinue the study treatment but remain on the study without disease 
progression or new anti-lymphoma therapy.  Perform assessments until disease progression, start of new anti-lymphoma therapy, withdrawal from study 
participation, or until the Month 30 tumor assessment visit is completed, whichever occurs first.  Continue to follow participants on this schedule timed from the 
end of treatment/early termination visit (within 30 days after the last dose of mosunetuzumab administered; with the exception for tumor assessment, which is 
timed from Cycle 1, Day 1).  Visits should occur within  1 month from the scheduled date.  Other assessments/procedures can be performed at an earlier 
timepoint to align with the schedule of tumor assessment visit. 
d When discontinued from treatment or post-treatment follow-up due to disease progression, start of new anti-lymphoma therapy, or after completing the Month 
30 tumor assessment visit, participants should be followed for survival follow-up and new anti-lymphoma therapy via telephone calls, participant medical 
records, and/or clinic visits approximately every 3 months   1 month until death (unless the participant withdraws consent or the Sponsor terminates the study). 
All participants may be contacted periodically for additional survival and/or new anti -lymphoma therapy information unless the participant requests to be 
withdrawn from the study.   If the participant withdraws from the study, the site’s staff may use a public information source (e.g., county records) to obtain 
information about survival status only. 
e Informed consent must be documented before any study-specific screening procedure is performed. 
f 
Medication (e.g., prescription drugs, over-the-counter drugs, vaccines, herbal or homeopathic remedies, nutritional supplements) used by a participant in addition 
to protocol-mandated treatment from 7 days prior to initiation of study drug until 90 days after the last dose of study treatment or the initiation of next 
anti-lymphoma therapy, whichever is earlier.  After this period, concomitant medications should be collected if they were used to manage serious adverse events 
that are believed to be related to prior study treatment. 
g After informed consent has been obtained but prior to initiation of study drug, only serious adverse events caused by a protocol-mandated intervention should be 
reported.  After initiation of study drug, all adverse events will be reported until 90 days after the last dose of study treatment or the initiation of next 
anti-lymphoma therapy, whichever is earlier.  After this period, the Sponsor should be notified if the investigator becomes aware of any serious adverse event 
(if believed to be related to prior study drug treatment) that occurs after the end of the adverse event reporting period.  The investigator should follow each 
adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the participant is lost to follow-up, or 
the participant withdraws consent.  Every effort should be made to follow all serious adverse events considered to be related to study drug or trial-related 
procedures until a final outcome can be reported. 
h Includes systolic and diastolic blood pressure, respiratory rate, pulse oximetry, pulse rate, and body temperature while the participant is in a sitting or 
semi-supine position.  Record abnormalities observed at baseline on the General Medical History and Baseline Conditions eCRF.  At subsequent visits, record 
new or worsened clinically significant abnormalities on the Adverse Event eCRF.  During the administration of rituximab in Cycle 1, vital signs are to be obtained 
before infusion of rituximab then after the start of the infusion, approximately every 15 ( 5) minutes for 90 minutes, and then every 30 ( 10) minutes until 1 hour 
after the end of the infusion.  During administration of rituximab in subsequent cycles, vital signs are to be recorded before infusion of rituximab, then after the 
start of infusion, and approximately every 30 ( 10) minutes until 1 hour after the end of infusion. 
i 
Height and BSA are required at screening only.  After initiation of the study if there has been a  10% change in body weight since the last BSA assessment, 
BSA should be recalculated and documented in the eCRF. 
j Complete physical examination includes an evaluation of the head, eyes, ears, nose, and throat, and the cardiovascular, dermatologic, musculoskeletal, 
respiratory, gastrointestinal, and neurologic systems.  Record abnormalities observed at baseline on the General Medical History and Baseline Conditions eCRF.  
As part of the complete physical examination, the presence and degree of enlarged lymph nodes, hepatomegaly, and splenomegaly will be recorded on the 
appropriate Tumor Assessment eCRF.  At subsequent visits, record new or worsened clinically significant abnormalities on the Adverse Event eCRF. 
k Targeted physical examinations should be limited to systems of primary relevance (i.e., cardiovascular, respiratory, neurologic, and any system that might be 

Table 2 
Schedule of Activities:  Arm B (cont.) 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
33/Protocol GO43643, Version 5  
associated with tumor assessment [e.g., lymph nodes, liver, and spleen and those systems associated with symptoms], or potential drug-related toxicity 
[e.g., clinical assessment for peripheral neuropathy in participants receiving polatuzumab vedotin]).  Record new or worsened clinically significant abnormalities 
on the Adverse Event eCRF.  For pre-infusion timepoints, targeted physical examinations may be performed within 96 hours preceding study treatment 
administration unless otherwise specified. 
l Assess response with use of image based evaluation, using standard Lugano 2014 criteria.  Positron emission tomography and diagnostic-quality CT scans are 
required at screening and at the interim response assessment at 8, 16 and 24 weeks (± 1 weeks).  Subsequent follow-up imaging studies should be performed 
every 3 months ( 1 month) for the first two years on study, then at month 30 (  2 months) after Cycle 1 Day 1, until disease progression, start of new anti-
lymphoma therapy, or study discontinuation, whichever is earlier.  For participants who are in CR at 24 weeks, CT scan with or without PET scan will be 
acceptable for subsequent scans.  For participants who are not in CR at 24 weeks, continue imaging studies with PET and diagnostic-quality CT scans until CR 
or PD.  A full tumor assessment, including radiographic assessment, must be performed any time disease progression or relapse is suspected.  Scans should be 
performed according to the guidelines in the imaging manual provided to all sites. 
m Submission of pretreatment biopsy tissue is mandatory.  Tumor tissue biopsies are optional during the study.  For China participants (if China participates in the 
study), collection of tissue samples should be in accordance with local regulatory requirements. 
Pretreatment biopsy:  Fresh pretreatment biopsy is preferred but archival tissue obtained preferably after the last anti-cancer treatment is acceptable if the 
conditions for fresh biopsy cannot be met.  Biopsy tissues, whether fresh or archival, must be accompanied by the associated pathology report. 
Optional biopsy during the study:  Obtain biopsy during the study between Cycle 1, Day 16 and Cycle 2, Day 8.  A blood sample (ctDNA and PBMC) is required 
when a tumor biopsy is collected during the study for biomarker analysis (see Table 4 for biomarker sample collection). 
Optional tumor biopsies:  Additional tumor biopsies are optional and may be performed at the investigator’s discretion (e.g., to confirm disease recurrence or 
progression or to confirm an alternate histologic diagnosis). 
Archival tissue samples must be accompanied by the associated pathology report.  Tumor tissue samples should consist of representative tumor specimens in 
FFPE blocks (preferred) or at least 10 slides (preferably 15) containing unstained, freshly cut, serial sections.  
n Not applicable for a site that has not been granted approval for RBR sampling.  Performed only for participants at participating sites who have provided written 
informed consent to participate.  Obtain prior to study treatment. 
o Questionnaires will be self-administered before the participant receives any information on disease status, prior to the performance of non-PRO assessment 
(with the only exception of laboratory blood collection which needs to be performed prior to PRO questionnaire completion due to logistic reasons), and prior to 
administration of study treatment, unless otherwise specified. 
p Details of protocol required safety laboratory assessments are listed in Table A2-1. 
q HBsAg, HBsAb, HBcAb, HCV antibody, and HIV antibody serology are required.  Participants with occult or prior hepatitis B infection (defined as positive total 
HBcAb and negative HBsAg) may be included if HBV DNA is undetectable at the time of screening.  These participants should be considered for prophylactic 
antivirals (e.g., entecavir) before and throughout the treatment, and must undergo monthly DNA testing while the patient is on treatment.  During post treatment 
follow up, the HBV DNA testing will continue every 3 months ( 4 weeks) for 12 months after end of treatment visit.  Participants who are positive for HCV 
antibody must be negative for HCV by PCR to be eligible for study participation.  Participants who are positive for HIV may be eligible provided they are stable on 
antiretroviral therapy for at least 4 weeks, have a CD4 count   200/L, have an undetectable viral load, and have not had a history of opportunistic infection 
attributable to AIDS within the last 12 months.  Participants with a positive HIV result at screening should be monitored after receiving study treatment.  HIV viral 
load will be performed every 3 months (  4 weeks) until end of study treatment, and then every 6 months ( 4 weeks) during post treatment follow up for 12 
months after end of treatment visit.  If the HIV viral load is detected (positive), the participant should be treated per local institutional standards, and the Medical 

Table 2 
Schedule of Activities:  Arm B (cont.) 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
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Monitor should be notified.  Testing may be performed at the local institution.  If local laboratory assessments are not available for testing, local laboratory 
collections may be waived only if samples are collected for central laboratory assessments of viral infections. 
r Quantitative PCR for detection of active EBV and CMV should be performed at screening, Cycle 2, Day 1, and when clinically indicated on a peripheral blood 
sample per local laboratory requirements.  If EBV or CMV DNA levels are detected (positive), contact the Medical Monitor for additional recommendations, and 
repeat quantitative PCR monitoring weekly until DNA levels decrease, and then continue to monitor by quantitative PCR at every cycle until two consecutive 
negative (undetectable) results. 
s SARS-CoV-2 testing by antigen or PCR is required within 7 days prior to enrollment. 
t 
Hematology includes CBC (including hemoglobin, hematocrit, RBC, WBC), platelet count, ANC, eosinophils, basophils, monocytes, absolute lymphocyte 
count, and other cells. 
u Chemistry panel (serum) includes sodium, potassium, chloride, bicarbonate (or total carbon dioxide if considered the standard of care for the region, may be 
measured using blood gas test per institutional practice), glucose, BUN or urea, creatinine, calcium, magnesium, phosphorous, total and direct bilirubin, total 
protein, albumin, ALT, AST, ALP, GGT, LDH, and uric acid. 
v All women of childbearing potential will have a serum pregnancy test at screening.  Serum pregnancy should be performed within 7 days preceding the first dose 
of study treatment.  Urine or serum pregnancy tests will be performed at specified subsequent visits.  If a urine pregnancy test is positive, it must be confirmed by 
a serum pregnancy test. 
w Total IgA, IgG, IgM should be collected at least Q3M including post-treatment follow-up period. 

 
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Table 3 
Schedule of Pharmacokinetic, Immunogenicity, and Biomarker Samples (Arm A) 
Visits 
Timepoints 
Pre a 
Post 
Polatuzumab 
vedotin b 
Pre a 
Pre a 
Pre a 
Pre a 
Pre a 
Post 
Polatuzumab 
vedotin b 
Rituximab and 
Obinutuzumab 
PK (serum) f 
x 
 
 
 
 
 
 
 
 
 
 
Mosunetuzumab 
PK (serum) 
x g, h 
 
x g 
x 
x 
x 
x 
 
x 
x 
 
Polatuzumab 
vedotin for total 
Antibody PK 
(serum) 
x g 
x g 
 
 
x 
 
x 
x 
x 
x 
 
Polatuzumab 
acMMAE and 
MMAE PK 
(plasma) i 
x g 
x g 
 
 
x 
 
x 
x 
 
x 
 
Mosunetuzumab 
ADA (serum)  
x g, h 
 
 
 
x 
 
x 
 
x 
x 
 
Polatuzumab 
vedotin ADA 
(serum) 
x g 
 
 
 
x 
 
x 
 
x 
x 
 
ctDNA (plasma) j 
x g, h 
 
 
 
x 
x 
x 
 
x 
x 
x 

 
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Visits 
Timepoints 
Pre a 
Post 
Polatuzumab 
vedotin b 
Pre a 
Pre a 
Pre a 
Pre a 
Pre a 
Post 
Polatuzumab 
vedotin b 
PBMC j 
(whole blood) 
x g, h 
 
 
 
x 
x 
x 
x 
x 
x 
x 
TBNK 
(whole blood) 
x g, h 
 
 
 
x 
x 
x 
 
x 
x 
x 
Cytokines 
(plasma)  
x g, h 
x g, h 
x g 
x 
x 
 
 
 
 
 
 
acMMAE  antibody-conjugated monomethyl auristatin E; ADA  anti-drug antibody; ctDNA  circulating tumor DNA; MMAE  monomethyl auristatin E; 
PBMC  peripheral blood mononuclear cells; PK  pharmacokinetic; TBNK  T-cell, B-cell and natural killer cell.  
Note:  For any dose delays resulting in a treatment free interval  6 weeks, repeat step-up dosing of mosunetuzumab is required, with
mg administered on Day 1 of 
the first cycle after the dose delay (in combination with polatuzumab vedotin, if applicable), followed by the next planned dose on Day 8.  
In the event that a participant has a toxicity necessitating mosunetuzumab interruption for >7 days prior to the Cycle 1, Day 8 dose, the participant is required to repeat 
the
mg dose prior to resuming the planned treatment schedule (7 days after the administration of the
mg dose).  The schedule of PK, ADA and biomarker samples 
after treatment resumption is described in the footnotes.  Rituximab and/or obinutuzumab collections are not required for participants who need to repeat step- up 
dosing. 
a 
  8 hours prior to the first study drug administration. 
b 0−30 minutes after the end of infusion of polatuzumab vedotin. 
c Anytime between Cycle 8, Day 15 and Cycle 8, Day 35. 
d When discontinuation is decided. 
e Every 3 months  1 month starting from 90 days after the treatment completion for the first 2 years on study and then at month 30 (  2 months) after Cycle 1 Day 1, 
or until disease progression or treatment with a new anti-lymphoma therapy, whichever occurs first.  Obtain samples at the closest corresponding scans or visits. 
f 
The serum sample can be split into 2 samples for analysis of rituximab and obinutuzumab PK analysis. 
 

Table 3 
Schedule of Pharmacokinetic, Immunogenicity, and Biomarker Samples (Arm A) (cont.) 
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g For any dose delay resulting in a treatment-free interval of 6 weeks or longer, step-up dosing of mosunetuzumab is required with
mg administered on Day 1 of the 
first cycle after the dose delay (in combination with polatuzumab vedotin, if applicable), followed by the next planned dose on Day 8.  The PK, ADA and biomarker 
sample collection on the two dosing days should follow the Cycle 1, Day 1 and Cycle 1, Day 8 schedule, respectively. 
h In the event that a participant has a toxicity necessitating mosunetuzumab interruption for > 7 days prior to the Cycle 1, Day 8 dose, the participant is required to 
repeat the
mg mosunetuzumab (without polatuzumab vedotin) prior to resuming the planned treatment schedule (7 days after re-administration of the
mg dose).  
The PK, ADA and biomarker sample collection on the dosing day of the repeated
mg dose should follow the Cycle 1, Day 1 schedule. 
i The plasma sample will be split into 2 samples for analyses of antibody-conjugated MMAE and unconjugated MMAE. 
j ctDNA and PBMC samples will be collected at time points in the table and when an on-treatment biopsy is collected.  
 

 
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Table 4 
Schedule of Pharmacokinetic, Immunogenicity, and Biomarker Samples (Arm B) 
Visits 
Timepoints 
Pre a 
Pre a 
Pre a 
Pre a 
ctDNA e (plasma) 
x 
x 
x 
x 
x 
x 
x 
PBMC e 
(whole blood) 
x 
x 
x 
x 
x 
x 
x 
TBNK 
(whole blood) 
x 
x 
x 
x 
x 
x 
x 
ctDNA  circulating tumor DNA; PBMC  peripheral blood mononuclear cell; TBNK  T cell, B cell, natural killer cell. 
Pharmacokinetic or immunogenicity evaluation is not required in participants in Arm B. 
a  8 hours prior to the first study drug administration. 
b Anytime between Cycle 8, Day 15 and Cycle 8, Day 35. 
c When discontinuation is decided. 
d Every 3 months ( 1 month) starting from 90 days after the treatment completion for the first 2 years on study, then at month 30 (  2 months) 
after Cycle 1 Day 1, or until disease progression or treatment with a new anti-lymphoma lymphoma therapy, whichever occurs first.  Obtain 
samples at the closest corresponding scans or visits. 
e ctDNA and PBMC samples will be collected at timepoints in the table and when an on-treatment biopsy is collected. 
 

 
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Table 5 
Schedule for Tocilizumab Treatment of Cytokine Release 
Syndrome 
Assessment/Procedure a 
Pre-TCZ Tx 
(within 
24 hours) 
TCZ IV 
Admin. 
Post-TCZ Treatment b, c 
TCZ administration (8 mg/kg [not 
exceeding 800 mg per infusion]) 
 
x 
 
Vital signs d 
x e 
 
Measure at least once daily 
or more as clinically 
indicated until resolution of 
CRS 
Pressor documentation f 
x e 
 
FiO2 
x e 
 
Pulse oximetry, resting 
x e 
 
Local Laboratory Assessments 
Hematology 
x 
 
Measure at least once daily 
or more as clinically 
indicated until resolution of 
CRS 
Liver function tests (AST, ALT, total 
bilirubin) 
x 
 
Serum chemistry and creatinine g 
x 
 
CRP, LDH, and serum ferritin 
x 
 
Coagulation (aPTT, PT/INR, 
fibrinogen) 
x 
 
Measure at least once every 
2 days or more as clinically 
indicated until resolution of 
CRS 
Infection workup h 
x 
 
 
Central Laboratory Assessments 
Serum cytokines i 
x 
 
15 ( 5) minutes after 
completion of TCZ.  
Then 6 ( 0.5) hours later, 
then 1, 2, 3 and 8 days later 
Serum TCZ PK i 
x 
 
15 ( 5) minutes after 
completion of TCZ.  
Then 6 ( 0.5) hours later, 
then 1, 2, 3 and 8 days later.  
And approximately 8 weeks 
later. 
Serum TCZ ADA 
x 
 
Approximately 8 weeks after 
 

 
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Table 5 Schedule for Tocilizumab Treatment of Cytokine Release Syndrome 
(cont.) 
ADA  anti-drug antibodies; Admin.  administration; CRP  C-reactive protein; CRS  cytokine 
release syndrome; EBV  Epstein-Barr virus; eCRF  electronic Case Report Form; FIO2  fraction 
of inspired oxygen; LDH  lactate dehydrogenase; PK  pharmacokinetic; T/B/NK  T cell/B 
cell/natural killer cell; TCZ  tocilizumab; Tx  treatment.  
Note:  Record abnormalities or worsened clinically significant abnormalities on the Adverse Event 
eCRF. 
a An assessment/procedure may be waived if a participant is hospitalized at a facility that does 
not have the capacity to perform the study assessment.  Hospitalization should not be 
prolonged to perform study assessments in this schedule of assessments. 
b If the TCZ dose is repeated, follow the same collection schedule to collect post-TCZ treatment 
samples after the second TCZ dose. 
c For post-TCZ treatment timepoints:  6 hours ( 30 minutes), 1 day (24  4 hours), 2 days 
(48  4 hours), 3 days (72  4 hours), 8 days (192  48 hours), and 8 weeks (56 days  48 hours) 
after completion of TCZ infusion. 
d Includes respiratory rate, pulse rate, and systolic and diastolic blood pressure while the 
participant is in a seated or supine position, and temperature. 
e The maximum and minimum values for any 24-hour period should be recorded in the clinical 
database. 
f Document vasopressor type and dose in the concomitant medication eCRF. 
g Includes sodium, potassium, chloride, bicarbonate, glucose, and BUN. 
h Includes assessment for bacterial, fungal, and viral infections:  cultures, serologies and 
molecular diagnostic tests.  Assessment of pretreatment and on-treatment EBV status should 
be conducted, including enumeration of EBV viral load in PBMC and plasma, and evaluation of 
EBV encoded ribonucleotides (EBER) or EBV nuclear antigen (EBNA) with T/B/NK cell 
markers. 
i Blood draws performed 15 minutes after the completion of TCZ infusion should not be drawn 
from the same line that was used to administer TCZ. 
 
 
 

 
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2. 
INTRODUCTION 
2.1 
STUDY RATIONALE 
The purpose of this study is to assess the efficacy and safety of mosunetuzumab in 
combination with polatuzumab vedotin (M + P) in participants with relapsed or refractory 
(R/R) diffuse-large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, transformed 
follicular lymphoma (FL) and FL Grade 3B (FL3B) in comparison with a commonly used 
regimen in this participant population, rituximab, gemcitabine and oxaliplatin (R-GemOx).  
While there have been recent advances in treatments for patients with R/R DLBCL, 
including those with novel mechanisms of action, a high unmet medical need continues 
to exist particularly for those who are not eligible for autologous stem cell transplant 
(ASCT). 
2.2 
BACKGROUND 
Diffuse-large B-cell lymphoma is the most common aggressive form of non-Hodgkin’s 
lymphoma (NHL; Armitage and Weisenburger 1998).  Additionally, each year, 
around 3% of FLs transform into a higher-grade NHL, most commonly DLBCL 
(Lossos and Gascoyne 2011), leading to histologic transformation in one-third of patients 
in 10 years.  These transformed follicular lymphoma (trFL), as well as the high-grade 
form of FL, namely FL3B, are treated with the same standard therapies as high-grade 
lymphomas. 
While a majority of patients are cured with the combination of chemoimmunotherapy, the 
management of R/R disease can be challenging.  For these patients, high-dose 
chemotherapy followed by ASCT offers an additional chance for a cure, but more than 
half of the patients who are considered for ASCT will experience R/R disease due to 
insufficient response to salvage therapy or relapsed disease after ASCT 
(Seyfarth et al. 2006; Gisselbrecht et al. 2010).  Moreover, older and more frail patients 
are often ineligible for ASCT.  Outcomes for patients who are not eligible for ASCT are 
poor (Thieblemont and Coiffier 2007) after available therapy such as R-GemOx 
(Mounier et al. 2013) or the combination of bendamustine and rituximab 
(BR; Ohmachi et al. 2013). 
Mosunetuzumab (RO7030816; BTCT4465A), is a full length, humanized anti-cluster of 
differentiation (CD)20/CD3 bispecific IgG1 antibody (Atwell et al. 1997; 
Spiess et al. 2013) engineered for minimal binding to fragment crystallizable (Fc)- 
receptors.  CD20 is a validated target in B-cell NHL, which provides a rationale for the 
development of a T−cell-recruiting bispecific antibody targeting CD20 for the treatment of 
these diseases.  Mosunetuzumab has shown single-agent activity in indolent and 
aggressive NHL (aNHL), and has a manageable safety profile, which makes it an 
attractive agent to evaluate in combination with other agents.  
Mosunetuzumab (Lunsumio) as a monotherapy has been approved by the European 
Commission (conditional marketing authorization) and by the FDA (accelerated 
approval) for the treatment of adult patients with R/R FL who have received at least two 

 
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prior systemic therapies.  Clinical development is ongoing for additional indications 
including aNHL.  
Polatuzumab vedotin (DCDS4501S) is an antibody-drug conjugate (ADC) that contains a 
humanized IgG1 anti-human CD79b monoclonal antibody (MCDS4409A) and a potent 
anti-mitotic agent, monomethyl auristatin E (MMAE), linked through a protease-labile 
linker, maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl.  CD79b is a cell 
surface antigen whose expression is restricted to all mature B cells except plasma cells.  
It is expressed in a majority of B−cell-derived malignancies, including nearly all NHLs 
and chronic lymphocytic leukemias (CLLs; Dornan et al. 2009).  Relating specifically to 
DLBCL, CD79b is expressed by essentially all tumor cells (Olejniczak et al. 2006; 
Pfeifer et al. 2015), enabling its use as a target in all subtypes of DLBCL, independent of 
dominant signaling pathways.  Antibodies bound to CD79b are rapidly internalized, 
making CD79b ideally suited for targeted delivery of cytotoxic agents (Polson et al. 2007; 
2009).  Polatuzumab vedotin has shown single-agent activity in indolent and aggressive 
NHLs and has a manageable safety profile. 
Polatuzumab vedotin in combination with BR is approved for the treatment of 
R/R DLBCL in many countries, including the European Union and the United States.  
Polatuzumab vedotin in combination with rituximab plus cyclophosphamide, doxorubicin, 
and prednisone (R-CHP) has been approved by the European Commission for the 
treatment of adult patients with previously untreated DLBCL.  On 19 April 2023, the FDA 
approved polatuzumab vedotin in combination with R-CHP for treatment of adult patients 
who have previously untreated DLBCL, not otherwise specified (NOS) or high-grade B-
cell lymphoma and who have an International Prognostic Index (IPI) score of 2 or 
greater. 
Detailed information on mosunetuzumab and polatuzumab vedotin is provided in the 
Mosunetuzumab and Polatuzumab Vedotin Investigator's Brochures. 
2.3 
BENEFIT-RISK ASSESSMENT 
The purpose of this study is to assess the efficacy and safety of M + P, to address a 
significant unmet medical need in patients with R/R DLBCL, high-grade B-cell 
lymphoma, trFL, and FL3B. 
Mosunetuzumab administered as a single agent has shown an acceptable safety profile 
and promising activity in a Phase I/II clinical trial (Study GO29781) in participants with 
B-cell NHL.  Identified risks of mosunetuzumab include cytokine release syndrome 
(CRS), neutropenia, infections, injection-site reactions, tumor lysis syndrome (TLS), 
tumor flare, neurologic toxicity including immune effector cell-associated neurotoxicity 
syndrome (ICANS), hemophagocytic lymphohistiocytosis (HLH).  Potential risks of 
mosunetuzumab include thrombocytopenia, elevated liver enzymes, and immunogenicity 
(ADAs).  

 
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Polatuzumab vedotin has shown an acceptable safety profile and clinical activity 
administered as either a single agent (Study DCS4968g), in combination with an 
anti-CD20 antibody (Study GO27834) or in combination with BR (Study GO29365; 
see Section 4.2.1) in B-cell NHL.  Identified risks of polatuzumab vedotin include 
myelosuppression, peripheral neuropathy, infections, infusion-related reactions (IRRs) 
and gastrointestinal toxicity.  Potential risks of polatuzumab vedotin are TLS, 
immunogenicity, reproductive toxicity, hyperglycemia, hepatoxicity and carcinogenicity.  
See the Polatuzumab Vedotin Investigator’s Brochure for details of risks associated with 
polatuzumab vedotin. 
A nonclinical mouse xenograft model of human B-cell lymphoma has shown that M + P 
showed synergistic anti-lymphoma activity.  Supported by this data, the combination of 
mosunetuzumab (IV) and polatuzumab vedotin has been tested in participants with 
R/R B-cell NHL in a Phase Ib/II trial (Study GO40516), showing promising safety and 
efficacy (Budde et al. 2021). 
See Appendix 6 for information on anticipated risks for mosunetuzumab and 
polatuzumab vedotin and risk mitigation measures, including guidelines for managing 
adverse events associated with mosunetuzumab and polatuzumab vedotin. 
More detailed information about the known and expected benefits and risks of 
mosunetuzumab and polatuzumab vedotin may be found in the respective 
Investigator’s Brochures. 
Considering the poor prognosis of patients with R/R DLBCL, the efficacy data of M + P in 
this participant population with R/R DLBCL, the safety profile for mosunetuzumab and 
polatuzumab vedotin administered as monotherapy, and the risk mitigation measures for 
the study, the benefit−risk ratio is expected to be acceptable for M + P in the treatment 
setting of R/R DLBCL. 
2.3.1 
COVID-19 Benefit-Risk Assessment 
In the setting of the coronavirus disease 2019 (COVID-19) pandemic, participants with 
comorbidities, including those with DLBCL, may be a more vulnerable participant 
population; however, it is unclear whether or how cancer therapies, such as 
chemotherapy, targeted therapy, or immunotherapy, impact the incidence or severity of 
COVID-19.  Severe COVID-19 is associated with dysregulated immune response 
involving the inflammatory cytokines interleukin (IL)-6, IL-10, IL-2, and IFN-.  
Participants with known active severe acute respiratory syndrome (SARS−CoV-2) 
infection will be excluded from the study (Section 5.2) and guidance on the risk of 
infection is provided in Appendix 6.  Both mosunetuzumab and polatuzumab vedotin are 
B−cell-targeted therapies and mosunetuzumab has the identified risk of CRS.  
However, it is not known if there may be a potential for an increased risk of an enhanced 
inflammatory response in case of a SARS−CoV-2 infection while receiving 
mosunetuzumab. 

 
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CRS is a risk for mosunetuzumab that occurs most commonly during step-up dosing.  
Many COVID-19 vaccines are highly immunogenic and the associated risk of 
potentiating CRS is unknown. 
Based on the mechanism of action and role of B-cells immune response, participants 
may have an increased risk of SARS−CoV-2 infection during CD20 targeted therapy. 
Investigators should highlight to study participants the precautions that can prevent or 
mitigate SARS-CoV-2 infections (e.g., masking, social distancing, avoiding close contact 
with anyone infected with SARS-CoV-2, and informing their health care provider or 
general practitioner about close contacts and/or at first signs of infection). 
To reduce the risk of COVID-19 during the study, administration of 
COVID‑19 prophylaxis with the use of available agents in accordance with local 
institutional guidance (including but not limited to vaccines and monoclonal antibodies) is 
recommended before initiation of study treatment (El Chaer et al. 2022; 
see Section 6.8.1). 
3. 
OBJECTIVES AND ENDPOINTS 
This study will evaluate the efficacy and safety of M + P compared with R-GemOx in 
participants with R/R aNHL, including DLBCL, high-grade B-cell lymphoma, trFL, and 
FL3B, who received at least one prior systemic therapy and are not candidates for 
ASCT.  Specific objectives and corresponding endpoints for the study are outlined in 
Table 6. 
In this protocol, "study treatment" refers to the combination of treatments assigned to 
participants as part of this study (i.e., M + P and R-GemOx). 

 
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Table 6 
Objectives and Corresponding Endpoints 
Primary Objective 
Efficacy Objective 
Corresponding Dual Primary Endpoints 
 
To evaluate the efficacy of 
M  P (Arm A) compared with 
R-GemOx (Arm B) 
 
ORR, defined as the proportion of participants in 
whom an objective response (CR or PR) was 
observed at any time during the study as determined 
by IRF  
 
PFS, defined as the time from randomization to the 
first occurrence of disease progression as determined 
by IRF, or death due to any cause, whichever occurs 
first 
Secondary Objectives 
Efficacy Objective 
Corresponding Endpoints 
 
To evaluate the efficacy of 
M  P compared with 
R-GemOx 
 
ORR, defined as the proportion of participants in 
whom an objective response (CR or PR) was 
observed at any time during the study as determined 
by the investigator 
 
DOR, defined as the time from the first occurrence of 
a documented objective response to disease 
progression, or death from any cause, whichever 
occurs first as determined by the investigator and IRF 
 
OS, defined as the time from randomization to death 
from any cause 
 
PFS, defined as the time from randomization to the 
first occurrence of disease progression as determined 
by the investigator, or death due to any cause, 
whichever occurs first 
 
CRR, defined as the proportion of participants in 
whom CR was observed at any time during the study 
as determined by IRF and by the investigator 
 
DOCR, defined as the time from the first occurrence 
of a documented CR to disease progression, or death 
from any cause, whichever occurs first.  This will be 
determined by IRF and by investigator. 
 
Time to deterioration in physical functioning and 
fatigue, as measured by the EORTC QLQ-C30 
 
Time to deterioration in lymphoma symptoms, as 
measured by FACT-LymS 
 

 
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4. 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
4.1.1 
Overview of Study Design 
This is a Phase III, open-label, multicenter, randomized, controlled trial in participants 
with R/R DLBCL, high-grade B-cell lymphoma, trFL, or FL3B, who are not candidates for 
ASCT.  Approximately 222 eligible participants will be randomized in a 2:1 ratio 
(see Section 4.2.3) to receive either M  P (Arm A) or R-GemOx (Arm B); this is the 
population from which the primary analysis will be performed.  If China is included as a 
participating country, additional participants may be enrolled in an extended China 
enrollment cohort at China’s sites, 
, to ensure 
a total of approximately 
 participants with R/R aNHL in a China subpopulation.  
The global population will include all participants enrolled during the global enrollment 
phase (including participants enrolled at China’s sites during that phase), and the China 
subpopulation will include all participants enrolled at China’s sites (i.e., during both the 
global enrollment phase and the extended China enrollment cohort). 
A study schema is provided in Section 1.2 (see Figure 1).  A schedule of activities and a 
sample collection schedule are provided in Section 1.3 (see Table 1 and Table 3 
[Arm A]; Table 2 and Table 4 [Arm B]). 
4.1.1.1 
Randomization 
Participants in this trial will be stratified at the time of randomization for the following 
2 factors: 
 
Number of previous lines of systemic therapy for aggressive lymphoma (1 vs. ≥ 2) 
 
Outcome after last systemic therapy (relapsed vs. refractory) 
– 
Relapsed disease in this study is defined as disease that has recurred after 
having a documented history of response (CR or PR)  6 months in duration 
from completion of the last treatment. 
– 
Refractory disease is defined as disease that either did not respond to, or 
progressed within 6 months ( 6 months) of last treatment. 
 
4.1.1.2 
Arm A Treatment (Mosunetuzumab  Polatuzumab Vedotin) 
The Arm A treatment consists of mosunetuzumab administered subcutaneous (SC) and 
polatuzumab vedotin administered IV (see Figure 2).  One cycle of treatment is 21 days.  
Mosunetuzumab will be administered
mg SC on Cycle 1, Day 1; 
mg on Cycle 1, 
Day 8; Cycle 1, Day 15; and Day 1 of Cycles 2−8.  Polatuzumab vedotin will be 
administered IV at 1.8 mg/kg on Day 1 of Cycles 1−6.  Prophylactic (preemptive) or 
therapeutic use of granulocyte colony-stimulating factor (G-CSF) is permitted at the 
treating physician’s discretion.  Dosing will occur if a participant’s clinical assessment 
and laboratory test values are acceptable, including peripheral neuropathy and other 
treatment related adverse events resolved to Grade  1, ANC ≥ 1000/mm3 and platelet 

 
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count  75,000/mm3 (see Section A6–2.2).  Details of each drug administration are 
described in Section 6.1. 
4.1.1.3 
Arm B Treatment (Rituximab, Gemcitabine, Oxaliplatin) 
The Arm B treatment consists of R-GemOx (see Figure 3).  One cycle of treatment is 
14 days.  Rituximab 375 mg/m2, gemcitabine 1000 mg/m2, and oxaliplatin 100 mg/m2 will 
be administered IV on Day 1.   Gemcitabine should be administered before 
administration of oxaliplatin.  Prophylactic (preemptive) or therapeutic use of G-CSF is 
permitted at the treating physician’s discretion.  Dosing will occur if a participant’s clinical 
assessment and laboratory test values are acceptable, including treatment-related 
adverse events resolved to Grade  1, ANC  1000/mm3 and platelet count  75,000/mm3 
(see Section A6–2.2).  If these required hematologic parameters are not met within 
2 weeks after the last treatment, the treatment will be delayed.  If such a delay occurs, it 
is acceptable to change the treatment cycle to every 21 days, instead of 14 days for the 
subsequent treatment.  Treatment is administered for up to 8 cycles.  Details of each 
drug administration is described in Section 6.1. 

 
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4.1.1.5 
Continued Treatment of Non-Hodgkin Lymphoma in Arm A 
After Suspected Disease Progression  
Experience with cancer immunotherapy for solid tumors has demonstrated that 
responding tumors may initially increase in size due to the influx of immune cells, a 
phenomenon known as “pseudoprogression” (Wolchok et al. 2009).  
Pseudoprogression has also been described in the context of lymphoma 
(Cheson et al. 2016; Salles et al. 2016), and similarly it is possible that mosunetuzumab 
and/or polatuzumab vedotin therapy may initially increase tumor size and metabolic 
activity by inducing the influx of T‑cells into the tumor.  Given this, a repeat tumor biopsy, 
if clinical disease progression is observed, is strongly encouraged.  Additionally, if the 
study investigator believes that a participant with NHL receiving mosunetuzumab is 
deriving clinical benefit despite radiographic evidence of PD as defined by the Lugano 
2014 criteria (Appendix 10), that participant in Arm A may continue study treatment 
provided the following criteria are met: 
 
There is an absence of symptoms and signs (including worsening of laboratory 
values) indicating unequivocal progression of disease. 
 
There is no decline in Eastern Cooperative Oncology Group Performance Status 
(ECOG PS). 
 
There is an absence of tumor progression at critical anatomical sites including the 
central airway, the great vessels, and other organs or tissues where compromised 
function secondary to tumor progression would be expected to result acutely in 
severe and/or irreversible disability or death. 
 
Participants must provide written consent to acknowledge discussion with the treating 
investigator of the benefit-risk balance of continuing study treatment in Arm A beyond 
radiographic progression.  Participants continuing study treatment despite apparent 
radiographic progression will be strongly encouraged to undergo a repeat tumor biopsy 
to assess whether increases in tumor volume are due to immune cell infiltration or 
neoplastic proliferation, provided that such a biopsy can be performed safely on a 
non-target lesion.  If true progression is suspected based on the investigator’s judgment, 
clinical factors, or biopsy findings that are consistent with neoplastic proliferation, or if 
radiographic disease progression is confirmed at a subsequent tumor assessment, the 
participant will be ineligible to receive further study treatment. 
4.1.2 
Independent Review Facility 
An Independent Review Facility (IRF) will perform a centralized, independent review of 
images, and other clinical data as needed, prior to the efficacy analyses.  
Independent Review Facility membership and procedures will be detailed in an 
IRF charter.  The IRF will be used to evaluate the study endpoints of progression-free 
survival (PFS), complete response rate (CRR), duration of response (DOR), duration of 
complete response (DOCR), and objective response rate (ORR) in a blinded manner. 

 
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4.1.3 
Independent Data Monitoring Committee 
An independent Data Monitoring Committee (iDMC) will evaluate safety and efficacy 
data periodically during the study.  The analysis supporting iDMC review will be 
conducted by an independent Data Coordinating Center and provided to the iDMC.  
Sponsor affiliates will be excluded from iDMC membership.  The iDMC will follow a 
charter that outlines the iDMC roles and responsibilities. 
After each safety review, the iDMC may recommend continuing, modifying, stopping the 
study, or putting the study on hold pending further iDMC recommendation, as defined in 
the iDMC charter. 
 
  If any of the 
following criteria are met, then accrual to the study will be paused and the iDMC will 
conduct a comprehensive review of safety data and may recommend continuing, 
modifying, or stopping the study. 
The first iDMC review will occur after a minimum of 
 participants 
(approximately 
 participants in Arm A and approximately 
 participants in Arm B) 
receive  cycles of treatment.  The safety monitoring parameters and the predefined 
stopping rules include: 
 
 
 
 
After the first iDMC review, reviews of safety data by iDMC will occur approximately 
every  months until the prespecified timepoint defined in the iDMC charter.   
Two reviews of overall survival (OS) data by the iDMC will be performed for futility 
assessment.  The first OS futility analysis by the iDMC will be conducted when there are 
approximately 
 OS events observed.  The second OS futility analysis by the iDMC will 
be conducted at the time of the dual primary endpoint ORR analysis. 
One futility analysis of progression-free survival (PFS) by IRF will be performed by the 
iDCC for iDMC review on the first 
 randomized participants at the time of the dual 
primary endpoint ORR analysis when the first 
 randomized participants have a 
minimum of  months of follow-up from the first response assessment.   
The safety monitoring parameters and the predefined stopping rules include: 
 
 
 

 
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 
 
 
Any outcomes of these data reviews that affect study conduct will be communicated in a 
timely manner to the investigators for notification of their respective Institutional Review 
Boards (IRBs)/Ethics Committees (ECs). 
4.2 
RATIONALE FOR STUDY DESIGN 
This study will enroll participants with a history of hematologic malignancy that is 
expected to express the CD20 antigen and CD79b antigen, specifically DLBCL, 
high-grade B-cell lymphoma, trFL, and FL3B.  Local assessment to confirm CD20 
expression is required during screening.  Central confirmation of CD20 expression will 
not be required during eligibility screening prior to enrollment, but it will be evaluated 
retrospectively.  
4.2.1 
Rationale for Study Population 
Up to 40% of patients with DLBCL who are treated in the first-line setting will experience 
disease progression within 3−4 years (Friedberg 2011), and more than half of the 
patients treated with second-line therapies do not achieve a complete remission 
(Gisselbrecht et al. 2010).  Furthermore, since the introduction of the monoclonal 
anti-CD20 antibody rituximab, it has become more challenging to find effective therapies 
for the large proportion of patients with R/R DLBCL who have prior exposure to 
anti-CD20 antibody. 
Each year around 3% of FLs transform into higher-grade NHL, most commonly DLBCL 
(Lossos and Gascoyne 2011), leading to almost a third of histologic transformation in 
10 years.  These patients with DLBCL transformed from a previous FL histology and 
have been treated with the same standard therapies as high-grade lymphomas.  
The study includes participants with this disease. 
Follicular lymphoma Grade 3B is a distinct subgroup of FL that is more in common 
genetically, immunophenotypically, and clinically with DLBCL than with other indolent 
FLs, and the coexistence with DLBCL is frequent (Harris and Kluin 2011).  The clinical 
course of patients with FL3B is similar to those with DLBCL, and FL3B is commonly 
treated as DLBCL (National Comprehensive Cancer Network [NCCN] 2020).  
Therefore, the study includes participants with FL3B in the primary analysis. 
Several novel therapeutic agents have been approved for the management of 
R/R DLBCL in some countries. 
Polatuzumab Vedotin, an ADC Targeting CD79b 
In the randomized, Phase II part of Study GO29365 that evaluated participants with 
R/R DLBCL who were transplant-ineligible, polatuzumab vedotin in combination with BR 

 
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(n  40) showed significant and clinically meaningful efficacy benefit over BR alone 
(n  40) marked by a CRR at the end of the treatment (40.0% vs. 17.5%; p  0.026), 
PFS (median 9.5 months vs. 3.7 months; p   0.001) both assessed by IRF, and 
OS (median 12.4 months vs. 4.7 months; p  0.002; Sehn et al. 2019). 
Tafasitamab, a Humanized Anti-CD19 Monoclonal Antibody 
Tafasitamab in combination with lenalidomide was evaluated in 81 participants with 
R/R DLBCL after receiving at least one line of therapy.  The best response rate was 
60%, including a best CRR of 43%, with a median DOR of 21.7 months 
(Salles et al. 2020).  While the response rates and the duration of therapy were clinically 
significant, the study excluded or limited enrollment of a very high-risk population such 
as participants with primary refractory disease and double-hit lymphoma, and thus, 
provides a limited benefit in the area of the highest unmet medical need. 
Selinexor®, an XPO1 Inhibitor 
Selinexor was evaluated in 127 participants with R/R DLBCL (Kalakonda et al. 2020).  
Grade 3/4 thrombocytopenia was observed in 46% of participants.  The ORR was 29%, 
including a CRR of 13%.  While this is an oral dosing regimen with significant 
convenience, the untrivial myelosuppression and the low response rates may limit the 
actual use of this regimen in this setting. 
Zynlonta® (loncastuximab tesirine), an ADC Targeting CD19 
Loncastuximab tesirine was evaluated in 145 participants with R/R DLBCL after at least 
one line of therapy (Caimi et al. 2021).  The best response rate was 48.3%, including a 
best CRR of 24.1%, with a median DOR of 10.3 months. 
CD19 Chimeric Antigen Receptor (CAR) T cells 
In addition, CD19-directed chimeric antigen receptor (CAR) T-cell therapies have 
become available in some countries (axicabtagene ciloleucel, tisagenlecleucel, and 
Breyanzi [lisocabtagene maraleucel]).  While these therapies have shown efficacy with 
durable CRs, their use may be limited for the general population with R/R DLBCL due to 
the toxicity profile which requires carefully selected participants and treatment in centers 
with specially trained staff.  In addition, the waiting period associated with CAR T 
manufacture may be prohibitive in participants with rapidly progressing disease. 
Despite the above-mentioned improvement in the therapeutic approaches in 
R/R DLBCL, the clinical outcome of patients with this condition, especially those who are 
not eligible for transplant, is still poor.  Of note, tafasitamab, loncastuximab tesirine and 
CAR T products target the same antigen, CD19, raising the concern for potential cross 
resistance.  Taken together, there remains a significant unmet medical need for patients 
with transplant-ineligible R/R DLBCL. 

