A Phase IB/II Study Evaluating the Safety and Efficacy of Atezolizumab in Combination With Either Obinutuzumab Plus Bendamustine or Obinutuzumab Plus CHOP in Patients With Follicular Lymphoma or Rituximab Plus CHOP in Patients With Diffuse Large B-Cell Lymphoma
Phase: PHASE1
Conditions: Diffuse Large B-Cell Lymphoma, Lymphoma Follicular
Sponsor: Hoffmann-La Roche

 
Official Title: A Phase IB/II Study Evaluating the Safety and Efficacy of 
Atezolizumab in Combination With Either Obinutuzumab Plus 
Bendamustine or Obinutuzumab Plus CHOP in Patients With Follicular 
Lymphoma or Rituximab Plus CHOP in Patients With Diffuse Large B-
Cell Lymphoma 
NCT Number: NCT02596971 
Document Date: Protocol Version 6: 07-November-2018 
 
 
 

PROTOCOL AMENDMENT APPROVAL
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unpublished data, is the property of F. Hoffmann-La Roche Ltd (or under its control) and therefore 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.
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
Protocol BO29563, Version 6
PROTOCOL
TITLE:
A PHASE IB/II STUDY EVALUATING THE SAFETY AND 
EFFICACY OF ATEZOLIZUMAB IN COMBINATION WITH EITHER 
OBINUTUZUMAB PLUS BENDAMUSTINE OR OBINUTUZUMAB 
PLUS CHOP IN PATIENTS WITH FOLLICULAR LYMPHOMA OR 
RITUXIMAB PLUS CHOP IN PATIENTS WITH DIFFUSE LARGE B-
CELL LYMPHOMA
PROTOCOL NUMBER:
BO29563
VERSION NUMBER:
6
EUDRACT NUMBER:
2015-001364-19
IND NUMBER:
122847
TEST PRODUCTS:
Obinutuzumab (RO5072759)
Rituximab (RO452294)
Atezolizumab (RO5541267)
MEDICAL MONITOR:
, Ph.D.
SPONSOR:
F. Hoffmann-La Roche Ltd
DATE FINAL:
Version 1:  13 May 2015
DATE AMENDED:
Version 2:  23 October 2015
Version 3:  7 September 2016
Version 4:  26 May 2017
Version 5:  22 December 2017
Version 6:  See electronic date stamp below.
 
07-Nov-2018 02:09:35
Title
Approver's Name
Company Signatory
Date and Time (UTC)

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd 
2/Protocol BO29563, Version 6 
PROTOCOL AMENDMENT, VERSION 6: 
RATIONALE 
Protocol BO29563 has been amended to include new safety information.  Changes to 
the protocol, along with a rationale for each change, are summarized below: 
 
Lists of risks for atezolizumab and guidelines for managing patients who experience 
atezolizumab-associated adverse events have been revised to include nephritis 
(Sections 5.1.3 and 5.1.7.2 [Table 14]). 
 
Considering no new safety signals have been identified with atezolizumab in 
combination with obinutuzumab plus CHOP or with atezolizumab in combination 
with rituximab plus CHOP, once all patients have completed/discontinued study 
treatment (maintenance/consolidation), regular Internal Monitoring Committee 
assessments will no longer take place and ad hoc meetings maybe called at the 
discretion of the Medical Monitor in case of newly identified safety signals 
(Section 3.1.3). 
 
Post-trial access language was changed allowing patients still under study treatment 
to enter an extension study in case of earlier closure of Study BO29563 
(Section 4.3.4). 
 
The Medical Monitor information has been updated (Section 5.4.1). 
 
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. 
 

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
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TABLE OF CONTENTS
PROTOCOL AMENDMENT ACCEPTANCE FORM .......................................... 12
PROTOCOL SYNOPSIS .................................................................................... 13
1.
BACKGROUND .......................................................................................... 25
1.1
Background on Non-Hodgkin's Lymphoma ........................... 25
1.1.1
Follicular Lymphoma ............................................................. 25
1.1.2
Diffuse Large B-Cell Lymphoma............................................ 25
1.2
Background on Obinutuzumab .............................................. 26
1.2.1
Nonclinical Studies with Obinutuzumab................................. 27
1.2.2
Clinical Studies with Obinutuzumab ...................................... 27
1.2.2.1
Summary of Clinical Efficacy of Obinutuzumab in 
Patients with NHL .................................................................. 27
1.2.2.2
Summary of Clinical Safety of Obinutuzumab ....................... 28
1.3
Background on Atezolizumab................................................ 29
1.3.1
Nonclinical Studies with Atezolizumab .................................. 29
1.3.2
Clinical Studies with Atezolizumab ........................................ 30
1.3.2.1
Summary of Clinical Safety of Atezolizumab ......................... 30
1.3.2.2
Summary of Clinical Activity of Atezolizumab........................ 32
1.4
Study Rationale and Benefit-Risk Assessment...................... 32
1.4.1
PD-L1/PD-1 Pathway in Lymphoma ...................................... 32
1.4.2
Clinical Experience with PD-L1/PD-1 Pathway 
Inhibitors in Lymphoma.......................................................... 33
1.4.3
Rationale for Treatment Combination.................................... 34
2.
OBJECTIVES AND ENDPOINTS ............................................................... 37
2.1
Safety Objective .................................................................... 37
2.2
Efficacy Objectives ................................................................ 37
2.2.1
Primary Efficacy Objective..................................................... 37
2.2.2
Secondary Efficacy Objective................................................ 38
2.2.3
Exploratory Efficacy Objective............................................... 38
2.3
Pharmacokinetic Objectives .................................................. 38
2.4
Immunogenicity Objectives.................................................... 39