 
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4.2.2 
Rationale for Control Group 
The type of control group in this study is an active treatment concurrent control.  
In participants with R/R DLBCL who are not candidates for ASCT, R-GemOx is a 
recommended regimen in the NCCN Guideline 2021.  Given the established role as a 
commonly used therapy for patients with R/R DLBCL who are not candidates for ASCT, 
the R-GemOx regimen, as described by Mounier et al. (2013) serves as a reasonable 
option for the active treatment concurrent control.  The study intends to show the 
difference in the PFS between participants treated with M  P and those treated with 
R-GemOx. 
4.2.3 
Rationale for Randomization Ratio 
This study plans to enroll more participants into Arm A (M  P) than Arm B (R-GemOx) 
using the randomization ratio of 2:1.  Unequal allocation of participants in randomized 
cancer clinical trials is used to ensure a larger population of participants is exposed to 
experimental treatment to assess adverse events known to be associated with the 
experimental agent.  Because of the potentially serious nature of CRS with 
T−cell-engaging therapies such as mosunetuzumab, and because this trial represents 
the first randomized study utilizing mosunetuzumab in combination with 
polatuzumab vedotin, increasing exposure in the experimental arm would be beneficial 
to fully inform the safety profile of this combination therapy and management guidelines 
in the event that this fully powered trial meets its primary efficacy endpoint. 
In Arm J of the clinical Study GO40516, mosunetuzumab given IV in combination with 
polatuzumab vedotin in participants with R/R DLBCL showed an ORR of 66% and CR 
rate of 49% based on 41 patients as of a clinical cutoff date [CCOD] of 15 March 2021.  
The Phase II study of R-GemOx (Mounier et al. 2013) showed an ORR of 55% and CR 
rate of 42% in 31 participants with R/R DLBCL who had been previously treated with 
rituximab; the median PFS and median OS was 4 months and 8 months, respectively.  
In the recent retrospective analysis of real-world data in participants with R/R DLBCL 
treated with R-GemOx, an end of treatment ORR of 38% and CR rate of 33% 
(Cazelles et al. 2021) was observed.  The median PFS of R-GemOx in this population 
was 5 months and the median OS was 10 months.  The difference in the response rates 
demonstrates the potentially meaningful benefit for participants to receive 
mosunetuzumab in combination with polatuzumab vedotin. 
4.2.4 
Rationale for Biomarker Assessments 
Predictive and prognostic biomarkers, including biomarkers associated with disease 
biology, drug targets, the mechanism of action of the individual components or the 
synergistic activity of the combination may correlate with the outcome in participants with 
R/R DLBCL, high-grade B-cell lymphoma, trFL and FL3B treated in this study.  
Tumor biopsies will be obtained at baseline from participants with safely accessible 
tumors as detailed in Section 8.1.1 to assess tumor and tumor-immune 
microenvironment profiles using technologies such as immunohistochemistry (IHC), 

 
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gene expression or mutation profiling to evaluate associations with the drugs, prognostic 
subtypes or outcomes. 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Additionally, exploratory research on safety biomarkers may be conducted to support 
future drug development.  Research may include further characterization of a safety 
biomarker or identification of safety biomarkers that are associated with susceptibility to 
developing adverse events or can lead to improved adverse event monitoring or 
investigation.  Adverse event reports will not be derived from safety biomarker data by 
the Sponsor, and safety biomarker data will not be included in the formal safety analyses 
for this study.  In addition, safety biomarker data will not inform decisions on participant 
management. 
A loss of CD20 expression after mosunetuzumab treatment is a potential mechanism of 
resistance to anti-CD20 therapy, potentially similar to antigen-loss escape resistance 
mechanisms observed with other T-cell bispecific therapies (Topp et al. 2011).  A repeat 
biopsy from a safely accessible tumor site should be considered at the time of disease 
progression after M  P treatment, which may be used to confirm CD20 expression and 
the status of lymphoma-infiltrating T cells. 
In addition to the exploratory objectives listed above, specimens (if consent is given) 
stored in the Research Biosample Repository (RBR) will also be used for the following: 
 
To evaluate the association of biomarkers with efficacy and/or adverse events 
associated with M  P 
 
To increase the knowledge and understanding of disease biology and/or to develop 
biomarker or diagnostic assays and to establish the performance characteristics of 
these assays 

 
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Based on the continuous analysis of the data in this study and other cancer 
immunotherapy nonclinical and clinical studies, as well as new data from literature, the 
collection of samples or biomarker analyses with exploratory purposes may be stopped 
at any time. 
4.2.5 
Rationale for Pharmacokinetic and Anti-Drug Antibody 
Sampling Schedule 
Sparse PK samples (see Table 3 and Table 4) will be collected in this Phase III study in 
order to estimate the population PK parameters of mosunetuzumab and polatuzumab 
vedotin and to compare these parameters with historical data.  In addition, the effect of 
clinically relevant covariates (such as demographics) on the PK of mosunetuzumab will 
be examined, if possible, to understand their impacts.  Lastly, exposure/safety and 
exposure/efficacy relationships will be assessed, as the data permit, to provide support 
for the clinical dose evaluated. 
Since mosunetuzumab has demonstrated low immunogenicity rates in the Phase I/II 
Study GO29781, the frequency of ADA sampling times for mosunetuzumab will be 
reduced in this study compared with Study GO29781.  Available information in the 
polatuzumab vedotin U.S. Food and Drug Administration (FDA) product label also have 
demonstrated low immunogenicity; thus, the frequency of ADA sampling times for 
polatuzumab vedotin will be kept at a minimum. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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4.3 
JUSTIFICATION FOR DOSE AND SCHEDULE 
The dose and schedule of mosunetuzumab and polatuzumab vedotin for this study is 
based on experience from multiple studies, including Studies DCS4968g (polatuzumab 
vedotin), GO27834 (polatuzumab vedotin), GO29781 (mosunetuzumab), and GO40516 
(combination of mosunetuzumab and polatuzumab vedotin). 
4.3.1 
Rationale for Polatuzumab Vedotin Dose and Schedule 
Polatuzumab vedotin will be administered at 1.8 mg/kg IV for 6 cycles, which is the 
approved dose based on previous clinical studies.  At the dose of 1.8 mg/kg every 21 
days, polatuzumab vedotin was well-tolerated as monotherapy (Study DCS4968g) or in 
combination with an anti-CD20 monoclonal antibody (Study GO27834) in participants 
with R/R B-cell NHL, with expected toxicities including cytopenias and peripheral 
neuropathy.  Study GO29365 then evaluated polatuzumab vedotin 1.8 mg/kg in 
combination with BR every 21 days for 6 cycles, which led to the approval of this 
combination in the US and internationally for R/R DLBCL. 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
  
 
 
 
 

 
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4.4 
END OF STUDY DEFINITION 
A participant is considered to have completed the study if he or she has completed all 
required study visits of the study, including the last visit shown in the schedule of 
activities (see Section 1.3, Table 1 and Table 2). 
The end of this study is defined as the date of the last visit of the last participant in the 
study (i.e., last participant in the global and extended China enrollment cohort combined 
if China is included), or the date at which the last data point required for statistical 
analysis (i.e., OS) or safety follow-up is received from the last participant (global 
enrollment and extended China enrollment cohort combined if China is included), 
whichever occurs later.  The end of the study is expected to occur 2.5 years after the last 
participant is enrolled.  The total length of the study, from the screening of the first 
participant to the end of the study, is expected to be approximately 5 years. 
In addition, the Sponsor may decide to terminate the study at any time. 
4.5 
DURATION OF PARTICIPATION 
For Arm A (M + P) and Arm B (R-GemOx), treatment will continue for a total of 
8 treatment cycles.  Treatment will be discontinued if there is disease progression or 
unacceptable toxicity.  The average duration of study participation for each participant is 
expected to be approximately 2.5 years. 
5. 
STUDY POPULATION 
Approximately 222 participants with R/R aNHL will be enrolled in this study.  If China is 
included as a participating country, additional participants may be enrolled in an 
extended China enrollment cohort to ensure a total of approximately 
 participants 
in China. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 

 
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5.1 
INCLUSION CRITERIA 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
 
Participants who are capable of giving signed informed consent as described in 
Appendix 1 which includes compliance with the requirements and restrictions listed 
in the Informed Consent Form and in this protocol 
 
Participants who are age  18 years at the time of signing Informed Consent Form 
 
Participants who have an Eastern Cooperative Oncology Group (ECOG) 
Performance Status of 0, 1, or 2 (see Appendix 12) 
 
Participants who have a life expectancy of at least 12 weeks 
 
Participants who have CD20  aggressive lymphoma as determined by the local 
hematopathology laboratory from the following diagnoses by 2016 World Health 
Organization classification of lymphoid neoplasms: 
– 
DLBCL, not otherwise specified (NOS) 
– 
High-grade B-cell lymphoma (NOS or double/triple hit) 
– 
trFL:  The disease must be R/R to standard therapies for trFL 
– 
FL3B 
 
Participants who have received at least one prior systemic therapy for aNHL 
 
Participants who have either relapsed or have become refractory to a prior regimen 
must meet the following criteria: 
– 
Relapsed to prior regimen(s) after having a documented history of response 
(CR or PR) of ≥ 6 months in duration from completion of regimen(s) 
– 
Refractory to any prior regimen, defined as no response to the prior therapy, or 
progression within 6 months of completion of the last dose of therapy 
 
Participants must be ineligible for ASCT 
 
Participants who have measurable disease, defined as at least 1 bi-dimensionally 
measurable nodal lesion, defined as  1.5 cm in its longest dimension, or at least 
1 bi-dimensionally measurable extra nodal lesion, defined as  1.0 cm in its longest 
dimension 
 
Participants who have a pathology report for the initial histopathology diagnosis and 
the most recent histopathology diagnosis prior to entering the study.  
A pathology report for the initial histopathology diagnosis (if available) and the most 
recent histopathology diagnosis prior to study entry, whether it is for fresh or archival 
tumor specimen, must be provided. 
– 
Participants with trFL must also have a pathology report completed at the time 
of disease transformation 
 
Participants whose representative tumor specimen and the corresponding pathology 
report are available for confirmation of diagnosis as well as for biomarker analysis.  

 
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– 
– 
– 
– 
 
Participants who have adequate hepatic, hematologic, and renal functions defined 
by laboratory values below: 
– 
Hepatic function 
AST and ALT  2.5  upper limit of normal (ULN). 
Total bilirubin  1.5  ULN. 
Participants with a documented history of Gilbert syndrome and in whom 
total bilirubin elevations are accompanied by elevated indirect bilirubin are 
eligible. 
– 
Hematologic function 
Platelet count  75,000/mm3 without platelet transfusion within 14 days prior to 
first dose of study treatment. 
ANC  1000/mm3. 
Total hemoglobin  9 g/dL without red blood cell transfusion within 14 days prior 
to first dose of study treatment. 
– 
Participants with extensive marrow involvement of lymphoma and/or 
disease-related cytopenias (e.g., immune thrombocytopenia) may be enrolled if 
below is met 
Platelet count  50,000/mm3 without platelet transfusion within 14 days of study 
treatment. 
ANC  500/mm3. 
Any hemoglobin but without red blood cell transfusion within 7 days prior to first 
dose of study treatment. 
– 
Renal function 
Estimated creatinine clearance (CrCl)  30 mL/min by Cockroft-Gault method or 
other institutional standard methods (see Appendix 15). 
– 
Participants who have a negative HIV test at screening, with the following 
exception:  

 
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Individuals with a positive HIV test at screening are eligible provided they 
are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count 
 200/L, have an undetectable viral load, and have not had a history of 
opportunistic infection attributable to AIDS within the last 12 months, and 
must be willing to undergo repeated HIV viral load testing. 
 
For women of childbearing potential:  participants who agree to remain abstinent 
(refrain from heterosexual intercourse) or use contraception and agree to refrain 
from donating eggs, as defined below: 
Women must remain abstinent or use contraceptive methods with a failure rate 
of  1% per year during the treatment period and for 3 months after the final 
dose of mosunetuzumab, 9 months after the final dose of polatuzumab vedotin, 
12 months after the final dose of rituximab, 6 months after the final dose of 
gemcitabine, 9 months after the final dose of oxaliplatin, and 3 months after the 
final dose of tocilizumab, as applicable.  Women must refrain from donating 
eggs during this same period. 
A woman is considered to be of childbearing potential if she is postmenarchal, 
has not reached a postmenopausal state ( 12 continuous months of 
amenorrhea with no identified cause other than menopause), and is not 
permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, 
and/or uterus) or another cause as determined by the investigator 
(e.g., Müllerian agenesis).  The definition of childbearing potential may be 
adapted for alignment with local guidelines or regulations. 
Examples of contraceptive methods with a failure rate of  1% per year include 
bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit 
ovulation, hormone-releasing intrauterine devices, and copper intrauterine 
devices. 
The reliability of sexual abstinence should be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the individual.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not adequate methods of contraception.  
If required per local guidelines or regulations, locally recognized adequate 
methods of contraception and information about the reliability of abstinence will 
be described in the local Informed Consent Form. 
 
For men:  participants who agree to remain abstinent (refrain from heterosexual 
intercourse) or use a condom, and agree to refrain from donating sperm, as defined 
below: 
With a female partner of childbearing potential or pregnant female partner, men 
must remain abstinent or use a condom during the treatment period and for 
6 months after the final dose of polatuzumab vedotin, 3 months after the final 
dose of rituximab, 6 months after the final dose of oxaliplatin or gemcitabine, 
and 2 months after the final dose of tocilizumab, as applicable, to avoid 
exposing the embryo.  Men must refrain from donating sperm during this same 
period. 

 
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The reliability of sexual abstinence should be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the individual.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not adequate methods of preventing drug 
exposure.  If required per local guidelines or regulations, information about the 
reliability of abstinence will be described in the local Informed Consent Form. 
 
For participants enrolled in the extended China enrollment cohort at China’s sites 
(if China participates in the study):  must be current residents of 
 
 and be of Chinese ancestry 
 
5.2 
EXCLUSION CRITERIA 
Participants are excluded from the study if any of the following criteria apply: 
 
Participants who are pregnant, breastfeeding, or intending to become pregnant 
during the study or within 3 months after the final dose of mosunetuzumab, 
9 months after the final dose of polatuzumab vedotin, 12 months after the final dose 
of rituximab, 6 months after the final dose of gemcitabine, 9 months after the final 
dose of oxaliplatin, and 3 months after the final dose of tocilizumab, as applicable.   
– 
If breastfeeding stops prior to the first dose of study treatment, the participant 
can be eligible but breastfeeding should not resume for that child and for the 
time period as specified above. 
 
Women of childbearing potential must have a negative serum pregnancy test result 
within 7 days prior to initiation of study treatment 
 
Participants who have the inability to comply with protocol-mandated activity 
restrictions 
 
Participants who have received prior treatment with mosunetuzumab or other 
CD20-directed bispecific antibodies 
 
Participants who have received prior treatment with polatuzumab vedotin with the 
following exceptions:  
– 
Participants who have a documented response (PR or CR) to polatuzumab 
vedotin and an absence of PD within 12 months from the last dose of 
polatuzumab vedotin are allowed to enroll 
– 
Participants who received up to 2 doses of polatuzumab vedotin-containing 
regimen as bridging to CAR-T therapy, and either had a documented disease 
control (stable disease [SD], PR or CR), or were not assessed for response 
following treatment with polatuzumab vedotin are allowed to enroll 
 
Participants who have received prior treatment with R-GemOx or GemOx 
 
Participants who have a contraindication to any component of the study treatment 
 
Participants with current Grade  1 peripheral neuropathy 
 
Participants with Grade  1 persistent toxicity related to prior anti-lymphoma 
treatment (except for alopecia and anorexia, or other toxicities not considered a 
safety risk for the participant per investigator's judgment)  

 
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 
Participants who have received anti-lymphoma treatments with monoclonal 
antibodies, radio-immunoconjugates or ADCs within 4 weeks before the first dose of 
study treatment 
 
Participants who have received treatment with any chemotherapeutic agent, or 
treatment with any other anti-lymphoma agent (investigational or otherwise) within 
4 weeks or 5 half-lives of the drug, whichever is shorter, prior to the first dose of 
study treatment 
 
Participants who have received treatment with radiotherapy within 2 weeks prior to 
the first dose of study treatment 
Participants who have received radiotherapy within 4 weeks prior to the first study 
treatment administration must have at least one measurable lesion outside of the 
radiation field.  Participants who have only one measurable lesion that was 
previously irradiated but subsequently progressed are eligible. 
 
Participants who have ASCT within 100 days prior to the first study treatment 
administration 
 
Participants who received prior treatment with CAR T therapy within 30 days before 
the first study treatment administration 
 
Participants who have had prior allogeneic stem cell transplantation 
 
Participants who have had solid organ transplantation 
 
Participants who have a known or suspected history of HLH 
 
Participants who have a history of confirmed progressive multifocal 
leukoencephalopathy 
 
Participants who have a history of severe allergic or anaphylactic reactions to 
monoclonal antibody therapy (or recombination antibody-related fusion proteins) 
 
History of other malignancy that could affect compliance with the protocol or 
interpretation of results, with the exception of malignancies with a negligible risk of 
metastasis or death (e.g., 5-year OS rate  90%), such as adequately treated 
carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate 
cancer, ductal carcinoma in situ, or Stage I uterine cancer 
– 
Participants who have prostate cancer with no evidence of metastatic disease 
and are not on active therapy except for anti-androgen therapy are allowed  
– 
Participants who have a history of curatively treated basal or squamous cell 
carcinoma of the skin or in situ carcinoma of the cervix are allowed 
– 
Participants who have a malignancy that has been treated with curative intent 
and has been in remission without treatment for  2 years prior to the first study 
treatment administration will be allowed 
 
Participants who currently have or have had a history of CNS involvement of 
lymphoma 
 
Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or 
neurodegenerative disease 

 
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– 
Participants with a history of stroke who have not experienced a stroke or 
transient ischemic attack in the past 2 years and have no residual neurologic 
deficits as judged by the investigator are allowed 
– 
Participants with a history of epilepsy who have had no seizures in the past 
2 years while not receiving any anti-epileptic medications are allowed 
 
Participants who have significant cardiovascular disease such as New York Heart 
Association Class III or IV cardiac disease, myocardial infarction within the last 
6 months, unstable arrhythmias, or unstable angina 
 
Participants who have significant active pulmonary disease (e.g., bronchospasm 
and/or obstructive pulmonary disease) 
 
Participants with active symptoms of interstitial lung disease and/or pneumonitis, or 
those with a history of interstitial lung disease and/or pneumonitis within 6 months 
prior to the first dose of study treatment 
 
Participants who have a known active bacterial, viral, fungal, mycobacterial, 
parasitic, or other infection (excluding fungal infections of the nail beds) at study 
enrollment, or any major episode of infection requiring treatment with IV antibiotics 
or hospitalization (relating to the completion of the course of antibiotics) within 
2 weeks prior to the first study treatment administration  
 
Participants who have a known or suspected chronic active EBV infection 
 
Participants who have had a recent major surgery within 4 weeks prior to the first 
study treatment administration 
Protocol-mandated procedures (e.g., tumor biopsies and bone marrow 
biopsies) are permitted. 
 
Participants who have positive test results for chronic hepatitis B infection 
(defined as positive hepatitis B surface antigen [HBsAg] serology) 
Participants with occult or prior hepatitis B infection (defined as positive total 
hepatitis B core antibody and negative HBsAg) may be included if hepatitis B 
virus (HBV) DNA is undetectable at the time of screening.  These participants 
should be considered for prophylactic antivirals (e.g., entecavir) before and 
throughout the treatment, and must be willing to undergo repeated DNA testing. 
 
Participants who have acute or chronic hepatitis C virus (HCV) infection 
Participants who are positive for HCV antibody must be negative for HCV by 
polymerase chain reaction (PCR) to be eligible for study participation 
 
Participants who have been administered a live, attenuated vaccine within 4 weeks 
before the first dose of study treatment administration or anticipation that such a 
live, attenuated vaccine will be required during the study 
Participants must not receive live, attenuated vaccines (e.g., FluMist®) while 
receiving study treatment and after the last dose until B-cell recovery to the 
normal ranges.  Killed vaccines or toxoids should be given at least 4 weeks 
prior to the first dose of study treatment to allow development of sufficient 

 
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immunity.  See Section 6.8.1.1 for a guideline on COVID-19 vaccine 
administration. 
Inactivated influenza vaccination should be given during local influenza season 
only. 
 
Participants who have positive SARS-CoV-2 test within 7 days prior to enrollment.  
Rapid antigen test result is acceptable 
 
Participants with a history of autoimmune disease, including, but not limited to, 
myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, 
rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated 
with antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, 
Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis 
– 
Participants with a history of autoimmune disease with no ongoing symptoms, 
and with a treatment-free interval from immunosuppressive therapy for 
12 months may be eligible to enroll if judged to be safe by the investigator  
– 
Participants with a history of autoimmune-related hypothyroidism on a stable 
dose of thyroid replacement hormone may be eligible 
– 
Participants with controlled Type 1 diabetes mellitus who are on an insulin 
regimen are eligible for the study 
– 
Participants with a history of disease-related immune thrombocytopenic 
purpura, or autoimmune hemolytic anemia may be eligible as long as relevant 
blood counts meet the criteria listed in the inclusion criteria 
 
Participants who have received systemic immunosuppressive medications 
(including, but not limited to, cyclophosphamide, azathioprine, methotrexate, 
thalidomide, and anti-TNF agents) with the exception of corticosteroid treatment 
 10 mg/day prednisone or equivalent within 2 weeks prior to first dose of study 
treatment 
– 
Participants who have received acute, low-dose, systemic immunosuppressant 
medications (e.g., single dose of dexamethasone for nausea or B-symptoms) 
may be enrolled in the study 
– 
The use of inhaled corticosteroids is permitted 
– 
The use of mineralocorticoids for management of orthostatic hypotension 
is permitted 
– 
The use of physiologic doses of corticosteroids for management of adrenal 
insufficiency is permitted 
 
Participants who received investigational therapy, whether or not intended for 
lymphoma treatment, within 7 days prior to initiation of study treatment 
 
Participants who have a clinically significant history of liver disease, including viral or 
other hepatitis, or cirrhosis 
 
Participants who have any serious medical condition or abnormality in clinical 
laboratory tests that, precludes the participant’s safe participation in and in the 

 
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completion of the study, or which could affect compliance with the protocol or 
interpretation of results 
 
Participants who do not meet the criteria for participation in this study (screen failure) 
may qualify for a re-screening opportunity.  The investigator will record reasons for 
screen failure in the screening log. 
5.3 
LIFESTYLE CONSIDERATIONS 
5.3.1 
Meals and Dietary Restrictions 
This study has no meal or dietary restrictions. 
5.3.2 
Caffeine, Alcohol, and Tobacco 
This study has no caffeine, alcohol, or tobacco restrictions. 
5.3.3 
Activity 
This study has no activity restrictions. 
5.3.4 
Contraception Requirements 
During the study, participants must use contraception or take other precautions as 
described in Section 5.1 and Appendix 4. 
5.4 
SCREEN FAILURES 
Individuals who do not meet the criteria for participation in this study (screen failure) may 
qualify for 2 re-screening opportunities (for a total of 3 screenings per individual) at the 
investigator’s discretion.  Individuals are not required to re-sign the Consent Form if they 
are re-screened within 28 days after previously signing the Consent Form.  
The investigator will maintain a record of reasons for screen failure (see Section 8). 
5.5 
CRITERIA FOR TEMPORARILY DELAYING RANDOMIZATION 
OR ADMINISTRATION OF STUDY INTERVENTION 
The following conditions may allow a participant to be randomized or administered study 
treatment once the conditions have resolved and the participant is otherwise eligible for 
participation in the study:  
 
Participant had active infection or required IV antibiotics within 2 weeks 
 
Participant has received systemic corticosteroid treatment  10 mg/day prednisone 
or equivalent within 2 weeks, with the exception listed in the exclusion criteria 
Section 5.2 
 
6. 
STUDY TREATMENTS AND CONCOMITANT THERAPY 
Study treatment is defined as any investigational treatment or marketed product 
intended to be administered to a study participant according to the study protocol. 

 
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The investigational medicinal products (IMPs) for this study are mosunetuzumab, 
polatuzumab vedotin, rituximab, gemcitabine, oxaliplatin, and tocilizumab. 
All other medicines described in the protocol and not specifically listed as IMPs should 
be considered non-investigational medicinal products (NIMPs). 
6.1 
STUDY TREATMENTS ADMINISTERED 
The treatment regimens are summarized in Table 10 (Arm A) and Table 11 (Arm B) that 
provide a description of assigned study treatments for this study. 
Table 10 Study Treatment Description (Arm A) 
 
Mosunetuzumab 
Polatuzumab 
vedotin 
Tocilizumab 
Use 
Experimental 
Experimental 
Other 
Type of medicinal product 
IMP 
IMP 
IMP 
Drug form 
Refer to the Pharmacy Manual and Investigator’s Brochure 
Unit Dose Strength(s) 
Packaging 
Formulation(s) 
Dosage Level(s) 
Cycle 1, Day 1:  
mg 
Cycle 1, Day 8:  
 mg 
Cycle 1, Day 15:  
 mg 
Cycles 2−8, 
Day 1:  
 mg 
1.8 mg/kg Q3W 
for 6 cycles 
See Section 6.1.3 
Labeling 
Per local requirements 
Route of administration 
SC 
IV 
IV 
Source 
Sponsor  
Sponsor  
Sponsor or Site a 
IMP  investigational medicinal product; Q3W  every 3 weeks. 
a Tocilizumab may be obtained locally by the study sites for emergency purposes if permitted 
by local regulations and will be formulated, prepared, and handled according to standard 
practice. 
 

 
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Table 11 Study Treatment Description (Arm B) 
 
Rituximab 
Gemcitabine 
Oxaliplatin 
Use 
Active comparator 
Active comparator 
Active comparator 
Type of medicinal product 
IMP 
IMP 
IMP 
Drug form 
Refer to the Local Institutional Guidelines and 
Prescribing Information 
Unit Dose Strength(s) 
Packaging 
Formulation(s) 
Dosage Level(s) 
375 mg/m2 
1000 mg/m2 
100 mg/m2 
Route of administration 
IV 
IV 
IV 
Source 
Sponsor 
Sponsor 
Sponsor 
IMP  investigational medicinal product. 
  
On days when two of the IMPs are given, the order of the administration in Arm A should 
be polatuzumab vedotin, followed by mosunetuzumab, and the interval between the end 
of polatuzumab vedotin infusion and the mosunetuzumab injection should be at least 
60 minutes (see Section 6.1).  In Arm B, gemcitabine should be administered before 
oxaliplatin.  The administration of rituximab can be either before gemcitabine or after 
oxaliplatin (see Section 4.1.1.3). 
Administration of study treatments will be performed in a monitored setting with 
immediate access to trained critical care personnel and facilities, and adequate 
equipment to respond to and manage potentially serious reactions and medical 
emergencies. 
For management of IRRs associated with polatuzumab vedotin and CRS associated 
with mosunetuzumab, please see Appendix 6.  For anaphylaxis precautions, 
see Appendix 7.  For guidance on premedication, please see Sections 6.1.1 and 6.1.2. 
Guidelines for dose modification and treatment interruption or discontinuation for 
participants who experience adverse events are provided in Appendix 6. 
6.1.1 
Polatuzumab Vedotin 
The dose of polatuzumab vedotin will be 1.8 mg/kg.  The total dose of polatuzumab 
vedotin for each participant will depend on the participant’s weight on Cycle 1, Day 1 
(or within 96 hours before Cycle 1, Day 1).  If the participant’s weight within 96 hours 
prior to Day 1 of a given treatment cycle increases or decreases  10% from the weight 
obtained for Cycle 1, Day 1, the most recent weight should be used to calculate the 
dose.  The weight that triggered a dose adjustment will be taken as the new reference 
weight for future dose adjustments.  All subsequent doses should be modified 
accordingly. 

 
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After reconstitution with sterile water for injection and dilution into IV bags that contain 
isotonic sodium chloride solution (0.9% NaCl), polatuzumab vedotin will be administered 
by IV infusion with use of a dedicated standard administration set with 0.2 M or 
0.22 M in-line filters at a final polatuzumab vedotin concentration determined by the 
participant-specific dose.  Compatibility of polatuzumab vedotin with IV bags, 
infusion lines, filters, and other infusion aids have been established with items made of 
specific materials of construction.  Consult the pharmacy manual and the 
Polatuzumab Vedotin Investigator’s Brochure for a list of compatible materials and 
specific dose preparation instructions. 
The initial dose will be administered over 90 ( 10) minutes to participants who are 
well-hydrated.  Premedication (e.g., 5001000 mg of oral acetaminophen or paracetamol 
and 50100 mg diphenhydramine as per institutional standard practice) may be 
administered to an individual participant before administration of polatuzumab vedotin.  
Administration of corticosteroids is permitted at the discretion of the treating physician.  
If IRRs are observed with the first infusion in the absence of premedication, 
premedication must be administered before subsequent doses. 
The polatuzumab vedotin infusion may be slowed or interrupted for participants 
experiencing infusion-associated symptoms.  Following the initial dose, participants will 
be observed for 90 minutes for fever, chills, rigors, hypotension, nausea, or other 
infusion-associated symptoms.  If prior infusions have been well-tolerated, subsequent 
doses of polatuzumab vedotin may be administered over 30 ( 10) minutes, followed by 
a 30-minute observation period after the infusion.  The time interval between the end of 
infusion of polatuzumab vedotin and the start of mosunetuzumab injection should always 
be at least 60 minutes. 
6.1.2 
Mosunetuzumab 
Mosunetuzumab will be administered SC with a Cycle 1 step-up-dosing regimen.  
Flat dosing, 
, will be used for mosunetuzumab.  In Cycle 1, 
participants will receive mosunetuzumab on Day 1 (  mg), Day 8 (
 mg), and Day 15 
(
 mg).  In Cycles 2−8, participants will receive mosunetuzumab on Day 1 (
 mg). 
Mosunetuzumab will be delivered by standard medical syringe with a final volume not to 
exceed 2.0 mL.  Compatibility testing has shown that mosunetuzumab is stable in 
extension sets and polypropylene syringes. 
Mosunetuzumab will be administered to well-hydrated participants.  
Corticosteroid premedication with 20 mg dexamethasone (preferred) or 80 mg 
methylprednisolone, either IV or oral, should be administered prior to the administration 
of each mosunetuzumab dose.  The administration of corticosteroid premedication may 
be optional for Cycle 2 and beyond at the investigator’s discretion.  However, if the 
participant experiences CRS with prior administration of mosunetuzumab, premedication 
with steroids must be administered for subsequent doses until no additional CRS events 

 
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are observed.  In addition, premedication with oral acetaminophen or paracetamol 
(e.g., 5001000 mg) and/or 50100 mg diphenhydramine may be administered per 
standard institutional practice prior to administration of mosunetuzumab. 
Mosunetuzumab will be administered by qualified staff over 30 seconds to 2 minutes.  
Refer to the pharmacy manual for more details, including syringe size and preferred 
injection site.  During Cycles 1 and 2, and later cycles if CRS occurred after the last 
mosunetuzumab, participants will be observed for at least 30 minutes after 
mosunetuzumab for fever, chills, rigors, hypotension, nausea, or other signs and 
symptoms of CRS.  Vital signs should be recorded pre-injection (within 30 minutes) and 
then 30 ( 15) minutes after mosunetuzumab administration.  In Cycle 3 and beyond, in 
the absence of CRS after the last dose of mosunetuzumab, the observation time after 
the mosunetuzumab injection will be at least 15 minutes.  Vital signs should be assessed 
prior to the mosunetuzumab injection (within 30 minutes prior to injection) and then at 
least once after the injection during the observation period. 
Guidelines for mosunetuzumab dosage and schedule modification and treatment 
interruption or discontinuation are provided in Appendix 6, Table A6-3. 
Although hospitalization is not mandated for participants in Arm A, the investigator 
should actively assess the need for hospitalization based on their individual conditions. 
6.1.3 
Tocilizumab 
Tocilizumab will be administered IV only to those participants who experience a 
CRS event for which tocilizumab is indicated.  Tocilizumab will be supplied by the 
Sponsor as an IMP.  Due to the need to manage CRS urgently and potential 
accessibility limitations at the site, commercial tocilizumab can be obtained locally by the 
study site for emergency use purposes.  It will be prepared, handled, and managed 
according to standard institutional practices. 
All tocilizumab used in the study will be tracked and accounted for as required by 
International Council for Harmonisation (ICH) GCP.  Tocilizumab supplied by the 
Sponsor will include a clinical study drug/IMP label.  Commercial tocilizumab obtained 
locally by the study site will have the marketed product label.  Refer to the local 
prescribing information for further instructions regarding recommended storage 
conditions and packaging configuration, as well as the Pharmacy Manual and the 
Tocilizumab Investigator’s Brochure. 
Note:  If tocilizumab is administered, see Table 5 for the schedule of activities for 
tocilizumab treatment of CRS. 
Tocilizumab should be administered at a dose of 8 mg/kg IV (not exceeding 800 mg per 
infusion).  The infusion should be administered IV over 60 minutes.  If no clinical 
improvement in the signs and symptoms of CRS occurs after the first dose, a second 

 
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dose may be administered at least 8 hours apart (maximum 2 doses per CRS event).  
Within each time-period of 6 weeks of mosunetuzumab treatment, the total number of 
tocilizumab doses should not exceed 3 doses. 
6.1.4 
Rituximab 
Rituximab will be administered at a dose of 375 mg/m2 by IV infusion on Day 1 of each 
14-day cycle (Cycles 18).  The dose of rituximab should not be modified. 
Rituximab must be administered in a clinic or hospital equipped for systemic cancer 
treatment.  Full emergency resuscitation facilities should be immediately available.  
For the management of adverse events, including IRRs, please consult the local 
prescribing information.  For management of anaphylaxis, also see Appendix 7.  
Once the rituximab infusion is complete, participants are to be observed for 30 minutes 
before the start of the other infusions.  The infusion of rituximab may be split over 2 days 
if the participant is at increased risk for an IRR (high tumor burden or high peripheral 
lymphocyte count).  For participants who experience an adverse event during a 
rituximab infusion, administration of R-GemOx may be continued on the following day, if 
required.  Rituximab can be given either before gemcitabine or after oxaliplatin on the 
same day. 
Table 12 Administration of Rituximab 
First Infusion (Cycle 1, Day 1) 
Subsequent Infusions 
 
Begin infusion at an initial rate of 
50 mg/hour 
 
If no infusion-related or 
hypersensitivity reaction occurs, 
increase the infusion rate in 
50-mg/hour increments every 
30 minutes, to a maximum of 
400 mg/hour 
 
If an infusion-related reaction 
develops, stop or slow the infusion.  
Administer infusion‑reaction 
medications and supportive care in 
accordance with institutional 
guidelines.  If the reaction resolves, 
resume the infusion at a 
50% reduction in rate (i.e., 50% of 
rate being used at the time that the 
reaction occurred). 
 
If the participant experienced an 
infusion‑related or hypersensitivity reaction 
during the prior infusion, begin infusion at 
an initial rate of 50 mg/hour and follow 
instructions for the first infusion 
 
If the participant tolerated the prior infusion 
well (defined as an absence of Grade 2 
reactions during a final infusion rate of 
 100 mg/hour), begin the infusion at a rate 
of 100 mg/hour 
 
If no infusion-related reaction occurs, 
increase the infusion rate in 100 mg/hour 
increments every 30 minutes, to a 
maximum of 400 mg/hour 
 
If an infusion reaction develops, stop or 
slow the infusion.  Administer infusion 
reaction medications and supportive care in 
accordance with institutional guidelines.  
If the reaction resolves, resume the infusion 
at a 50% reduction in rate (i.e., 50% of rate 
being used at the time that the reaction 
occurred). 
 

 
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6.1.5 
Gemcitabine 
Gemcitabine will be administered at 1000 mg/m2 IV on Day 1 of each 14-day cycle 
(Cycles 18).  Gemcitabine should be administered before oxaliplatin on the same day.  
Gemcitabine should be administered in accordance with local institutional guidelines and 
prescribing information. 
6.1.6 
Oxaliplatin 
Oxaliplatin will be administered at 100 mg/m2 IV on Day 1 of each 14-day cycle 
(Cycles 18).  Oxaliplatin should be administered after gemcitabine on the same day.  
Oxaliplatin should be administered in accordance with local institutional guidelines and 
prescribing information. 
6.2 
PREPARATION, HANDLING, STORAGE, AND 
ACCOUNTABILITY 
All IMPs required for completion of this study will be provided by the Sponsor.  
Tocilizumab may be obtained locally by the study sites for emergency purposes, if 
permitted by local regulations, and will be prepared and handled according to standard 
practice.  The study site is responsible for maintaining records of IMP delivery to the site, 
IMP inventory at the site, IMP use by each participant, and disposition or return of 
unused IMP, thus enabling reconciliation of all IMP received, and for ensuring that 
participants are provided with doses specified by the protocol. 
The study site should follow all instructions included with each shipment of IMP.  
The study site will acknowledge receipt of IMPs supplied by the Sponsor with use of the 
interactive voice or Web-based response system (IxRS) by returning the appropriate 
documentation form to confirm the shipment condition and content.  Any damaged 
shipments will be replaced.  The investigator or designee must confirm that appropriate 
temperature conditions have been maintained during transit, either by time monitoring 
(shipment arrival date and time) or temperature monitoring, for all IMPs received and 
that any discrepancies have been reported and resolved before use of the IMPs.  
All IMPs must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions, with 
access limited to the investigator and authorized staff. 
Only participants enrolled in the study may receive IMPs, and only authorized staff may 
supply or administer IMPs. 
Investigational medicinal products will either be disposed of at the study site according to 
the study site’s institutional standard operating procedure or be returned to the Sponsor 
with the appropriate documentation.  The site’s method of destroying Sponsor-supplied 
IMPs must be agreed to by the Sponsor.  The site must obtain written authorization from 
the Sponsor before any Sponsor-supplied IMP is destroyed, and IMP destruction must 
be documented on the appropriate form. 

 
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Accurate records of all IMPs received at, dispensed from, returned to, and disposed of 
by the study site should be recorded on the drug accountability log. 
Refer to the pharmacy manual and/or the applicable Investigator’s Brochure or local 
prescribing information for information on IMP preparation, storage, handling, and 
accountability. 
6.3 
TREATMENT ASSIGNMENT 
This is a randomized, open-label study.  After initial written informed consent has been 
obtained, all screening procedures and assessments have been completed, and 
eligibility has been established for a participant, the study site will obtain the participant’s 
identification number and treatment assignment from an IxRS. 
Participants will be randomly assigned to one of two treatment arms:  Arm A or Arm B.  
Randomization will occur in a 2:1 ratio through use of a permuted-block randomization 
method to ensure a balanced assignment to each treatment arm (see Section 4.2.3).  
Randomization will be stratified by the number of prior treatment regimens for 
aggressive lymphoma (1 vs.  2) and the outcome after the last therapy (relapsed vs. 
refractory).  See Section 4.1 for details. 
6.4 
STUDY TREATMENT COMPLIANCE 
When participants are dosed at the site, they will receive study treatment directly from 
the investigator or designee, under medical supervision.  The date and time of each 
dose administered in the clinic will be recorded in the source documents and recorded 
on the electronic Case Report Form (eCRF).  The dose of study treatment and study 
participant identification will be confirmed at the time of dosing by a member of the study 
site staff other than the person administering the study treatment.  Cases of accidental 
overdose, or medication error, along with any associated adverse events, should be 
reported as described in Appendix 3. 
6.5 
DOSE MODIFICATION 
The dose modification of mosunetuzumab, polatuzumab vedotin and oxaliplatin is 
permitted for management of drug-related- toxicities, as described in Appendix 6.  
The dose modification of rituximab, gemcitabine or tocilizumab is not permitted. 
6.6 
CONTINUED ACCESS TO STUDY TREATMENT AFTER THE 
END OF THE STUDY 
Currently, the Sponsor does not have any plans to provide Roche IMPs 
(mosunetuzumab, polatuzumab vedotin, rituximab, and tocilizumab) or any other study 
treatments to participants who have completed the study.  The Sponsor may evaluate 
whether to continue providing mosunetuzumab, polatuzumab vedotin, rituximab, or 
tocilizumab in accordance with the Roche Global Policy on Continued Access to 
Investigational Medicinal Product, available at the following website: 

 
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https://www.roche.com/policy_continued_access_to_investigational_medicines.pdf 
6.7 
TREATMENT OF OVERDOSE 
An overdose is the administration of a drug in a quantity that is higher than the assigned 
dose.  There is no known antidote for treating an overdose of mosunetuzumab or 
polatuzumab vedotin.  Cases of overdose, along with any associated adverse events, 
should be reported as described in Appendix 3. 
In the event of an overdose, the investigator should take the following steps: 
1. 
Contact the Medical Monitor immediately 
2. 
Closely monitor the participant for any adverse event or serious adverse event and 
laboratory abnormalities 
 
Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor on the basis of clinical evaluation of the 
participant. 
6.8 
CONCOMITANT THERAPY 
Information on any medication or vaccine, including over-the-counter or prescription 
medicines, vitamins, and/or herbal supplements, used by a participant in addition to 
protocol−mandated treatment from 7 days prior to initiation of study treatment until 
90 days after the last dose of study treatment or start of new anti-lymphoma therapy, 
whichever is earlier, must be collected.  The information on COVID-19 vaccine, 
prophylaxis, or COVID-19 directed therapy administration should be collected even if it 
was given more than 7 days prior to initiation of study treatment.  After this period, 
concomitant medications should be collected if they were used to manage serious 
adverse events that are believed to be related to prior study treatment.  All such 
medications should be reported to the investigator and recorded on the Concomitant 
Medications eCRF along with the following information: 
 
Reason for use 
 
Dates of administration, including start and end dates 
 
Dosage information, including dose and frequency 
 
The Medical Monitor may be consulted if there are any questions related to concomitant 
or prior therapy. 
6.8.1 
Permitted Therapy 
In general, investigators may manage a participant’s care (including preexisting 
conditions) through use of supportive therapies, as clinically indicated and per local 
standard practice, with the exception of prohibited therapies defined in Section 6.8.3 and 
taking into account cautionary therapies defined in Section 6.8.2.  Participants who 
experience infusion-associated symptoms may be treated symptomatically with 
acetaminophen, ibuprofen, diphenhydramine, and/or H2-receptor antagonists 

 
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(e.g., famotidine, cimetidine), or equivalent medications per local standard practice.  
Serious infusion-associated events manifested by dyspnea, hypotension, wheezing, 
bronchospasm, tachycardia, reduced oxygen saturation, or respiratory distress should 
be managed with supportive therapies as clinically indicated (e.g., supplemental oxygen 
and 2-adrenergic agonists).  See Appendix 6. 
Prophylactic use of hematopoietic growth factors or anti-infectives for viral, fungal, 
bacterial, or Pneumocystis infections are permitted and should be instituted per 
institutional practice or investigator preference based on individual participant risk 
factors.  Participants in countries where prophylactic anti-viral medications for hepatitis B 
reactivation are the standard of care may be treated prophylactically (Taplitz et al. 2018; 
NCCN 2020). 
Premedication with antihistamines, anti-pyretics, and/or analgesics may be administered 
at the discretion of the investigator. 
Administration of antiSARS-CoV-2 prophylaxis, if available, should be considered for all 
participants.  The best timing of administration (i.e., before initiation of study treatment or 
during the study) should be in the investigator’s judgment. 
In the event of new onset of SARS-CoV-2 infection during study treatment, appropriate 
therapy including, but not limited to, antivirals and/or monoclonal antibodies in 
accordance with local institutional guidance) is recommended (El Chaer et al. 2022). 
6.8.1.1 
COVID-19 Vaccines 
COVID-19 vaccines (approved, non-live), including booster vaccines for novel variants, 
are strongly recommended for all participants.  Information on SARS-CoV-2 vaccine 
administration should be collected even if it was given more than 7 days prior to initiation 
of study treatment.   
Factors to consider by investigators when making individualized decisions for 
participants receiving mosunetuzumab: 
 
General condition of the patient and severity/seriousness of underlying disease 
 
Potential risks associated with SARS-CoV-2 infection and potential benefits and 
risks from COVID-19 vaccination 
 
Epidemiology of SARS-CoV-2 infection in the patient’s location 
 
Providers should follow local practice guidelines for the timing of vaccination 
administration prior to initiating therapy to maximize potential therapeutic benefit. 
If COVID-19 vaccines are administered during study treatment, vaccination should be 
administered after completion of mosunetuzumab step-up dosing and at least one week 
after administration of the target mosunetuzumab dose.  For subsequent treatment 
cycles after study treatment target dose has been administered, COVID-19 vaccines can 
be given at least one week before or after mosunetuzumab dosing. 

 
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6.8.2 
Cautionary Therapy 
6.8.2.1 
Medications Given with Precaution due to Effects Related to 
CYP Enzymes and P-glycoprotein Inhibitors 
Mosunetuzumab 
Given the expected pharmacology of mosunetuzumab, the transient release of cytokines 
(most resolved within the first 24 hours of the Cycle 1, Day 1 dose) may suppress 
CYP450 enzymes and cause drug-drug interactions.  Preliminary clinical data indicate 
that mosunetuzumab following IV dosing induced a transient elevation in plasma IL-6, 
with peak levels occurring in the majority of participants within 4−6 hours of the Cycle 1, 
Day 1 dose, and returned to baseline by 24 hours.  Participants who may be of highest 
risk of a drug-drug interaction are those receiving concomitant medications that are 
CYP450 substrates and have a narrow therapeutic index (Appendix 20).  
Such concomitant medications should be monitored for toxicity, and dose adjusted 
accordingly. 
Polatuzumab Vedotin 
In vitro data suggest that unconjugated MMAE is mainly metabolized by CYP3A4 and, to 
a lesser extent, by CYP2D6.  Based on a validated physiological-based PK model 
simulation (Chen et al. 2015), strong CYP3A4 inhibitors may increase the exposure 
(e.g., AUC) of unconjugated MMAE by approximately 50%, while antibody-conjugated 
monomethyl auristatin E (acMMAE) PK is not affected.  MMAE is also a P-glycoprotein 
(P-gp) substrate.  Concomitant medications that are strong CYP3A4 and/or P-gp 
inhibitors (Appendix 20) should be considered cautionary as they may potentially lead to 
adverse reactions, which require close monitoring. 
If a participant is taking any of the medications in the categories of strong 
CYP3A4 inhibitors and inducers and/or P-gp inhibitors, the investigator will assess and 
document the use of these medications known or suspected to fall in those categories. 
A sample list of cautionary medications including CYP3A inhibitors/inducers and 
P-glycoprotein (P-gp) inhibitors can be found in Appendix 20.  The lists of medications 
are not necessarily comprehensive.  The investigator should consult the prescribing 
information when determining whether a concomitant medication can be safely 
administered with study treatment.  In addition, the investigator should contact the 
Medical Monitor if questions arise regarding medications not listed in Appendix 20. 
Tocilizumab 
Cytochrome P450 enzymes in the liver are down-regulated by infection and 
inflammatory stimuli, including cytokines such as IL-6.  Inhibition of IL-6 signaling in 
participants with rheumatoid arthritis who are treated with tocilizumab may restore 
CYP450 activities to higher levels than those participants not treated with tocilizumab, 
leading to increased metabolism of drugs that are CYP450 substrates.  In vitro studies 
showed that tocilizumab has the potential to affect expression of multiple CYP enzymes, 
including CYP1A2, CY2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4.  The effects of 

 
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tocilizumab on CYP2C8 or transporters are unknown.  In vivo studies with omeprazole 
(metabolized by CYP2C19 and CYP3A4) and simvastatin (metabolized by CYP3A4) 
showed up to a 28% and 57% decrease in exposure 1 week following a single dose of 
tocilizumab, respectively. 
The effect of tocilizumab on CYP enzymes may be clinically relevant for 
CYP450 substrates with narrow therapeutic index (see Appendix 20), where the dose is 
individually adjusted: 
 
Upon initiation or discontinuation of tocilizumab in participants being treated with 
these types of medicinal products, therapeutic monitoring of effect (e.g., warfarin) or 
drug concentration (e.g., cyclosporine or theophylline) should be performed and the 
individual dose of the medicinal product adjusted as needed 
 
Prescribers should exercise caution when tocilizumab is coadministered with 
CYP3A4 substrate drugs where a decrease in effectiveness is undesirable 
(e.g., oral contraceptives, lovastatin, atorvastatin) 
 
The effect of tocilizumab on CYP450 enzyme activity may persist for several weeks 
after stopping therapy 
 
6.8.2.2 
Herbal Therapies 
Concomitant use of herbal therapies is not recommended because their 
pharmacokinetics, safety profiles, and potential drug-drug interactions are generally 
unknown.  Herbal therapies intended for the treatment of lymphoma are prohibited. 
6.8.3 
Prohibited Therapy 
 
Concomitant therapy intended for the treatment of cancer (including, but not limited 
to, chemotherapy, hormonal therapy, immunotherapy, radiotherapy, and 
herbal therapy), whether health authority−approved or experimental, is prohibited for 
various time periods prior to starting study treatment, depending on the agent 
(see Section 5.2), and during study treatment, until disease progression is 
documented and the participant has discontinued study treatment 
Adjuvant endocrine therapy for non-metastatic, hormone receptor positive breast 
cancer and anti-androgen therapy for non-metastatic prostate cancer are permitted. 
 
Investigational therapy, whether intended for the treatment of lymphoma or not, is 
prohibited within 7 days prior to initiation of study treatment and during study 
treatment 
 
Systemic immunosuppressive therapy is prohibited (except medications indicated 
per protocol, including corticosteroids and tocilizumab) 
 
Live virus vaccines are prohibited for at least 4 weeks before initiation of or at any 
time during study treatment 
 

 
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7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION OR WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY TREATMENT 
It may be necessary for a participant to permanently discontinue 
(definitive discontinuation) study treatment.  If study treatment is definitively 
discontinued, the participant will remain in the study for additional assessments.  See the 
schedule of activities (see Section 1.3, Table 1 and Table 2) for data to be collected at 
the time of discontinuation of study treatment and for any further follow-up evaluations 
that need to be completed. 
Participants must permanently discontinue study treatment if they experience any of the 
following: 
 
Any medical condition that the investigator or Sponsor determines may jeopardize 
the participant’s safety if he or she continues to receive study treatment 
 
Investigator or Sponsor determination that treatment discontinuation is in the best 
interest of the participant 
 
Pregnancy 
 
Use of an anti-lymphoma therapy not required per protocol 
 
Symptomatic deterioration attributed to disease progression 
 
Confirmed disease progression per investigator assessment according to 
Lugano 2014 criteria 
 
The primary reason for study treatment discontinuation should be documented on the 
appropriate eCRF. 
Participants will return to the clinic for a treatment completion or treatment 
discontinuation visit 30 ( 7) days after the final dose of study drug. 
Participants who discontinue study treatment for reasons other than documented 
disease progression or relapse, start of new anti‑lymphoma therapy, or withdrawal from 
study participation should continue to be followed during post-treatment follow-up, as 
described in schedule of activities (see Section 1.3, Table 1 and Table 2).  Participants 
should continue post-treatment follow-up until disease progression, start of new anti-
lymphoma therapy, withdrawal from study participation, or until the Month 30 tumor 
assessment visit is completed, whichever occurs first.  
During survival follow up, information on survival status and new anti-lymphoma therapy 
will be collected via telephone calls, participant medical records, and/or clinic visits 
approximately every 3 months   1 month until death (unless the participant withdraws 
consent or the Sponsor terminates the study).  All participants may be contacted 
periodically for additional survival and/or new anti-lymphoma therapy (NALT) 
information unless the participant requests to be withdrawn from the study.   If the 

 
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participant withdraws from the study, the site’s staff may use a public information source 
(e.g., county records) to obtain information about survival status only. 
7.2 
PARTICIPANT DISCONTINUATION OR WITHDRAWAL FROM 
THE STUDY 
A participant may withdraw from the study at any time at his or her own request, or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. 
The primary reason for discontinuation from the study should be documented on the 
appropriate eCRF.  If a participant requests to be withdrawn from the study, this request 
must be documented in the source documents and signed by the investigator.  
The participant will be permanently discontinued both from the study treatment and from 
the study at this time. 
If a participant withdraws consent from the study, the Sponsor may retain and continue 
to use any data collected before withdrawal of consent.  Samples collected prior to 
withdrawal may be analyzed, unless the participant specifically requests that the 
samples be destroyed (as documented in the source documents) or local laws require 
destruction of the samples.  However, if samples have been tested prior to withdrawal, 
results from those tests will remain as part of the overall research data. 
If a participant withdraws from the study, the study staff may use a public information 
source (e.g., county records) to obtain information about survival status. 
7.3 
PARTICIPANTS LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
 
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule.  If the participant is unable or unwilling to comply with study 
visits, site personnel should assess reasons the participant is unable or unwilling to 
return to the clinic, and determine if there are ways to support participant 
participation. 
 
Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods).  These contact attempts should be 
documented in the participant’s medical record. 
 
Should the participant continue to be unreachable, he or she will be considered lost 
to follow-up and will be withdrawn from the study 

 
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Discontinuation of specific sites or of the study as a whole are handled as part of 
Appendix 1. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Written informed consent for participation in the study must be obtained before 
performing any study-related procedures (including screening evaluations).  
Informed Consent Forms for enrolled participants and for participants who are not 
subsequently enrolled will be maintained at the study site. 
Study procedures and their timing are summarized in the schedule of activities 
(see Section 1.3, Table 1 and Table 2).  Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study treatment. 
Adherence to the study design requirements, including those specified in the schedule of 
activities, is essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
Procedures conducted as part of the participant’s routine clinical management 
(e.g., blood count) and obtained before signing of the Informed Consent Form may 
be utilized for screening or baseline purposes provided the procedures meet the 
protocol-specified criteria and are performed within the timeframe defined in the 
schedule of activities. 
Medical history and baseline conditions, including clinically significant diseases, 
surgeries and cancer history (including prior cancer therapies and procedures), will be 
recorded at baseline.  Any medication and vaccines (including over-the-counter or 
prescription medicines, vitamins, and/or herbal supplements) used by the participant 
within 7 days prior to initiation of study treatment will be recorded at baseline.  
Demographic data, including age, sex, and self-reported race/ethnicity, will also be 
recorded.  At the time of each follow-up physical examination, an interval medical history 
should be obtained and any changes in medications and allergies should be recorded. 
Participants will be closely monitored for safety throughout the study.  
Participants should be assessed for toxicity prior to each dose; treatment will be 
administered only if the clinical assessment and local laboratory test values are 
acceptable.  Urgent safety concerns should be discussed with the Sponsor immediately 

 
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upon occurrence or awareness to determine if the participant should continue or 
discontinue study treatment. 
8.1 
EFFICACY ASSESSMENTS 
8.1.1 
Tumor and Response Evaluations 
Participants will undergo tumor assessments at screening, every 8 weeks ( 1 week) for 
the first 6 months following treatment initiation, and every 3 months ( 1 month) for the 
first two years on study, then at month 30 (  2 months) after Cycle 1 Day 1, regardless 
of dose delay, until disease progression, start of new anti-lymphoma therapy, or study 
discontinuation, whichever is earlier, per Lugano Criteria 2014 (Cheson et al. 2014; 
Appendix 10).  At the investigator’s discretion, tumor assessments may be repeated at 
any time if PD is suspected. 
All measurable and/or evaluable lesions should be assessed and documented at 
screening.  Tumor assessments performed as standard of care prior to obtaining 
informed consent and within 28 days prior to initiation of study treatment do not have to 
be repeated at screening, so long as they meet criteria outlined below. 
8.1.1.1 
Radiographic Assessments 
Fluorodeoxyglucose (FDG) PET-CT scans, in conjunction with diagnostic-quality 
CT scans, are required at screening, the interim response assessment, and at the 
end-of-treatment (see Table 1 and Table 2 for details).  After the end-of-treatment, 
radiographic assessments should be performed according to the schedule outlined in the 
schedule of activities (Section 1.3, Table 1 and Table 2).  For participants who achieve 
metabolic CR at 24 weeks, a CT scan with or without PET scan will be acceptable for 
subsequent scans.  For participants who do not achieve CR at 24 weeks, continue 
imaging studies with PET and diagnostic-quality CT scans until CR or PD.  Diagnosis of 
disease progression based on clinical examination must be confirmed radiographically 
by imaging (e.g., CT scan, FDG PET-CT scan) or histopathologically by biopsy as soon 
as feasible (within 30 days) and prior to initiation of non–protocol-specified anti-
lymphoma therapy. 
All measurable and/or evaluable disease must be documented at screening and 
re-assessed at each subsequent tumor evaluation.  Response will be assessed by the 
investigator and the IRF on the basis of physical examinations, CT scans, 
FDG PET-CT scans. 
Fluorodeoxyglucose PET-CT scans should extend from skull base to mid-thigh.  
Full-body FDG PET-CT scans should be performed when clinically appropriate. 
Computed tomography scans with contrast (per institutional standard operating 
procedures) should include the chest, abdomen, and pelvis.  

 
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Computed tomography or magnetic resonance imaging (MRI) scans of other disease 
sites should be performed as clinically indicated.  If a CT scan with contrast is 
contraindicated (e.g., in participants with contrast allergy or impaired renal clearance), a 
non-contrast CT scan is permitted if it allows for consistent and precise measurement of 
target lesions during the study.  Magnetic resonance imaging scans may be used 
instead of CT scans in participants for whom they are contraindicated.  The same 
radiographic procedures used to assess disease sites at screening should be used for 
subsequent tumor assessments (e.g., the same contrast protocol for CT scans). 
Radiographic images will be submitted to an IRF for a quality and completeness check, 
for central review, and for temporary storage prior to transferring images to the Sponsor. 
Radiographic images, whether reviewed locally or centrally, must be evaluated by a 
qualified, certified expert. 
8.1.1.2 
Bone Marrow Examinations 
Participants may use screening PET/CT scans to assess bone marrow involvement; 
bone marrow examinations are not required unless clinically indicated 
(Cheson et al. 2014). 
8.1.1.3 
Response Evaluation 
Objective response will be determined by the investigator and the IRF at specified 
timepoints according to the Lugano Response Criteria (Cheson et al. 2014; 
see Appendix 10).  Assessments should be performed by the same individual, if 
possible, to ensure internal consistency across visits. 
Endpoints (e.g., ORR, CRR, PFS, DOR, DOCR), will be calculated programmatically by 
the Sponsor on the basis of investigator and IRF assessments of response at each 
specified timepoint. 
8.2 
SAFETY ASSESSMENTS 
8.2.1 
Physical Examinations 
A complete physical examination will include, at a minimum, assessments of the head, 
eyes, ears, nose, throat and the cardiovascular, dermatologic, musculoskeletal, 
respiratory, gastrointestinal, and neurologic systems.  Any abnormality identified at 
baseline should be recorded on the General Medical History and Baseline Conditions 
eCRF.  As part of the complete physical examination, the presence and degree of 
enlarged lymph nodes, hepatomegaly, and splenomegaly will be recorded on the 
appropriate Tumor Assessment eCRF.  At subsequent visits, record new or worsened 
clinically significant abnormalities on the Adverse Event eCRF. 
A targeted, symptom-directed physical examination should be limited to systems of 
primary relevance (i.e., cardiovascular, respiratory, neurologic, and any system that 
might be associated with tumor assessment [e.g., lymph nodes, liver, and spleen and 

 
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those systems associated with symptoms], or potential drug-related toxicity [e.g., clinical 
assessment for peripheral neuropathy in participants receiving polatuzumab vedotin]).  
Record new or worsened clinically significant abnormalities on the Adverse Event eCRF.   
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
Clinical assessments of peripheral neuropathy should be performed at screening, at 
Day 1 of each cycle, and at the treatment completion visit and recorded on the 
appropriate eCRF.  These may be performed within 48 hours prior to the study visit date. 
Changes from baseline abnormalities should be recorded in participant notes.  New or 
worsened clinically significant abnormalities should be recorded as adverse events on 
the Adverse Event eCRF. 
8.2.2 
Vital Signs 
Vital signs will be measured in a seated position after 5 minutes’ rest and will include 
temperature, systolic and diastolic blood pressure, pulse rate, blood oxygen saturation 
and respiratory rate. 
Record abnormalities observed at baseline on the General Medical History and Baseline 
Conditions eCRF.  At subsequent visits, record new or worsened clinically significant 
abnormalities on the Adverse Event eCRF. 
8.2.3 
Electrocardiograms 
Single 12-lead ECGs will be obtained during screening period (see Section 1.3, Table 1 
and Table 2) with use of an ECG machine to calculate the heart rate and measures 
PR interval, QRS interval, QT interval, and QT interval corrected with use of Fridericia’s 
formula (QTcF)/QT interval. 
All ECG recordings must be performed with use of a standard high-quality, high-fidelity 
digital electrocardiograph machine.  Lead placement should be as consistent as 
possible. 
For safety monitoring purposes, the investigator must review, sign, and date all 
ECG reports.  Paper copies of ECG tracings will be kept as part of the participant’s 
permanent study file at the site.  The following should be recorded on the appropriate 
eCRF:  heart rate, RR interval, QRS interval, PR duration, uncorrected QT interval, and 
QTcF based on machine readings of the individual ECG tracings.  Any morphologic 
waveform changes or other ECG abnormalities must be documented on the eCRF.  
If considered appropriate by the Sponsor, ECGs may be analyzed retrospectively at a 
central laboratory. 

 
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8.2.4 
Clinical Safety Laboratory Assessments 
See Appendix 2 for the list of clinical laboratory tests to be performed and the schedule 
of activities (see Section 1.3, Table 1 and Table 2) for the timing and frequency. 
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the Adverse Event Case Report 
Form (CRF).  The laboratory reports must be filed with the source documents.  
Clinically significant abnormal laboratory findings are those that are not associated with 
the underlying disease, unless judged by the investigator to be more severe than 
expected for the participant’s condition.  A laboratory test result must be reported as an 
adverse event if it meets any of the following criteria: 
 
Is accompanied by clinical symptoms 
 
Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation) 
 
Results in a medical intervention (e.g., potassium supplementation for hypokalemia) 
or a change in concomitant therapy 
 
Is clinically significant in the investigator’s judgment 
Note:  For oncology trials, certain abnormal values may not qualify as adverse 
events. 
 
Medical and scientific judgment should be exercised in deciding whether an isolated 
laboratory abnormality should be classified as an adverse event. 
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 90 days after the last dose of study treatment or until 
start of a new line of anti-lymphoma therapy, whichever is earlier, should be repeated 
until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or Medical Monitor.  If such values do not return to normal 
or baseline within a period of time judged reasonable by the investigator, the etiology 
should be identified and the Sponsor notified. 
All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the laboratory manual and the schedule of activities 
(see Section 1.3, Table 1 and Table 2). 
If laboratory values from non-protocol-specified laboratory assessments performed at 
the institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (e.g., serious adverse event or 
adverse event or dose modification), the results must be recorded on the eCRF. 
Samples collected for safety laboratory tests will be destroyed no later than the time of 
completion of the final Clinical Study Report. 

 
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8.2.5 
Pregnancy Testing 
The schedule for pregnancy testing for enrolled female participants is outlined in 
Section 1.3, Table 1 and Table 2 and will be conducted as outlined in Appendix 2. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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8.3 
ADVERSE EVENTS, SERIOUS ADVERSE EVENTS, AND OTHER 
SAFETY REPORTING 
The definitions of adverse event and serious adverse event can be found in Appendix 3. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant’s legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, 
and recording events that meet the definition of an adverse event or serious adverse 
event and remain responsible for following up adverse events that are serious, are 
considered related to the study treatment or study procedures, or caused the participant 
to discontinue the study treatment (see Section 7). 
8.3.1 
Time Period and Frequency for Collecting Adverse Event and 
Serious Adverse Event Information 
After informed consent has been obtained but prior to initiation of study drug, only 
serious adverse events caused by a protocol-mandated intervention 

 
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(e.g., invasive procedures such as biopsies, discontinuation of medications) should be 
reported.  The paper Clinical Trial Adverse Event/Special Situations Form provided to 
investigators should be completed and submitted to the Sponsor or its designee 
immediately (i.e., no more than 24 hours after learning of the event), either by faxing or 
by scanning and e-mailing the form using the fax number or e-mail address provided to 
investigators.  All other medical occurrences that begin before the start of study 
treatment but after obtaining informed consent will be recorded on the General Medical 
History and Baseline Conditions eCRF, not the Adverse Event eCRF. 
After initiation of study drug, all adverse events will be reported from the start of 
treatment until 90 days after the final dose of study treatment or the initiation of next 
anti‑lymphoma therapy, whichever is earlier, at the timepoints specified in the schedule 
of activities (see Section 1.3, Table 1 and Table 2). 
All serious adverse events will be recorded and reported to the Sponsor or designee 
immediately and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3.  The investigator will submit any updated serious adverse event data to the 
Sponsor within 24 hours of it being available. 
Investigators are not obligated to actively seek adverse event or serious adverse event 
information after conclusion of study participation.  However, if the investigator learns of 
any serious adverse event, including a death, at any time after a participant has been 
discontinued from the study and he or she considers the event to be reasonably related 
to the study treatment or study participation, the investigator must promptly notify the 
Sponsor. 
8.3.2 
Method of Detecting Adverse Events and Serious Adverse 
Events 
The method of recording, evaluating, and assessing causality of adverse events and 
serious adverse events and the procedures for completing and transmitting serious 
adverse event reports are provided in Appendix 3. 
Care will be taken not to introduce bias when detecting adverse events and/or serious 
adverse events.  Open-ended and non-leading verbal questioning of the participant is 
the preferred method to inquire about adverse event occurrences. 
8.3.3 
Follow-Up of Adverse Events and Serious Adverse Events 
After the initial adverse event or serious adverse event report, the investigator is 
required to proactively follow each participant at subsequent visits or contacts.  
All adverse events will be followed until the event has resolved to baseline grade or 
better, the event is assessed as stable by the investigator, the participant is lost to 
follow-up (as defined in Section 7.3), or the participant withdraws consent.  
Further information on follow-up procedures is provided in Appendix 3. 

 
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8.3.4 
Regulatory Reporting Requirements for Serious Adverse 
Events 
Prompt notification by the investigator to the Sponsor of a serious adverse event is 
essential so that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study treatment under clinical investigation are met. 
The Sponsor has a legal responsibility to notify regulatory authorities about the safety of 
a study treatment under clinical investigation.  The Sponsor will comply with regulatory 
requirements for expedited safety reporting to regulatory authority (which includes the 
use of applicable systems, such as EudraVigilance), IRBs or ECs, and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and Sponsor policy and forwarded 
to investigators as necessary. 
To determine reporting requirements for serious adverse event cases, the Sponsor will 
assess the expectedness of these events through use of the reference safety 
information in the documents listed below: 
Drug 
Document 
Mosunetuzumab 
Mosunetuzumab Investigator’s Brochure 
Polatuzumab vedotin 
Polatuzumab vedotin Investigator’s Brochure 
Tocilizumab 
Tocilizumab Investigator’s Brochure 
Rituximab 
Rituximab Investigator’s Brochure 
Gemcitabine 
Gemcitabine U.S. Prescribing Information 
Oxaliplatin 
Oxaliplatin U.S. Prescribing Information 
 
The Sponsor will compare the severity of each event and the cumulative event 
frequency reported for the study with the severity and frequency reported in the 
applicable reference document. 
Reporting requirements will also be based on the investigator’s assessment of causality 
and seriousness, with allowance for upgrading by the Sponsor as needed. 
An investigator who receives an investigator safety report describing a serious adverse 
event or other specific safety information (e.g., summary or listing of serious adverse 
events) from the Sponsor will review and then file it along with the associated study 
drug’s Investigator’s Brochure and will notify the IRB/EC, if appropriate according to local 
requirements. 
8.3.5 
Pregnancy 
Female participants of childbearing potential will be instructed through the 
Informed Consent Form to immediately inform the investigator if they become pregnant 

 
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during the study or within 9 months after the final dose of polatuzumab vedotin, 
3 months after the final dose of mosunetuzumab or tocilizumab, 12 months after the final 
dose of rituximab, 9 months after the final dose of oxaliplatin, and 6 months after the 
final dose of gemcitabine. 
Male participants will be instructed through the Informed Consent Form to immediately 
inform the investigator if a female partner becomes pregnant during the study or within 
6 months after the final dose of polatuzumab vedotin, gemcitabine or oxaliplatin, 
2 months after the final dose of tocilizumab, and 3 months after the final dose of 
rituximab. 
If a pregnancy is reported, the investigator should inform the Sponsor within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 4. 
All pregnancies reported during the study should be followed until pregnancy outcome, 
with follow-up information on the infant collected according to procedures outlined in 
Appendix 4.  The Sponsor or a designee may follow up by telephone, fax, e-mail, and/or 
a monitoring visit to obtain additional case details and outcome information 
(e.g., from hospital discharge summaries, consultant reports, autopsy reports) in order to 
perform an independent medical assessment of the reported case. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered serious adverse events. 
8.3.6 
Death Events 
Information on reporting deaths is provided in Appendix 3. 
8.3.7 
Anticipated Events Not Qualifying for Expedited Reporting 
Events not qualifying for expedited reporting will not be defined for this study. 
8.3.8 
Adverse Events of Special Interest 
Adverse events of special interest are required to be reported by the investigator to the 
Sponsor immediately (i.e., no more than 24 hours after the investigator becomes aware 
of the event; see Section A3–5 for reporting instructions).  Adverse events of special 
interest for this study are as follows: 
 
Cases of potential drug-induced liver injury that include an elevated ALT or AST in 
combination with either an elevated bilirubin or clinical jaundice, as defined by 
Hy’s Law (see Section A3–7.8) 
 
Suspected transmission of an infectious agent by a study treatment, as defined 
below: 
Any organism, virus, or infectious particle (e.g., prion protein transmitting 
transmissible spongiform encephalopathy), pathogenic or non-pathogenic, is 
considered an infectious agent.  A transmission of an infectious agent may be 
suspected from clinical symptoms or laboratory findings that indicate an infection in 

 
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a participant exposed to a medicinal product.  This term applies only when a 
contamination of the study treatment is suspected. 
 
8.3.8.1 
Adverse Events of Special Interest Specific to Mosunetuzumab 
 
Grade  2 CRS 
 
Grade  2 neurologic adverse event 
 
Grade  2 injection-site reaction 
 
Any suspected HLH or macrophage activation syndrome 
 
Grade  3 TLS 
 
Grade  3 febrile neutropenia 
 
Grade  2 AST, ALT, or total bilirubin elevation 
 
Any Grade disseminated intravascular coagulation (minimum Grade 2 by definition) 
 
Grade  2 tumor flare (e.g., manifestation of signs/symptoms associated with an 
increase in size of known nodal or extranodal lesions by clinical or radiographic 
assessment, new onset or worsening of preexisting pleural effusions) 
 
Any grade pneumonitis, interstitial lung disease, acute respiratory distress 
syndrome, pulmonary fibrosis, organizing pneumonia, and/or pulmonary toxicity 
 
8.3.8.2 
Adverse Events of Special Interest Specific to Polatuzumab 
Vedotin 
 
TLS any grade (minimum Grade 3 by definition) 
 
Second malignancies 
 
8.3.9 
Medical Monitors and Emergency Medical Contacts 
Contact Information for All Sites 
Medical Monitor: 
 Ph.D. (Primary) 
Mobile Telephone No.: 
 
Medical Monitor: 
 MD, Ph.D. (Backup) 
Mobile Telephone No.: 
 
Roche Medical Responsible: 
 Ph.D. (Secondary) 
Mobile Telephone No.: 
 
To ensure the safety of study participants, an Emergency Medical Call Center will be 
available 24 hours per day, 7 days per week, in case the above-listed contacts cannot 
be reached.  The Emergency Medical Call Center will connect the investigator with an 
Emergency Medical Contact, provide medical translation service if necessary, and track 
all calls.  Contact information, including toll-free numbers for the Emergency Medical Call 
Center, will be distributed to investigators. 

 
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8.4 
PHARMACOKINETICS 
Serum/plasma samples will be collected for measurement of serum/plasma 
concentrations of mosunetuzumab and polatuzumab vedotin as specified in the 
schedule of activities (see Section 1.3, Table 3 and Table 4).  Predose serum rituximab 
and obinutuzumab PK samples are required to characterize any potential interactions 
between rituximab or obinutuzumab PK and the clinical effects of mosunetuzumab. 
Samples may be collected at additional timepoints during the study if warranted and 
agreed upon between the investigator and the Sponsor.  The timing of sampling may be 
altered during the course of the study on the basis of newly available data to ensure 
appropriate monitoring. 
Instructions for the collection and handling of biological samples will be provided by the 
Sponsor.  The actual date and time (24-hour clock time) of each sample will be 
recorded. 
Samples will be used to evaluate the pharmacokinetics of mosunetuzumab and 
polatuzumab vedotin.  Samples collected for analyses of mosunetuzumab and 
polatuzumab vedotin concentrations may also be used to evaluate safety or efficacy 
aspects related to concerns arising during or after the study. 
Mosunetuzumab concentration data may be pooled with data from other studies using 
population PK model to derive PK parameters, as warranted by the data.  
Potential correlations of relevant PK parameters with safety, efficacy, or biomarker 
outcomes may be explored.  In addition, these data may be used to explore and 
characterize the potential PK interactions between mosunetuzumab and polatuzumab 
vedotin. 
Genetic analyses will not be performed on serum samples unless consent for this was 
included in the Informed Consent Form.  Participant confidentiality will be maintained.  
At visits during which serum samples for the determination of the PK of mosunetuzumab 
and polatuzumab vedotin will be taken, 1 sample of sufficient volume can be used. 
Serum/plasma samples collected for PK analysis may be used for additional PK assay 
development and validation.  Samples will be destroyed no later than 5 years after final 
Clinical Study Report has been completed. 
8.5 
PHARMACODYNAMICS 
See Section 8.7 for information on pharmacodynamic biomarkers. 
8.6 
GENETICS 
See Section 8.11.3 on the RBR for more information on genetic biomarkers. 

 
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8.7 
BIOMARKER ASSESSMENTS 
The following biomarker samples will be collected, as applicable, from participants at all 
sites: 
 
Blood, peripheral blood mononuclear cells (PBMCs), and plasma samples for 
exploratory research on biomarkers 
 
Archival or newly collected tumor tissue sample obtained at baseline for 
determination of CD20 expression, for exploratory research on biomarkers, and for 
biomarker assay development 
 
 
  
 
 
  
 
  
 
 
 
 
 
 
 
Biomarker samples collected at participating sites and biomarker samples 
requiring separate consent are described in Section 8.11. 
 
 
 
 
 
 
 
 
 
 
Screening plasma, blood (if applicable) and tumor tissue samples, including those 
collected from individuals who do not enroll in the study (if permitted by the study 
participant and per institutional or country regulatory guidelines), may be used for future 
research and/or development of disease-related tests or tools. 
Biomarker samples will be collected according to the schedule outlined in Section 1.3 
(see Table 3 and Table 4).  Biomarker samples will be sent to one or several central 

 
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laboratories or to the Sponsor or a designee.  Instructions for the collection and handling 
of biomarker samples, including sampling procedures, storage conditions, and shipment 
instructions, are provided in the laboratory manual. 
Unless the participant gives specific consent for his or her leftover samples to be stored 
for optional exploratory research (see Section 8.11) biomarker samples will be destroyed 
no later than 5 years after the final Clinical Study Report has been completed, with the 
following exceptions: 
 
 
 However, the storage period will be in 
accordance with the IRB/EC−approved Informed Consent Form and applicable laws 
(e.g., health authority requirements). 
 
For enrolled participants, remaining archival tissue blocks will be returned to the site 
upon request or no later than the date of final closure of the clinical database, 
whichever occurs first.  For individuals who are not enrolled, remaining archival 
tissue blocks will be returned to the site no later than 6 weeks after eligibility 
determination. 
 
Given the complexity and exploratory nature of exploratory biomarker analyses, data 
derived from these analyses will generally not be provided to study investigators or 
participants unless required by law.  The aggregate results of any conducted research 
will be available in accordance with the effective Sponsor policy on study data 
publication. 
8.8 
IMMUNOGENICITY ASSESSMENTS 
Antibodies to mosunetuzumab and polatuzumab vedotin will be evaluated in serum 
samples collected from all participants according to the schedule of assessments 
(see Section 1.3, Table 3 and Table 4).  Additionally, serum samples should also be 
collected at the final visit from participants who discontinued study treatment or were 
withdrawn from the study.  These samples will be tested by the Sponsor or Sponsor’s 
designee. 
Serum samples will be screened for antibodies binding to mosunetuzumab and 
polatuzumab vedotin and the titer of confirmed positive samples will be reported.  
Other analyses may be performed to verify the stability of antibodies to mosunetuzumab 
and polatuzumab vedotin and/or further characterize the immunogenicity of 
mosunetuzumab and polatuzumab vedotin. 
The detection and characterization of antibodies to mosunetuzumab and 
polatuzumab vedotin will be performed through use of validated assay methods by or 
under the supervision of the Sponsor.  All samples collected for detection of antibodies 
to study treatment will also be evaluated for mosunetuzumab and polatuzumab vedotin 
serum concentration to enable interpretation of the antibody data.  Antibodies may be 
further characterized and/or evaluated for their ability to neutralize the activity of the 

 
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study treatment.  Serum samples collected for immunogenicity analysis may be stored 
for a maximum of 5 years (or according to local regulations) after Clinical Study Report 
has been completed to enable further characterization of immunogenicity as well as 
development and validation of immunogenicity assay. 
8.9 
HEALTH ECONOMICS AND MEDICAL RESOURCE 
UTILIZATION 
Health utility data from the 
 will be evaluated in pharmacoeconomic models.  
Results from health economic data analyses will be reported separately from the 
Clinical Study Report. 
8.10 
CLINICAL OUTCOME ASSESSMENTS 
Participant-reported outcome (PRO) instruments will be completed to assess the 
treatment benefit of M  P compared with R-GemOx.  In addition, PRO instruments will 
enable the capture of each participant’s direct experience with M  P. 
Participant-reported outcomes data will be collected through use of the following 
instruments: 
 
The European Organisation for Research and Treatment of Cancer (EORTC) 
Quality of Life-Core 30 (QLQ-C30) 
 
Functional Assessment of Cancer TherapyLymphoma subscale (FACT-LymS) 
 
Functional Assessment of Cancer Therapy−Gynecologic Oncology 
Group−Neurotoxicity (FACT/GOG-Ntx) 
 
 
 
8.10.1 
Data Collection Methods for Clinical Outcome Assessments 
Participant-reported outcomes instruments will be self-administered at the clinic at 
specified timepoints during the study (see schedule of activities in Section 1.3, Table 1 
and Table 2).  In the event participants are not able to come to the clinic for their 
scheduled assessment during post treatment follow up or long term survival follow up 
period., sites can call participants, and, using phone scripts, read questions verbatim to 
participants while capturing their responses on the paper questionnaire the participants 
would have completed upon coming to the clinic.  Source documentation sufficient to 
pass an audit should be obtained, which includes information that the questionnaires 
were administered via phone.  At the clinic, instruments will be administered before the 
participant receives any information on disease status, prior to the performance of non-
PRO assessments (with the only exception of laboratory blood collection which needs to 
be performed prior to PRO questionnaire completion due to logistic reasons), and prior 
to the administration of study treatment, unless otherwise specified. 
Participant-reported outcomes instruments, translated into the local language as 
appropriate, will be provided by the Sponsor in pre-printed booklets to enable the 

 
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appropriate instruments to be administered in the correct order at each specified 
timepoint.  The booklets will be labeled with the timepoint of administration. 
During clinic visits, PRO instruments should be administered as outlined below: 
 
Participants’ health status should not be discussed prior to administration of the 
instruments 
 
Sites must administer the official version of each instrument, as provided by the 
Sponsor.  Instruments must not be copied from the protocol. 
 
Sites should allow sufficient time for participants to complete the instruments, 
estimated to be 18 minutes at each specified visit 
 
Sites should administer the instruments in a quiet area with minimal distractions and 
disruptions 
 
Participants should be instructed to answer questions to the best of their ability; 
there are no right or wrong answers 
 
Site staff should not interpret or explain questions, but may read questions verbatim 
upon request 
 
Participants should not obtain advice or help from others (e.g., family members or 
friends) when completing the instruments 
 
Site staff should review all completed instruments and should ask the participants to 
rectify any response that is not clearly marked in the appropriate location.  If a response 
is missing, site staff should ask the participants to complete the item or confirm that the 
item was intentionally left blank. 
8.10.2 
Description of Clinical Outcome Assessment Instruments 
8.10.2.1 
EORTC QLQ-C30 
The EORTC QLQ-C30 is a validated, reliable self-report measure (Aaronson et al. 1993; 
Fitzsimmons et al. 1999; see Appendix 8).  It consists of 30 questions that assess 
5 aspects of participant functioning (physical, emotional, role, cognitive, and social), 
3 symptom scales (fatigue, nausea and vomiting, and pain), global health status and 
quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, 
diarrhea, and financial difficulties) with a recall period of the previous week.  
Scale scores can be obtained for the multi-item scales.  The functioning and symptoms 
items are scored on a 4-point scale that ranges from “not at all” to “very much,” and the 
global health status and QoL items are scored on a 7-point scale that ranges from 
“very poor” to “excellent.”  The EORTC QLQ-C30 takes approximately 10 minutes to 
complete. 
 
 

 
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8.10.2.3 
FACT-Lym and LymS Subscale 
The FACT-Lym is a validated, reliable self-report measure of health-related quality of life 
(HRQoL) aspects relevant to patients with lymphoma (Hlubocky et al. 2013).  The full 
measure consists of the FACT-G physical, social/family, emotional, and functional 
well-being scales (27 items), as well as a lymphoma-specific symptoms scale (15 items).  
For this study, only the items that comprise the lymphoma-specific symptoms (LymS) 
scale (FACT-LymS) will be administered to participants (see Appendix 13).  Each item is 
rated on a 5-point response scale that ranges from “not at all” to “very much,” with higher 
scores indicative of better HRQoL. 
8.10.2.4 
FACT/GOG-Ntx 
The FACT/GOG-Ntx is a validated self-report measure for assessing platinum/paclitaxel-
induced peripheral neuropathy (Huang et al. 2007).  This measure is used to assess 
polatuzumab vedotin−induced neuropathy, as symptoms of chemotherapy-induced 
neuropathy caused by microtubule inhibitors do overlap with those seen in 
platinum/paclitaxel−containing regimens.  The full measure consists of the FACT-G 
physical, social/family, emotional, and functional well-being scales (27 items), as well as 
a peripheral neuropathy symptoms scale (11 items).  For this study, only the items that 
comprise the peripheral neuropathy scale will be administered to participants 
(see Appendix 14).  The scale contains 4 subscales that assess sensory neuropathy 
(4 items), hearing neuropathy (2 items), motor neuropathy (3 items), and dysfunction 
associated with neuropathy (2 items), which can be summed to create a total score.  
Each item is rated on a 5-point response scale that ranges from “not at all” to 
“very much,” with higher scores indicative of more extreme neuropathy. 
8.11 
ADDITIONAL ASSESSMENTS AND PROCEDURES 
REQUIRING SEPARATE CONSENT OR PERFORMED 
ONLY AT PARTICIPATING SITES 
8.11.1 
Blood Samples for Whole-Genome Sequencing or 
Whole-Exome Sequencing (Participants at Participating Sites) 
At participating sites, blood samples will be collected for DNA extraction to enable WGS 
or WES to identify variants that are predictive of response to study treatment, are 
associated with progression to a more severe disease state, are associated with 
acquired resistance to study treatment, are associated with susceptibility to developing 
adverse events, can lead to improved adverse event monitoring or investigation, or can 
increase the knowledge and understanding of disease biology and drug safety. 