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2.5
Biomarker Objective .............................................................. 39
3.
STUDY DESIGN......................................................................................... 39
3.1
Description of Study .............................................................. 39
3.1.1
Overview of Study ................................................................. 39
3.1.2
Treatment Regimens ............................................................. 43
3.1.3
Internal Monitoring Committee............................................... 45
3.1.4
Independent Review Committee............................................ 45
3.1.5
Post-Treatment Follow-Up and Survival 
Follow-Up .............................................................................. 46
3.2
End of Study and Length of Study......................................... 46
3.3
Rationale for Study Design.................................................... 46
3.3.1
Rationale for Patient Population ............................................ 46
3.3.2
Rationale for Dose and Schedule.......................................... 47
3.3.2.1
Rationale for Atezolizumab Dose and Schedule.................... 47
3.3.2.2
Rationale for Obinutuzumab, Bendamustine, 
Rituximab, and CHOP Dose and Schedule ........................... 49
3.3.2.3
Rationale for Treatment Duration .......................................... 50
3.3.3
Rationale for PET-CTBased Complete 
Response as the Primary Efficacy Endpoint.......................... 51
3.3.4
Rationale for Biomarker Assessments................................... 51
3.3.4.1
Rationale for Analysis of DLBCL Subtype, BCL2, 
and MYC................................................................................ 51
3.3.4.2
Rationale for Assessment of Immune-Related 
Biomarkers ............................................................................ 52
3.3.4.3
Rationale for Assessment of Minimal Residual 
Disease.................................................................................. 53
4.
MATERIALS AND METHODS .................................................................... 53
4.1
Patients.................................................................................. 53
4.1.1
Inclusion Criteria.................................................................... 53
4.1.2
Exclusion Criteria................................................................... 55
4.2
Method of Treatment Assignment.......................................... 57
4.3
Study Treatment.................................................................... 58
4.3.1
Formulation, Packaging, and Handling.................................. 58
4.3.1.1
Obinutuzumab ....................................................................... 58

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4.3.1.2
Atezolizumab......................................................................... 58
4.3.1.3
CHOP .................................................................................... 58
4.3.1.4
Bendamustine........................................................................ 58
4.3.1.5
Rituximab............................................................................... 59
4.3.2
Dosage, Administration, and Compliance.............................. 59
4.3.2.1
Obinutuzumab ....................................................................... 59
4.3.2.2
Atezolizumab......................................................................... 62
4.3.2.3
CHOP .................................................................................... 62
4.3.2.4
Bendamustine........................................................................ 63
4.3.2.5
Rituximab............................................................................... 63
4.3.2.6
Induction Treatment with Atezo-G-Benda.............................. 64
4.3.2.7
Induction Treatment with Atezo-G-CHOP or 
Atezo-R-CHOP ...................................................................... 65
4.3.2.8
Post-Induction Treatment ...................................................... 67
4.3.2.9
Premedication........................................................................ 68
4.3.3
Investigational Medicinal Product Accountability ................... 71
4.3.4
Post-Trial Access to Obinutuzumab, Rituximab, 
Atezolizumab, and Bendamustine ......................................... 71
4.4
Concomitant Therapy ............................................................ 71
4.4.1
Permitted Therapy................................................................. 71
4.4.2
Prohibited Therapy ................................................................ 72
4.5
Study Assessments ............................................................... 72
4.5.1
Informed Consent Forms and Screening Log........................ 73
4.5.2
Medical History and Demographic Data ................................ 73
4.5.3
Physical Examinations........................................................... 74
4.5.4
Vital Signs.............................................................................. 74
4.5.5
Tumor and Response Evaluations......................................... 74
4.5.5.1
Radiographic Assessments ................................................... 75
4.5.5.2
Bone Marrow Assessments................................................... 75
4.5.6
Laboratory, Biomarker, and Other Biological 
Samples................................................................................. 76
4.5.7
Electrocardiograms................................................................ 79
4.5.8
Echocardiogram or MUGA..................................................... 79
4.5.9
Samples for Roche Clinical Repository.................................. 79