 
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DNA extracted from blood may be compared with DNA extracted from tissue to identify 
somatic variants by distinguishing germline variants from somatic variants. 
The samples may be sent to one or more laboratories for analysis. 
Collection and submission of blood samples for WGS or WES is contingent upon the 
review and approval of the exploratory research by each site’s IRB/EC and, if applicable, 
an appropriate regulatory body.  If a site has not been granted approval for WGS or 
WES, this section of the protocol (Section 8.11.1) will not be applicable at that site. 
Genomics is increasingly informing researcher’s understanding of disease pathobiology.  
Whole-genome sequencing and WES provide a comprehensive characterization of the 
genome and exome, respectively, and, along with clinical data collected in this study, 
may increase the opportunity for developing new therapeutic approaches or new 
methods for monitoring efficacy and safety or predicting which participants are more 
likely to respond to a drug or develop adverse events.  Data will be analyzed in the 
context of this study but may also be explored in aggregate with data from other studies.  
The availability of a larger dataset will assist in identification and characterization of 
important biomarkers and pathways to support future drug development. 
For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual. 
Blood samples collected for WGS or WES are to be stored until they are no longer 
needed or until they are exhausted.  However, the storage period will be in accordance 
with the IRB/EC−approved Informed Consent Form and applicable laws 
(e.g., health authority requirements). 
See Section 8.7 for information on availability of data from biomarker analyses. 
8.11.2 
Optional Tumor Biopsies (Participants Providing Separate 
Consent) 
Consenting participants will undergo optional tumor biopsies after study treatment 
initiation and may undergo additional biopsies during the study at any other time at the 
investigator’s discretion (if deemed clinically feasible by the investigator).  
Samples collected via resection, core--needle biopsy (at least three cores preferred), or 
excisional, incisional, punch, or forceps biopsy are preferred. 
The Informed Consent Form will contain a separate section that addresses optional 
biopsies.  The investigator or authorized designee will explain to each participant the 
objectives, methods, and potential hazards of undergoing optional biopsies.  
Participants will be told that they are free to choose not to undergo optional biopsies and 
may withdraw their consent at any time and for any reason.  A separate, specific 
signature will be required to document a participant’s agreement to undergo optional 

 
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biopsies.  Participants who choose not to undergo optional biopsies will not provide a 
separate signature.  The investigator should document whether or not the participant has 
given consent to undergo optional biopsies and (if applicable) the date of consent, by 
completing the Sample Informed Consent/Withdrawal eCRF. 
Samples may be used for exploratory biomarker research as described in Section 8.7.  
For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual.  See Section 8.7 for information on duration of sample storage and 
availability of data from biomarker analyses. 
8.11.3 
Samples for Research Biosample Repository 
(Participants Providing Separate Consent at Participating 
Sites) 
8.11.3.1 
Overview of the Research Biosample Repository 
The RBR is a centrally administered group of facilities used for the long-term storage of 
human biological specimens, including body fluids, solid tissues, and derivatives thereof 
(e.g., DNA, RNA, proteins, peptides).  The collection, storage, and analysis of 
RBR samples will facilitate the rational design of new pharmaceutical agents and the 
development of diagnostic tests, which may allow for individualized drug therapy for 
patients in the future. 
Samples for the RBR will be collected from participants who give specific consent to 
participate in this optional research.  Research Biosample Repository samples will be 
analyzed to achieve one or more of the following objectives: 
 
To study the association of biomarkers with efficacy or disease progression 
 
To identify safety biomarkers that are associated with susceptibility to developing 
adverse events or can lead to improved adverse event monitoring or investigation 
 
To increase knowledge and understanding of disease biology and drug safety 
 
To study drug response, including drug effects and the processes of drug absorption 
and disposition 
 
To develop biomarker or diagnostic assays and establish the performance 
characteristics of these assays 
 
8.11.3.2 
Approval by the Institutional Review Board or 
Ethics Committee 
Collection, storage, and analysis of RBR samples is contingent upon the review and 
approval of the exploratory research and the RBR portion of the Informed Consent Form 
by each site’s IRB/EC and, if applicable, an appropriate regulatory body.  If a site has not 
been granted approval for RBR sampling, this section of the protocol (Section 8.11.3) 
will not be applicable at that site. 

 
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8.11.3.3 
Sample Collection 
The following samples will be stored in the RBR and used for research purposes, 
including, but not limited to, research on biomarkers related to M  P, diseases, or drug 
safety: 
 
Blood samples collected at baseline 
 
Tumor tissue samples collected at screening 
 
Tumor tissue samples collected at timepoints defined in Section 1.3 (Table 1 and 
Table 2) 
 
Tumor tissue samples from biopsies performed at the investigator’s discretion 
during the study 
 
Leftover blood, serum, plasma, PBMC, and tumor tissue samples (with the 
exception of remaining archival tissue blocks, which will be returned to sites) and 
any derivatives thereof (e.g., DNA, RNA, proteins, peptides) 
 
The above samples may be sent to one or more laboratories for analysis of germline or 
somatic variants via WGS, WES, or other genomic analysis methods.  Genomics is 
increasingly informing researcher’s understanding of disease pathobiology.  
Whole-genome sequencing and WES provide a comprehensive characterization of the 
genome and exome, respectively, and, along with clinical data collected in this study, 
may increase the opportunity for developing new therapeutic approaches or new 
methods for monitoring efficacy and safety or predicting which participants are more 
likely to respond to a drug or develop adverse events. 
Data generated from RBR samples will be analyzed in the context of this study but may 
also be explored in aggregate with data from other studies.  The availability of a larger 
dataset will assist in identification and characterization of important biomarkers and 
pathways to support future drug development. 
For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual. 
Research Biosample Repository samples are to be stored until they are no longer 
needed or until they are exhausted.  However, the RBR storage period will be in 
accordance with the IRB/EC−approved Informed Consent Form and applicable laws 
(e.g., health authority requirements). 
8.11.4 
Confidentiality 
Research Biosample Repository samples and associated data will be labeled with a 
unique participant identification number. 
Participant medical information associated with RBR samples is confidential and may be 
disclosed to third parties only as permitted by the Informed Consent Form (or separate 

 
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authorization for use and disclosure of personal health information) signed by the 
participant, unless permitted or required by law. 
Given the complexity and exploratory nature of the analyses of RBR samples, data 
derived from these analyses will generally not be provided to study investigators or 
participants unless required by law.  The aggregate results of any conducted research 
will be available in accordance with the effective Sponsor policy on study data 
publication. 
Data generated from RBR samples must be available for inspection upon request by 
representatives of national and local health authorities, and Sponsor monitors, 
representatives, and collaborators, as appropriate. 
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of the RBR data will become and remain the exclusive and unburdened property 
of the Sponsor, except where agreed otherwise. 
8.11.5 
Consent to Participate in the Research Biosample Repository 
The Informed Consent Form will contain a separate section that addresses participation 
in the RBR.  The investigator or authorized designee will explain to each participant the 
objectives, methods, and potential hazards of participation in the RBR.  Participants will 
be told that they are free to choose not to provide optional RBR samples and may 
withdraw their consent at any time and for any reason during the storage period.  
A separate, specific signature will be required to document a participant’s agreement to 
provide optional RBR samples.  Participants who choose not to provide optional 
RBR samples will not provide a separate signature.  The investigator should document 
whether or not the participant has given consent to provide optional RBR samples and 
(if applicable) the date(s) of consent, by completing the Sample Informed 
Consent/Withdrawal eCRF. 
In the event of an RBR participant’s death or loss of competence, the participant’s 
samples and data will continue to be used as part of the RBR research. 
8.11.6 
Withdrawal from the Research Biosample Repository 
Participants who give consent to provide RBR samples have the right to withdraw their 
consent at any time for any reason.  After withdrawal of consent, any remaining samples 
will be destroyed.  However, if RBR samples have been tested prior to withdrawal of 
consent, results from those tests will remain as part of the overall research data.  If a 
participant wishes to withdraw consent to the testing of his or her RBR samples during 
the study, the investigator must inform the Medical Monitor in writing of the participant’s 
decision through use of the appropriate RBR Subject Withdrawal Form and must enter 
the date of withdrawal on the Sample Informed Consent/Withdrawal eCRF.  If a 
participant wishes to withdraw consent to the testing of his or her RBR samples after 
closure of the site, the investigator must inform the Sponsor by e-mailing the study 
number and participant number to the following e-mail address: 

 
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110/Protocol GO43643, Version 5  
global.rcr-withdrawal@roche.com 
 
A participant’s withdrawal from this study does not, by itself, constitute withdrawal of 
consent for testing of RBR samples.  Likewise, a participant’s withdrawal of consent for 
testing of RBR samples does not constitute withdrawal from this study. 
8.11.7 
Monitoring and Oversight 
Research Biosample Repository samples will be tracked in a manner consistent with 
Good Clinical Practice by a quality-controlled, auditable, and appropriately validated 
laboratory information management system, to ensure compliance with data 
confidentiality as well as adherence to authorized use of samples as specified in this 
protocol and in the Informed Consent Form.  Sponsor monitors and auditors will have 
direct access to appropriate parts of records relating to an individual’s participation in the 
RBR for the purposes of verifying the data provided to the Sponsor.  The site will permit 
monitoring, audits, IRB/EC review, and health authority inspections by providing direct 
access to source data and documents related to the RBR samples. 
9. 
STATISTICAL CONSIDERATIONS 
9.1 
STATISTICAL HYPOTHESES 
Analysis for ORR by IRF, one of the dual primary endpoints, will be conducted for the 
first 
 randomized participants (interim analysis population [IAP]) to test the following 
hypothesis (Section 9.2.2): 
Analysis for PFS by IRF, one of the dual primary endpoints, will test the equality of PFS 
distribution in M  P versus R-GemOx in the intent-to-treat (ITT) population: 
 
Details of the hierarchical testing for the dual primary endpoints and key secondary 
endpoint will be provided in Section 9.2.1 and in the Statistical Analysis Plan. 
9.2 
SAMPLE SIZE DETERMINATION 
Assuming a median PFS of  months in the R-GemOx arm based on the largest 
multisite Phase II study of R-GemOx, other similar references and a real-world data 
analysis (Mounier et al. 2013; Cazelles et al. 2019; Schade et al. 2019), and a 
randomization ratio of 2:1 (see Section 4.2.3), 
 events are required to detect a 
between-group difference of 
 months in median PFS (hazard ratio  
) assuming 
an exponential distribution of PFS, with use of a log-rank test with 
% power and a 
-sided  of 
.  At the interim efficacy analysis for Study GO40516 (CCOD of 
15 March 2021), a median PFS of 
 months (95% CI: 3.5, NE) was observed in 
60 patients with R/R DLBCL receiving M  P.  Although immature, these results are 
consistent with the assumed median PFS of 
 months for M  P. 

 
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Assuming a median OS of 
 months in the R-GemOx arm (Mounier et al. 2013; 
Cazelles et al. 2019; Schade et al. 2019), and considering an interim OS efficacy 
analysis at the time of the primary PFS analysis, a between-group difference of 
 
months in median OS (hazard ratio  
) assuming an exponential distribution of OS 
would be detected with use of a log-rank test with 
% power and a -sided  of 
 
(Section 9.2.4). 
A total of approximately 222 participants will be randomized in this study.   
The actual numbers of events for PFS and OS, and the analysis timings as described 
above have changed due to an extended enrollment timeline (See Sections 9.2.3 and 
9.2.4 for updated projections).  SUNMO completed enrollment except for the US and 
China, leading to extended follow up of patients enrolled outside the US and China.  
Initially the primary PFS analysis was powered at 
%, and the final OS analysis was 
powered at 
%.  The extended enrollment timeline has increased the power for the 
primary analysis, as PFS events continue to accumulate beyond the target number of 
events throughout trial enrollment.  Therefore, the study has adequate power to 
reclassify objective response rate as a dual primary endpoint along with PFS, and 
therefore, add an earlier interim analysis based on objective response rate to detect 
clinically meaningful improvement based on this intermediate efficacy endpoint 
(Sections 9.2.1 and 9.2.2). 
9.2.1 
Type I Error Control 
The overall type I error rate for this study is strictly controlled at % (
-sided) using the 
Fallback Method (see Section IV C in FDA Guidance on Multiple Endpoints in Clinical 
Trials 2017).  
The ORR analysis will occur when the first 
 randomized participants have a minimum 
of  months of follow-up from the first response assessment.  ORR will be tested at the 
% 
-sided  level. 
The first PFS by IRF analysis will be performed by the iDCC for iDMC review to assess 
futility, at the time of the dual primary endpoint ORR analysis, on the first 
 
randomized participants.  The PFS futility boundary is set at PFS HR greater than  for 
mosunetuzumab and polatuzumab in comparison with R-GemOx.  The second PFS 
analysis will be tested once at the planned primary PFS analysis 
months after the 
last patient in (LPI), which is expected approximately 
 months after first patient in 
(FPI).  If the ORR analysis is positive, the PFS analysis will use a % 
-sided  level.  
If the ORR analysis is negative, the PFS analysis will use a 
% 
-sided  level. 
Depending on the number of events, there will be 
 analyses for the key 
secondary endpoint of OS based on hierarchical testing order to ensure the final OS 
analysis was powered at 
% (Figure 7).  The first and second OS analyses will be 
performed by the independent data coordinating center (iDCC) for iDMC review to 

 
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9.2.2 
Dual Primary Endpoint:  Objective Response Rate in Interim 
Analysis Population (IAP) 
The ORR analysis will be conducted after the first 
randomized participants (i.e. IAP) 
have a minimum of  months of follow-up from the first response assessment by IRF. 
Assuming the ORR is 
% in R-GemOx versus 
% in M + P, this analysis has 
approximately 
% power to detect a difference in ORR at 
% 
-sided α level.  The 
following hypothesis will be tested at the 
% 
-sided α level for the first 
 R/R 
LBCL participants: 
 
It is projected that an observed ORR of 
% or better will result in a statistically 
significant difference between treatment arms.  That is, a ORR of 
% will be the 
minimal detectable difference for the analysis.  
9.2.3 
Dual Primary Endpoint:  Progression-Free Survival in ITT 
The first PFS by IRF analysis will be performed by the iDCC for iDMC review to assess 
futility, at the time of the dual primary endpoint ORR analysis, on the first 
 
randomized participants.  The PFS futility boundary is set at PFS HR greater than  for 
mosunetuzumab and polatuzumab in comparison with R-GemOx. 
The primary PFS analysis will be conducted  months after LPI on the ITT population 
when approximately 
 events are observed.  This analysis will have 
% power at % 
 sided α level if ORR analysis in IAP (Section 9.2.2) is positive or 
% power at 
% 
-sided α level if ORR analysis is negative to detect a hazard ratio of 
 in M + P in 
comparison with R-GemOx (Figure 7). 
The following assumptions are made for PFS: 
 
PFS curve follows an exponential distribution. 
 
Median PFS of  months in R-GemOX arm and 
 months in M +P arm 
(corresponding to a target HR of 
). 
 
The drop out rate is % over a 
-month period. 
 
An observed HR of 
 or better for PFS will result in a statistically significant 
difference between treatment arms if ORR is positive.  An observed HR of 
 will be 
the minimal detectable difference for the analysis.  Alternatively, an observed HR of 
 
or better for PFS will result in a statistically significant difference between treatment arms 
if ORR is negative.  
The timing of the primary PFS analysis is no longer event-driven because of the 
extended enrollment timeline.  An event driven primary PFS analysis would likely result 
in sufficient events prior to LPI on study.  Instead, the primary PFS analysis is conducted 
months after LPI (i.e., 
 months from FPI) to allow all patients to complete treatment. 

 
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9.2.4 
Key Secondary Endpoint:  Overall Survival in ITT 
Depending on the number of events, there will be three or four analyses for the key 
secondary endpoint of OS based on hierarchical testing order to ensure the final OS 
analysis is powered at 
% (Figure 7).  The first and second OS analyses will be 
performed by the independent data coordinating center (iDCC) for iDMC review to 
assess futility.  The first OS analysis will be performed when approximately 
 OS 
events are observed. The second OS analysis will be performed at the time of the dual 
primary endpoint ORR analysis.  For the first and second OS analyses, OS effect is 
considered detrimental if OS HR is greater than 
 for mosunetuzumab and 
polatuzumab vedotin compared to R-GemOx.   
The third OS analysis will be conducted at the time of the primary PFS analysis to 
assess safety and efficacy.  OS effect is considered detrimental if the observed OS HR 
is greater than .  OS will be formally tested for efficacy only if PFS is positive.    
If ORR analysis in IAP (Section 9.2.2) is positive and PFS is positive, the third OS 
analysis will be conducted at the time of the primary PFS analysis when approximately 
 OS events are observed.  This may be the only one OS analysis needed for 
efficacy, as power is approximately 
%, at 
-sided α of %, to detect a hazard ratio 
of 
 in M + P in comparison with R-GemOx.  
If ORR is negative and PFS is positive, a third OS analysis will be conducted at the time 
of the PFS analysis when approximately 
 OS events are observed, with 
% power 
and a 
-sided local α of 
%.  If the third OS analysis is negative, a fourth OS 
analysis will be conducted approximately 
 months after LPI when approximately 
 
events are observed, with 
% power and a 
-sided local α of 
%, to detect a 
hazard ratio of 
 in M + P in comparison with R-GemOx.  
In general, depending on the number of events, if the power for the third OS analysis is 
at least 
% at the same α level as PFS (either at α = 
), the third OS 
analysis is considered final.  If the power for the third OS analysis is less than 
%, a 
group sequential test will be used, and a fourth OS analysis may be needed.  The fourth 
OS analysis will be conducted when there are sufficient OS events to achieve a power of 
%.  The actual  levels for OS analyses depend on the spending function boundaries 
and actual number of OS events.    
The following assumptions are made for OS: 
 
OS curve follows an exponential distribution 
 
Median OS of 
 months in the R-GemOx arm and 
months in the M  P arm 
(corresponding to a target HR of 
) 
 
The drop-out rate is % over a 
-month period 
 

 
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An observed HR of 
 or better for OS will result in a statistically significant difference 
between the treatment arms if ORR is positive and PFS is positive.  Alternatively, an 
observed HR of 
 at interim OS analysis and 
 at final OS analysis will result in a 
statistically significant difference between treatment arms if ORR is negative and PFS is 
positive.  

 
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Table 13 Analysis Timing and Stopping Boundaries for Overall Survival 

 
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9.3 
ANALYSIS SETS 
The following populations are defined: 
Participant Analysis Set 
Description 
Enrolled 
All participants who sign the Informed Consent Form 
IAP 
The first 
 randomized participants 
ITT 
All randomized participants 
Evaluable 
Safety-evaluable 
All participants randomly assigned to study treatment and who 
take at least 1 dose of study treatment, with participants grouped 
according to the treatment regimen actually received 
PK-evaluable 
The PK population for analysis will include all participants who 
have at least received 1 dose of mosunetuzumab and have at 
least 1 evaluable PK sample postdose for at least 1 analyte 
Immunogenicity-evaluable 
All participants who have at least 1 predose or 1 post-dose 
ADA assessment 
PRO-evaluable 
All randomized participants who have a baseline and at least 
1 post-baseline assessment.  The PRO-evaluable population will 
be used for descriptive analyses of visit summary and change 
from baseline analyses.  All randomized participants (ITT) will be 
used for completion analyses and time to deterioration analyses. 
ADA  anti-drug antibody; IAP = interim analysis population; ITT  intent-to-treat; 
PK  pharmacokinetic; PRO  participant-reported outcomes. 
 
9.4 
STATISTICAL ANALYSES 
The Statistical Analysis Plan will be finalized prior to database lock, and it will include a 
more technical and detailed description of the statistical analyses described in this 
section.  This section is a summary of the planned statistical analyses of the most 
important endpoints, including primary and key secondary endpoints. 
9.4.1 
General Considerations 
The analysis population for the primary and secondary efficacy analyses will consist of 
all randomized participants, with participants grouped according to the treatment 
assigned at randomization.  The safety analysis population will consist of all randomized 
participants who received at least 1 dose of study treatment, with participants grouped 
according to the treatment received. 
Hypothesis tests will be -sided, unless otherwise indicated.  The overall type I error () 
for this study will be controlled at

 
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9.4.2 
Dual Primary Endpoints 
9.4.2.1 
ORR by IRF 
The dual primary endpoint of ORR is defined as the proportion of participants in whom 
an objective response (CR or PR) was observed at any time during the study as 
determined by the IRF, according to Lugano 2014 Response Criteria. 
The ORR analysis will be conducted after the first 
 randomized participants (i.e., IAP) 
have a minimum of  months of follow-up from the first response assessment by the IRF. 
ORR by IRF will be evaluated once more at the time of primary PFS analysis.  However, 
at the time of primary PFS analysis, ORR will be a supportive secondary endpoint that 
will not be included in the overall Type I error control strategy. 
Assuming the ORR is 
% in R-GemOx versus 
% in M  P, this analysis has 
approximately 
% power to detect a difference in ORR at 
% 
-sided α level.  The 
following hypothesis will be tested at the 
% 
-sided α level for the first 
 R/R 
LBCL participants: 
 
It is projected that an observed ΔORR of 
% or better will result in a statistically 
significant difference between treatment arms.  That is, a ΔORR of 
% will be the 
minimal detectable difference (MDD) for the analysis. 
ORR will be compared between treatment arms using the Cochran-Mantel-Haenszel test 
stratified by the IxRS-recorded stratification factors.  Responses after initiation of NALT 
will not be included in the analysis of ORR. 
9.4.2.1.1 
Target of Estimation for the Dual Primary Efficacy Endpoint of 
ORR by IRF 
To provide clarity on the target of estimation, the 5 attributes in the estimand framework 
are defined below: 
Population:   
 
At the time of dual primary ORR analysis, the first 
 randomized participants (IAP 
population), analyzed by randomized treatment group.   
 
At the time of dual primary PFS analysis, all randomized participants (ITT 
population), analyzed by randomized treatment group.   
 
Variable:  ORR by IRF 
Treatment:  Participants will be randomized into either Arm A (M  P) or Arm B 
(R-GemOx).  During the conduct of the study participants may also receive concomitant 
medications as detailed in Section 6.8 of the Protocol. 

 
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Intercurrent event and handling strategies:  
 
 
 
 
 
Population-level summary for the variable:  Difference in proportion for ORR. 
9.4.2.2 
PFS by IRF 
The dual primary endpoint of PFS is defined as the time from randomization to the first 
occurrence of disease progression, as determined by the IRF with use of the 
Lugano 2014 Response criteria, or death from any cause, whichever occurs first.  
For participants who have neither progressed nor died as of the CCOD for analysis, 
PFS will be censored on the date of last disease assessment when the participant is 
known to be progression-free.  For participants who do not have any evaluable 
post-baseline tumor assessments, PFS will be censored on the date of randomization.  
Additional censoring rules for participants who initiated new anti-lymphoma therapy or 
participants with two or more consecutive missed assessments are detailed in 
Section 9.4.2.2.1. 
The primary endpoint of the study will test the equality of PFS distribution in M  P 
compared with R-GemOx: 
 
Treatment comparisons will be made with use of a stratified log-rank test with a -sided 
 level if ORR analysis in IAP (Section 9.2.2) is positive or 
 level if ORR 
analysis is negative.  The randomization stratification factors to be used in the efficacy 
analyses are the number of previous lines of systemic therapy for DLBCL
and 
the outcome after the last systemic therapy (relapsed vs. refractory). 
The Kaplan-Meier method will be used to estimate the median PFS, if reached, and 
PFS distribution for each treatment arm.  The Brookmeyer-Crowley methodology 
(Brookmeyer and Crowley 1982) will be used to construct the 
% CI for the median 
PFS for each treatment arm.  Stratified Cox proportional-hazards models will be used to 
estimate the hazard ratio and its 
% CI. 

 
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Further details will be provided in the Statistical Analysis Plan. 
9.4.2.2.1 
Target of Estimation for the Dual Primary Efficacy Endpoint of 
PFS by IRF 
To provide clarity on the target of estimation, the 5 attributes in the estimand framework 
are defined below: 
Population:  Defined as all randomized participants, analyzed by randomized treatment 
group.  Inclusion and exclusion criteria have been described in detail in Sections 5.1 and 
5.2. 
Variable:  Progression-free survival, defined as time from randomization to the first 
occurrence of disease progression, as determined by the IRF with use of the 
Lugano 2014 Response criteria, or death from any cause, whichever occurs first.  
Participants who have neither progressed nor died at the CCOD for analysis and 
participants who are lost to follow-up will be censored on the date of the last evaluable 
tumor assessment.  Participants who did not undergo a post-baseline tumor assessment 
and did not have a death event will be censored at the time of randomization. 
Treatment:  Participants will be randomized into either Arm A (M  P) or Arm B 
(R-GemOx).  During the conduct of the study participants may also receive concomitant 
medications as detailed in Section 6.8. 
Intercurrent events and handling strategies: 
 
 
 
 
 
  
 
 
 
 
 
Population-level summary for the variable:  Stratified hazard ratio. 
9.4.3 
Secondary Endpoints 
To control the overall type I error rate at a -sided 
 level of significance, a 
hierarchical testing procedure will be used to adjust for multiple statistical testing of the 

 
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primary and key secondary efficacy endpoints (Section 9.2.1 and Figure 7).  The 
following key secondary endpoint will be formally tested: 
 
OS, defined as the time from randomization to death from any cause 
 
The hierarchical ordering of selected secondary endpoints, and method for multiple 
testing adjustment are described in Section 9.2.1 and in the Statistical Analysis Plan. 
The remaining secondary endpoints will be tested without adjusting for multiplicity. 
 
PFS, defined as the time from randomization to the first occurrence of disease 
progression as determined by the investigator, or death due to any cause, 
whichever occurs first 
 
CRR, defined as the proportion of participants in whom a CR was observed at any 
time during the study as determined by the IRF and by the investigator 
 
ORR, defined as the proportion of participants in whom an objective response (CR 
or PR) was observed at any time during the study as determined by the investigator 
 
DOR, defined as the time from the first occurrence of a documented objective 
response to disease progression, or death from any cause, whichever occurs first, 
as determined by the IRF and by the investigator 
 
DOCR, defined as the time from the first occurrence of a documented CR to disease 
progression, or death from any cause, whichever occurs first, as determined by the 
IRF and by the investigator 
 
Time to deterioration in physical functioning and fatigue, as measured by the 
EORTC QLQ-C30 
 
Time to deterioration in lymphoma symptoms, as measured by FACT-LymS 
 
For the secondary endpoint of OS, for participants who have not died at the CCOD for 
the analysis, OS will be censored on the last date when the participants are known to be 
alive.  Participants who do not have information after randomization will be censored at 
the date of randomization.  The methodologies detailed for the PFS analysis (see 
Section 9.4.2) will be used for the OS analysis.  
For the secondary efficacy endpoints of CRR and ORR, an estimate of CRR or ORR and 
its 
% CI will be calculated with use of the Clopper-Pearson method for each treatment 
arm.  The CIs for the difference in CRRs and ORRs between the two treatment arms will 
be determined with use of the Hauck-Andersen method.  CRR and ORR will be 
compared between treatment arms using the Cochran-Mantel-Haenszel test stratified by 
the randomization stratification factors.  Responses after initiation of new anti-lymphoma 
therapy will not be included in the analysis of CRR and ORR. 
For the secondary efficacy endpoints of DOR and DOCR, participants who have not 
progressed and who have not died at the time of analysis will be censored at the time of 
last tumor assessment date.  If no tumor assessments were performed and no death 
event occurred after the date of the first occurrence of a response (or complete response 

 
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for DOCR), DOR and DOCR will be censored at the date of the first occurrence of a 
response.  The methodologies detailed for the PFS analysis (Section 9.4.2) will be used 
for the DOR and DOCR analysis, except that the analysis will not be stratified.  DOR and 
DOCR analysis will be based on a non-randomized subset of participants (specifically, 
participants who achieved an objective response or a complete response); therefore, 
comparisons between treatment arms will be made for descriptive purposes. 
Time to deterioration analyses will be performed on the EORTC QLQ-C30 and 
FACT-LymS.  For the EORTC QLQ-C30 physical functioning and fatigue scores, time to 
deterioration in physical functioning and/or fatigue is defined as the time from 
randomization to the first documentation of a 10-point or more decrease and increase, 
respectively, from baseline.  For the FACT-LymS, time to deterioration in 
lymphoma-specific symptoms is defined as the time from randomization to the first 
documentation of a 3-point or more decrease, from baseline.  The hazard ratio for 
deterioration will be estimated using a stratified Cox proportional hazards model.  The 
% CI for the hazard ratio will be provided.  Participants who do not have an observed 
deterioration at the time of clinical data cut-off date will be censored at the last 
non-missing assessment date.  Participants without a post-baseline assessment will be 
censored at randomization. 
Secondary Safety Endpoints: 
 
Incidence and severity of adverse events, with severity determined according to the 
NCI CTCAE v5.0, including CRS, with severity determined according to the 
ASTCT CRS grading criteria (Lee et al. 2019; Appendix 11) 
 
Change from baseline in targeted vital signs 
 
Change from baseline in targeted clinical laboratory test results 
 
Tolerability, as assessed by dose interruptions, dose reductions, and dose intensity, 
and study treatment discontinuation because of adverse events 
 
Change from baseline in peripheral neuropathy, as measured by the 
FACT/GOG-Ntx (Appendix 14) 
 
All verbatim adverse event terms occurring on or after first study treatment will be 
mapped to MedDRA thesaurus terms, and adverse event severity will be graded 
according to NCI CTCAE v5.0 (except CRS events, which will be graded according to 
the ASTCT CRS grading criteria [Lee et al. 2019; Appendix 11]). 
9.4.4 
Exploratory Endpoints 
Exploratory endpoints are defined in Section 3 (see Table 6).  Although no formal 
statistical analysis of exploratory biomarkers will be performed, data may be analyzed in 
the context of this study and in aggregate with data from other studies. 

 
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9.4.5 
Other Safety Analyses 
Incidence of ADA response (presence of serum anti-mosunetuzumab or 
anti-polatuzumab vedotin) and the potential correlation with PK, pharmacodynamics, and 
safety parameters may be assessed. 
9.4.6 
Other Analyses 
9.4.6.1 
Summaries of Conduct of Study 
Enrollment, study treatment administration, and discontinuation from the study will be 
summarized by treatment arm.  The reasons for study treatment discontinuation will also 
be tabulated.  Major protocol deviations, including major deviations with regard to the 
inclusion and exclusion criteria, will be summarized by treatment arm. 
9.4.6.2 
Summaries of Treatment Group Comparability/Demographics 
and Baseline Characteristics 
Demographics and baseline characteristics (including age, sex, and race/ethnicity) will 
be summarized by treatment arm.  Baseline data are the last data obtained prior to 
initiation of study treatment.  Descriptive statistics (mean, standard deviation, median, 
and range) will be presented for continuous variables and counts and percentages will 
be presented for categorical variables. 
9.4.6.3 
Pharmacokinetic Analyses 
The PK population for analysis will include all participants who have received at least 
1 dose of mosunetuzumab and polatuzumab vedotin and have at least 1 evaluable PK 
sample post-dose for at least 1 analyte. 
Individual and mean concentrations of mosunetuzumab (serum) and polatuzumab total 
antibody (serum), acMMAE (plasma) and unconjugated MMAE (plasma) versus time 
data will be tabulated and plotted.  The pharmacokinetics of the above analytes will be 
summarized as the data will allow for by estimating selected PK parameters.  
The population PK analysis will investigate the effects of certain covariates on the 
pharmacokinetics of mosunetuzumab, as data will allow for and at the Sponsor’s 
discretion. 
Exposure-response (safety and efficacy) analysis may be conducted using 
plasma/serum concentrations or relevant PK parameters and available drug effect 
(e.g., response rate and PFS) and toxicity data, per the Sponsor’s discretion and as the 
data will allow for. 
To assess for potential PK drug-drug interactions, PK parameters for mosunetuzumab 
and each analyte of polatuzumab vedotin will be compared with historical data, as the 
data will allow for. 

 
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9.4.6.4 
Immunogenicity Analyses 
The numbers and proportions of ADA-positive participants and ADA-negative 
participants at baseline (baseline prevalence) and after drug administration 
(post-baseline incidence) will be summarized by treatment group.  When determining 
post-baseline incidence, 
 
 
 
 
  
 
 
 
The relationship between ADA status and safety, efficacy, PK, and biomarker endpoints 
may be analyzed and reported with use of standard language/terminology. 
9.4.6.5 
Clinical Outcome Assessment Analyses 
Participant-reported outcomes endpoints include time to deterioration in the 
EORTC QLQ-C30 physical functioning and fatigue scores and the FACT-LymS; 
a comparison of the FACT/GOG-NTx peripheral neuropathy score between the 
two treatment arms will be assessed.  Time to deterioration will be compared between 
treatment arms with use of a stratified log-rank test.  For EORTC QLQ-C30 physical 
functioning and fatigue scores, clinically meaningful deterioration is defined as a 
 10-point decrease and increase, respectively, from baseline (Osoba et al. 1998; 
Cocks et al. 2012).  For the FACT-LymS, clinically meaningful deterioration is defined as 
≥ 3-point decrease from baseline (Carter et al. 2008; Hlubocky et al. 2013).  The hazard 
ratio for deterioration will be estimated with use of a stratified Cox proportional hazards 
model.  The 
% CI for the hazard ratio will be provided.  Kaplan-Meier methodology will 
be used to estimate 1-year and 2-year rates, as well as the median time to deterioration 
(if reached) for each treatment arm, and Kaplan-Meier curves will be produced.  
Participants who do not have an observed deterioration at the time of the CCOD will be 
censored at the last non-missing assessment date.  Participants without a post-baseline 
assessment will be censored at randomization.  Supplemental item-level analyses will be 
conducted with the individual B-symptom items of the FACT-LymS using a raw 1-point 
worsening. 
A mixed effects model for repeated measures will be used for comparing the 
EORTC QLQ-C30 treatment-related symptom score and the FACT/GOG-Ntx peripheral 
neuropathy score between treatment arms. 
 
 
. 

 
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9.6 
ASIAN SUBPOPULATION ANALYSES 
The Asian subpopulation analysis will be conducted only for China to meet local 
regulatory requirements, if China is included as a participating country.  The objective of 
this subgroup analysis is to assess the treatment effect of M  P compared with 
R-GemOx in the Asia subpopulation, and to investigate the consistency in treatment 
effect between this Asian subpopulation and the global population for the purpose of 
registration in China. 
The Asian subpopulation will include all participants enrolled at China’s sites (i.e., during 
both the global enrollment phase and the extended China enrollment cohort) and the 
participants enrolled from other Asian countries/regions (e.g., 
, 
etc. during the global enrollment phase).  Results from these analyses will be 
summarized in a separate Clinical Study Report. 
The analysis of PFS in the Asian subpopulation will be performed when at least half of 
the Asian participants have had PFS events and no earlier than the primary analysis for 
the global population. 
9.7 
INDEPENDENT DATA MONITORING COMMITTEE 
See Section 4.1.3 for information on the iDMC for this study. 

 
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10. 
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Appendix 1  
Regulatory, Ethical, and Study Oversight Considerations 
TABLE OF CONTENTS 
A1–1 
Regulatory and Ethical Considerations ..................................... 133 
A1–2 
Financial Disclosure .................................................................. 133 
A1–3 
Informed Consent Process........................................................ 134 
A1–4 
Data Protection ......................................................................... 134 
A1–5 
Administrative Structure ............................................................ 135 
A1–6 
Dissemination of Clinical Study Data ........................................ 135 
A1–7 
Data Quality Assurance ............................................................ 136 
A1–8 
Source Documents ................................................................... 137 
A1–9 
Study and Site Closure ............................................................. 137 
A1–10 
Publication Policy ...................................................................... 138 
A1–11 
Protocol Deviations ................................................................... 138 

Appendix 1:  Regulatory, Ethical, and Study Oversight Considerations 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
133/Protocol GO43643, Version 5 
A1–1 
REGULATORY AND ETHICAL CONSIDERATIONS 
This study will be conducted in accordance with the protocol and with the following: 
 
Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences international ethical guidelines 
 
Applicable International Council for Harmonisation (ICH) Guideline for Good Clinical 
Practice 
 
Applicable laws and regulations 
 
The protocol, Informed Consent Form, Investigator’s Brochure, and other relevant 
documents (e.g., advertisements) must be submitted to an Institutional Review Board 
(IRB) or Ethics Committee (EC) by the investigator and reviewed and approved by the 
IRB/EC before the study is initiated. 
Any substantial amendments to the protocol will require IRB/EC and health authority 
approval (as locally required) before implementation of changes, with the exception of 
administrative changes or changes necessary to eliminate an immediate hazard to study 
participants. 
The investigator will be responsible for the following: 
 
Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC 
 
Notifying the IRB/EC of serious adverse events or other significant safety findings, 
as required by IRB/EC procedures 
 
Providing oversight of the conduct of the study at the site and ensuring adherence to 
requirements of 21 Code of Federal Regulations (CFR; U.S. sites only), the 
ICH Guideline for Good Clinical Practice, the IRB/EC, Clinical Trials Directive 
(2001/20/EC) or Clinical Trials Regulation (536/2014 (EEA sites only), and all other 
applicable local regulations 
 
A1–2 
FINANCIAL DISCLOSURE 
Investigators will provide the Sponsor with sufficient, accurate financial information in 
accordance with local regulations to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate health authorities.  
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study (see definition of end of 
study in Section 4.4). 

Appendix 1:  Regulatory, Ethical, and Study Oversight Considerations 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
134/Protocol GO43643, Version 5  
A1–3 
INFORMED CONSENT PROCESS 
The investigator or authorized designee will explain the nature of the study to the 
participant or his or her legally authorized representative and answer all questions 
regarding the study. 
Participants must be informed that their participation is voluntary.  Participants or their 
legally authorized representative will be required to sign a statement of informed consent 
that meets the requirements of 21 CFR 50 (U.S. sites only), the ICH Guideline for 
Good Clinical Practice, and the IRB/EC. 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was 
obtained.  The authorized person obtaining the informed consent must also sign the 
Informed Consent Form. 
If the Informed Consent Form is revised (through an amendment or an addendum) to 
communicate information that might affect a participant’s willingness to continue in the 
study, the participant or the participant’s legally authorized representative must 
re-consent by signing the most current version of the Informed Consent Form or the 
addendum, in accordance with applicable laws and IRB/EC policy. 
A copy of each Informed Consent Form must be provided to the participant or the 
participant’s legally authorized representative. 
Participants who are re-screened are required to sign a new Informed Consent Form. 
A1–4 
DATA PROTECTION 
Information technology systems used to collect, process, and store study-related data 
are secured by technical and organizational security measures designed to protect such 
data against accidental or unlawful loss, alteration, or unauthorized disclosure or access.  
In the event of a data security breach, appropriate mitigation measures will be 
implemented. 
Participants will be assigned a unique identifier by the Sponsor.  Any participant records 
or datasets that are transferred to the Sponsor will contain the identifier only; 
the participant’s name or any information that would make the participant identifiable will 
not be transferred. 
Participants must be informed that their personal study-related data will be used by the 
Sponsor in accordance with local data protection law.  The level of disclosure must also 

Appendix 1:  Regulatory, Ethical, and Study Oversight Considerations 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
135/Protocol GO43643, Version 5  
be explained to participants, who will be required to give consent for their data to be 
used as described in the Informed Consent Form. 
Participants must be informed that their medical records may be examined by auditors or 
other authorized individuals representing the Sponsor or Sponsor collaborators and 
licensees, by appropriate IRB/EC members, and by inspectors from health authorities. 
A1–5 
ADMINISTRATIVE STRUCTURE 
This trial will be sponsored and managed by F. Hoffmann-La Roche Ltd.  The Sponsor 
will provide clinical operations management, data management, and medical monitoring. 
Approximately 75 sites globally will participate to enroll approximately 222 participants.  
Enrollment will occur through an interactive voice or Web-based response system. 
Central facilities will be used for certain assessments throughout the study 
(e.g., specified laboratory tests, biomarker and pharmacokinetic analyses), as specified 
in Section 8.2.4 and Appendix 2.  Accredited local laboratories will be used for routine 
monitoring; local laboratory ranges will be collected. 
An independent Data Monitoring Committee will be employed to monitor and evaluate 
participant safety throughout the study.  An Independent Review Facility (IRF) will 
collect, store, and review imaging data. 
A1–6 
DISSEMINATION OF CLINICAL STUDY DATA 
Study data, which may include imaging data and data on genomic variants, may be 
submitted to government or other health research databases or shared with researchers, 
government agencies, companies, or other groups that are not participating in this study.  
These data may be combined with or linked to other data and used for research 
purposes, to advance science and public health, or for analysis, development, and 
commercialization of products to treat and diagnose disease.  In addition, redacted 
Clinical Study Reports and/or other summaries of clinical study results may be available 
in health authority databases for public access, as required by local regulation, and will 
be provided upon request.  For more information, refer to the Roche Global Policy on 
Sharing of Clinical Study Information at the following website: 
 
https://www.roche.com/innovation/process/clinical-trials/data-sharing/  
Given the complexity and exploratory nature of exploratory biomarker analyses, data 
derived from these analyses will generally not be provided to study investigators or 
participants unless required by law.  The aggregate results of any conducted research 
will be available in accordance with the effective Roche policy on study data publication. 

Appendix 1:  Regulatory, Ethical, and Study Oversight Considerations 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
136/Protocol GO43643, Version 5  
A1–7 
DATA QUALITY ASSURANCE 
All participant data relating to the study will be recorded on printed or electronic Case 
Report Forms (CRFs) unless transmitted to the Sponsor or designee electronically 
(e.g., laboratory data).  The investigator is responsible for verifying that data entries are 
accurate and correct by physically or electronically signing the CRF. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents. 
Monitoring details describing strategy (e.g., risk-based initiatives in operations and 
quality such as risk management and mitigation strategies and analytical risk-based 
monitoring), methods, responsibilities, and requirements, including handling of 
non-compliance issues and monitoring techniques (central, remote, or on-site 
monitoring), are provided prior to study initiation, in the various functional monitoring 
plans (including, but not limited to, Quality Tolerance Limit Management Plan and Trial 
Monitoring Plan). 
The Sponsor or designee is responsible for the data management of this study, including 
quality checking of the data. 
The Sponsor assumes accountability for actions delegated to other individuals 
(e.g., contract research organizations). 
Study monitors will perform ongoing monitoring activities as specified in the 
Trial Monitoring Plan to confirm that data entered into the CRF by authorized site 
personnel are accurate, complete, and verifiable from source documents; that the safety 
and rights of participants are being protected; and that the study is being conducted in 
accordance with the currently approved protocol and any other study agreements, the 
ICH Guideline for Good Clinical Practice, and all applicable regulatory requirements. 
Records and documents pertaining to the conduct of this study, including signed 
Informed Consent Forms, must be retained by the investigator for 15 years after study 
completion unless local regulations or institutional policies require a longer retention 
period.  No records may be destroyed during the retention period without the written 
approval of the Sponsor.  No records may be transferred to another location or party 
without written notification to the Sponsor. 

Appendix 1:  Regulatory, Ethical, and Study Oversight Considerations 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
137/Protocol GO43643, Version 5  
The Sponsor will retain study data for 25 years after the final study results have been 
reported or for the length of time required by relevant national or local health authorities, 
whichever is longer. 
A1–8 
SOURCE DOCUMENTS 
Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected.  Source documents are filed at the investigator’s site. 
Data reported on the CRF or entered in the electronic Case Report Form (eCRF) that 
are transcribed from source documents must be consistent with the source documents, 
or the discrepancies must be explained.  The investigator may need to request previous 
medical records or transfer records, depending on the study.  Also, current medical 
records must be available. 
Definition of what constitutes source data can be found in the Trial Monitoring Plan. 
A1–9 
STUDY AND SITE CLOSURE 
The Sponsor or designee reserves the right to close the study site or terminate the study 
at any time for any reason at the sole discretion of the Sponsor.  Study sites will be 
closed upon study completion.  A study site is considered closed when all required 
documents and study supplies have been collected and a site closure visit has been 
performed. 
The investigator may initiate site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or investigator may include, 
but are not limited to, the following: 
 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the Sponsor’s procedures, or the ICH Guideline 
for Good Clinical Practice 
 
Inadequate recruitment of participants by the investigator 
 
Discontinuation of further study treatment development 
 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform 
the investigators, the IRBs/ECs, the health authorities, and any contract research 
organizations used for the study of the reason for termination or suspension, as 
specified by the applicable regulatory requirements.  The Investigator shall promptly 
inform the participants and should ensure appropriate participant therapy and/or follow-
up. 

Appendix 1:  Regulatory, Ethical, and Study Oversight Considerations 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
138/Protocol GO43643, Version 5  
A1–10 
PUBLICATION POLICY 
The results of this study may be published or presented at scientific meetings.  If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the Sponsor 
before submission.  This allows the Sponsor to protect proprietary information and to 
provide comments. 
The Sponsor will comply with the requirements for publication of study results.  
In accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of results of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement. 
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
A1–11 
PROTOCOL DEVIATIONS 
The investigator should document and explain any protocol deviations.  The investigator 
should promptly report any deviations that might have an impact on participant safety 
and data integrity to the Sponsor and to the IRB/EC in accordance with established 
IRB/EC policies and procedures.  The Sponsor will review all protocol deviations and 
assess whether any represent a serious breach of Good Clinical Practice guidelines and 
require reporting to health authorities.  As per the Sponsor’s standard operating 
procedures, prospective requests to deviate from the protocol, including requests to 
waive protocol eligibility criteria, are not allowed. 
 

 
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Appendix 2  
Clinical Safety Laboratory Tests 
The tests detailed in Table A2-1 will be performed by the local laboratory. 
Protocol-specific requirements for inclusion and exclusion of participants are detailed in 
Section 5. 
Additional tests may be performed at any time during the study if determined to be 
necessary by the investigator or if required by local regulations. 
Investigators must document their review of each laboratory safety report. 
Table A2-1 Protocol-Required Safety Laboratory Assessments 
Local Laboratory Tests 
 
Hematology:  WBC count, RBC count, hemoglobin, hematocrit, platelet count, and 
differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, and other 
cells) 
 
Chemistry panel (serum):  sodium, potassium, chloride, bicarbonate (or total carbon dioxide 
if considered standard of care for the region; may be measured using blood gas test per 
institutional practice), glucose, BUN or urea, creatinine, calcium, magnesium, phosphorus, 
total and direct bilirubin, total protein, albumin, ALT, AST, ALP, GGT, LDH, and uric acid 
 
C-reactive protein, serum ferritin 
 
Coagulation:  INR, aPTT, PT, and fibrinogen a 
 
HIV serology and viral load:  HIV-1/2 antibody and HIV PCR testing b 
 
HBV serology:  HBsAg, HBsAb, and total HBcAb for all individuals; HBV DNA c for 
individuals with negative HBsAg and a positive HBcAb test 
 
HCV serology:  HCV antibody for all individuals; HCV RNA for individuals with a positive 
HCV antibody test 
 
EBV and CMV by quantitative PCR with use of peripheral blood samples 
 
Quantitative immunoglobulins:  IgA, IgG, and IgM 
 
Pregnancy test 
 
All women of childbearing potential will have a serum pregnancy test at screening. 
Urine pregnancy tests will be performed at specified subsequent visits.  If a urine 
pregnancy test is positive, it must be confirmed by a serum pregnancy test. 
 
 

Appendix 2:  Clinical Safety Laboratory Tests 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
140/Protocol GO43643, Version 5  
Table A2-1  
Protocol-Required Safety Laboratory Assessments (cont.) 
CMV cytomegalovirus; EBV  Epstein-Barr virus; GGT  gamma-glutamyl transferase; HBcAb  hepatitis 
B core antibody; HBsAb  hepatitis B surface antibody; HBsAg  hepatitis B surface antigen; 
HBV  hepatitis B virus; HCV  hepatitis C virus; LDH  lactate dehydrogenase; PCR  polymerase chain 
reaction.  
a Fibrinogen is only tested after tocilizumab is administered following Table 5. 
b Participants with a positive HIV result at screening should be monitored after receiving study 
treatment.  The HIV viral load will be performed every 3 months ( 4 weeks) until end of study 
treatment, and then every 6 months ( 4 weeks) during post treatment follow up for 12 months after 
end of treatment visit.  If the HIV viral load is detected (positive), the participant should be treated per 
local institutional standards, and the Medical Monitor should be notified.  Testing may be performed at 
the local institution.  If local laboratory assessments are not available for testing, local laboratory 
collections may be waived only if samples are collected for central laboratory assessments of viral 
infections. 
c Participants with occult or prior hepatitis B infection should undergo monthly DNA testing while the 
patient is on treatment.  During post treatment follow up, the HBV test will continue every 3 months 
( 4 weeks) for 12 months after end of treatment visit. 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
141/Protocol GO43643, Version 5 
Appendix 3  
Adverse Events:  Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting 
TABLE OF CONTENTS 
A3–1 
Definition of Adverse Event ....................................................... 142 
A3–2 
Definition of Serious Adverse Event .......................................... 143 
A3–3 
Recording and Follow-Up of Adverse Events and Serious 
Adverse Events ......................................................................... 144 
A3–3.1 
Adverse Event and Serious Adverse Event Recording ............. 144 
A3–3.2 
Assessment of Severity ............................................................ 145 
A3–3.3 
Assessment of Causality ........................................................... 146 
A3–3.4 
Follow-up of Adverse Events and Serious Adverse Events ...... 147 
A3–3.4.1 
Investigator Follow-Up .............................................................. 147 
A3–3.4.2 
Sponsor Follow-Up ................................................................... 148 
A3–4 
Reporting of Serious Adverse Events ....................................... 148 
A3–4.1 
Serious Adverse Event Reporting to The Sponsor via an 
Electronic Collection Tool.......................................................... 148 
A3–4.2 
Serious Adverse Event Reporting to The Sponsor via Paper 
CRF .......................................................................................... 148 
A3–5 
Reporting Requirements for Serious Adverse Events and 
Adverse Events of Special Interest ........................................... 149 
A3–5.1 
Events That Occur Prior to Study Treatment Initiation .............. 149 
A3–5.2 
Events That Occur After Study Treatment Initiation .................. 149 
A3–6 
Reporting Adverse Events That Occur after the Adverse 
Event Reporting Period ............................................................. 149 
A3–7 
Procedures for Recording Adverse Events ............................... 150 
A3–7.1 
Cytokine Release Syndrome/Injection-Related Reactions 
Attributed to Monsunetuzumab ................................................. 150 
A3–7.2 
Infusion-Related Reactions ....................................................... 151 
A3–7.3 
Diagnosis Versus Signs And Symptoms ................................... 151 
A3–7.4 
Adverse Events that are Secondary to Other Events ................ 151 
A3–7.5 
Persistent or Recurrent Adverse Events ................................... 152 
A3–7.6 
Abnormal Laboratory Values..................................................... 152 
A3–7.7 
Abnormal Vital Sign Values....................................................... 153 
A3–7.8 
Abnormal Liver Function Tests ................................................. 154 
A3–7.9 
Deaths ...................................................................................... 154 
A3–7.10 
Preexisting Medical Conditions ................................................. 155 
A3–7.11 
Lack of Efficacy or Worsening of Lymphoma ............................ 155 
A3–7.12 
Hospitalization or Prolonged Hospitalization ............................. 155 
A3–7.13 
Cases of Accidental Overdose or Medication Error .................. 156 
A3–7.14 
Participant-Reported Outcome Data ......................................... 157 
 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
142/Protocol GO43643, Version 5  
A3–1 
DEFINITION OF ADVERSE EVENT 
Adverse Event Definition 
An adverse event is any untoward medical occurrence in a patient or clinical study 
participant temporally associated with the use of a study treatment, whether or not 
considered related to the study treatment. 
Note:  An adverse event can; therefore, be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention. 
Events Meeting the Adverse Event Definition 
The following events meet the definition of adverse event: 
 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, or are considered clinically significant in 
the medical and scientific judgment of the investigator (i.e., not related to 
progression of underlying disease) 
 
Exacerbation of a chronic or intermittent preexisting condition, including either an 
increase in frequency and/or intensity of the condition 
 
New condition detected or diagnosed after study treatment administration, even 
though it may have been present before the start of the study 
 
Signs, symptoms, or clinical sequelae of a suspected drug−drug interaction 
 
Signs, symptoms, or clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication 
Overdose per se will not be reported as an adverse event or serious adverse event 
unless it is an intentional overdose taken with possible suicidal or self-harming 
intent.  Such overdoses should be reported regardless of sequelae. 
 
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an adverse event or serious adverse event.  Such instances will be 
captured in the efficacy assessments.  However, the signs, symptoms, and/or 
clinical sequelae resulting from lack of efficacy will be reported as an adverse event 
or serious adverse event if they fulfill the definition of an adverse event or serious 
adverse event. 
 
Events NOT Meeting the Definition of Adverse Event 
The following events do not meet the definition of adverse event: 
 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
143/Protocol GO43643, Version 5  
 
The disease or disorder being studied or expected progression, signs, or symptoms 
of the disease or disorder being studied, unless more severe than expected for the 
participant’s condition 
 
Medical or surgical procedure (e.g., endoscopy, appendectomy) 
The condition that leads to the procedure is the adverse event. 
 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital) 
 
Anticipated day-to-day fluctuations of a preexisting disease or condition present or 
detected at the start of the study that do not worsen 
 
A3–2 
DEFINITION OF SERIOUS ADVERSE EVENT 
If an event is not an adverse event per the definition in Section A3–1, it cannot be a 
serious adverse event even if serious conditions are met (e.g., hospitalization for signs 
or symptoms of the disease under study, death due to progression of disease). 
A serious adverse event is defined as any untoward medical occurrence that, at any 
dose: 
 
Results in death 
 
Is life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which 
the participant was at risk of death at the time of the event.  It does not refer to an 
event that hypothetically might have caused death if it were more severe. 
 
Requires in-patient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained 
(usually involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting.  Complications that occur during 
hospitalization are adverse events.  If a complication prolongs hospitalization or 
fulfills any other seriousness criteria, the event is serious.  When in doubt as to 
whether “hospitalization” occurred or was necessary, the adverse event should be 
considered serious. 
Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an adverse event. 
 
Results in persistent disability or incapacity 
The term “disability” means a substantial disruption of a person’s ability to conduct 
normal life functions. 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
144/Protocol GO43643, Version 5  
influenza, and accidental trauma (e.g., sprained ankle) that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
 
Is a congenital anomaly or birth defect 
 
Other situations: 
Medical or scientific judgment should be exercised in deciding whether serious 
adverse event reporting is appropriate in other situations such as important medical 
events that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the participant or may require medical or surgical 
intervention to prevent one of the other outcomes listed in the above definition.  
These events should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse. 
 
The terms “severe” and “serious” are not synonymous.  Severity refers to the intensity of 
an adverse event (e.g., rated as mild, moderate, or severe, or according to 
National Cancer Institute Common Terminology Criteria for Adverse Events 
[NCI CTCAE]; see Section A3–3.2); the event itself may be of relatively minor medical 
significance (such as severe headache without any further findings). 
Severity and seriousness need to be independently assessed for each adverse event 
recorded on the electronic Case Report Form (eCRF). 
Serious adverse events are required to be reported by the investigator to the Sponsor 
immediately (i.e., no more than 24 hours after the investigator becomes aware of the 
event; see Section A3–5 for reporting instructions). 
A3–3 
RECORDING AND FOLLOW-UP OF ADVERSE EVENTS AND 
SERIOUS ADVERSE EVENTS 
A3–3.1 
 ADVERSE EVENT AND SERIOUS ADVERSE EVENT 
RECORDING 
When an adverse event or serious adverse event occurs, it is the responsibility of the 
investigator to review all documentation (e.g., hospital progress notes, laboratory 
reports, and diagnostics reports) related to the event. 
The investigator will then record all relevant adverse event or serious adverse event 
information on the eCRF. 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
145/Protocol GO43643, Version 5  
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to the Sponsor in lieu of completion of the Adverse Event eCRF. 
There may be instances when copies of medical records for certain cases are requested 
by the Sponsor.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to the Sponsor. 
The investigator will attempt to establish a diagnosis of the event on the basis of signs, 
symptoms, and/or other clinical information.  Whenever possible, the diagnosis (not the 
individual signs or symptoms) will be documented as the adverse event or serious 
adverse event. 
A3–3.2 
ASSESSMENT OF SEVERITY 
The investigator will assess the severity of each adverse event reported during the study 
through use of the NCI CTCAE (v5.0) grading scale; for CRS, severity will be determined 
according to the American Society for Transplantation and Cellular Therapy (ASTCT) 
CRS Consensus grading criteria.  The investigator will use the grading scale in 
Table A3-1 for assessing the severity of adverse events that are not specifically listed in 
the NCI CTCAE. 
New events of ICANS and HLH that occur after approval of Protocol Version 5 will 
continue to be graded according to NCI CTCAE v5.0.  In addition, ASTCT grading 
(Appendix 21 for ICANS and Table A6-8 for HLH) should be provided when describing 
the case within the additional case details of the Adverse Events eCRF (refer to the 
eCRF completion guidelines for additional details). 
Table A3-1 Adverse Event Severity Grading Scale for Events Not 
Specifically Listed in NCI CTCAE 
Grade 
Severity 
1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
or intervention not indicated 
2 
Moderate; minimal, local or non-invasive intervention indicated; or limiting 
age-appropriate instrumental activities of daily living a 
3 
Severe or medically significant, but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; or 
limiting self-care activities of daily living b, c 
4 
Life-threatening consequences or urgent intervention indicated d 
5 
Death related to adverse event d 
 
 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
146/Protocol GO43643, Version 5  
Table A3-1 Adverse Event Severity Grading Scale for Events Not 
Specifically Listed in NCI CTCAE (cont.) 
NCI CTCAE = National Cancer Institute Common Terminology Criteria for Adverse Events. 
Note:  Based on the most recent version of NCI CTCAE (v 5.0), which can be found at: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
a Examples of instrumental activities of daily living include preparing meals, shopping for 
groceries or clothes, using the telephone, managing money, etc. 
b Examples of self-care activities of daily living include bathing, dressing and undressing, 
feeding oneself, using the toilet, and taking medications, as performed by participants who 
are not bedridden. 
c If an event is assessed as a “significant medical event,” it must be reported as a serious 
adverse event (see Section A3–5 for reporting instructions), per the definition of serious 
adverse event in Section A3–2. 
d Grade 4 and 5 events must be reported as serious adverse events (see Section A3–5 for 
reporting instructions), per the definition of serious adverse event in Section A3–2. 
 
A3–3.3 
 ASSESSMENT OF CAUSALITY 
The investigator is obligated to assess the relationship between study treatment and 
each occurrence of each adverse event or serious adverse event. 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled 
out. 
The investigator will use clinical judgment to determine the relationship. 
Alternative causes, such as underlying diseases, concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study treatment 
administration, will be considered and investigated. 
The investigator will also consult the Investigator’s Brochure and/or prescribing 
information (for marketed products) in his or her assessment. 
For each adverse event or serious adverse event, the investigator must document in the 
medical notes that he or she has reviewed the adverse event or serious adverse event 
and has provided an assessment of causality. 
There may be situations in which a serious adverse event has occurred and the 
investigator has minimal information to include in the initial report to the Sponsor.  
However, it is very important that the investigator always make an assessment of 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
147/Protocol GO43643, Version 5  
causality for every event before the initial transmission of the serious adverse event data 
to the Sponsor. 
The investigator may change his or her opinion of causality in light of follow-up 
information and send a serious adverse event follow-up report with the updated causality 
assessment. 
For participants receiving combination therapy, causality will be assessed individually for 
each protocol-mandated therapy. 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
A3–3.4 
 FOLLOW-UP OF ADVERSE EVENTS AND SERIOUS ADVERSE 
EVENTS 
A3–3.4.1 
Investigator Follow-Up 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
Sponsor to elucidate the nature and/or causality of the adverse event or serious adverse 
event as fully as possible.  This may include additional laboratory tests or investigations, 
histopathologic examinations, or consultation with other health care professionals. 
New or updated information will be recorded in the originally completed CRF. 
The investigator will submit any updated serious adverse event data to the Sponsor 
within 24 hours of receipt of the information.  New or updated information should be 
recorded on the originally completed Adverse Event eCRF.  For serious adverse events 
and adverse events of special interest, the investigator must report new significant 
follow-up information to the Sponsor immediately (i.e., no more than 24 hours after the 
investigator becomes aware of the information).  New significant information includes the 
following: 
 
New signs or symptoms or a change in the diagnosis 
 
Significant new diagnostic test results 
 
Change in causality based on new information 
 
Change in the event’s outcome, including recovery 
 
Additional narrative information on the clinical course of the event 
 
During the adverse event reporting period (defined in Section 8.3.1), resolution of 
adverse events (with dates) should be documented on the Adverse Event eCRF and in 
the participant’s medical record to facilitate source data verification. 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
148/Protocol GO43643, Version 5  
A3–3.4.2 
Sponsor Follow-Up 
For serious adverse events and adverse events of special interest, the Sponsor or a 
designee may follow up by telephone, fax, e-mail, and/or a monitoring visit to obtain 
additional case details and outcome information (e.g., from hospital discharge 
summaries, consultant reports, autopsy reports) in order to perform an independent 
medical assessment of the reported case. 
A3–4 
REPORTING OF SERIOUS ADVERSE EVENTS 
A3–4.1 
 SERIOUS ADVERSE EVENT REPORTING TO THE SPONSOR 
VIA AN ELECTRONIC COLLECTION TOOL 
The primary mechanism for reporting a serious adverse event to the Sponsor will be the 
electronic data collection tool, as described in Section A3–5. 
If the electronic system is unavailable, the site will use the paper Clinical Trial Adverse 
Event/Special Situations Form, as described in Section A3–5, to report the event within 
24 hours. 
The site will enter the serious adverse event data into the electronic system as soon as it 
becomes available. 
After the study is completed at a given site, the electronic data collection tool will be 
taken off line to prevent the entry of new data or changes to existing data. 
If a site receives a report of a new serious adverse event from a study participant or 
receives updated data on a previously reported serious adverse event after the 
electronic data collection tool has been taken off line, the site can report this information 
on a paper Clinical Trial Adverse Event/Special Situations Form, as described in Section 
A3–5. 
A3–4.2 
 SERIOUS ADVERSE EVENT REPORTING TO THE SPONSOR 
VIA PAPER CRF 
Under certain circumstances, serious adverse events may be reported to the Sponsor 
through use of a paper Clinical Trial Adverse Event/Special Situations Form, as 
described in Section A3–5. 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
149/Protocol GO43643, Version 5  
A3–5 
REPORTING REQUIREMENTS FOR SERIOUS ADVERSE 
EVENTS AND ADVERSE EVENTS OF SPECIAL INTEREST 
A3–5.1 
 EVENTS THAT OCCUR PRIOR TO STUDY TREATMENT 
INITIATION 
After informed consent has been obtained but prior to initiation of study treatment, only 
serious adverse events caused by a protocol-mandated intervention 
(e.g., biopsy, discontinuation of medications) should be reported.  The paper Clinical 
Trial Adverse Event/Special Situations Form provided to investigators should be 
completed and submitted to the Sponsor or its designee immediately (i.e., no more than 
24 hours after the investigator becomes aware of the event), either by faxing or by 
scanning and e-mailing the form, using the fax number or e-mail address provided to 
investigators. 
A3–5.2 
 EVENTS THAT OCCUR AFTER STUDY TREATMENT 
INITIATION 
After initiation of study treatment, serious adverse events and adverse events of special 
interest will be reported until 90 days after the final dose of study treatment or the 
initiation of next anti-lymphoma therapy, whichever is earlier.  Investigators should 
record all case details that can be gathered immediately (i.e., within 24 hours after the 
investigator becomes aware of the event) on the Adverse Event eCRF and submit the 
report via the electronic data capture (EDC) system.  A report will be generated and sent 
to Roche Safety Risk Management by the EDC system. 
In the event that the EDC system is unavailable, the paper Clinical Trial Adverse 
Event/Special Situations Form provided to investigators should be completed and 
submitted to the Sponsor or its designee immediately (i.e., no more than 24 hours after 
the investigator becomes aware of the event), either by faxing or by scanning and 
e-mailing the form, using the fax number or e-mail address provided to investigators.  
Once the EDC system is available, all information will need to be entered and submitted 
via the EDC system. 
Instructions for reporting serious adverse events that occur more than 90 days after the 
final dose of study treatment are provided in Section A3–6. 
A3–6 
REPORTING ADVERSE EVENTS THAT OCCUR AFTER THE 
ADVERSE EVENT REPORTING PERIOD 
After the end of the adverse event reporting period (defined as 90 days after the final 
dose of study treatment or the initiation of next anti-lymphoma therapy, whichever is 
earlier), all deaths, regardless of cause, should be reported through use of the 
Long-Term Survival Follow-Up eCRF. 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
150/Protocol GO43643, Version 5  
In addition, if the investigator becomes aware of a serious adverse event that is believed 
to be related to prior exposure to study treatment, the event should be reported through 
use of the Adverse Event eCRF.  However, if the EDC system is not available, the 
investigator should report these events directly to the Sponsor or its designee, either by 
faxing or by scanning and e-mailing the paper Clinical Trial Adverse Event/Special 
Situations Form, using the fax number or e-mail address provided to investigators. 
A3–7 
PROCEDURES FOR RECORDING ADVERSE EVENTS 
When an adverse event occurs, it is the responsibility of the investigator to review all 
documentation related to the event (e.g., hospital progress notes, laboratory reports, and 
diagnostics reports).  The investigator will then record all relevant adverse event 
information on the Adverse Event eCRF.  It is not acceptable for the investigator to send 
photocopies of the participant’s medical records to the Medical Monitor in lieu of 
completion of the eCRF.  Investigators should use correct medical terminology and 
concepts when recording adverse events on the Adverse Event eCRF.  
Avoid colloquialisms and abbreviations.  Only 1 adverse event term should be recorded 
in the event field of the Adverse Event eCRF. 
There may be instances when copies of medical records for certain cases are requested 
by the Sponsor.  In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to the Sponsor. 
A3–7.1 
 CYTOKINE RELEASE SYNDROME/INJECTION-RELATED 
REACTIONS ATTRIBUTED TO MONSUNETUZUMAB 
Systemic injection-related reactions with symptoms (e.g., fever, headache, myalgia, 
chills, and fatigue) and CRS may be indistinguishable from one another, given the 
mechanism of action of mosunetuzumab.  Therefore, all adverse events consistent with 
a diagnosis of systemic reaction or CRS attributed to mosunetuzumab will be recorded 
singularly as CRS.  Adverse events of CRS are graded using the ASTCT CRS 
Consensus Grading (Appendix 11).  The one exception to this reporting guidance is if a 
clinical presentation suggests an immediate, acute hypersensitivity (e.g., generalized 
hives, mucosal edema, with or without wheezing and hypotension), a diagnosis of 
“allergic reaction” or “hypersensitivity reaction” or “anaphylaxis” should be used. 
For adverse events with a diagnosis of “cytokine release syndrome” related to 
mosunetuzumab SC, associated signs, symptoms, and laboratory abnormalities should 
be recorded on the dedicated eCRF for CRS events.  Each CRS event should be 
recorded separately on the Adverse Event eCRF.  The associated signs, symptoms, and 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
151/Protocol GO43643, Version 5  
laboratory abnormalities should be graded according to NCI CTCAE v5.0 and also 
recorded separately on the dedicated eCRF for CRS events. 
Localized injection-site reactions following SC mosunetuzumab administration should be 
captured as a diagnosis of "injection site reactions."  Associated signs and symptoms 
will be recorded separately on the dedicated Injection Reaction eCRF.  Please see 
Section A6–1.1.1 for details. 
If a participant experiences both a local and systemic reaction to a single administration 
of study treatment, each reaction should be recorded separately on the Adverse Event 
eCRF. 
In addition to documentations on the Adverse Event eCRF, non-serious Grade ≥ 2 
CRS events and Grade  2 injection-site reactions should be reported as a non-serious 
adverse event of special interest. 
A3–7.2 
 INFUSION-RELATED REACTIONS 
Adverse events that occur during or within 24 hours after the infusion of polatuzumab 
vedotin, rituximab, gemcitabine or oxaliplatin and are judged to be related to study 
treatment infusion should be captured as a diagnosis of infusion-related reaction on the 
Adverse Event eCRF.  If possible, avoid ambiguous terms such as “systemic reaction.”  
Associated signs and symptoms should be recorded on the dedicated eCRF.   
A3–7.3 
 DIAGNOSIS VERSUS SIGNS AND SYMPTOMS 
For adverse events other than cytokine release syndrome/infusion-related/injection 
reactions (see Section A3–7.1), a diagnosis (if known) should be recorded on the 
Adverse Event eCRF rather than individual signs and symptoms (e.g., record only liver 
failure or hepatitis rather than jaundice, asterixis, and elevated transaminases).  
However, if a constellation of signs and/or symptoms cannot be medically characterized 
as a single diagnosis or syndrome at the time of reporting, each individual event should 
be recorded on the Adverse Event eCRF.  If a diagnosis is subsequently established, all 
previously reported adverse events based on signs and symptoms should be nullified 
and replaced by one adverse event report based on the single diagnosis, with a starting 
date that corresponds to the starting date of the first symptom of the eventual diagnosis. 
A3–7.4 
ADVERSE EVENTS THAT ARE SECONDARY TO OTHER 
EVENTS 
In general, adverse events that are secondary to other events (e.g., cascade events or 
clinical sequelae) should be identified by their primary cause, with the exception of 
severe or serious secondary events.  A medically significant secondary adverse event 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
152/Protocol GO43643, Version 5  
that is separated in time from the initiating event should be recorded as an independent 
event on the Adverse Event eCRF.  For example: 
 
If vomiting results in mild dehydration with no additional treatment in a healthy adult, 
only vomiting should be reported on the eCRF 
 
If vomiting results in severe dehydration, both events should be reported separately 
on the eCRF 
 
If a severe gastrointestinal hemorrhage leads to renal failure, both events should be 
reported separately on the eCRF 
 
If dizziness leads to a fall and consequent fracture, all 3 events should be reported 
separately on the eCRF 
 
If neutropenia is accompanied by an infection, both events should be reported 
separately on the eCRF 
 
All adverse events should be recorded separately on the Adverse Event eCRF if it is 
unclear as to whether the events are associated. 
A3–7.5 
 PERSISTENT OR RECURRENT ADVERSE EVENTS 
A persistent adverse event is one that extends continuously, without resolution, between 
participant evaluation timepoints.  Such events should only be recorded once on the 
Adverse Event eCRF.  The initial severity (intensity or grade) of the event will be 
recorded at the time the event is first reported.  If a persistent adverse event becomes 
more severe, the most extreme severity should also be recorded on the Adverse Event 
eCRF.  If the event becomes serious, it should be reported to the Sponsor immediately 
(i.e., no more than 24 hours after the investigator becomes aware that the event became 
serious; see Section A3–5 for reporting instructions).  The Adverse Event eCRF should 
be updated by changing the event from “non-serious” to “serious,” providing the date that 
the event became serious, and completing all data fields related to serious adverse 
events. 
A recurrent adverse event is one that resolves between participant evaluation timepoints 
and subsequently recurs.  Each recurrence of an adverse event should be recorded as a 
separate event on the Adverse Event eCRF. 
A3–7.6 
 ABNORMAL LABORATORY VALUES 
Not every abnormal laboratory value qualifies as an adverse event.  A laboratory value 
abnormality that is associated with the underlying disease should not be reported as an 
adverse event unless judged by the investigator to be more severe than expected.  
A laboratory value abnormality that is not associated with the underlying disease must 
be reported as an adverse event if it meets any of the following criteria: 
 
Is accompanied by clinical symptoms 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
153/Protocol GO43643, Version 5  
 
Results in a change in study treatment (e.g., dose modification, treatment 
interruption, or treatment discontinuation) 
 
Results in a medical intervention (e.g., potassium supplementation for hypokalemia) 
or a change in concomitant therapy 
 
Is clinically significant in the investigator’s judgment 
 
It is the investigator’s responsibility to review all laboratory findings.  Medical and 
scientific judgment should be exercised in deciding whether an isolated laboratory 
abnormality should be classified as an adverse event. 
If a clinically significant laboratory abnormality is a sign of a disease or syndrome 
(e.g., ALP and bilirubin 5 × upper limit of normal [ULN] associated with cholestasis), only 
the diagnosis (i.e., cholestasis) should be recorded on the Adverse Event eCRF. 
If a clinically significant laboratory abnormality is not a sign of a disease or syndrome, 
the abnormality itself should be recorded on the Adverse Event eCRF, along with a 
descriptor indicating whether the test result is above or below the normal range 
(e.g., “elevated potassium,” as opposed to “abnormal potassium”).  If the laboratory 
abnormality can be characterized by a precise clinical term per standard definitions, the 
clinical term should be recorded as the adverse event.  For example, an elevated serum 
potassium level of 7.0 mEq/L should be recorded as “hyperkalemia.” 
Observations of the same clinically significant laboratory abnormality from visit to visit 
should only be recorded once on the Adverse Event eCRF (see Section A3–7.5 for 
details on recording persistent adverse events). 
A3–7.7 
 ABNORMAL VITAL SIGN VALUES 
Not every abnormal vital sign value qualifies as an adverse event.  A vital sign 
abnormality that is associated with the underlying disease should not be reported as an 
adverse event unless judged by the investigator to be more severe than expected.  
A vital sign abnormality that is not associated with the underlying disease must be 
reported as an adverse event if it meets any of the following criteria: 
 
Is accompanied by clinical symptoms 
 
Results in a change in study treatment (e.g., dose modification, treatment 
interruption, or treatment discontinuation) 
 
Results in a medical intervention or a change in concomitant therapy 
 
Is clinically significant in the investigator’s judgment 
 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
154/Protocol GO43643, Version 5  
It is the investigator’s responsibility to review all vital sign findings.  Medical and scientific 
judgment should be exercised in deciding whether an isolated vital sign abnormality 
should be classified as an adverse event. 
If a clinically significant vital sign abnormality is a sign of a disease or syndrome 
(e.g., high blood pressure), only the diagnosis (e.g., hypertension) should be recorded 
on the Adverse Event eCRF. 
Observations of the same clinically significant vital sign abnormality from visit to visit 
should only be recorded once on the Adverse Event eCRF (see Section A3–7.5 for 
details on recording persistent adverse events). 
A3–7.8 
 ABNORMAL LIVER FUNCTION TESTS 
The finding of an elevated ALT or AST ( 3  ULN) in combination with either an elevated 
total bilirubin (2  ULN) or clinical jaundice in the absence of cholestasis or other causes 
of hyperbilirubinemia is considered to be an indicator of severe liver injury (as defined by 
Hy’s Law).  Therefore, investigators must report as an adverse event the occurrence of 
either of the following: 
 
Treatment-emergent ALT or AST 3  ULN in combination with total bilirubin 
2  ULN 
 
Treatment-emergent ALT or AST 3  ULN in combination with clinical jaundice 
 
The most appropriate diagnosis or (if a diagnosis cannot be established) the abnormal 
laboratory values should be recorded on the Adverse Event eCRF (see Section A3–7.2) 
and reported to the Sponsor immediately (i.e., no more than 24 hours after the 
investigator becomes aware of the event), either as a serious adverse event or an 
adverse event of special interest (see Section A3–5). 
A3–7.9 
 DEATHS 
For this protocol, mortality is an efficacy endpoint.  Deaths that occur during the 
protocol-specified adverse event reporting period (see Section 8.3.1) that are attributed 
by the investigator solely to progression of aggressive NHL should be recorded on the 
Death Attributed to Progressive Disease eCRF.  All other deaths that occur during the 
adverse event reporting period, regardless of relationship to study treatment, must be 
recorded on the Adverse Event eCRF and immediately reported to the Sponsor 
(see Section A3–5). 
Death should be considered an outcome and not a distinct event.  The event or condition 
that caused or contributed to the fatal outcome should be recorded as the single medical 
concept on the Adverse Event eCRF.  Generally, only one such event should be 
reported.  If the cause of death is unknown and cannot be ascertained at the time of 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
155/Protocol GO43643, Version 5  
reporting, “unexplained death” should be recorded on the Adverse Event eCRF.  If the 
cause of death later becomes available (e.g., after autopsy), “unexplained death” should 
be replaced by the established cause of death.  The term “sudden death” should not 
be used unless combined with the presumed cause of death (e.g., “sudden cardiac 
death”). 
Deaths that occur after the adverse event reporting period should be reported as 
described in Section A3–6. 
A3–7.10 
PREEXISTING MEDICAL CONDITIONS 
A preexisting medical condition is one that is present at the screening visit for this study.  
Such conditions should be recorded on the General Medical History and Baseline 
Conditions eCRF. 
A preexisting medical condition should be recorded as an adverse event only if the 
frequency, severity, or character of the condition worsens during the study.  
When recording such events on the Adverse Event eCRF, it is important to convey the 
concept that the preexisting condition has changed by including applicable descriptors 
(e.g., “more frequent headaches”). 
A3–7.11 
LACK OF EFFICACY OR WORSENING OF LYMPHOMA 
Deterioration that is judged by the investigator to have unexpectedly worsened in 
severity or frequency or changed in nature (i.e., deterioration beyond the expected 
pattern of progression of the underlying disease) should be recorded as an 
adverse event.  When recording an unanticipated worsening of lymphoma on the 
Adverse Event eCRF, it is important to convey the concept that the condition has 
changed by including applicable descriptors (e.g., “accelerated worsening of 
lymphoma”).  Events that are clearly consistent with the expected pattern of progression 
of the underlying disease should not be recorded as adverse events.  These data will be 
captured as efficacy assessment data only.  In most cases, the expected pattern of 
progression will be based on Lugano Criteria (Cheson et al. 2014; Appendix 10).  In rare 
cases, the determination of clinical progression will be based on symptomatic 
deterioration.  However, every effort should be made to document progression through 
use of objective criteria.  If there is any uncertainty as to whether an event is due to 
disease progression, it should be reported as an adverse event. 
A3–7.12 
HOSPITALIZATION OR PROLONGED HOSPITALIZATION 
Any adverse event that results in hospitalization (i.e., in-patient admission to a hospital) 
or prolonged hospitalization should be documented and reported as a serious adverse 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
156/Protocol GO43643, Version 5  
event (per the definition of serious adverse event in Section A3–2), except as outlined 
below. 
An event that leads to hospitalization under the following circumstances should not be 
reported as an adverse event or a serious adverse event: 
 
Hospitalization for respite care 
 
Planned hospitalization for study treatment administration and monitoring up to 
24 hours 
 
Hospitalization for a preexisting condition, provided that all of the following criteria 
are met: 
– 
The participant was hospitalized for an elective procedure that was planned 
prior to the study, was scheduled during the study despite the fact that the 
condition had not worsened, or was scheduled during the study when treatment 
became necessary because of the expected normal progression of the 
condition 
– 
The participant has not experienced an adverse event 
 
Hospitalization due solely to progression of the underlying cancer 
 
An event that leads to hospitalization under the following circumstances is not 
considered to be a serious adverse event, but should be reported as an adverse event 
instead: 
 
Hospitalization that was necessary because of participant requirement for outpatient 
care outside of normal outpatient clinic operating hours 
 
A3–7.13 
CASES OF ACCIDENTAL OVERDOSE OR MEDICATION ERROR 
Accidental overdose and medication error (hereafter collectively referred to as 
“special situations”) are defined as follows: 
 
Accidental overdose:  accidental administration of a drug in a quantity that is higher 
than the assigned dose.  
 
Medication error:  accidental deviation in the administration of a drug 
In some cases, a medication error may be intercepted prior to administration of the 
drug. 
 
Special situations are not in themselves adverse events, but may result in 
adverse events.  Each adverse event associated with a special situation should be 
recorded separately on the Adverse Event eCRF.  If the associated adverse event fulfills 
seriousness criteria or qualifies as an adverse event of special interest, the event should 
be reported to the Sponsor immediately (i.e., no more than 24 hours after the 
investigator becomes aware of the event; see Section A3–5).  For mosunetuzumab, 

Appendix 3:  Adverse Events:  Definitions and Procedures for Recording, Evaluating, 
Follow-Up, and Reporting 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
157/Protocol GO43643, Version 5  
polatuzumab vedotin, rituximab, and tocilizumab, adverse events associated with special 
situations should be recorded as described below for each situation: 
 
Accidental overdose:  Enter the adverse event term.  Check the 
“Accidental overdose” and “Medication error” boxes. 
 
Medication error that does not qualify as an overdose:  Enter the adverse event 
term.  Check the “Medication error” box. 
 
Medication error that qualifies as an overdose:  Enter the adverse event term.  
Check the “Accidental overdose” and “Medication error” boxes. 
 
In addition, all special situations associated with mosunetuzumab, polatuzumab vedotin, 
rituximab, or tocilizumab, regardless of whether they result in an adverse event, should 
be recorded on the Adverse Event eCRF as described below: 
 
Accidental overdose:  Enter the Drug Name and “accidental overdose” as the event 
term.  Check the “Accidental overdose” and “Medication error” boxes. 
 
Medication error that does not qualify as an overdose:  Enter the name of the drug 
administered and a description of the error (e.g., wrong dose administered, wrong 
dosing schedule, incorrect route of administration, wrong drug, expired drug 
administered) as the event term.  Check the “Medication error” box. 
 
Medication error that qualifies as an overdose:  Enter the Drug Name and 
“accidental overdose” as the event term.  Check the “Accidental overdose” and 
“Medication error” boxes.  Enter a description of the error in the additional case 
details. 
 
Intercepted medication error:  Enter the Drug Name and “intercepted medication 
error” as the event term.  Check the “Medication error” box.  Enter a description of 
the error in the additional case details. 
 
As an example, an accidental overdose that resulted in a headache would require 
2 entries on the Adverse Event eCRF, 1 entry to report the accidental overdose and 
1 entry to report the headache.  The “Accidental overdose” and “Medication error” boxes 
would need to be checked for both entries. 
A3–7.14 
PARTICIPANT-REPORTED OUTCOME DATA 
Adverse event reports will not be derived from participant-reported outcomes (PRO) data 
by the Sponsor.  In addition, the Sponsor will make no attempt to reconcile participant 
reports of treatment-related symptoms via PRO data with investigator reports of 
adverse events.  Sites are not expected to review the PRO data for adverse events. 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
158/Protocol GO43643, Version 5 
Appendix 4  
Contraceptive and Barrier Guidance 
TABLE OF CONTENTS 
A4–1 
Pregnancies in Female Participants .......................................... 159 
A4–2 
Pregnancies in Female Partners of Male Participants .............. 159 
A4–3 
Abortions ................................................................................... 160 
A4–4 
Abnormal Pregnancy Outcomes ............................................... 160 
 
 

Appendix 4:  Contraceptive and Barrier Guidance 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
159/Protocol GO43643, Version 5 
A4–1 
PREGNANCIES IN FEMALE PARTICIPANTS 
Female participants of childbearing potential will be instructed through the 
Informed Consent Form to immediately inform the investigator if they become pregnant 
during the study or within 3 months after the final dose of mosunetuzumab, 9 months 
after the final dose of polatuzumab vedotin, 3 months after the final dose of tocilizumab, 
12 months after the final dose of rituximab, 6 months after the final dose of gemcitabine, 
9 months after your dose of oxaliplatin.  A paper Clinical Trial Pregnancy Reporting Form 
should be completed and submitted to the Sponsor or its designee immediately 
(i.e., no more than 24 hours after the investigator becomes aware of the pregnancy), 
either by faxing or by scanning and e-mailing the form, using the fax number or e-mail 
address provided to investigators.  Pregnancy should not be recorded on the Adverse 
Event eCRF.  The investigator should discontinue study treatment and counsel the 
participant, discussing the risks of the pregnancy and the possible effects on the fetus.  
Monitoring of the participant should continue until conclusion of the pregnancy.  
Any serious adverse events associated with the pregnancy (e.g., an event in the fetus, 
an event in the mother during or after the pregnancy, or a congenital anomaly or birth 
defect in the child) should be reported on the Adverse Event eCRF.  In addition, the 
investigator will submit a Clinical Trial Pregnancy Reporting Form when updated 
information on the course and outcome of the pregnancy becomes available. 
Attempts should be made to collect and report infant health information.  When permitted 
by the site, an Authorization for the Use and Disclosure of Infant Health Information 
would need to be signed by one or both parents (as per local regulations) to allow for 
follow-up on the infant.  If the authorization has been signed, the infant's health status at 
birth should be recorded on the Clinical Trial Pregnancy Reporting Form.  In addition, the 
Sponsor may collect follow-up information on the infant's health status at 6 and 
12 months after birth. 
A4–2 
PREGNANCIES IN FEMALE PARTNERS OF MALE 
PARTICIPANTS 
Male participants will be instructed through the Informed Consent Form to immediately 
inform the investigator if a female partner becomes pregnant during the study or within 
6 months after the final dose of polatuzumab vedotin, and 2 months after the final dose 
of tocilizumab, 6 months after the final dose of oxaliplatin or gemcitabine, and 3 months 
after the final dose of rituximab.  The investigator should report the pregnancy on the 
paper Clinical Trial Pregnancy Reporting Form and submit the form to the Sponsor or its 
designee immediately (i.e., no more than 24 hours after learning of the pregnancy), 
either by faxing or by scanning and e-mailing the form using the fax number or e-mail 
address provided to investigators.  Attempts should be made to collect and report details 
of the course and outcome of any pregnancy in the partner of a male participant 

Appendix 4:  Contraceptive and Barrier Guidance 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
160/Protocol GO43643, Version 5  
exposed to study treatment.  When permitted by the site, the pregnant partner would 
need to sign an Authorization for the Use and Disclosure of Pregnancy Health 
Information to allow for follow-up on her pregnancy.  If the authorization has been 
signed, the investigator should submit a Clinical Trial Pregnancy Reporting Form with 
additional information on the pregnant partner and the course and outcome of the 
pregnancy as it becomes available. 
Attempts should be made to collect and report infant health information.  When permitted 
by the site, an Authorization for the Use and Disclosure of Infant Health Information 
would need to be signed by one or both parents (as per local regulations) to allow for 
follow-up on the infant.  If the authorization has been signed, the infant’s health status at 
birth should be recorded on the Clinical Trial Pregnancy Reporting Form.  In addition, the 
Sponsor may collect follow-up information on the infant’s health status at 6 and 
12 months after birth. 
An investigator who is contacted by the male participant or his pregnant partner may 
provide information on the risks of the pregnancy and the possible effects on the fetus, 
to support an informed decision in cooperation with the treating physician and/or 
obstetrician. 
A4–3 
ABORTIONS 
A spontaneous abortion should be classified as a serious adverse event (as the Sponsor 
considers abortions to be medically significant), recorded on the Adverse Event eCRF, 
and reported to the Sponsor immediately (i.e., no more than 24 hours after the 
investigator becomes aware of the event; see Section A3–5). 
If a therapeutic or elective abortion was performed because of an underlying maternal or 
embryofetal toxicity, the toxicity should be classified as a serious adverse event, 
recorded on the Adverse Event eCRF, and reported to the Sponsor immediately 
(i.e., no more than 24 hours after the investigator becomes aware of the event; 
see Section A3–5).  A therapeutic or elective abortion performed for reasons other than 
an underlying maternal or embryofetal toxicity is not considered an adverse event. 
All abortions should be reported as pregnancy outcomes on the paper Clinical Trial 
Pregnancy Reporting Form. 
A4–4 
ABNORMAL PREGNANCY OUTCOMES 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomaly, birth defect, ectopic pregnancy) in a female participant exposed to 
study treatment or the female partner of a male participant exposed to study treatment 
should be classified as a serious adverse event, recorded on the Adverse Event eCRF, 

Appendix 4:  Contraceptive and Barrier Guidance 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
161/Protocol GO43643, Version 5  
and reported to the Sponsor immediately (i.e., no more than 24 hours after the 
investigator becomes aware of the event; see Section A3–5). 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
162/Protocol GO43643, Version 5 
Appendix 5  
Genetics:  Use and Analysis of DNA 
Genetic variation may impact a participant’s response to study treatment and 
susceptibility to, and severity and progression of, disease.  Variable response to study 
treatment may be due to genetic determinants that impact drug absorption, distribution, 
metabolism, and excretion; mechanism of action of the drug; disease etiology; and/or 
molecular subtype of the disease being treated.  Therefore, where local regulations and 
the Institutional Review Board or Ethics Committee allow, a blood sample will be 
collected for DNA analysis from consenting participants. 
DNA samples will be used for research related to mosunetuzumab and polatuzumab 
vedotin and related diseases.  They may also be used to develop tests or assays, 
including diagnostic tests related to mosunetuzumab and polatuzumab vedotin and 
aNHL.  Genetic research may consist of the analysis of one or more candidate genes or 
the analysis of genetic markers throughout the genome (as appropriate). 
DNA samples will be analyzed for molecular subsets of diffuse-large B-cell lymphoma.  
Additional analyses may be conducted if it is hypothesized that this may help further 
understand the clinical data. 
The samples may be analyzed as part of a multistudy assessment of genetic factors 
involved in the response to mosunetuzumab and polatuzumab vedotin or study 
treatments of this class to understand the study disease or related conditions. 
The results of genetic analyses may be reported in the Clinical Study Report or in a 
separate study summary. 
The Sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 
The samples will be retained while research on mosunetuzumab and polatuzumab 
vedotin or cancer continues but no longer than 5 years or other period as per local 
requirements. 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
163/Protocol GO43643, Version 5 
Appendix 6  
Safety Plan:  Management of Identified and Potential Risks 
TABLE OF CONTENTS 
A6–1 
Risks Associated with the Study Drugs ..................................... 165 
A6–1.1 
Risks Associated with Mosunetuzumab .................................... 165 
A6–1.1.1 
Known Risks Associated with Mosunetuzumab ........................ 165 
A6–1.1.1.1 
Cytokine Release Syndrome ..................................................... 166 
A6–1.1.1.2 
Neutropenia .............................................................................. 167 
A6–1.1.1.3 
Infections................................................................................... 167 
A6–1.1.1.4 
Tumor Flare .............................................................................. 168 
A6–1.1.1.5 
Tumor Lysis Syndrome ............................................................. 168 
A6–1.1.1.6 
Injection-Site Reactions ............................................................ 169 
A6–1.1.1.7 
Neurologic Toxicity Including ICANS ..................................... 169 
A6–1.1.1.8 
Hemophagocytic Lymphohistiocytosis ...................................... 170 
A6–1.1.2 
Potential Risks Associated with Mosunetuzumab ..................... 170 
A6–1.1.2.1 
Thrombocytopenia .................................................................... 171 
A6–1.1.2.2 
Elevated Liver Enzymes ........................................................... 171 
A6–1.1.2.3 
Immunogenicity (Anti-Drug Antibodies) ..................................... 171 
A6–1.2 
Risks Associated With Polatuzumab Vedotin............................ 172 
A6–1.2.1 
Known Risks Associated with Polatuzumab Vedotin ................ 172 
A6–1.2.1.1 
Myelosuppression:  Consolidation of Neutropenia 
(Including Febrile Neutropenia), Thrombocytopenia, and 
Anemia ...................................................................................... 172 
A6–1.2.1.2 
Peripheral Neuropathy (Sensory and/or Motor) ........................ 172 
A6–1.2.1.3 
Infections................................................................................... 172 
A6–1.2.1.4 
Infusion-Related Reactions ....................................................... 173 
A6–1.2.1.5 
Gastrointestinal Toxicity (Diarrhea, Nausea, Vomiting, 
Constipation) ............................................................................. 173 
A6–1.2.2 
Potential Risks Associated with Polatuzumab Vedotin ............. 173 
A6–1.2.2.1 
Progressive Multifocal Leukoencephalopathy ........................... 173 
A6–1.2.2.2 
Immunogenicity (Anti-Drug Antibodies) ..................................... 174 
A6–1.2.2.3 
Hepatotoxicity (Hyperbilirubinemia, Transaminase (ALT 
and/or AST Elevations) ............................................................. 174 
A6–1.2.2.4 
Reproductive Toxicity ................................................................ 174 
A6–1.2.2.5 
Fatigue and Asthenia ................................................................ 174 
A6–1.2.2.6 
Hyperglycemia .......................................................................... 174 
A6–1.2.2.7 
Renal Toxicity (Increased Serum Creatinine)............................ 175 
A6–1.2.2.8 
Pulmonary Toxicity (Interstitial Lung Disease) .......................... 175 
A6–1.2.2.9 
Joint Pain, Arthralgia, Skeletal Pain .......................................... 175 
A6–1.2.2.10 
Alopecia .................................................................................... 175 
A6–1.2.2.11 
Cardiac Arrhythmias ................................................................. 175 
A6–1.2.2.12 
Ocular Toxicity .......................................................................... 175 
A6–1.2.2.13 
Dysgeusia ................................................................................. 175 
A6–1.2.2.14 
Tumor Lysis Syndrome ............................................................. 175 
A6–1.2.2.15 
Genotoxicity/Carcinogenicity (Myelodysplastic Syndrome) ....... 176 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
164/Protocol GO43643, Version 5 
A6–1.2.2.16 
Drug-Drug Interaction (DDI) ...................................................... 176 
A6–1.3 
Risks of Overlapping Toxicities with Mosunetuzumab and 
Polatuzumab Vedotin ................................................................ 176 
A6–1.4 
Risks Associated with Rituximab .............................................. 176 
A6–1.5 
Risks Associated with Gemcitabine and Oxaliplatin .................. 176 
A6–2 
Management of Participants Who Experience Adverse 
Events ....................................................................................... 176 
A6–2.1 
Dose Modifications .................................................................... 176 
A6–2.2 
Treatment Interruption .............................................................. 177 
A6–2.3 
Management Guidelines ........................................................... 184 
A6–2.3.1 
Management of Cytokine Release Syndrome (Arm A) ............. 185 
A6–2.3.2 
Management of Hemophagocytic Lymphohistiocytosis (Arm 
A) .............................................................................................. 192 
A6–2.3.3 
Injection-Site Reactions After Mosunetuzumab SC (Arm A) ..... 196 
A6–2.3.4 
Tumor Lysis Syndrome (Arm A and B) ..................................... 197 
A6–2.3.5 
Neurologic Toxicity Including ICANS (Arm A) ........................ 198 
A6–2.3.6 
Elevated Liver Enzymes and Hepatotoxicity (Arm A) ................ 201 
A6–2.4 
Management of Adverse Events (Arm B) .................................. 202 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
165/Protocol GO43643, Version 5 
On 3 June 2022 and 22 December 2022, mosunetuzumab (Lunsumio) as a 
monotherapy has been approved by the European commission (via conditional approval) 
and the FDA (via accelerated approval) for the treatment of adult patients with relapsed 
or refractory follicular lymphoma who have received at least two prior systemic 
therapies.  Clinical development is ongoing for additional indications, including 
aggressive non-Hodgkin’s lymphoma (aNHL).  On 24 May 2022, the European 
Commission granted the full marketing authorization for the use of polatuzumab vedotin 
in combination with R-CHP for the treatment of adult patients with first-line diffuse large 
B-cell lymphoma (DLBCL).  On 19 April 2023, the FDA approved polatuzumab vedotin in 
combination with R-CHP for treatment of adult patients who have previously untreated 
DLBCL, NOS or high-grade B-cell lymphoma and who have an IPI score of 2 or greater.  
Polatuzumab vedotin has also been approved in combination with bendamustine and 
rituximab in some countries for the treatment of relapsed or refractory (R/R) diffuse large 
B-cell lymphoma (DLBCL).  Rituximab, gemcitabine, and oxaliplatin are approved and 
used for the treatment of cancer, including lymphoma.  The rituximab, gemcitabine, and 
oxaliplatin treatment regimen (R-GemOx) is commonly used in clinical practice for the 
treatment of relapsed or refractory aNHL and is listed in national and international 
guidelines (National Comprehensive Cancer Network/European Society for Medical 
Oncology).  Refer to local prescribing information for further details of approved use of 
approved study drugs.  The safety plan for participants in this study is based on clinical 
experience with study drugs in completed and ongoing studies.  The anticipated 
important safety risks for study drugs are outlined below.  Please refer to the 
Mosunetuzumab and Polatuzumab Vedotin Investigator’s Brochure, or local prescribing 
information for a complete summary of safety information. 
Several measures will be taken to ensure the safety of study participants.  
Eligibility criteria have been designed to exclude individuals at higher risk for toxicities.  
Participants will undergo safety monitoring during the study, including assessment of the 
nature, frequency, and severity of adverse events.  In addition, guidelines for managing 
adverse events, including criteria for dose modification and treatment interruption or 
discontinuation, are provided below. 
A6–1 
RISKS ASSOCIATED WITH THE STUDY DRUGS 
A6–1.1 
 RISKS ASSOCIATED WITH MOSUNETUZUMAB 
A6–1.1.1 
Known Risks Associated with Mosunetuzumab 
On the basis of clinical data to date with mosunetuzumab, the identified risks are 
described below.  Refer to the Mosunetuzumab Investigator’s Brochure for a description 
of all anticipated risks for mosunetuzumab. 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
166/Protocol GO43643, Version 5 
A6–1.1.1.1 Cytokine Release Syndrome 
CRS is a known risk associated with mosunetuzumab.  The mechanism of action of 
mosunetuzumab is immune cell activation against CD20-expressing cells; therefore, a 
spectrum of events involving injection-related reactions, target-mediated cytokine 
release, and/or hypersensitivity with or without emergent anti-drug antibodies (ADAs), 
may occur.  Other CD20-directed therapies and immunomodulatory therapies have been 
associated with IRRs, CRS, and/or hypersensitivity (Rituxan U.S. Prescribing 
Information [USPI]; Gazyva USPI; Blincyto USPI). 
CRS following mosunetuzumab administration has been reported in clinical trials of 
mosunetuzumab and is an identified risk of mosunetuzumab.  Refer to the current 
mosunetuzumab Investigator’s Brochure for details.  To date CRS events observed with 
mosunetuzumab have been mostly mild to moderate in severity, and include symptoms 
such as fever, headache, and myalgia, and respond to symptomatic treatment with 
analgesics, anti-pyretics, and antihistamines as indicated. 
Severe or life-threatening presentations of CRS, such as hypotension, tachycardia, 
dyspnea, or chest discomfort, should be treated aggressively with supportive and 
resuscitative measures as indicated, including the use of tocilizumab and/or high-dose 
corticosteroids, IV fluids, and other supportive measures per institutional practice.  
Severe CRS may be associated with other clinical sequelae such as disseminated 
intravascular coagulation, capillary leak syndrome, or may manifest as HLH.  The 
standard of care for severe or life-threatening CRS resulting from immune-based 
monoclonal antibody therapy has not been established; case reports and 
recommendations for CD19 chimeric antigen receptor (CAR) T-cell therapy have been 
published (Teachey et al. 2013; Lee et al. 2014, Maude et al. 2014; Neelapu et al. 2018; 
also see U.S. Food and Drug Administration (FDA) approval for 3 products describing 
risk management for CRS [Yescarta USPI; Kymriah USPI; Tecartus USPI]). 
Disease-related factors may be associated with an increased risk of severe CRS 
following CAR T-cell therapy.  Therefore, similar features may be associated with 
increased CRS risk with T−cell-engaging therapies.  These include, but are not limited 
to, lymphoma bone marrow involvement, extranodal disease, B-cell lymphocytosis, and 
the presence of circulating peripheral malignant cells.  Additional monitoring (i.e., more 
frequent measurements of vital signs) during mosunetuzumab dosing (especially first 
dose) should be undertaken and management of treatment-emergent adverse events 
(including CRS) must adhere to guidance in Section A6–2.3.1. 
To minimize the risk and sequelae of CRS, corticosteroid premedication should be 
administered as described in Section 6.1.2. 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
167/Protocol GO43643, Version 5 
See Appendix 3 for adverse event reporting procedures related to CRS.  See Table A6-5 
for CRS grading scale.  See Appendix 7 for anaphylaxis management.  Management 
guidelines for CRS are described in Section A6–2.3.1. 
A6–1.1.1.2 Neutropenia 
Neutropenia is a known risk associated with mosunetuzumab and is a class effect 
associated with other CD20-directed therapies as well as blinatumomab (Blincyto USPI).  
Reversible neutropenia has been observed following mosunetuzumab treatment in 
Study GO29781.  Some participants developing neutropenia have received growth factor 
support and/or temporary treatment holds.  See the Mosunetuzumab 
Investigator’s Brochure for details.  The use of growth factor should be considered in 
participants who experience Grade 3−4 neutropenia, and such participants should be 
closely monitored with more frequent assessments as applicable.  See Table A6-3 and 
Section A6–2.2. 
A6–1.1.1.3 Infections 
Infections are a known risk associated with mosunetuzumab.  Infections have been 
observed in Study GO29781. 
Mosunetuzumab should not be administered in the presence of active severe infections.  
Investigators should exercise caution when considering the use of mosunetuzumab in 
participants with history of recurring or chronic infections or with underlying conditions 
that may predispose participants to infections.  See Section 4.1.1.2 and Section A6–2.2. 
Investigators should strongly advise participants to implement behavioral modifications 
such as masking and social distancing in order to reduce the risk of contracting severe 
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. 
A positive PCR test for SARS-CoV-2 infection in an asymptomatic individual may be a 
sign of possible active infection that would require interruption of study therapy and 
clinical evaluation to assess the clinical course of the infection and administration of 
appropriate SARS-CoV-2 infection directed therapies. 
If the participant develops SARS-CoV-2 infection during study treatment, study treatment 
should be interrupted and the infection should be managed as per local or institutional 
guidelines (see Section 6.8.1).  The infection must be clinically resolved before 
resumption of study treatment.  Investigators must rule out active infection and re-assess 
benefit-risk balance prior to resuming study treatment.  Examples of ruling out an active 
infection include clinical evaluation of respiratory symptoms, radiological tests to confirm 
absence of pneumonia, and consideration of negative serial viral testing.  
Mosunetuzumab administration is not permitted during the presence of active infection. 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
168/Protocol GO43643, Version 5 
Investigators should evaluate for and aggressively manage concomitant infections that 
may occur in the presence of SARS-CoV-2 infections. 
Participants who are HIV positive may be eligible to enroll in the study if specific criteria 
are met (see Section 5.1).  Signs and symptoms of HIV may confound assessment of 
the safety profile of mosunetuzumab in combination with polatuzumab vedotin.  HIV has 
also been associated with development of secondary HLH.  Participants with positive 
HIV should be monitored per local institutional standards while receiving study 
treatment. 
A6–1.1.1.4 Tumor Flare 
Adverse events associated with tumor flare have been reported with T-cell-engaging 
therapies and are consistent with the mechanism of action of mosunetuzumab, leading 
to the influx of T cells into tumor sites.  Events involving tumor flare have been reported 
with mosunetuzumab.  These events tend to occur with a short time to onset following 
mosunetuzumab administration and present with varying degrees of severity.   In 
addition, depending on tumor size and anatomic location, events associated with tumor 
flare may potentially result in mass effects on vital structures, including airways, major 
blood vessels, and/or major organs.  Depending on the nature of the tumor flare, further 
medical and/or surgical management may be necessary.  If such manifestations are 
associated with mosunetuzumab, the investigator should consider those events to be 
tumor flare and report as “tumor flare”. 
The recognition of tumor flare may be supported by clinical presentation and temporal 
association.  Tumor flare events tend to have an early onset (Cycles 1 and 2), are 
transient, and affect organ systems in proximity to tumor involvement.  When medically 
feasible and clinically indicated, a biopsy of the involved site should be obtained to 
confirm the diagnosis of tumor flare (characterized by immune cell infiltrates) and to 
exclude other causes, including infection and disease progression.  If the clinical 
presentation involves a new or worsening of pleural or pericardial effusion or ascites, a 
sample of the fluid may be collected and analyzed. 
Participants with tumors involving critical anatomic locations should be closely monitored 
for tumor flare, and prospective preventive or interventional measures may need to be 
considered or planned prior to dosing.  See the Mosunetuzumab Investigator’s Brochure 
for the most updated information on tumor flare. 
A6–1.1.1.5 Tumor Lysis Syndrome 
Tumor lysis syndrome (TLS) is a known risk associated with mosunetuzumab and is a 
known pharmacodynamic effect of anti-tumor therapy in hematologic malignancies, 
including non-Hodgkin’s lymphoma (NHL).  Tumor lysis syndrome has been reported 
with blinatumomab, CAR T-cell therapy, and other CD20-directed therapy 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
169/Protocol GO43643, Version 5 
(Blincyto USPI; Gazyva USPI; Rituxan USPI; Porter et al. 2011).  The inherent risk of 
TLS is dependent on the malignancy being treated and individual participant 
characteristics (Coiffier et al. 2008).  There is the theoretical risk of TLS if treatment with 
mosunetuzumab results in the rapid destruction of tumor cells. 
The risk of TLS with mosunetuzumab in participants with NHL is predicted to be highest 
for those with bulky disease (defined in the context of TLS as any lesion  10 cm on the 
screening computed tomography [CT] scan) and elevated pretreatment LDH levels, 
particularly in the presence of dehydration or compromised renal function.  
While DLBCL, transformed lymphomas, and mantle cell lymphomas may be at higher 
risk of TLS as compared with follicular, marginal, and small-cell lymphomas 
(Cairo et al. 2010), any risk stratification based on tumor type must be considered along 
with the effectiveness of therapy (Howard et al. 2011). 
Management guidelines for TLS, including prophylactic measures, are described in 
Section A6–2.3.4. 
A6–1.1.1.6 Injection-Site Reactions 
As CD4  and CD8  T cells (Mueller et al. 2014) as well as B cells 
(Egbuniwe et al. 2015) reside in the skin, localized reactions following mosunetuzumab 
SC administration may occur.  The injection-site reactions are an identified risk of 
mosunetuzumab.  Injection-site reactions have been observed in Study GO29781.  As of 
2 June 2021, injection-site reactions have been reported in 32 participants (47.7%) of 
67 participants receiving SC administration of mosunetuzumab.  Thirty-one events 
(46.2%) were Grade 1 and 3 events (4.5%) were Grade 2.  No serious injection-site 
reactions were reported. 
See Appendix 3 for adverse event reporting procedures related to injection-site 
reactions.  Management guidelines for injection-site reactions are described in 
Section A6–2.3.3. 
A6–1.1.1.7 
Neurologic Toxicity Including ICANS 
The symptoms and the presentation of ICANS are varied.  The earliest manifestations of 
ICANS are tremor, dysphagia, mild difficulty with expressive speech (especially in 
naming objects), impaired attention, apraxia, and mild lethargy.  Subtle manifestations 
can progress to more severe and potentially life-threatening presentations, including 
seizures, raised intracranial pressure with cerebral edema, and coma (Lee et al. 2019, 
Borrega et al. 2019).  ICANS has been reported with T cell-redirecting therapies such 
as bispecific antibodies and CAR T-cell therapies (Maude et al. 2014; Kochenderfer et 
al. 2015; Blincyto U.S. Prescribing Information [USPI]; Columvi USPI; 
Lunsumio USPI; Tecvayli USPI). 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
170/Protocol GO43643, Version 5 
Neurologic toxicity including ICANS has been reported in patients receiving 
mosunetuzumab, including severe and life-threatening events. ICANS may occur 
concurrently with or independently from CRS. 
Manifestations of ICANS reported in patients receiving mosunetuzumab included 
confusional state, delirium, disturbance in attention and cognitive disorder, 
disorientation, lethargy, memory impairment, and encephalopathy.  The majority of 
cases of ICANS occurred during Cycle 1 of mosunetuzumab treatment. 
Management guidelines for neurologic toxicity including ICANS are described in 
Section A6–2.3.5. 
A6–1.1.1.8 Hemophagocytic Lymphohistiocytosis 
HLH, a rare condition characterized by inappropriate immune activation, is an 
identified risk with mosunetuzumab. 
HLH is a pathological and biochemical hyperinflammatory syndrome that may present 
with fever, hepatosplenomegaly, organ failure, and neurologic toxicities and is 
associated with progression or new onset of hyperferritinemia, cytopenias, coagulopathy 
with hypofibrinogenemia, and/or elevation of liver enzymes (Hines et al. 2023).  HLH 
may be precipitated by other conditions, such as infections, autoimmune disease, and 
malignancies (Ramos-Casals et al. 2014; Setiadi et al. 2022), and has been reported 
with T cell−redirecting therapies such as bispecific antibodies and CAR T-cell therapies 
(Teachey et al. 2013; Sandler et al. 2020; Kennedy et al. 2021; Abecma  U.S. 
Prescribing Information [USPI]; Blincyto USPI; Carvykti USPI).  In the context of 
CAR T-cell and other immune effector cell therapies, this phenomenon has been 
described as immune effector cell−associated hemophagocytic lymphohistiocytosis−like 
syndrome (Hines et al. 2023).   
Proposed criteria for diagnosing secondary or reactive HLH in the adult population 
have been published (Henter et al. 2007; Hejblum et al. 2014; Fardet et al. 2014; 
McClain and Eckstein 2014; Hines et al. 2023).  For management guidelines, see A6–
2.3.2. 
A6–1.1.2 
Potential Risks Associated with Mosunetuzumab 
The clinical risks associated with mosunetuzumab are not fully known at this time.  
This section summarizes the potential risks of treatment with mosunetuzumab.  
The risks described below are based on available clinical and nonclinical data, the 
anticipated mechanism of action and clinical experience from molecules of the same 
class.  

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
171/Protocol GO43643, Version 5 
A6–1.1.2.1 Thrombocytopenia 
Thrombocytopenia is a potential risk associated with mosunetuzumab and is associated 
with other CD20 directed therapies as well as blinatumomab (Blincyto USPI).  
Reversible thrombocytopenia has been observed following mosunetuzumab treatment in 
Study GO29781.  Refer to the Mosunetuzumab Investigator’s Brochure for details. 
In nonclinical testing of mosunetuzumab in cynomolgus monkeys, hematology findings 
included transiently decreased WBC, lymphocyte, monocyte, eosinophil, basophil, and 
platelet counts within the first day of mosunetuzumab exposure, followed by recovery or 
rebound recovery between Days 48.  See the Mosunetuzumab Investigator’s Brochure 
for further details on nonclinical assessments on mosunetuzumab. 
Participants should be closely monitored for thrombocytopenia; regular laboratory tests 
should be performed until the event resolves.  Transfusion of blood products 
(e.g., platelet transfusion) according to institutional practice is at the discretion of the 
treating physician.  Use of all concomitant therapies, which could possibly worsen 
thrombocytopenia related events such as platelet inhibitors and anticoagulants, should 
also be taken into consideration.  See Section 4.1.1.2 and Section A6–2.2. 
A6–1.1.2.2 Elevated Liver Enzymes 
Elevated liver enzymes are a potential risk associated with mosunetuzumab.  
Transient Grade 3 AST elevation in the setting of Grade 2 CRS as well as Grade 3 
hepatic encephalopathy/Grade 4 elevation in LFTs have been observed following 
mosunetuzumab treatment. 
In nonclinical testing with mosunetuzumab in cynomolgus monkeys, dose-dependent 
increases in serum total bilirubin along with C-reactive protein, fibrinogen, PT, and aPTT 
were observed, consistent with mosunetuzumab-induced cytokine release and an 
acute-phase protein response, with minimal activation of the coagulation system.  
Possible drug-related microscopic findings in the liver included single-cell hepatocyte 
degeneration/necrosis and immune cell infiltration in the portal area.  All findings showed 
evidence of reversibility.  See the Mosunetuzumab Investigator’s Brochure for further 
details on nonclinical assessments on mosunetuzumab. 
Participants with elevated LFTs at screening will be excluded from this trial 
(see Section 5.2). 
Management guidelines for elevated liver enzymes are described in Section A6–2.3.6. 
A6–1.1.2.3 Immunogenicity (Anti-Drug Antibodies) 
As with any recombinant antibody, mosunetuzumab may elicit an immune response, and 
participants may develop antibodies against the molecule.  Participants will be closely 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
172/Protocol GO43643, Version 5 
monitored for any potential immune response to mosunetuzumab, which may have an 
impact on the benefit-risk profile of the agent.  Therefore, a risk-based strategy 
(Rosenberg and Worobec 2004a, 2004b, 2005; Koren et al. 2008) will be utilized to 
detect and characterize ADA responses to mosunetuzumab. 
A6–1.2 
 RISKS ASSOCIATED WITH POLATUZUMAB VEDOTIN 
A6–1.2.1 
Known Risks Associated with Polatuzumab Vedotin 
Based on clinical experience with polatuzumab vedotin in patients treated in the current 
Phase I and Phase II studies, the identified risks are described below.  Refer to the 
Polatuzumab Vedotin Investigator’s Brochure for a description of all anticipated risks for 
polatuzumab vedotin. 
A6–1.2.1.1 Myelosuppression:  Consolidation of Neutropenia 
(Including Febrile Neutropenia), Thrombocytopenia, and 
Anemia 
Neutropenia, neutropenia-associated events, thrombocytopenia, and anemia, including 
serious and severe cases, have been reported in participants receiving 
polatuzumab vedotin.  Adequate hematologic function should be confirmed before 
initiation of study treatment.  Participants receiving study treatment will be regularly 
monitored for evidence of marrow toxicity with complete blood counts.  Treatment may 
be delayed or modified for hematologic toxicities as described in Table A6-3.  
The prophylactic (preemptive) or therapeutic use of G-CSF is permitted at the treating 
physician’s discretion.  Transfusion support for anemia and thrombocytopenia is 
permitted at the discretion of the investigator. 
A6–1.2.1.2 Peripheral Neuropathy (Sensory and/or Motor) 
Peripheral neuropathy (sensory and/or motor) is a known risk associated with 
polatuzumab vedotin.  Participants receiving study treatment should be monitored for 
symptoms of neuropathy, including hypoesthesia, hyperesthesia, paresthesia, 
dysesthesia, discomfort, a burning sensation, weakness, gait disturbance, or 
neuropathic pain.  Participants experiencing new or worsening peripheral neuropathy 
may require a dose delay, change in dose, or discontinuation of treatment.  
Study treatment dose and schedule modifications for peripheral neuropathy are 
described in Table A6-3.  Supportive care measures may be implemented per 
investigator preference (e.g., gabapentin). 
A6–1.2.1.3  
Infections 
Infection is a known risk associated with polatuzumab vedotin.  Participants receiving 
polatuzumab vedotin may be at a higher risk of developing infections.  
Serious infections, including opportunistic infections, such as pneumonia 
(including Pneumocystis jirovecii and other fungal pneumonia), bacteremia, sepsis, 
herpes infection, and cytomegalovirus infection have been reported in participants 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
173/Protocol GO43643, Version 5 
treated with polatuzumab vedotin.  Several other risk factors in the participant population 
under study influencing participants’ vulnerability to a higher risk of infections, 
particularly serious and opportunistic infection, include predisposition of the indication 
disease to infections, elderly population, and comorbidity. 
In addition, neutropenia is a known risk for polatuzumab vedotin.  Granulocytopenia is a 
major predisposing factor to infections in participants with B-cell lymphoma.  
The reported incidence of infection in chemotherapy courses for B-cell lymphoma 
associated with  500 granulocytes/L was higher than those with  500 granulocytes/L.  
Neutropenia events should be monitored closely and any signs of infection should be 
treated as appropriate (Flowers et al. 2013; National Comprehensive Cancer 
Network 2017).  Anti-infective prophylaxis should be considered and is described in 
Section 6.8.1. 
A6–1.2.1.4 Infusion-Related Reactions 
Infusion-related reactions have been reported in participants receiving 
polatuzumab vedotin.  Commonly experienced events included nausea, vomiting, chills, 
fever, pruritus, hypotension, flushing, and other symptoms.  In the majority of the 
participants, the events were Grade 12. 
Premedication for polatuzumab vedotin infusion administration are outlined in 
Section 6.1.1.  Close monitoring throughout the infusion is required, IRRs should be 
managed as outlined in Table A6-3, and reporting of infusion-related reactions are 
outlined in Section A3–7.2. 
A6–1.2.1.5 Gastrointestinal Toxicity (Diarrhea, Nausea, Vomiting, 
Constipation) 
Diarrhea, nausea, vomiting, constipation, and abdominal pain are reported frequently, 
with diarrhea and nausea being the most common ( 20%) treatment-emergent adverse 
events in Phase I and II clinical studies with polatuzumab vedotin.  Diarrhea has been 
responsible for study drug modification and discontinuation.  Most cases were low grade, 
with more serious cases being confounded by polypharmacy, comorbidities, or disease 
under study. 
A6–1.2.2 
Potential Risks Associated with Polatuzumab Vedotin 
A6–1.2.2.1 Progressive Multifocal Leukoencephalopathy 
One case of progressive multifocal leukoencephalopathy (PML) has been reported with 
polatuzumab vedotin treatment.  Participants should be monitored closely for new or 
worsening neurological, cognitive, or behavioral changes suggestive of PML.  
Polatuzumab vedotin and any concomitant chemotherapy should be held if PML is 
suspected and permanently discontinued if the diagnosis is confirmed. 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
174/Protocol GO43643, Version 5 
A6–1.2.2.2 Immunogenicity (Anti-Drug Antibodies) 
As with any recombinant antibody, polatuzumab vedotin may elicit an immune response, 
and participants may develop antibodies against it.  Participants will be closely 
monitored for any potential immune response to polatuzumab vedotin.  
Appropriate screening, confirmatory, and characterization assays will be employed to 
assess ADAs before, during, and after the treatment with polatuzumab vedotin. 
A6–1.2.2.3 Hepatotoxicity (Hyperbilirubinemia, Transaminase (ALT and/or 
AST Elevations) 
Hepatotoxicity has been observed in participants treated with polatuzumab vedotin in 
both the Phase I and Phase II trials.  Although the relationship between hepatotoxicity 
and polatuzumab vedotin has not been definitively determined, transient, dose-related 
increases in hepatic enzymes were noted in nonclinical rat studies.  No hepatotoxicity 
was noted following administration of the surrogate antibody-drug conjugate in 
cynomolgus monkeys. 
Elevations of transaminases have been reported in participants receiving 
polatuzumab vedotin and have ranged in intensity from Grades 14.  These have been 
reversible with and without dose modification/discontinuation.  For additional information, 
please refer to the current Polatuzumab Vedotin Investigator’s Brochure. 
For polatuzumab vedotin dose delay, modification, and discontinuation instructions, 
see Table A6-1. 
A6–1.2.2.4 Reproductive Toxicity 
Adverse effects on human reproduction and fertility are anticipated with the 
administration of polatuzumab vedotin, given the mechanism of action of monomethyl 
auristatin E (MMAE).  Standard exclusion criteria are used to ensure that participants of 
childbearing potential (male or female) are using adequate contraceptive methods. 
A6–1.2.2.5 Fatigue and Asthenia 
Fatigue or asthenia is a frequent treatment-emergent adverse event reported by 
participants with cancer while on many different therapies, and is considered a class 
effect of MMAE, other similar antibody-drug conjugates (ADCs), and with vincristine 
sulfate.  Participants with cancer are more likely to experience fatigue/asthenia while not 
on any therapeutic regimen. 
A6–1.2.2.6 Hyperglycemia 
Hyperglycemia has been observed in participants treated with polatuzumab vedotin as 
well as with other ADCs that use the same valine-citrulline-MMAE platform.  
Hyperglycemia has been reversible upon holding or discontinuing treatment of the ADCs 
and/or initiation or adjustment of anti-hyperglycemic medications. 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
175/Protocol GO43643, Version 5 
A6–1.2.2.7 Renal Toxicity (Increased Serum Creatinine) 
Preliminary safety observations in clinical trials with ADCs using the same linker and 
MMAE have suggested that some participants experience reduction of renal function 
during clinical trials.  Most events occurred in the setting of dehydration or other inciting 
illnesses. 
A6–1.2.2.8 Pulmonary Toxicity (Interstitial Lung Disease) 
Pulmonary toxicities have been reported from ongoing clinical trials of similar ADCs with 
the same linker and cytotoxic agent MMAE.  As there is no identified antibody-antigen 
binding in the lung, this is considered to be possibly due to MMAE. 
A6–1.2.2.9 Joint Pain, Arthralgia, Skeletal Pain 
Joint pain, arthralgia and skeletal pain are reported from the ongoing clinical trials of 
similar ADCs with the same linker and cytotoxic agent MMAE, and are considered an 
effect of MMAE as this is commonly reported with Adcetris (brentuximab vedotin; 
Adcetris USPI) other similar ADCs, and with vincristine sulfate. 
A6–1.2.2.10 Alopecia 
Alopecia is reported from the ongoing clinical trials of similar ADCs with the same linker 
and cytotoxic agent MMAE, and is considered a class effect of MMAE as this is 
commonly reported with brentuximab vedotin (Adcetris USPI), other similar ADCs, and 
with vincristine sulfate.  It is known to improve with cessation of treatment. 
A6–1.2.2.11 Cardiac Arrhythmias 
While not observed in the non-clinical Good Laboratory Practice studies, several serious 
adverse events of cardiac toxicities have been experienced by participants receiving an 
ADC-vc-MMAE, which is in the same class as polatuzumab vedotin. 
A6–1.2.2.12 Ocular Toxicity 
While not observed in non-clinical GLP studies, treatment-emergent adverse events of 
ocular toxicities have been experienced by participants receiving antibody drugs with the 
same drug conjugate (ADC-vc-MMAEs) as polatuzumab vedotin. 
A6–1.2.2.13 Dysgeusia 
While not observed in the non-clinical GLP studies, treatment-emergent adverse events 
of dysgeusia or alteration of taste have been experienced by participants receiving 
ADC-vc-MMAEs which are in the same class as polatuzumab vedotin. 
A6–1.2.2.14 Tumor Lysis Syndrome 
There is a potential risk of TLS if treatment with polatuzumab vedotin results in the rapid 
destruction of tumor cells.  If any evidence of TLS occurs during the study, tumor lysis 
prophylaxis measures will be instituted.   

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
176/Protocol GO43643, Version 5 
Management guidelines for TLS, including prophylactic measures, are described in 
Section A6–2.3.4. 
A6–1.2.2.15 Genotoxicity/Carcinogenicity (Myelodysplastic Syndrome) 
Polatuzumab vedotin may have carcinogenic potential given the mechanism of action of 
MMAE, the cytotoxic component of polatuzumab vedotin.  Myelodysplastic syndrome 
and other second malignancies have been reported in Phase I and II clinical studies with 
polatuzumab vedotin.  The majority of these participants had received multiple prior lines 
of anti-lymphoma therapy, and this was considered as a significant contributory factor. 
A6–1.2.2.16 Drug-Drug Interaction (DDI) 
Drug-drug interactions are a theoretical risk for polatuzumab vedotin.  No clinically 
relevant DDIs have been identified in the ongoing studies.  Participants who are 
receiving strong CYP3A inhibitors should be closely monitored for adverse reactions 
when given polatuzumab vedotin. 
A6–1.3 
 RISKS OF OVERLAPPING TOXICITIES WITH 
MOSUNETUZUMAB AND POLATUZUMAB VEDOTIN 
Potential overlapping toxicities between mosunetuzumab and polatuzumab vedotin 
include thrombocytopenia, neutropenia and infections, TLS, and hepatotoxicity.  
As such, when these toxicities occur, attribution to a particular agent may be difficult.  
Treatment hold or discontinuation decisions should in general, apply to both agents in 
response to these toxicities.  See Section A6–2 for details. 
A6–1.4 
 RISKS ASSOCIATED WITH RITUXIMAB 
Please see the current Rituximab Investigator’s Brochure for full information. 
A6–1.5 
 RISKS ASSOCIATED WITH GEMCITABINE AND OXALIPLATIN 
Please see the Prescribing Information/Summary of Product Characteristics for 
Gemcitabine and Oxaliplatin for full information on risks. 
A6–2 
MANAGEMENT OF PARTICIPANTS WHO EXPERIENCE 
ADVERSE EVENTS 
A6–2.1 
 DOSE MODIFICATIONS 
Dose modifications of tocilizumab, rituximab or gemcitabine are not allowed.  
Dose modifications are allowed for mosunetuzumab, polatuzumab vedotin and 
oxaliplatin for specific non-hematologic adverse events, as detailed in Section A6–2.3.  
The doses of the drugs must not be escalated after a dose reduction except for CRS 
events as indicated in Table A6-5.  The doses of study drugs must not be modified for 
hematologic toxicities. 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
177/Protocol GO43643, Version 5 
Table A6-1 Dose Levels and Doses for Study Drugs 
Dose Level 
Mosunetuzumab 
Polatuzumab 
Vedotin 
Oxaliplatin 
Standard dose 
See Table A6-5 for Dose 
Adjustment after Grade 3 CRS 
1.8 mg/kg 
100 mg/m2 
Dose level −1 
1.4 mg/kg 
75 mg/m2 
Dose level −2 
Discontinue drug 
Discontinue drug 
CRS  cytokine-release syndrome. 
 
A6–2.2 
TREATMENT INTERRUPTION 
For both Arm A and Arm B treatment, subsequent cycles of therapy may commence 
when ANC reaches  1000/L, platelet count reaches  75,000/L, and related 
non-hematologic toxicities have resolved to Grade  1, otherwise delay the treatment.  
For participants with extensive bone marrow involvement of lymphoma, and/or 
disease-related cytopenias at study entry, subsequent cycles of therapy may commence 
when ANC reaches  500/L, platelet count reaches  50,000/L, and related 
non-hematologic toxicities have resolved to Grade  1.  
For participants receiving mosunetuzumab, if dose delay results in a treatment-free 
interval of 6 weeks or longer, step-up dosing of mosunetuzumab is required with  mg 
mosunetuzumab (in combination with polatuzumab vedotin, if applicable) administered 
on Day 1 of the first cycle after the dose delay, followed by the next planned dose on 
Day 8 (Table A6-2).  Corticosteroid prophylaxis should be administered on both days to 
mitigate CRS risks. 
In general, if one study drug is delayed, the administration of the other study drugs 
should be delayed for the same time frame (i.e., all study drugs should be delayed for 
the same time frame so that they are all given together beginning on D1 of the same 
cycle).  Exceptions may occur to maintain the schedule of mosunetuzumab step-up. 
In the event that a participant has a toxicity necessitating mosunetuzumab interruption 
for  7 days prior to the Cycle 1 Day 8 dose (i.e. time since the  mg dose is greater than 
2 weeks), the participant is required to repeat the  mg mosunetuzumab dose 
(without polatuzumab vedotin) prior to resuming the planned treatment schedule 7 days 
after the administration of the  mg dose; Table A6-2).  Corticosteroid prophylaxis should 
be administered on both days to mitigate CRS risks. 
After the  mg step-up dose is administered, local and central study assessment should 
be repeated as specified in Table 1 and Table 3.  

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
178/Protocol GO43643, Version 5 
For treatment interruptions after Cycle 1, Day 8 or Cycle 1, Day 15, treatment should be 
continued without repeating step-up dosing, unless the treatment-free interval is 6 weeks 
or longer (see above).  
For Arm B, if these required hematologic parameters are not met within 2 weeks after 
the last treatment, and a similar delay is expected to occur for subsequent treatment, it is 
acceptable to change the treatment cycle to every 21 days, instead of 14 days.  
For treatment delays more than 14 days due to decreased neutrophil or platelet counts, 
discontinue study treatment.  In case a cycle of therapy is delayed for more than 14 days 
for reasons other than toxicity, re-initiation of treatment may be allowed if the investigator 
and Sponsor consider this in the best interest of the participant. 
If scheduled dosing coincides with a holiday that precludes dosing, dosing should 
commence on the nearest following date, with subsequent dosing continuing a 14 or 21-
day schedule as applicable. 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
179/Protocol GO43643, Version 5 
Table A6-2 Recommendations for Restarting Therapy Following Dose 
Delay for Patients in Arm A (Mosunetuzumab SC 
 mg) 
Last Dose Administered 
Time Since the Last 
Dose Administered 
Action for Next Dose(s) 
 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
180/Protocol GO43643, Version 5 
Table A6-3 Guidelines for Dose Delay, Modification or Discontinuation of Mosunetuzumab, Polatuzumab Vedotin 
and Rituximab 
Event(s) 
Dose Delay or Modification 
Grade 3 or 4 neutropenia with or 
without infection or fever a 
First occurrence 
 
Delay study treatment for a maximum of 14 days. 
 
Growth factors (e.g., G-CSF) for neutropenia are permitted (in addition to primary prophylaxis per 
Section A6–1.1.1.2).  
 
Dose of mosunetuzumab, polatuzumab vedotin, and rituximab should not be modified for this reason. 
 
For participants receiving mosunetuzumab, see Section A6–1.1.  Consider holding mosunetuzumab for 
persistent Grade 4 neutropenia. 
Recurrent Grade 3 or 4 
neutropenia 
 
Delay study treatment for a maximum of 14 days. 
 
Growth factors (e.g., G-CSF) for neutropenia are permitted (in addition to primary prophylaxis per 
Section A6–1.1.1.2). 
 
Dose of mosunetuzumab, polatuzumab vedotin, and rituximab should not be modified for this reason. 
 
For participants receiving mosunetuzumab, see Section A6–1.1.  Consider holding mosunetuzumab for 
persistent Grade 4 neutropenia. 
 
If Grade 34 neutropenia persists despite growth factor support, in the absence of fever, participant may 
continue study treatment at the investigator’s discretion. 
Grade 3 or 4 thrombocytopenia 
First occurrence 
 
Delay study treatment for a maximum of 14 days. 
 
If platelet count recovers to  75,000/L  Day 7 of the scheduled date of the next cycle, administer full 
dose of study treatment. 
 
Dose of mosunetuzumab polatuzumab vedotin, and rituximab should not be modified for this reason. 
 
For participants receiving mosunetuzumab, see Section A6–1.1.  Consider holding mosunetuzumab for 
persistent Grade 4 thrombocytopenia. 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
181/Protocol GO43643, Version 5 
Table A6−3 Guidelines for Dose Delay, Modification or Discontinuation of Mosunetuzumab, Polatuzumab Vedotin 
and Rituximab (cont.) 
Event(s) 
Dose Delay or Modification 
Recurrent Grade 3 or 4 
thrombocytopenia 
 
Delay all study treatment for a maximum of 14 days. 
 
If platelet count recovers to  75,000/L  Day 7 after the scheduled date of the next cycle, administer 
full dose of all study drugs.  
 
Dose of mosunetuzumab, polatuzumab vedotin, and rituximab should not be modified for this reason. 
 
For participants receiving mosunetuzumab, see Section A6–1.1.  Consider holding mosunetuzumab for 
persistent Grade 4 thrombocytopenia. 
Grade 1 peripheral neuropathy 
 
No study treatment modification is recommended for Grade 1 sensory or motor peripheral neuropathy. 
Grade 2 or 3 peripheral 
neuropathy (including peripheral 
sensory or motor neuropathy) 
 
Delay all study treatment. 
 
If recovered to Grade  1 within  14 days of the scheduled date of the next cycle: 
– 
If the dose of polatuzumab vedotin is 1.8 mg/kg, then reduce polatuzumab vedotin to 1.4 mg/kg 
(permanent dose reduction).  Mosunetuzumab may be administered at the recommended dose. 
– 
If there was a prior dose reduction of polatuzumab vedotin to 1.4 mg/kg for Grade 2 or 3 peripheral 
neuropathy, polatuzumab vedotin must be permanently discontinued.  Mosunetuzumab may be 
administered at the recommended dose. 
 
If not recovered to Grade  1 until  14 days or after the scheduled date for the next cycle, polatuzumab 
vedotin must be permanently discontinued.  Mosunetuzumab may be administered at the recommended 
dose. 
Grade 4 peripheral neuropathy 
(including peripheral sensory or 
motor neuropathy) 
 
Discontinue polatuzumab vedotin treatment permanently. 
 
Participants should be evaluated regarding the continuation of mosunetuzumab on the basis of their 
benefit-risk. 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
182/Protocol GO43643, Version 5 
Table A6−3 Guidelines for Dose Delay, Modification or Discontinuation of Mosunetuzumab, Polatuzumab Vedotin 
and Rituximab (cont.) 
Event(s) 
Dose Delay or Modification 
Bilirubin  3.0 mg/dL 
 
Delay all treatment until resolution to  1.5 mg/dL within  14 days.  Evaluate for causality. 
 
Dose delay should be avoided if hyperbilirubinemia is not related to hepatic injury (i.e., hemolysis or 
Gilbert disease).  In these cases, dose delay considerations should be guided by direct bilirubin levels. 
 
Consider withholding mosunetuzumab (see Section A6–2.3.6, Elevated Liver Enzymes and Hepatotoxicity). 
Grade 3 or 4 constipation 
or ileus 
 
Withhold polatuzumab vedotin until improvement to Grade  2.  Mosunetuzumab may be continued or delayed 
at the discretion of the investigator. 
 
Consider reducing polatuzumab vedotin to the next dose level (see Table A6-1) after improvement to 
Grade  2. 
Grade 3 or 4 TLS 
 
Withhold all study treatment.  The participant’s next dose may be delayed for up to 14 days. 
 
Following complete resolution TLS, study treatment may be re-administered at the full dose during next 
scheduled infusion, in conjunction with prophylactic therapy. 
 
For mosunetuzumab-specific TLS guidance, see Section A6–2.3.4, Tumor Lysis Syndrome. 
Grade 3 IRR, second 
episode 
 
Discontinue polatuzumab vedotin or rituximab permanently. 
– 
If IRR is attributed to polatuzumab vedotin, discontinue polatuzumab vedotin and continue mosunetuzumab 
and follow Table A6-4 
– 
If IRR is attributed to rituximab, discontinue rituximab and continue with GemOx and follow Table A6-4. 
 
 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
183/Protocol GO43643, Version 5 
Table A6−3 Guidelines for Dose Delay, Modification or Discontinuation of Mosunetuzumab, Polatuzumab Vedotin 
and Rituximab (cont.) 
Event(s) 
Dose Delay or Modification 
Grade 3 or 4 non-hematologic 
toxicity not specifically 
described above 
(excluding alopecia, nausea, 
and vomiting) 
 
Consider delaying all study treatment for a maximum of 14 days. 
 
Subsequent recurrence:  Based on the nature of the toxicity, decrease polatuzumab vedotin to a lower 
dose as described in Table A6-1).  There are no dose reductions for mosunetuzumab. 
 
Second and subsequent recurrence:  Based on the nature of the toxicity and if the event is not clinically 
manageable and resolving within 14 days of the date of the next scheduled cycle, consider 
discontinuation of suspect study treatment permanently. 
Hepatitis B reactivation 
(as noted by new detectable 
HBV-DNA levels) 
 
HBV-DNA levels between WHO-recommended range of 29−100 IU/mL:  Re-test within 2 weeks.  If still 
positive, hold all study treatment and treat participant with an appropriate nucleoside analogue.  
Immediately refer participant to a gastroenterologist or hepatologist. 
 
HBV-DNA levels at WHO-recommended cutoff of  100 IU/mL:  Hold all study treatment and treat the 
participant with an appropriate nucleoside analogue.  Immediately refer participant to a 
gastroenterologist or hepatologist. 
 
Rising HBV-DNA viral load (exceeding 100 IU/mL) while on an appropriate anti-viral therapy:  
Discontinue all study treatment immediately. 
G-CSF  granulocyte colony-stimulating factor; GemOx  gemcitabine, oxaliplatin; HBV  hepatitis B virus; IRR  infusion-related reaction; 
TLS  tumor lysis syndrome; WHO  World Health Organization. 
a All based on laboratory test results obtained within 72 hours before infusion of Day 1 of that cycle. 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
184/Protocol GO43643, Version 5 
A6–2.3 
 MANAGEMENT GUIDELINES 
Table A6-4 Management of Infusion-Related Reactions from Polatuzumab 
Vedotin (Arm A) or Rituximab (Arm B) 
Infusion-Related 
Symptoms 
Guidance 
Grade 1−2 
 
Slow or hold infusion. 
 
Give supportive treatment. a 
 
Upon symptom resolution, may resume infusion-rate escalation at 
the investigator’s discretion. 
 
Note:  For Grade 2 wheezing or urticaria, participant must be 
premedicated for any subsequent doses.  If symptoms recur, stop 
the infusion immediately and permanently discontinue study drug. 
Grade 3 
 
Discontinue infusion. 
 
Give supportive treatment. a 
 
Upon symptom resolution, may resume infusion-rate escalation, at 
investigator’s discretion. b 
 
Note:  If the same adverse event recurs with same severity, 
treatment must be permanently discontinued. 
 
Note:  For Grade 3 hypotension or fever, participant must be 
premedicated before re-treatment.  If symptoms recur, then study 
drug must be permanently discontinued. 
 
Note:  If participant has Grade 3 wheezing, bronchospasm, or 
generalized urticaria at first occurrence, permanently discontinue 
study drug. 
Grade 4 
 
Discontinue infusion immediately, treat symptoms aggressively, 
and permanently discontinue study drug. 
NCI CTCAE v5.0  National Cancer Institute Common Terminology Criteria for Adverse Events, 
Version 5.0. 
Refer to the NCI CTCAE v5.0 for the grading of symptoms.  Management of IgE-mediated 
allergic reactions should be as directed in the text following this table. 
a Supportive treatment:  Participants should be treated with acetaminophen/paracetamol and 
an antihistamine such as diphenhydramine if they have not been received in the previous 
4 hours.  Intravenous saline may be indicated.  For bronchospasm, urticaria, or dyspnea, 
participants may require antihistamines, oxygen, corticosteroids (e.g., prednisolone 100 mg 
IV or equivalent), and/or bronchodilators.  Participants with hypotension who require 
vasopressor support must be permanently discontinued from study drug. 
b Infusion rate escalation after re-initiation:  Upon complete resolution of symptoms, 
the infusion may be resumed at 50% of the rate achieved prior to interruption.  In the 
absence of infusion-related symptoms, the rate of infusion may be escalated in increments of 
50 mg/hour every 30 minutes. 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
185/Protocol GO43643, Version 5 
A6–2.3.1 
Management of Cytokine Release Syndrome (Arm A) 
Management guidelines for CRS following mosunetuzumab treatment are summarized 
with the grading of CRS following the American Society for Transplantation and Cellular 
Therapy (ASTCT) consensus grading criteria (Lee et al. 2019; Appendix 11) and 
described in Table A6-5. 
As participants may have received corticosteroid premedication, a fever response may 
be blunted.  Therefore, adverse events attributed to mosunetuzumab consistent with a 
diagnosis of CRS, and associated with fever, hypotension or hypoxia not attributable to 
any other cause, should be recorded as CRS.  Cytokine release syndrome events that 
manifest with hypotension and/or hypoxia, but with no fever, should be graded 
depending on management required for hypotension and/or hypoxia.  These types of 
events correspond to a minimum ASTCT Grade 2.  Other adverse events occurring 
within 24 hours after mosunetuzumab administration, should be reported as individual 
adverse events, e.g., headache or chills. 
Severe SARS−CoV-2 infection is associated with CRS involving the inflammatory 
cytokines interleukin (IL)-6, IL-10, IL-2, and IFN-.  If a participant develops severe CRS, 
the differential diagnosis should include SARS−CoV-2 and relevant testing performed at 
the discretion of the investigator.  If a diagnosis of COVID-19 is confirmed, the disease 
should be managed as per local or institutional guidelines. 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
186/Protocol GO43643, Version 5 
Table A6-5 Guidelines for Management of Cytokine Release Syndrome after Mosunetuzumab in Arm A (M  P) 
CRS Grade a 
Supportive Care 
Anti−IL-6 or 
Corticosteroid Therapy 
Action for Next 
Mosunetuzumab Dose 
Grade 1 
fever  38ºC 
 Symptomatic management of 
constitutional symptoms and 
organ toxicities; if symptoms do 
not resolve, manage per 
Grade 2 
 Consider empiric broad 
spectrum antibiotics 
 Consider G-CSF if participant is 
neutropenic 
 Maintenance IV fluids for 
hydration 
 Consider hospitalization until 
symptoms completely resolve 
 For prolonged CRS ( 2 days) in 
participants with significant symptoms 
and/or comorbidities (per investigator 
discretion, e.g., impaired cardiovascular 
function, reduced pulmonary reserve), 
consider tocilizumab and corticosteroids 
as per Grade 2 
 May receive the next dose of 
mosunetuzumab if symptoms resolve 
for 3 consecutive days 
 Administer premedications for next 
dose per Section 6.1.1 
 The participant should be monitored 
more frequently 
 
 
 
 
 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
187/Protocol GO43643, Version 5 
Table A6−5 Guidelines for Management of Cytokine Release Syndrome after Mosunetuzumab in Arm A (M+P) 
(cont.) 
CRS Grade a 
 
Supportive Care 
 
Anti−IL-6 or 
Corticosteroid Therapy 
 
Action for Next 
Mosunetuzumab Dose 
Grade 2 
fever  38ºC b 
with hypotension 
not requiring 
vasopressors 
and/or 
hypoxia requiring 
low-flow oxygen c 
by nasal cannula or 
blow-by 
 
Symptomatic management of 
constitutional symptoms and 
organ toxicities 
 
Consider ICU admission for 
hemodynamic monitoring 
 
For hypotension:  IV fluid 
bolus as needed; for 
persistent refractory 
hypotension (e.g., after 2 fluid 
boluses and antiIL-6 
therapy), start vasopressors 
and manage per Grade 3 
 
Consider tocilizumab d 
 
For persistent refractory hypotension 
after 1 or 2 doses of anti−IL-6 therapy, 
consider 10 mg IV dexamethasone 
every 6 hours (or equivalent) 
 
Manage per Grade 3 if no 
improvement within 24 hours after 
starting tocilizumab 
 
May receive the next dose of 
mosunetuzumab as planned if 
symptoms resolve to Grade  1 for 
3 consecutive days 
 
Consider enhanced premedications 
for next dose 
 
Consider hospitalization for the next 
dose if it is a higher dose e 
 
 
Rule out other inflammatory 
conditions, which can mimic 
severe CRS 
(e.g., infections/sepsis) 
 
Consider empiric broad 
spectrum antibiotics 
 
If no improvement within 
24 hours, initiate work-up and 
assess for signs and 
symptoms of HLH as 
described in Section A6–2.3  
 
 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
189/Protocol GO43643, Version 5 
Table A6−5 Guidelines for Management of Cytokine Release Syndrome after Mosunetuzumab in Arm A (M+P) 
(cont.) 
CRS Grade a 
Supportive Care 
Anti−IL-6 or 
Corticosteroid Therapy 
Action for Next 
Mosunetuzumab Dose 
 
 
If no improvement within 
24 hours, initiate work-up and 
assess for signs and 
symptoms of HLH 
(see Section A6–2.3) 
 
 
If the event occurred after 
 mg, the 
next dose should be 
 mg 
 
If the next dose is tolerated without 
Grade  3 CRS, the participant may 
return to the originally planned dose 
 
If Grade 3 CRS recurs with 
subsequent doses, consider 
permanent discontinuation 
Grade 4 
fever  38º b 
with hypotension 
requiring multiple 
vasopressors 
(excluding 
vasopressin) 
and/or 
hypoxia requiring 
oxygen by 
positive pressure 
(e.g., C-PAP, 
Bi-PAP, intubation, 
and mechanical 
ventilation) 
 
ICU admission and 
hemodynamic monitoring 
 
Mechanical ventilation as 
needed 
 
IV fluids and vasopressors as 
needed 
 
Symptomatic management of 
organ toxicities 
 
Rule out other inflammatory 
conditions that can mimic 
severe CRS (e.g., infections 
or sepsis) 
 
Consider empiric broad 
spectrum antibiotics 
 
Administer tocilizumab d 
 
For participant’s refractory to 
tocilizumab, consider siltuximab, 
anakinra, dasatinib, and emapalumab, 
based on discretion of the investigator; 
management should be discussed 
with the Medical Monitor f 
 
Administer 10 mg IV dexamethasone 
every 6 hours (or equivalent) 
 
If refractory, consider 1000 mg/day IV 
methylprednisolone g, h 
 
Permanently discontinue 
mosunetuzumab i 
 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
190/Protocol GO43643, Version 5 
Table A6−5 Guidelines for Management of Cytokine Release Syndrome after Mosunetuzumab in Arm A (M+P) 
(cont.) 
CRS Grade a 
Supportive Care 
Anti−IL-6 or 
Corticosteroid Therapy 
Action for Next 
Mosunetuzumab Dose 
 
 
If no improvement within 
24 hours, initiate work-up and 
assess for signs and 
symptoms HLH 
(see Section  A6–2.3) 
 
 
ASTCT = American Society for Transplantation and Cellular Therapy; BiPAP = bi-level positive airway pressure; C-PAP = continuous positive airway 
pressure; CRS = cytokine release syndrome; G-CSF = granulocyte colony-stimulating factor; HLH = hemophagocytic lymphohistiocytosis; 
ICU = intensive care unit; IL = interleukin; IRR = infusion-related reaction; M  mosunetuzumab; P  polatuzumab vedotin. 
a Cytokine release syndrome will be assessed according to the ASTCT Consensus Grading Criteria (Lee et al. 2019; see Appendix 11).  Fever is 
defined as temperature ≥ 38ºC not attributable to any other cause.  In participants who have CRS and then receive an anti-pyretic or 
anti-cytokine therapy such as tocilizumab or steroids, fever is no longer required to grade subsequent CRS severity.  Cytokine release syndrome 
grade is determined by the more severe event:  hypotension or hypoxia not attributable to any other cause. 
b As participants may have received corticosteroid premedication, a fever response may be blunted.  Therefore, adverse events attributed to 
mosunetuzumab consistent with a diagnosis of IRR or CRS, and associated with fever, hypotension or hypoxia not attributable to any other 
cause, should be recorded as CRS.  Cytokine release syndrome events that manifest with hypotension and/or hypoxia, but with no fever, should 
be graded depending on management required for hypotension and/or hypoxia.  These types of events correspond to minimum ASTCT Grade 2.  
Other adverse events occurring within 24 hours after mosunetuzumab administration, should be reported as individual adverse events, 
e.g., headache or chills. 
c Low-flow nasal cannula is defined as oxygen delivered at ≤ 6 L/min.  Low-flow also includes blow-by oxygen delivery.  High-flow nasal cannula is 
defined as oxygen delivered at > 6 L/min. 
d See Table 5 for tocilizumab treatment for CRS.  Tocilizumab should be administered at a dose of 8 mg/kg IV (not exceeding 800 mg per 
infusion).  If no clinical improvement in the signs and symptoms of CRS occurs after the first dose, a second dose may be administered at least 8 
hours apart (maximum 2 doses per CRS event).  Within each time-period of 6 weeks of mosunetuzumab treatment, the total number of 
tocilizumab doses should not exceed 3 doses. 
 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
191/Protocol GO43643, Version 5 
Table A6−5 Guidelines for Management of Cytokine Release Syndrome after Mosunetuzumab in Arm A (M+P) 
(cont.) 
e Although hospitalization is not mandated for participants in Arm A, the investigator should actively assess the need for hospitalization based on 
their individual conditions. 
f Riegler et al. 2019. 
g Anti-fungal prophylaxis should be strongly considered in participants receiving steroids for treatment of CRS. 
h For example, methylprednisolone 1000 mg/day IV for 3 days, followed by a rapid taper at 250 mg every 12 hours for 2 days, 125 mg every 
13 hours for 2 days, and 60 mg every 12 hours for 2 days. 
i Resumption of mosunetuzumab may be considered in participants who are deriving benefit and have fully recovered from the adverse event.  
Participants can be re-challenged if all the criteria below are met: 
• Individual risk-benefit assessment by Principal Investigator/treating physician favors continued treatment; 
• The participant has recovered from previous toxicities and has sufficient organ function/reserve to receive subsequent doses; 
• The participant has been adequately consented for risks associated with continued treatment and decides to receive subsequent doses; 
• Subsequent doses are well-planned with precautionary measures, including dose reduction, hospitalizations, and enhanced premedications. 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
192/Protocol GO43643, Version 5 
A6–2.3.2 
Management of Hemophagocytic Lymphohistiocytosis (Arm A) 
HLH and CRS that occur subsequent to T cell−redirecting therapy have overlapping 
features, and HLHlike symptoms may be seen in individuals with severe 
CRS.  Although HLH is distinct from CRS in this setting, overlapping clinical features 
may make it difficult to distinguish HLH from CRS.  Temporally, HLH may have a 
delayed onset and can occur as CRS is resolving or after CRS has resolved.  In addition, 
HLH can occur in the absence of CRS. 
HLH should be diagnosed on the basis of criteria developed by an ASTCT working 
group (Hines et al. 2023), as outlined in Table A6-6.  When reporting new HLH events, 
severity will continue be graded according to NCI CTCAE v.5.0.  In addition ASTCT 
grading (Table A6-8) should be used when describing event details within the 
Additional Case Details section on the Adverse Events eCRF page (refer to the eCRF 
guidelines for additional details).  Patients with suspected or confirmed HLH should be 
treated according to the guidelines in Table A6-7.   

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
193/Protocol GO43643, Version 5 
Table A6-6 Criteria for Diagnosing Hemophagocytic Lymphohistiocytosis 
Diagnostic Strength 
Clinical or Laboratory Manifestations a 
Required manifestation 
 
Ferritin rapidly rising and/or ferritin  2  ULN or baseline 
Most common 
manifestations 
 
Onset with resolving or resolved CRS, or worsening 
inflammatory response after initial improvement with CRS-
directed therapy b 
 
Hepatic transaminase   5  ULN if baseline was normal or 
  5   baseline if baseline was abnormal 
 
Fibrinogen   1.5 g/L (150 mg/dL) or   LLN 
 
Hemophagocytosis in bone marrow or other tissue 
 
Cytopenias: c new onset, worsening, or refractory 
Other manifestations 
that may be present 
 
Lactate dehydrogenase  ULN 
 
Other coagulation abnormalities (e.g., elevated PT or PTT) 
 
Direct bilirubin  ULN 
 
Splenomegaly:  new onset 
 
Fever: new onset d or persistent 
 
Neurotoxicity 
 
Pulmonary manifestations (e.g., hypoxia, pulmonary infiltrates, 
pulmonary edema) 
 
Renal insufficiency:  new onset 
 
Fasting triglycerides  2.99 mmol/L (265 mg/dL) 
CRS    cytokine release syndrome; HLH   hemophagocytic lymphohistiocytosis; LLN     lower 
limit of normal; ULN     upper limit of normal. 
a A diagnosis can be made only when manifestations are not attributable to alternative 
etiologies, including CRS, infection, and/or disease progression. 
b HLH can also occur in the absence of CRS. 
c Generally, at least one lineage (platelets, neutrophils, hemoglobin) will qualify as Grade 4 
cytopenia. 
d As distinguished from CRS onset or recrudescence. 
 
 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
194/Protocol GO43643, Version 5 
Table A6-7 Management Guidelines for Hemophagocytic 
Lymphohistiocytosis 
Event 
Management 
Suspected or 
confirmed HLH, any 
grade 
 For suspected HLH, withhold mosunetuzumab and initiate workup for 
HLH.  For confirmed HLH, permanently discontinue mosunetuzumab.  If 
HLH is not confirmed and participant improves, treatment may be 
resumed at the investigator's discretion following consultation with the 
Medical Monitor. 
 Contact the Medical Monitor. 
 Consult with hematologist with experience in managing HLH. 
 Identify triggering etiology.  Selection of therapy should be etiology-
driven.  
 Initiate supportive care.  Admit participant to ICU if clinically indicated. 
 Perform laboratory tests at least daily until participant is stable.  
Consider evaluating CBC with differential, creatinine, urea or BUN, PT, 
aPTT, fibrinogen, D-dimer, AST, ALT, ALP, total and direct bilirubin, 
albumin, LDH, ferritin, and CRP. 
 Assess for bacterial, viral, a and fungal infections in blood, urine, 
sputum, and (if indicated) in lung tissue (via bronchoscopy) or in 
cerebrospinal fluid, and manage infections as per institutional practice. 
 To support a diagnosis of HLH, consider testing for triglycerides, soluble 
CD25 (soluble IL-2 receptor), NK cell function, IFN-, CXCL9 ratio, 
CXCL10, IL-10, IL-18, and DNA sequencing panel for HLH 
susceptibility genes, as available. 
 Consider bone marrow aspiration with or without biopsy and (for new or 
increasing lymphadenopathy) lymph node biopsy to test for alternative 
etiologies. 
 Monitor cardiopulmonary, neurologic, and other organ function closely.  
Perform ECG and chest X-ray (or CT scan) if clinically indicated. 
 For HLH treatment, recommend administering an IL-1 blocking agent 
(e.g., anakinra) with or without IV corticosteroids (dexamethasone 
1040 mg daily [10 mg every 6 hours is most common] or equivalent if 
dexamethasone is unavailable). b  If an IL-1 blocking agent is not readily 
available, refer to local or institutional guidelines for management of 
HLH. 
 If event remains refractory or worsens, add corticosteroids if not already 
started, consider increasing the dose of the IL-1 blocking agent or 
corticosteroid, or consider adding a JAK inhibitor (e.g., ruxolitinib).  
 For life-threatening events, consider adding an agent in another class, 
such as a kinase inhibitor, cytotoxic agent, or cytokine blocker 
(e.g., ruxolitinib, etoposide, or emapalumab). 
 Participants with cytopenias or coagulopathy should be treated as per 
institutional practice. 
 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
195/Protocol GO43643, Version 5 
Table A6-7 Management Guidelines for Hemophagocytic 
Lymphohistiocytosis (cont.) 
CMV  cytomegalovirus; CRP  C-reactive protein; CRS  cytokine release syndrome; 
CT  computed tomography; EBV  Epstein Barr virus; HLH   hemophagocytic 
lymphohistiocytosis; ICU   intensive care unit; IFN   interferon; IL  interleukin; JAK  Janus 
kinase; LDH  lactate dehydrogenase; NK  natural killer; ULN  upper limit of normal. 
Note:  Refer to Hines et al. (2023) for additional information on management of participants with 
HLH. 
a Test for viral reactivation or new viral infections (e.g., EBV, CMV). 
b If corticosteroids have been initiated, they must be tapered as per institutional practice.  
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
196/Protocol GO43643, Version 5 
Table A6-8 ASTCT Grading Scale for Hemophagocytic 
Lymphohistiocytosis 
Term 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
HLH a Asymptomatic 
or mild 
symptoms; 
requires 
observation 
and/or clinical 
and diagnostic 
evaluation; 
intervention 
not indicated 
Mild to moderate 
symptoms, with 
intervention 
indicated (e.g., 
immunosuppress
ive agents 
directed at HLH, 
transfusions for 
asymptomatic 
hypofibrinogene
mia) 
Severe or medically 
significant but not 
immediately life-
threatening (e.g., 
coagulopathy with 
bleeding requiring 
transfusion support, 
or hospitalization 
required for new-
onset acute kidney 
injury, hypotension, 
or respiratory 
distress) 
Life-
threatening 
consequences; 
urgent 
intervention 
indicated 
(e.g., life-
threatening 
bleeding or 
hypotension, 
respiratory 
distress 
requiring 
intubation, 
dialysis 
indicated for 
acute kidney 
injury) 
Death 
ASTCT   American Society for Transplantation and Cellular Therapy; CRS    cytokine release 
syndrome; CTCAE v5.0    National Cancer Institute's Common Terminology Criteria for 
Adverse Events, Version 5.0; HLH     hemophagocytic lymphohistiocytosis; ULN    upper limit 
of normal. 
Note:  The ASTCT grading scale (Hines et al. 2023) is based on the CTCAE v5.0 "immune 
system disorders, other" category. 
a HLH is a pathological and biochemical hyperinflammatory syndrome that may present with 
fever, hepatosplenomegaly, organ failure, and neurologic toxicities and is associated with 
progression or new onset of hyperferritinemia, cytopenias, coagulopathy with 
hypofibrinogenemia, and/or elevation of liver enzymes.  HLH and CRS that occur subsequent 
to T cell−redirecting therapy have overlapping features, and HLH-like symptoms may be 
seen in individuals with severe CRS.  Although HLH is distinct from CRS in this setting, 
overlapping clinical features may make it difficult to distinguish HLH from 
CRS.  Temporally, HLH may have a delayed onset and can occur as CRS is resolving or after 
CRS has resolved.  In addition, HLH can occur in the absence of CRS. 
 
A6–2.3.3 
Injection-Site Reactions After Mosunetuzumab SC (Arm A) 
Participants who experience localized injection-site reactions following SC administration 
of mosunetuzumab should be managed according to the guidelines detailed in Table A6-
9. 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
197/Protocol GO43643, Version 5 
Table A6-9 Management Guidelines for Injection-Site Reactions 
Grade 
Management 
Grade 1 
 
Consider treatment with topical steroids. 
 
Continue mosunetuzumab in subsequent cycles. 
Grade 2 
 
Initiate treatment with topical steroids. 
 
If progressive after 24 hours, consider prednisone or equivalent 
1030 mg/day. 
 
Continue mosunetuzumab in subsequent cycles after improvement to 
Grade  1. 
Grade 3 
 
Withhold mosunetuzumab. 
 
Initiate prednisone 1 mg/kg/day or equivalent. 
 
Consult dermatology. 
 
Taper steroids after improvement to Grade  1. 
 
Continue mosunetuzumab in subsequent cycles after improvement to 
Grade  1. 
Grade 4 
 
Management as for Grade 3. 
 
Permanently discontinue subcutaneous mosunetuzumab 
 
A6–2.3.4 
Tumor Lysis Syndrome (Arm A and B) 
Treatment for laboratory and or clinical presentations of TLS will follow institutional 
practice.  Prophylaxis of TLS should follow local institutional practice; however, for 
participants in Arm A, the following measures must be implemented. 
All participants in Arm A should receive adequate hydration prior to study drug 
administration during Cycles 1 and 2.  In general, it is recommended that participants 
receive oral or IV hydration consisting of a fluid intake of approximately 23 L/day 
starting 24−48 hours prior to the study drug administration and at least 24 hours after 
study drug administration.  Modification of the fluid rate should be considered for 
individuals with specific medical needs.   
In addition, administration of an agent to reduce uric acid should be considered: 
 
Allopurinol (e.g., 300 mg/day orally beginning 72 hours prior to dose and continuing 
for 37 days afterward) for those participants judged to be of low or intermediate risk 
of developing TLS, per investigator’s discretion 
 
For participants with elevated uric acid levels prior to study treatment or considered 
to be at high risk for TLS:  Rasburicase (e.g., 0.2 mg/kg IV over 30 minutes prior to 
first dose mosunetuzumab and daily for up to 5 days thereafter) should be 
administered, unless contraindicated (Elitek USPI) 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
198/Protocol GO43643, Version 5 
 
Treatment with allopurinol/rasburicase should continue as specified above, or if 
laboratory evidence of TLS is observed until normalization of serum uric acid or 
other laboratory parameters 
 
A6–2.3.5 
Neurologic Toxicity Including ICANS (Arm A) 
All participants will be required to undergo a complete physical examination that 
includes a neurological system evaluation at screening (baseline) prior to study 
treatment and targeted physical examination as per the Schedule of Activities (see 
Section 1.3).  Record abnormalities observed at baseline on the General Medical History 
and Baseline Conditions eCRF.  If there is a baseline Immune Effector Cell-Associated 
Encephalopathy (ICE) score, record it in the participant’s chart. 
Participants should be routinely assessed for any signs or symptoms of neurologic 
toxicity including ICANS as part of the on-treatment clinical examination (see 
Section 8.2).  If new or worsening neurologic toxicity is suspected, see A6–2.3.5 for 
management guidelines and Section 8.3 for adverse event reporting. 
The American Society for Transplantation and Cellular Therapy (ASTCT) ICANS 
Consensus Grading for Adults (Lee et al. 2019) and Immune Effector Cell-Associated 
Encephalopathy (ICE) scoring system are summarized in Appendix 21 and Table A6-
10.  Imaging studies should be performed if clinically indicated.   
For participants developing peripheral neuropathy, see Table A6-3.  For participants 
receiving both polatuzumab vedotin and mosunetuzumab who develop Grade ≥ 2 
peripheral sensory neuropathy and/or peripheral motor neuropathy, consideration for 
holding or discontinuing mosunetuzumab in addition to action taken with polatuzumab 
vedotin should be made. 
The investigator should instruct participants to refrain from driving or engaging in 
hazardous occupations or activities if the participants develop specific adverse events 
while on mosunetuzumab:  
 
For participants who develop a neurologic toxicity, including ICANS, that may 
affect driving (see Appendix 22) and for participants who develop CRS, HLH, or 
Grade 34 LFT elevation, the investigator should advise participants to refrain from 
driving or engaging in hazardous occupations or activities until the event is resolved.  
 
Participants who develop tremor, dizziness, insomnia, or a Grade  3 neurologic 
adverse event should be assessed by neurologic examination to determine if the 
adverse event may impair the ability of the participant to drive or engage in 
hazardous occupations or activities.  For participants assessed to be at increased 
risk, the investigator should advise the participant to refrain from driving or engaging 
in hazardous occupations or activities until the event is resolved.  
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
199/Protocol GO43643, Version 5  
Table A6-10 
Management Guidelines for Neurologic Toxicity Including ICANS for Participants Receiving 
Mosunetuzumab 
Event a, b 
Action to Be Taken 
General Guidance 
 
Consider hospitalizing the participant for monitoring as clinically needed.  If clinically indicated, transfer 
participant to ICU and initiate measures for protection of airway. 
 
Assess patients for ICE using the ICE score. 
 
Consider imaging of the brain (MRI preferred), lumbar puncture, fundoscopy, and/or EEG, taking into 
account risks for procedures. 
 
Rule out other causes (e.g., infection, cerebral hemorrhage, electrolyte imbalance, concomitant 
medications, other medical conditions). 
 
Avoid medication that would cause further CNS depression. 
 
See Section A6–2.2 for guidance on restarting mosunetuzumab after dose delay. 
 
Consult the Medical Monitor  
 
Guidance for neurologic toxicity including ICANS concurrently with CRS:  
– 
Administer medications as outlined below: 
o 
Compare the corticosteroid regimen in the guidelines for ICANS below with the regimen in the 
guidelines for CRS (see Table A6-5) and administer the most aggressive regimen.  Dexamethasone 
is the preferred corticosteroid. 
– 
Administer tocilizumab as per guidelines for CRS (see Table A6-5). 
Grade 1 
 
Continue mosunetuzumab and monitor neurologic toxicity symptoms. 
 
If Grade 1 ICANS, b consider a single dose of dexamethasone 10 mg, if not taking other corticosteroids. 
Grade 2 
 
Withhold mosunetuzumab until neurologic toxicity symptoms improve to Grade 1 or baseline. c, d  
 
Provide supportive therapy and consider neurologic consultation and evaluation. 
 
If Grade 2 ICANS, b treat with dexamethasone 10 mg intravenously every 12 hours, if not taking other 
corticosteroids, until improvement to Grade 1, then taper.  

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
200/Protocol GO43643, Version 5  
Table A6-10 
Management Guidelines for Neurologic Toxicity Including ICANS for Participants Receiving 
Mosunetuzumab (cont.) 
Grade 3 
 
Withhold mosunetuzumab until neurologic toxicity symptoms improve to Grade 1 or baseline for at least 
7 days. d, e 
 
For Grade 3 neurologic events lasting more than 7 days, consider permanently discontinuing 
mosunetuzumab. 
 
Provide supportive therapy, which may include intensive care, and consider neurologic consultation and 
evaluation. 
 
If Grade 3 ICANS, b treat with dexamethasone 10 mg intravenously every 6 hours, if not taking other 
corticosteroids until improvement to Grade 1, then taper.  Consider non-sedating anti-seizure medication 
for seizure prophylaxis until resolution of ICANS.  Use anti-seizure medication for seizure management 
as needed. 
Grade 4 
 
Permanently discontinue mosunetuzumab. 
 
Provide supportive therapy, which may include intensive care, and consider neurology consultation and 
evaluation. 
 
If Grade 4 ICANS, b treat with dexamethasone 10 mg intravenously every 6 hours, if not taking other 
corticosteroids until improvement to Grade 1, then taper.  Consider non-sedating anti-seizure medication 
for seizure prophylaxis until resolution of ICANS.  Use anti-seizure medication for seizure management 
as needed. 
ASTCT  American Society for Transplantation and Cellular Therapy; CRS  cytokine release syndrome; ICANS  immune effector cell-
associated neurotoxicity syndrome; ICE   Immune Effector Cell-Associated Encephalopathy; ICU   intensive care unit; MRI   magnetic 
resonance imaging; NCI   National Cancer Institute.  
a Neurologic toxicity grading per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).  
b ASTCT consensus grading criteria. 
c Consider the type of neurologic toxicity before deciding to withhold mosunetuzumab.  
d See Section A6–2.2 for guidance on restarting mosunetuzumab after dose delay. 
e Evaluate benefitrisk before restarting mosunetuzumab. 
 
 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
201/Protocol GO43643, Version 5 
A6–2.3.6 
Elevated Liver Enzymes and Hepatotoxicity (Arm A) 
Guidelines for hepatotoxicity in Table A6-11 apply for participants receiving 
mosunetuzumab. 
For participants with isolated elevated bilirubin, see Table A6-3. 
For participants receiving both polatuzumab vedotin and mosunetuzumab who develop 
isolated elevated bilirubin, consideration for withholding or discontinuing 
mosunetuzumab in addition to action taken with polatuzumab vedotin should be made.  
Similarly, for participants developing elevated liver enzymes with or without elevated 
bilirubin, considerations for withholding or discontinuing polatuzumab vedotin should be 
made. 
Transient Grade 3 AST and ALT elevations have been observed with mosunetuzumab in 
the setting of CRS and have resolved with supportive treatment.  
Hemophagocytic lymphohistiocytosis (see Section A6–1.1.2.1) may present as acute 
liver failure (Lin et al. 2016; Jagtap et al. 2017).  In instances where no alternative 
etiology (e.g., viral, neoplastic) is identified, an immune mediated cause should be 
considered and evaluated. 
Table A6-11 
Management Guidelines for Liver Function Test 
Abnormalities and Hepatic Events for Participants Receiving 
Mosunetuzumab 
LFT Abnormality 
Management 
Grade 1 AST or 
ALT elevation 
 Continue mosunetuzumab. 
 Notify Medical Monitor and monitor LFTs (including AST, ALT, and 
bilirubin) weekly 
Grade 2 AST or 
ALT elevation 
All events: 
 Withhold mosunetuzumab 
 Monitor LFTs at least weekly and as clinically indicated until 
values resolve to normal or baseline 
 Resume mosunetuzumab when resolved to Grade  1 or baseline 
 Consider hepatology consultation 
 
Events  5 days’ duration: 
 Obtain hepatology consultation; evaluate etiology 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
202/Protocol GO43643, Version 5 
Table A6−11 
Management Guidelines for Liver Function Test 
Abnormalities and Hepatic Events for Participants Receiving 
Mosunetuzumab (cont.) 
LFT Abnormality 
Management 
Grade 3 AST or 
ALT elevation 
All events:  
 Withhold mosunetuzumab 
 Monitor LFTs every 2448 hours until decreasing, and then follow 
weekly 
 Obtain hepatology consultation; consider liver biopsy to assess 
hepatic injury a 
 Resume mosunetuzumab when resolved to Grade  1 or baseline 
 
Events  5 days’ duration 
 Resume mosunetuzumab when resolved to Grade  1 or baseline a 
Grade 4 AST or ALT 
elevation 
 Permanently discontinue mosunetuzumab b 
 Follow management guidelines as described for Grade 3 events 
CRS  cytokine release syndrome; LFT  liver function test; HLH  hemophagocytic 
lymphohistiocytosis. 
a Immune-related event should be considered when concurrent clinical and laboratory 
manifestations of CRS (Section A6–1.1.1.1) HLH (Section  A6–1.1.2.1) are present, or in 
instances where no alternative etiology (e.g., viral, neoplastic) can account for observed 
LFT abnormalities. 
b Resumption of mosunetuzumab may be considered in participants who are deriving benefit 
and who have fully recovered from the immune-related event.  Participants may resume 
dosing with mosunetuzumab only after discussion with the investigator and the 
Medical Monitor. 
 
A6–2.4 
 MANAGEMENT OF ADVERSE EVENTS (ARM B) 
The management guidelines for oxaliplatin-induced neuropathy in participants in Arm B 
is summarized in Table A6-12.  The management of other non-hematologic 
adverse events in Arm B should follow institutional standard or guidelines.  Of note, 
hematologic toxicities may lead to dose interruption as described in Section A6–2.2 but 
not dose modification. 

Appendix 6:  Safety Plan:  Management of Identified and Potential Risks 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
203/Protocol GO43643, Version 5 
Table A6-12 
Guidelines for Management of Participants who Experience 
Oxaliplatin-Induced Neuropathy (Arm B) 
Event 
Management Guidelines 
Acute pharyngolaryngeal 
dysesthesia 
(subjective sensation of 
dysphagia or dyspnea 
without stridor or wheezing) 
 
Avoid ice during infusion 
 
Limit exposure to cold temperature or cold objects 
 
Consider prolongation of infusion for up to 6 hours or per 
institutional guidelines 
Grade 2 peripheral sensory 
neuropathy, paresthesia, or 
gait disturbance 
 
For persistent Grade 2 neurosensory events that do not 
recover to at least Grade 1 by the time of the next 
scheduled oxaliplatin dose, reduce oxaliplatin by one level 
and continue other study treatments 
 
If the participant has Grade 2 neurosensory event at the 
time that subsequent doses are due, continue other study 
treatment and withhold oxaliplatin, and 
 
If neurosensory event recovered to Grade  1 at the start 
of subsequent cycle, continue treatment with reduced 
oxaliplatin dose by one level 
 
If neurosensory event does not recover to Grade  1 for 
another cycle, discontinue oxaliplatin 
Grade 3 peripheral sensory 
neuropathy, paresthesia, or 
gait disturbance 
 
If the participant has Grade 3 neurosensory event any 
time during the study that recovers to at least Grade 1 by 
the time of the next scheduled oxaliplatin dose, reduce 
oxaliplatin by one level and continue study treatments 
 
If the participant has Grade 3 neurosensory event any 
time during the study that does not recover to Grade  1 
by the time of next scheduled oxaliplatin dose, or for 
recurrent Grade 3 events, permanently discontinue 
oxaliplatin 
Grade 4 peripheral sensory 
neuropathy, paresthesia, or 
gait disturbance 
 
Permanently discontinue oxaliplatin 
 
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and STXBP2 are associated with adult-onset familial HLH. Blood 
2011;118:5794−8. 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
207/Protocol GO43643, Version 5 
Appendix 7  
Anaphylaxis Precautions 
These guidelines are intended as a reference and should not supersede pertinent local 
or institutional standard operating procedures. 
REQUIRED EQUIPMENT AND MEDICATION 
The following equipment and medication are needed in the event of a suspected 
anaphylactic reaction during study treatment administration in a clinical setting: 
 
Monitoring devices:  ECG monitor, blood pressure monitor, oxygen saturation 
monitor, and thermometer 
 
Oxygen 
 
Epinephrine for intramuscular (preferred route), SC, IV, or endotracheal 
administration in accordance with institutional guidelines 
 
Antihistamines 
 
Corticosteroids 
 
IV infusion solutions, tubing, catheters, and tape 
 
PROCEDURES 
In the event of a suspected anaphylactic reaction during study treatment administration, 
the following procedures should be performed: 
3. 
Stop the study treatment administration, if possible. 
4. 
Call for additional medical assistance. 
5. 
Maintain an adequate airway. 
6. 
Ensure that appropriate monitoring is in place, with continuous ECG and pulse 
oximetry monitoring if possible. 
7. 
Administer antihistamines, epinephrine, or other medications and IV fluids as 
required by participant status and as directed by the physician in charge. 
8. 
Continue to observe the participant and document observations. 
 

Appendix 8:  EORTC QLQ-C30 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
209/Protocol GO43643, Version 5 
 
18. Were you tired? 
1 
2 
3 
4 
 
19. Did pain interfere with your daily activities? 
1 
2 
3 
4 
 
20. Have you had difficulty in concentrating on things, 
 
like reading a newspaper or watching television? 
1 
2 
3 
4 
 
21. Did you feel tense? 
1 
2 
3 
4 
 
22. Did you worry? 
1 
2 
3 
4 
 
23. Did you feel irritable? 
1 
2 
3 
4 
 
24. Did you feel depressed? 
1 
2 
3 
4 
 
25. Have you had difficulty remembering things? 
1 
2 
3 
4 
 
26. Has your physical condition or medical treatment 
 
interfered with your family life? 
1 
2 
3 
4 
 
27. Has your physical condition or medical treatment 
 
interfered with your social activities? 
1 
2 
3 
4 
 
28. Has your physical condition or medical treatment 
 
caused you financial difficulties? 
1 
2 
3 
4 
 
 
For the following questions please circle the number between 1 and 7 that  
best applies to you 
29. 
How would you rate your overall health during the past week? 
 
 
 1 
2 
3 
4 
5 
6 
7 
 
Very poor 
 
 
 
 
 
Excellent 
 
30. 
How would you rate your overall quality of life during the past week? 
 
 
 1 
2 
3 
4 
5 
6 
7 
 
Very poor 
 
 
 
 
 
Excellent 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
212/Protocol GO43643, Version 5 
Appendix 10  
Lugano Response Criteria for Malignant Lymphoma  
(Cheson et al. 2014) 
TARGET AND NON-TARGET LESIONS 
Up to 6 of the largest target nodes, nodal masses, or other lymphomatous lesions that 
are measurable in 2 diameters should be identified from different body regions 
representative of the participant’s overall disease burden and include mediastinal and 
retroperitoneal disease, if involved.  At baseline, a measurable node must be greater 
than 15 mm in longest diameter (LDi).  Measurable extranodal disease may be included 
in the 6 representative, measured lesions.  At baseline, measurable extranodal lesions 
should be greater than 10 mm LDi. 
All other lesions (including nodal, extranodal, and assessable disease) should be 
followed as non-measured disease as non-target lesions (e.g., cutaneous, 
gastrointestinal, bone, spleen, liver, kidneys, pleural or pericardial effusions, ascites, 
bone, bone marrow). 
SPLIT LESIONS AND CONFLUENT LESIONS 
Lesions may split or may become confluent over time.  In the case of split lesions, the 
individual product of the perpendicular diameters (PPDs) of the nodes should be 
summed together to represent the PPD of the split lesion; this PPD is added to the sum 
of the PPDs of the remaining lesions to measure response.  If subsequent growth of any 
or all of these discrete nodes occurs, the nadir of each individual node is used to 
determine progression.  In the case of confluent lesions, the PPD of the confluent mass 
should be compared with the sum of the PPDs of the individual nodes, with more than 
50% increase in PPD of the confluent mass compared with the sum of individual nodes 
necessary to indicate progressive disease.  The LDi and smallest diameter (SDi) are no 
longer needed to determine progression. 

Appendix 10:  Lugano Response Criteria for Malignant Lymphoma 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
213/Protocol GO43643, Version 5 
Revised Criteria for Response Assessment 
Response and Site 
PET−CT-Based Response 
CT-Based Response 
Complete 
Complete metabolic response 
Complete radiologic response (all of the following) 
Lymph nodes and 
extralymphatic sites 
Score 1, 2, or 3 a with or without a residual mass on 5PS b 
It is recognized that in Waldeyer’s ring or extranodal 
sites with high physiologic uptake or with activation 
within spleen or marrow (e.g., with chemotherapy or 
myeloid colony-stimulating factors), uptake may be 
greater than normal mediastinum and/or liver.  In this 
circumstance, complete metabolic response may be 
inferred if uptake at sites of initial involvement is no 
greater than surrounding normal tissue even if the 
tissue has high physiologic uptake. 
Target nodes/nodal masses must regress to ≤ 1.5 cm in 
LDi 
No extralymphatic sites of disease 
Non-measured lesion 
Not applicable 
Absent 
Organ enlargement 
Not applicable 
Regress to normal 
New lesions 
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 b with reduced uptake compared with 
baseline and residual mass(es) of any size 
 50% decrease in SPD of up to 6 target measurable 
nodes and extranodal sites 
At interim, these findings suggest responding disease 
When a lesion is too small to measure on CT, assign 
5 mm × 5 mm as the default value 
At end-of-treatment, these findings indicate residual 
disease 
When no longer visible, 0  0 mm 
For a node  5 mm  5 mm, but smaller than normal, use 
actual measurement for calculation 
 

Appendix 10:  Lugano Response Criteria for Malignant Lymphoma 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
214/Protocol GO43643, Version 5 
Revised Criteria for Response Assessment 
Response and Site 
PET−CT-Based Response 
CT-Based Response 
Non-measured lesion 
Not applicable 
Absent/normal, regressed, but no increase 
Organ enlargement 
Not applicable 
Spleen must have regressed by  50% in length beyond 
normal 
New lesions 
None 
None 
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 b with no significant change in FDG uptake 
from baseline at interim or end-of-treatment 
 50% decrease from baseline in SPD of up to 
six dominant, measurable nodes and extranodal sites; 
no criteria for progressive disease are met 
Non-measured lesion 
Not applicable 
No increase consistent with progression 
Organ enlargement 
Not applicable 
No increase consistent with progression 
New lesions 
None 
None 
Bone marrow 
No change from baseline 
Not applicable 
 

Appendix 10:  Lugano Response Criteria for Malignant Lymphoma 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
215/Protocol GO43643, Version 5 
Revised Criteria for Response Assessment 
Response and Site 
PET−CT-Based Response 
CT-Based Response 
Progressive disease 
Progressive metabolic disease 
Progressive disease requires at least 1 of the following 
Individual target 
nodes/nodal masses 
Score 4 or 5 b with an increase in intensity of uptake 
from nadirc (baseline can be the nadir when there has not 
been prior regression of the involved lesions) 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 ( 13 cm), 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 
New or clear progression of preexisting non-measured 
lesions 
New lesions 
New FDG-avid foci consistent with lymphoma rather 
than another etiology (e.g., infection, inflammation); 
if uncertain regarding etiology of new lesions, biopsy 
or interval scan may be considered 
Regrowth of previously resolved lesions 
A new node  1.5 cm in any axis 
A new extranodal site > 1.0 cm in any axis; if  1.0 cm in 
any axis, its presence must be unequivocal and must be 
attributable to lymphoma 
Assessable disease of any size unequivocally attributable 
to lymphoma 
Bone marrow 
New or recurrent FDG-avid foci 
New or recurrent involvement 

Appendix 10:  Lugano Response Criteria for Malignant Lymphoma 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
216/Protocol GO43643, Version 5 
5PS  5-point scale; CT  computed tomography; FDG  fluorodeoxyglucose; GI  gastrointestinal; IHC  immunohistochemistry; 
LDi  longest transverse diameter of a lesion; MRI  magnetic resonance imaging; PET  positron emission tomography; PPD  cross 
product of the LDi and perpendicular diameter; SDi  shortest axis perpendicular to the LDi; SPD  sum of the product of the perpendicular 
diameters for multiple lesions. 
a A score of 3 in many participants indicates a good prognosis with standard treatment, especially if at the time of an interim scan.  
However, in trials involving PET where de-escalation is investigated, it may be preferable to consider a score of 3 as inadequate 
response (to avoid undertreatment). 
Measured dominant lesions:  Up to 6 of the largest dominant nodes, nodal masses, and extranodal lesions selected to be clearly 
measurable in 2 diameters.  Nodes should preferably be from disparate regions of the body and should include, where applicable, 
mediastinal and retroperitoneal areas.   Non-nodal lesions include those in solid organs (e.g., liver, spleen, kidneys, lungs), 
gastrointestinal involvement, cutaneous lesions, or those noted on palpation. 
Non-measured 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). 
b PET 5PS:  1  no uptake above background; 2  uptake  mediastinum; 3  uptake  mediastinum but  liver; 4  uptake moderately  liver; 
5  uptake markedly higher than liver and/or new lesions; X  new areas of uptake unlikely to be related to lymphoma. 
c Deviation from Lugano Criteria (Cheson 2014):  Progressive Metabolic Disease (PMD) assessment to be compared to nadir, not baseline (unless the 
nadir is the baseline visit) 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
217/Protocol GO43643, Version 5 
Appendix 11  
American Society for Transplantation and Cellular Therapy 
(ASTCT) Consensus Grading Criteria for Cytokine Release 
Syndrome 
CRS Parameter 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Fever a 
Temperature 
 38°C 
Temperature 
 38°C 
Temperature 
 38°C 
Temperature 
 38°C 
with 
Hypotension 
None 
Not requiring 
vasopressors 
Requiring a 
vasopressor with 
or without 
vasopressin 
Requiring multiple 
vasopressors 
(excluding 
vasopressin) 
and/or b 
Hypoxia 
None 
Requiring 
low-flow nasal 
cannula c or 
blow-by 
Requiring 
high-flow nasal 
cannula c, 
facemask, 
nonrebreather 
mask, or 
Venturi mask 
Requiring positive 
pressure 
(e.g., CPAP, 
BiPAP, intubation, 
and mechanical 
ventilation 
a Fever is defined as  38°C not attributable to any other cause.  In participants who have CRS 
and then receive anti-pyretic or anti-cytokine therapy such as tocilizumab or corticosteroids, 
fever is no longer required to grade subsequent CRS severity.  In this case, CRS grading is 
driven by hypotension and/or hypoxia. 
b CRS grade is determined by the more severe event:  hypotension or hypoxia not attributable 
to any other cause.  For example, a participant with temperature of 39.5°C, hypotension 
requiring 1 vasopressor, and hypoxia requiring low-flow nasal cannula is classified as having 
Grade 3 CRS. 
c Low-flow nasal cannula is defined as oxygen delivered at  6 L/min.  Low-flow also includes 
blow-by oxygen delivery, sometimes used in pediatrics.  High-flow nasal cannula is defined 
as oxygen delivered at  6 L/min. 
 
REFERENCE 
Lee DW, Santomasso BD, Locke FL et al. ASTCT consensus grading for cytokine 
release syndrome and neurologic toxicity associated with immune effector cells. 
Biol Blood Marrow Transplant 2019;25:62538. 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
218/Protocol GO43643, Version 5 
Appendix 12  
Eastern Cooperative Oncology Group (ECOG) Performance 
Status Scale 
Grade 
Description 
0 
Fully active; able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry 
out work of a light or sedentary nature (e.g., light housework or office work) 
2 
Ambulatory and capable of all self-care but unable to carry out any work 
activities.  Up and about  50% of waking hours 
3 
Capable of only limited self-care; confined to a bed or chair  50% of 
waking hours 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to 
bed or chair. 
5 
Dead 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
221/Protocol GO43643, Version 5 
Appendix 15  
Calculation of Creatinine Clearance With Use of the 
Cockcroft−Gault Formula 
Creatinine clearance (CrCl) will be calculated with use of the following formula: 
CrCl (men) = (140 − Age) × weight [in kilograms] / 
Serum Cr (mg/dL) × 72 
 
CrCl (women) = 0.85 × (140 − Age) × weight [in kilograms] / 
Serum Cr (mg/dL) × 72 
 
REFERENCE 
Gault MH, Longerich LL, Harnett JD, et al. Predicting glomerular function from adjusted 
serum creatinine [editorial]. Nephron 1992;62:249. 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
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Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
224/Protocol GO43643, Version 5 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
225/Protocol GO43643, Version 5 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
226/Protocol GO43643, Version 5 
REFERENCES 
Fondazione Italiana Linfomi. EPI Elderly Prognostic Index. [resource on the Internet] 
2022. Available from: https://redcap.filinf.it/surveys/?s=89AFXML8AK. 
Parmelee PA, Thuras PD, Katz IR, et al. Validation of the cumulative illness rating scale 
in a geriatric residential population. J Am Geriatr Soc 1995;43:1307.  
Merli F, Luminari S, Tucci A,  et al. Simplified geriatric assessment in older patients with 
diffuse large B-cell lymphoma: The prospective elderly project of the Fondazione 
Italiana Linfomi. J Clin Oncol 2021;39:121422. 
Merli F, Luminari S, Rossi G, et al. Outcome of frail elderly patients with diffuse large B-
cell lymphoma prospectively identified by Comprehensive Geriatric Assessment: 
Results from a study of the Fondazione Italiana Linfomi. Leuk Lymphoma 
2014;55:3843. 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
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REFERENCE 
Katz S, Downs TD, Cash HR, et al. Progress in the development of the index of ADL. 
Gerontologist 1970;10:2030. 
 

 
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REFERENCES 
Vellas B, Villars H, Abellan G, et al. Overview of the MNAIts history and challenges. J 
Nutr Health Aging 2006;10:45663. 
Rubenstein LZ, Harker JO, Salvà A, et al. Screening for undernutrition in geriatric 
practice: Developing the short-form mini nutritional assessment (MNA-SF). 
J Gerontol A Biol Sci Med Sci 2001;56:M36672. 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
232/Protocol GO43643, Version 5 
Appendix 20  
Sample List of Cautionary Medications 
(A) Inhibitors 
 
Strong Inhibitors 
Moderate Inhibitors 
Weak Inhibitors 
CYP3A 
Boceprevir, clarithromycin, 
cobicistat, conivaptan, 
danoprevir/ritonavir, 
elvitegravir/ritonavir, 
idelalisib,1 indinavir, 
itraconazole, ketoconazole, 
mibefradil, 
lopinavir/ritonavir, 
nefazodone, nelfinavir, 
paritaprevir/ritonavir 
combinations, ritonavir, 
posaconazole, saquinavir, 
telaprevir, telithromycin, 
tipranavir/ritonavir, 
troleandomycin, 
voriconazole 
Amprenavir, aprepitant, 
atazanavir, cimetidine, 
ciprofloxacin, 
clotrimazole, crizotinib, 1 
cyclosporine, 1 
darunavir/ritonavir, 
diltiazem, dronedarone, 
erythromycin, 
fluconazole, 
fluvoxamine, 
fosamprenavir, imatinib, 
1 isavuconazole, 
tofisopam, verapamil 
chlorzoxazone, 
cilostazol, 
fosaprepitant, 
istradefylline, ivacaftor, 
lomitapide, ranitidine, 
ranolazine, tacrolimus, 
ticagrelor 
1 These are the anti-cancer agents; contact Medical Monitor before use. 
 
P-gp 
amiodarone, carvedilol, clarithromycin, dronedarone, itraconazole, lapatinib, 
lopinavir and ritonavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir 
and ritonavir, telaprevir, tipranavir and ritonavir, verapamil 
 
(B) Inducers 
 
Strong Inducers 
Moderate Inducers 
Weak Inducers 
CYP3A 
Avasimibe, carbamazepine, 
enzalutamide, mitotane, 
phenytoin, rifampin, 
St. John’s wort 
bosentan, efavirenz, 
etravirine, modafinil, 
nafcillin 
armodafinil, rufinamide 
FDA = U.S. Food and Drug Administration. 
Source:  FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and 
Inducers. 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
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Appendix 21  
ASTCT ICANS Consensus Grading for Adults and 
ICE Assessment 
ASTCT ICANS Consensus Grading for Adults 
Neurotoxicity 
Domain 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
ICE score a  
79 
36 
02 
0 (patient is unarousable 
and unable to perform 
ICE Assessment) 
Depressed level of 
consciousness b 
Awakens 
spontaneously 
Awakens 
to voice 
Awakens only to 
tactile stimulus 
Patient is unarousable or 
requires vigorous or 
repetitive tactile stimuli 
to arouse.  Stupor or 
coma. 
Seizure 
NA 
NA 
Any clinical seizure 
focal or generalized 
that resolves rapidly 
or nonconvulsive 
seizures on EEG that 
resolve with 
intervention 
Life-threatening 
prolonged seizure 
(> 5 min); or repetitive 
clinical or electrical 
seizures without return 
to baseline in between 
Motor findings c 
NA 
NA 
NA 
Deep focal motor 
weakness such as 
hemiparesis or 
paraparesis 
Elevated 
ICP/cerebral 
edema 
NA 
NA 
Focal/local edema on 
neuroimaging d 
Diffuse cerebral edema 
on neuroimaging; 
decerebrate or 
decorticate posturing; or 
cranial nerve VI palsy; or 
papilledema; or 
Cushing's triad 
ASTCT = American Society for Transplantation and Cellular Therapy; CTCAE = Common 
Terminology Criteria for Adverse Events; ICANS = immune effector cell-associated neurotoxicity 
syndrome; ICE = Immune Effector Cell-Associated Encephalopathy; ICP = intracranial pressure; 
min = minute; NA = not applicable; NCI = National Cancer Institute.  
Note:  ICANS grade is determined by the most severe event (ICE score, level of consciousness, 
seizure, motor findings, raised ICP/cerebral edema) not attributable to any other cause; for 
example, a patient with an ICE score of 3 who has a generalized seizure is classified as Grade 3 
ICANS. 
a A patient with an ICE score of 0 may be classified as Grade 3 ICANS if awake with global 
aphasia, but a patient with an ICE score of 0 may be classified as Grade 4 ICANS if 
unarousable. 
b Depressed level of consciousness should be attributable to no other cause (e.g., no sedating 
medication). 
c Tremors and myoclonus associated with immune effector cell therapies may be graded 
accordingly to NCI CTCAE, but they do not influence ICANS grading. 
d Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity 
feature and is excluded from ICANS grading.  It may be graded according to NCI CTCAE. 
 

Appendix 21:  ASTCT ICANS Consensus Grading for Adults and ICE Assessment 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
234/Protocol GO43643, Version 5 
 
Immune Effector Cell-Associated Encephalopathy Assessment 
If patient is arousable and able to perform Immune Effector Cell-Associated 
Encephalopathy (ICE) Assessment, assess the following: 
 
Orientation (oriented to year, month, city, hospital  4 points) 
 
Naming (name three objects; e.g., point to clock, pen, button  3 points) 
 
Following commands (e.g., "show me two fingers" or "close your eyes and stick out 
your tongue"  1 point) 
 
Writing (ability to write a standard sentence  1 point), and  
 
Attention (count backwards from 100 by tens  1 point) 
 
If patient is unarousable and unable to perform ICE Assessment (Grade 4 
ICANS)  0 points 
 
Reference 
Lee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for cytokine 
release syndrome and neurologic toxicity associated with immune effector cells. 
Biol Blood Marrow Transplant 2019;25:62538. 
 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
235/Protocol GO43643, Version 5 
Appendix 22  
Neurologic Toxicity Including ICANS that May Affect Driving 
Participants should be advised by the study investigator of potential neurologic toxicity, 
which may include seizures and alterations of consciousness.  
Neurologic toxicity including ICANS with the potential to impact cognition or 
consciousness that may affect driving (driving-impacting cognition or consciousness 
neurologic events [DI-CCNAE]) include, but are not limited to:  amnesia, aphasia, 
confusional state, delirium, depressed level of consciousness, disturbance in attention, 
encephalopathy, hallucination, hepatic encephalopathy, insomnia, memory impairment, 
seizure, visual hallucination, and vertigo.  
Neurologic toxicity including ICANS with the potential to impact cognition or 
consciousness (cognition or consciousness neurologic events [CCNAE]) may include, 
but are not limited to:  dizziness, insomnia, postural dizziness, and tremor.  Participants 
with CCNAEs or Grade  3 neurologic toxicity including ICANS should be assessed by 
neurologic examination to evaluate risk of impairment for driving or engaging in 
hazardous occupations or activities.  When necessary, consult the Medical Monitor and 
obtain neurology consultation for evaluation of neurologic events that have the potential 
to impact cognition or consciousness.

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
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Appendix 23  
Protocol Amendment History 
A rationale for the current amendment precedes the Table of Contents. 
PROTOCOL AMENDMENT, VERSION 4 (20 February 2024): 
Protocol GO43643, Version 4 has been primarily amended to add objective response 
rate (ORR) as a dual primary endpoint and include additional futility analyses to 
incorporate 
  Changes to 
the protocol, along with a rationale for each change, are summarized below: 
 
ORR assessed by Independent Review Facility (IRF) has been designated as a dual 
primary endpoint for the efficacy objective (Figure 1 and Table 6).  
– 
Section 9.1, Section 9.2.2, and Section 9.4.2 have been updated to include the 
definition, hypothesis testing, and the target of estimation for the dual primary 
endpoint of ORR by IRF.  
– 
Section 9.5.1 has been updated to clarify the planned analysis for ORR.  The 
dual primary endpoint of ORR by IRF analysis will be conducted on the first 
 randomized participants.  This analysis is considered the primary analysis 
for ORR and the interim analysis for the study. 
 
Table 1, Table 2, and Table A2-1 have been updated to extend the polymerase chain 
reaction (PCR) monitoring time period for patients with occult or prior hepatitis B 
infection and patients with positive human immunodeficiency virus (HIV) test at 
screening, which will include the first 12 months during post-treatment follow-up: 
– 
Participants with occult or prior hepatitis B infection (defined as positive total 
hepatitis B core antibody [HBcAb] and negative hepatitis B surface antigen 
[HBsAg]) may be included if hepatitis B virus (HBV) DNA is undetectable at 
the time of screening.  These participants should be considered for prophylactic 
antivirals (e.g., entecavir) before and throughout the treatment, and must 
undergo monthly DNA testing while the patient is on treatment.  During post 
treatment follow up, the HBV DNA testing will continue every 
3 months ( 4 weeks) for 12 months after end of treatment visit.   
– 
Participants who are positive for HIV may be eligible provided they are stable 
on antiretroviral therapy for at least 4 weeks, have a CD4 count   200/L, have 
an undetectable viral load, and have not had a history of opportunistic 
infection attributable to acquired immunodeficiency syndrome (AIDS) within 
the last 12 months.  Participants with a positive HIV result at screening 
should be monitored after receiving study treatment.  HIV viral load will be 
performed every 3 months (  4 weeks) until end of study treatment, and then 
every 6 months (  4 weeks) during post treatment follow up for 12 months 
after end of treatment visit.   
– 
The relevant eligibility criteria (Section 5.1) has been clarify that participants 
with occult or prior hepatitis B infection or those who are positive for HIV 

Appendix 23:  Protocol Amendment History 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
237/Protocol GO43643, Version 5 
must be willing to undergo repeated testing during the study as specified 
above.  
 
Section 4.1.3 has been updated to clarify that the independent Data Monitoring 
Committee (iDMC) will evaluate both safety and efficacy data periodically during 
the study.   
 
Section 9.2.1 and Section 9.5.2 have been updated to include a futility analysis for 
progression-free survival (PFS) by IRF and a second overall survival (OS) futility 
analysis.  The first PFS by IRF analysis will be performed by the iDCC for iDMC 
review to assess futility, at the time of the dual primary endpoint ORR analysis, on 
the first 
 randomized participants.  The PFS futility boundary is set at PFS 
hazard ratio (HR) greater than 
for mosunetuzumab and polatuzumab in 
comparison with rituximab, gemcitabine, oxaliplatin (R-GemOx).  The first OS 
futility analysis will be performed when approximately 
 OS events are observed. 
The second OS futility analysis will be performed at the time of the dual primary 
endpoint ORR analysis. For the first and second OS analyses, OS effect is 
considered detrimental if OS HR is greater than 
 for mosunetuzumab and 
polatuzumab vedotin compared to R-GemOx. 
 
Additional minor changes have been made to improve clarity and consistency.  
Substantive new information appears in italics.  This amendment represents 
cumulative changes to the original protocol. 
 
PROTOCOL AMENDMENT, VERSION 3: (4 OCTOBER 2023) 
Protocol GO43643, Version 3 has been primarily amended to add an interim analysis 
based on overall response rate (ORR) and to incorporate 
 
  Changes to the protocol, along with a rationale for each 
change, are summarized below: 
 
, language related to participants with positive HIV test has 
been updated to clarify the viral monitoring plan for this population, given the 
potential risks associated with the use of mosunetuzumab.  Additionally, if local HIV 
laboratory assessments are not available for testing, local test may be waived if 
central laboratory assessment samples are collected (Tables 1 and 2 of Section 1.3, 
Table A2-1 of Appendix 2 and Appendix A.61.1.1.3).   
 
Language on participants with occult or prior hepatisis B infection in the Schedule of 
Activities has been updated to align with that in the the exclusion criteria (Tables 1 
and 2 of Section 1.3 and Table A2-1 of Appendix 2). 
 
Additional timepoint for radiographic studies and biomarker sample collections have 
been added at month 30 (  2 months) after Cycle 1 Day 1 for both Arm A and Arm B 
(Tables 1, 2, 3, and 4 of Section 1.3).  The average duration of study participation 
for each participant has been updated from 2 years to 2.5 years (Section 4.5). 

Appendix 23:  Protocol Amendment History 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
238/Protocol GO43643, Version 5 
 
A timepoint for mosunetuzumab and polatuzumab vedotin pharmacokinetics (PK) 
and anti-drug antibody (ADA) sample collection has been removed during post 
treatment follow up at   90 days after the last dose of mosunetuzumab (Table 3 of 
Section 1.3).  
 
Guidance regarding tocilizumab dosing for cytokine release syndrome (CRS) has 
been updated to maintain tocilizumab exposures within established clinical 
boundaries for the safety and efficacy of tocilizumab (Table 5 of Section 1.3, Section 
6.1.3., Table A6-5 of Appendix 6). 
 
Section 2.2 and Appendix 6 have been updated to include US FDA approval of  
mosunetuzumab as monotherapy for the treatment of adult patients with relapsed or 
refractory follicular lymphoma who have received at least two prior systemic 
therapies, and polatuzumab vedotin in combination with rituximab plus 
cyclophosphamide, doxorubicin, and prednisone (R-CHP) in adult patients who 
have previously untreated diffuse-large B-cell lymphoma, not otherwise specified or 
high-grade B-cell lymphoma and who have an International Prognostic Index score 
of 2 or greater. 
 
The benefitrisk assessment section has been updated to include CRS as a risk for 
mosunetuzumab that occurs most commonly during step-up dosing, and to clarify 
that the risk of COVID-19 vaccines potentiating CRS is unknown (Section 2.3.1). 
 
Section 4.1.3 has been updated to add assessment of potential overall survival (OS) 
detriment to the stopping rules based on the independent Data Monitoring 
Committee (iDMC) review.  The iDMC meeting frequency has been updated from 
approximately every  months to approximately every  months.  The stopping rule 
parameter regarding Grade  3 CRS has been updated from  10% to   5% for 
mosunetuzumab for the subsequent iDMC reviews after the first iDMC review.  
 
 
 
 
The total length of study has been adjusted to be approximately 5 years based on 
the current enrollment (Section 4.4). 
 
The sample size and timing of the China extension cohort has been clarified such 
that additional participants may be enrolled from China in an extended China 
enrollment cohort to ensure a total of approximately
participants in China 
(Section 5). 
 
The inclusion criteria have been updated to reflect that all participants on study are 
transplant ineligible, and the creatinine clearance threshold has been lowered 
to   30 mL/min (Section 5.1).  
 
The exclusion criteria have been updated to exclude participants with Grade   1 
persistent toxicity related to prior anti-lymphoma treatment (with certain exceptions), 
and to exclude participants with a history of interstitial lung disease and/or 

Appendix 23:  Protocol Amendment History 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
239/Protocol GO43643, Version 5 
pneumonitis within 6 months prior to the first dose of study treatment or those with 
active symptoms (Section 5.2).  
 
An exclusion criterion of a positive severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2) test within 7 days prior to enrollment (including rapid antigen test) 
has been added (Section 5.2).  
– 
The schedule of activities has been updated to include SARS-CoV-2 testing by 
antigen or PCR within 7 days prior to enrollment to determine study eligibility 
(Tables 1 and 2 of Section 1.3). 
 
Section 6 has been updated to specify that all other medicines described in the 
protocol and not specifically listed as investigational medicinal products 
(IMPs) should be considered non-investigational medicinal products (NIMPs). 
 
Section 6.8 has been updated such that information on coronavirus disease 2019 
vaccine administration should be collected even if it was given more than 7 days 
prior to initiation of study treatment.   
 
Additional language has been added in the Permitted Therapy section regarding 
recommendations on SARS-CoV-2 infection prophylaxis, vaccinations, and 
treatment (Section 6.8.1). 
 
The section on cautionary therapy has been updated to include P-glycoprotein 
inhibitors (Section 6.8.2.1). 
 
 
 
 
 
It has been made explicit that expedited safety reports are notified to EudraVigilance 
(Section 8.3.4). 
 
Additional terms (i.e., acute respiratory distress syndrome, pulmonary fibrosis, 
organizing pneumonia, and/or pulmonary toxicity) have been added to the Adverse 
Events of Special Interest section (Section 8.3.8.1). 
 
Section 8.10.1 has been modified to allow remote administration of participant-
reported outcome instruments in the event that participants were not able to come to 
the clinic for the scheduled assessment. 
 
An interim analysis for ORR has been incorporated (Study Schema Figure 1).  The 
extended enrollment timeline for the study has increased the power for the primary 
analysis, as PFS events will continue to accumulate beyond the target number of 
events while the trial enrolls.  Therefore, the study has adequate power to add an 
interim analysis for objective response rate, which will include the first 
 
randomized subjects.  The hypothesis testing, sample size, timing of analysis for the 
interim ORR analysis, as well as the Type I error control have been included 
(Sections 9.1, 9.2 and 9.5). 

Appendix 23:  Protocol Amendment History 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
240/Protocol GO43643, Version 5 
 
Section 9.4.3 has been updated to include statistical analysis methods used for the 
secondary efficacy endpoints. 
 
Section 9.5.3 has been updated to include assessment for OS detriment.  
 
Language has been clarified to indicate that any substantial amendments to the 
protocol will require IRB/EC and health authority approval (as locally required) 
before implementation of changes, except for administrative changes or changes 
necessary to eliminate an immediate hazard to study participants (Section A1-1 of 
Appendix 1). 
 
A description of the technical and organizational security measures taken to protect 
personal data has been added to align with Roche practices (Section A1-4 of 
Appendix 1). 
 
Additional language has been added to the Infections section to include 
recommendations for SARS-CoV-2 risk management, to provide guidance on study 
treatment interruption and resumption during and after a SARS-CoV-2 infection, and 
to emphasize that mosunetuzumab should not be administered in the presence of 
an active infection (Section A6-1.1.1.3 of Appendix 6). 
 
General guidance on assessment and reporting of tumor flare events has been 
updated to help the investigator identify tumor flare event following treatment with 
mosunetuzumab (Section A61.1.1.4 of Appendix 6). 
 
Additional language has been added to streamline dose delays and provide dosing 
flexibility due to logistics or holiday (Section A6-2.2 of Appendix 6).  
 
A new table (Table A6-2) has been added to provide additional clarity on how 
mosunetuzumab treatment should be re-initiated based on potential dose delay 
scenarios (Section A6-2.2 of Appendix 6).  
 
The CRS management table has been updated to provide additional guidance on 
action for the next mosunetuzuamb dose following Grade 1 CRS event (Table A6-5 
of Appendix 6). 
 
Recommendation for dose reduction following Grade 12 seizure has been 
removed, based on cumulated clinical data and exposure-response analyses (Table 
A6-7 of Appendix 6).  
 
Based on feedback from experts in the lymphoma disease area, one clarification 
has been added to Appendix 10 (Lugano Response Criteria for Malignant 
Lymphoma) regarding the disease progression assessment based on PET-CT.  For 
disease progression based on individual target nodes/nodal masses, the intensity of 
uptake should be compared from nadir instead of baseline to define progressive 
metabolic disease. 
 
 
 
  
 

Appendix 23:  Protocol Amendment History 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
241/Protocol GO43643, Version 5 
Additional minor changes have been made to improve clarity and consistency.  
Substantive new information appears in italics.  This amendment represents cumulative 
changes to the original protocol. 
PROTOCOL AMENDMENT, VERSION 2: (11 NOVEMBER 2022) 
Protocol GO43643 has been primarily amended to update the pharmacokinetic (PK) 
objectives and the corresponding endpoint; to add a simplified geriatric assessment 
(sGA) for participants 65 years and older; to clarify the study assessments during 
post-treatment follow-up and survival follow-up; to add instructions regarding continued 
treatment with mosunetuzumab in combination with polatuzumab vedotin after 
suspected disease progression; to add additional information for the mosunetuzumab 
subcutaneous (SC) dose and schedule rationale; to clarify exclusion criteria for current 
or past history of CNS disease and autoimmune disease; to update the corticosteroid 
prophylaxis schedule for mosunetuzumab SC injection; to add instructions on the need 
to repeat step-up dosing in Arm A after dose delays; to add a blood sample collection 
schedule after tocilizumab administration; to provide updated recommendations on 
coronavirus disease 2019 (COVID-19) management.  Changes to the protocol, along 
with a rationale for each change, are summarized below: 
 
Figure 1 Study Schema has been updated to include high-grade B-cell lymphoma 
(not otherwise specified or double/triple hit) to be consistent with the protocol 
inclusion criteria 
 
Tables 1 and 2 have been amended to include a sGA, to include footnotes to clarify 
the post-treatment follow up schedule and survival follow-up schedule, to provide 
clarification that bicarbonate or total carbon dioxide may be measured with use of a 
blood gas test per institutional guidelines, to add guidance on vital signs collections 
schedule after rituximab infusion, to add clarification on the concomitant medication 
data collection schedule in footnote d, and to allow quantitative polymerase chain 
reaction (PCR) for detection of active Epstein-Barr virus (EBV) and cytomegalovirus 
(CMV) to be performed 28 days prior to start of study drug administration in footnote 
a.  Blood for viral infection test by quantitative PCR, serum PK sample and serum 
anti-drug antibody (ADA) sample has been removed from central laboratory 
assessments in the schedule of activities for Arm B.  
 
Tables 1 and 3 have been amended to provide guidance on local assessments, PK, 
immunogenicity, and biomarker collection schedule if step-up dosing needs to be 
repeated after dose interruption 
 
Table 5 has been added to the protocol for to provide a sample collection schedule 
after tocilizumab administration for cytokine release syndrome (CRS) 
 
Table 6 PK objectives and endpoints have been amended to allow the Sponsor to 
conduct proper analysis as data permits 

Appendix 23:  Protocol Amendment History 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
242/Protocol GO43643, Version 5 
 
Section 2.3.1 and Section 6.8.1 have been amended to provide guidance on 
COVID-19 prophylaxis.  In addition, recommendations on COVID-19 testing during 
screening and guidance on treatment resumption after COVID-19 infection have 
been added in Section A61.1.1.3. 
 
Section 4.1.1 and Section 5 have been amended to include the language that if 
China participates in the study, additional participants may be enrolled in an 
extended China enrollment phase at China sites after completion of the global 
enrollment.  The definition of the end of the study if China participates in the study is 
further clarified in Section 4.4.  Additional guidance on sample collections according 
to local regulations if China participates in the study are specified in Section 5.1 and 
Section 8.7 
 
Section 4.1.1.1 has been amended to align the definition for refractory disease with 
that defined in Section 5.1 
 
Section 4.1.1.5 has been added to the protocol to provide guidance on continued 
treatment with mosunetuzumab in combination with polatuzumab vedotin after 
suspected disease progression 
 
Section 4.1.3 has been amended to clarify the participant number for Arm A and 
Arm B for the first independent Data Monitoring Committee (iDMC) review 
 
Section 4.2 has been amended to clarify that local assessment to confirm cluster of 
differentiation (CD) 20 expression is required during screening 
 
Section 4.2.6 has been added to the protocol to provide rationale for sGA 
 
Section 4.3.2 has been amended to provide additional information for 
mosunetuzumab SC dose selection and schedule 
 
Section 5.1 inclusion criteria have been amended to include participants with known 
HIV if they meet specific criteria 
 
Section 5.2 exclusion criteria have been amended to allow enrollment of 
breastfeeding women if breastfeeding stops, to provide additional clarification on 
enrollment of participants with history of specific CNS disease, to provide 
clarification that participants with certain autoimmune disease might be eligible to 
enroll if they meet protocol specified criteria, to allow participants who had 
previously received polatuzumab vedotin to enroll if certain criteria are met, and to 
specify tissue sample requirements for China sites if China participates in the study 
 
Section 6.1.2 has been amended to provide additional guidance on corticosteroid 
premedication to allow dexamethasone 20 mg or 80 mg methylprednisolone, either 
IV or orally, as prophylaxis for CRS for mosunetuzumab 
 
Section 6.8 has been amended to clarify the timeframe when concomitant 
medication information needs to be collected in the electronic Case Report Form 
 
Section 6.8.1.1 has been amended to replace all severe acute respiratory 
syndrome-coronavirus 2 (SARS-CoV-2) with COVID-19 and to provide guidelines on 
the timing for COVID-19 vaccine administration before or during treatment 

Appendix 23:  Protocol Amendment History 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
243/Protocol GO43643, Version 5 
 
Section 6.8.3 was amended to remove intrathecal chemotherapy for CNS 
prophylaxis as a permitted therapy due to the low probability of participants needing 
CNS prophylaxis in the study population as this study enrolls participants with 
aggressive non-Hodgkin’s lymphoma in the relapsed/refractory setting and excludes 
participants with active and historical CNS disease 
 
Section 7.1 has been amended to clarify the assessments required during 
post-treatment follow up for participants who discontinue study treatment for 
reasons other than disease progression, start of new anti-lymphoma therapy or 
withdraw consent 
 
Section 8.1.1.1 has been amended to clarify the radiographic assessment 
requirements for participants who achieve metabolic complete response (CR) at 
24 weeks vs. participants who do not achieve CR at 24 weeks.  For participants who 
achieve metabolic CR at 24 weeks, a computed tomography (CT) scan with or 
without positron emission tomography (PET) scan will be acceptable for subsequent 
scans.  For participants who do not achieve CR at 24 weeks, imaging studies with 
PET and diagnostic-quality CT scans should continue until CR or progressive 
disease (PD).  Additionally, this section added language to allow magnetic 
resonance imaging (MRI) scans instead of CT scans in participants who are 
contraindicated.  
 
Section 8.2.6 (8.2.6.1, 8.2.6.2, 8.2.6.3 and 8.2.6.4), have been added to the protocol 
to provide background information on sGA, including Activities of Daily Living (ADL), 
Instrumental Activities of Daily Living (IADL), Cumulative Illness Rating 
Scale-Geriatrics (CIRS-G), and Mini Nutritional Assessment-Short Form (MNA-SF) 
 
 
 
 
Section 8.4 has been amended to require predose serum rituximab and 
obinutuzumab PK samples to characterize any potential interactions between 
rituximab and/or obinutuzumab PK and the clinical effects of mosunetuzumab 
 
The email address for withdrawal from the Research Biosample Repository after site 
closure has been corrected (Section 8.11.6) 
 
Section 9.4.2.1 has been added to the protocol to provide clarity on the target of 
estimation and the 5 attributes in the estimand framework 
 
Section 9.4.6.6 has been added to the protocol to provide statistical analysis method 
on sGA prognostic impact on progression-free survival (PFS) and overall survival 
(OS) 
 
Section 9.6 has been added to provide guidance on Asian subpopulation analyses if 
China is included as a participating country 
 
Section A6-1.1.1.4 has been amended to provide guidance on how to assess a 
potential tumor flare event.   

Appendix 23:  Protocol Amendment History 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
244/Protocol GO43643, Version 5 
 
Section A6-1.2.2.1 has been added to include progressive multifocal 
leukoencephalopathy (PML) as a potential risk associated with polatuzumab 
vedotin.  
 
Section A6-2.2 has been amended to provide additional guidance on the need to 
repeat step-up dosing schedule after treatment interruption in Arm A.  
 
Table A6-2 has been added to the protocol to provide guidelines for dose delay, 
modifications or discontinuation of mosunetuzumab, polatuzumab vedotin and 
rituximab 
 
Section A6-2.3.5 and Appendix 21 have been amended to include instructions for 
participants to refrain from driving or engaging in hazardous occupations or activities 
if the participants develop specific adverse events while on mosunetuzumab 
treatment.  
 
 
 

 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
245/Protocol GO43643, Version 5 
Appendix 24  
Abbreviations 
Abbreviation or Term 
Definition 
acMMAE 
antibody-conjugated monomethyl auristatin E 
ADA 
anti-drug antibody 
ADC 
antibody-drug conjugate 
ADL 
activity of daily living 
AIDS 
acquired immunodeficiency syndrome 
aNHL 
aggressive non-Hodgkin’s lymphoma 
ASCT 
autologous stem cell transplant 
ASTCT 
American Society for Transplantation and Cellular Therapy 
BR 
bendamustine and rituximab 
CAR 
chimeric antigen receptor 
CCOD 
clinical cutoff date 
CD 
cluster of differentiation 
CGA 
comprehensive geriatric assessment 
CIRS-G 
Cumulative Illness Rating Scale-Geriatric 
COVID-19 
coronavirus disease 2019 
CR 
complete response 
CRR 
complete response rate 
CRS 
cytokine release syndrome 
CT 
computed tomography (scan) 
DLBCL 
diffuse-large B-cell lymphoma 
DOCR 
duration of complete response 
DOR 
duration of response 
EBV 
Epstein-Barr virus 
EC 
Ethics Committee 
ECOG PS 
Eastern Cooperative Oncology Group Performance Status 
eCRF 
electronic Case Report Form 
EDC 
electronic data capture 
EORTC 
European Organisation for Research and Treatment of Cancer 
FACT/GOG-Ntx 
Functional Assessment of Cancer Therapy−Gynecologic 
Oncology Group−Neurotoxicity 
FACT-LymS 
Functional Assessment of Cancer Therapy⎯Lymphoma 
Subscale 
FDA 
U.S. Food and Drug Administration 
FDG 
fluorodeoxyglucose 
FFPE 
formalin-fixed, paraffin embedded 
FIL 
Fondazione Italiana Linfomi 

Appendix 24:  Abbreviations 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
246/Protocol GO43643, Version 5 
Abbreviation or Term 
Definition 
FL 
follicular lymphoma 
FL3B 
follicular lymphoma Grade 3B 
G-CSF 
granulocyte colony-stimulating factor 
HBcAb 
hepatitis B core antibody 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HLH 
hemophagocytic lymphohistiocytosis 
HR 
Hazard ratio 
HRQoL 
health-related quality of life 
IADL 
Instrumental Activities of Daily Living 
ICANS 
immune effector cell-associated neurotoxicity syndrome 
ICH 
International Council for Harmonisation 
iDCC 
independent Data Coordinating Center 
iDMC 
independent Data Monitoring Committee 
IL 
interleukin 
IMP 
investigational medicinal product 
IPI 
International Prognostic Index 
IRB 
Institutional Review Board 
IRF 
Independent Review Facility 
IRR 
infusion-related reaction 
IxRS 
interactive voice or Web-based response system 
M  P 
mosunetuzumab in combination with polatuzumab vedotin 
MMAE 
monomethyl auristatin E 
MNA-SF 
Mini Nutritional Assessment-Short Form 
MRI 
magnetic resonance imaging 
NALT 
new anti-lymphoma therapy 
NCCN 
National Comprehensive Cancer Network 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for 
Adverse Events 
NHL 
non-Hodgkin’s lymphoma 
NOS 
not otherwise specified 
ORR 
objective response rate 
OS 
overall survival 
PBMC 
peripheral blood mononuclear cell 

Appendix 24:  Abbreviations 
Mosunetuzumab and Polatuzumab Vedotin—F. Hoffmann-La Roche Ltd 
247/Protocol GO43643, Version 5 
Abbreviation or Term 
Definition 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PET 
positron emission tomography (scan) 
PFS 
progression-free survival 
PK 
pharmacokinetic 
PML 
progressive multifocal leukoencephalopathy 
PopPK 
population pharmacokinetics 
PRO 
participant-reported outcome 
Q3W 
every 3 weeks 
QLQ-Core30 
Quality of Life-Core 30 
QoL 
quality of life 
QTcF 
QT interval corrected through use of Fridericia’s formula 
RBR 
Research Biosample Repository 
R-CHP 
rituximab plus cyclophosphamide, doxorubicin, and prednisone 
R-GemOx 
rituximab, gemcitabine, oxaliplatin 
R/R 
relapsed or refractory 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SC 
subcutaneous 
sGA 
simplified geriatric assessment 
TLS 
tumor lysis syndrome 
trFL 
transformed follicular lymphoma 
ULN 
upper limit of normal 
USPI 
United States Prescribing Information 
WES 
whole-exome sequencing 
WGS 
whole-genome sequencing 
 

Signature Page for Protocol - GO43643 - LUNSUMIO - v5 - Global/Core - Published
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05-Oct-2024 21:05:21 GMT+0000