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4.5.9.1
Overview of the Roche Clinical Repository............................ 79
4.5.9.2
Approval by the Institutional Review Board or 
Ethics Committee .................................................................. 79
4.5.9.3
Sample Collection.................................................................. 80
4.5.9.4
Confidentiality........................................................................ 80
4.5.9.5
Consent to Participate in the Roche Clinical 
Repository ............................................................................. 81
4.5.9.6
Withdrawal from the Roche Clinical Repository..................... 81
4.5.9.7
Monitoring and Oversight....................................................... 81
4.6
Patient, Treatment, Study, and Site 
Discontinuation...................................................................... 82
4.6.1
Patient Discontinuation.......................................................... 82
4.6.2
Study Treatment Discontinuation........................................... 82
4.6.3
Study and Site Discontinuation.............................................. 83
5.
ASSESSMENT OF SAFETY....................................................................... 84
5.1
Safety Plan ............................................................................ 84
5.1.1
Risks Associated with Obinutuzumab.................................... 84
5.1.1.1
Infusion-Related Reactions and Hypersensitivity 
Reactions............................................................................... 84
5.1.1.2
Tumor Lysis Syndrome.......................................................... 85
5.1.1.3
Neutropenia........................................................................... 85
5.1.1.4
Thrombocytopenia................................................................. 85
5.1.1.5
Infections ............................................................................... 86
5.1.1.6
Immunizations ....................................................................... 86
5.1.1.7
Worsening of Preexisting Cardiac Condition ......................... 87
5.1.1.8
Gastrointestinal Perforation ................................................... 87
5.1.2
Risks Associated with Rituximab........................................... 87
5.1.2.1
Infusion-Related Reactions.................................................... 87
5.1.2.2
Infections (Including Serious Infections) ................................ 87
5.1.2.3
Neutropenia........................................................................... 87
5.1.2.4
Tumor Lysis Syndrome.......................................................... 88
5.1.2.5
Hepatitis B Reactivation......................................................... 88
5.1.2.6
Progressive Multifocal Leukoencephalopathy........................ 88
5.1.2.7
Severe Mucocutaneous Reactions........................................ 88

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5.1.2.8
Gastrointestinal Perforation ................................................... 89
5.1.3
Risks Associated with Atezolizumab ..................................... 89
5.1.4
Risks Associated with Bendamustine .................................... 89
5.1.4.1
Myelosuppression.................................................................. 89
5.1.4.2
Infection................................................................................. 89
5.1.4.3
Infusion-Related Reactions and Anaphylaxis ........................ 90
5.1.4.4
Tumor Lysis Syndrome.......................................................... 90
5.1.4.5
Skin Reactions....................................................................... 90
5.1.4.6
Long-Term Stem-Cell Toxicity ............................................... 90
5.1.4.7
Extravasation Injury ............................................................... 90
5.1.4.8
Drug Interactions ................................................................... 90
5.1.5
Risks Associated with CHOP................................................. 91
5.1.6
Risk of Overlapping Toxicities ............................................... 91
5.1.7
Management of Specific Adverse Events .............................. 94
5.1.7.1
Systemic Immune Activation.................................................. 94
5.1.7.2
Toxicities during Induction Treatment.................................... 94
5.1.7.3
Toxicities during Consolidation or Maintenance 
Treatment ............................................................................ 111
5.2
Safety Parameters and Definitions ...................................... 111
5.2.1
Adverse Events ................................................................... 112
5.2.2
Serious Adverse Events (Immediately Reportable 
to the Sponsor).................................................................... 112
5.2.3
Adverse Events of Special Interest (Immediately 
Reportable to the Sponsor).................................................. 113
5.2.4
Selected Adverse Events..................................................... 114
5.3
Methods and Timing for Capturing and 
Assessing Safety Parameters.............................................. 114
5.3.1
Adverse Event Reporting Period ......................................... 115
5.3.2
Eliciting Adverse Event Information..................................... 115
5.3.3
Assessment of Severity of Adverse Events ......................... 115
5.3.4
Assessment of Causality of Adverse Events ....................... 116
5.3.5
Procedures for Recording Adverse Events.......................... 117
5.3.5.1
Infusion-Related Reactions.................................................. 117
5.3.5.2
Diagnosis versus Signs and Symptoms............................... 117

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5.3.5.3
Adverse Events That Are Secondary to Other 
Events.................................................................................. 117
5.3.5.4
Persistent or Recurrent Adverse Events.............................. 118
5.3.5.5
Abnormal Laboratory Values ............................................... 118
5.3.5.6
Abnormal Vital Sign Values ................................................. 119
5.3.5.7
Abnormal Liver Function Tests............................................ 120
5.3.5.8
Deaths ................................................................................. 120
5.3.5.9
Preexisting Medical Conditions............................................ 120
5.3.5.10
Lack of Efficacy or Worsening of Lymphoma....................... 121
5.3.5.11
Hospitalization or Prolonged Hospitalization........................ 121
5.3.5.12
Adverse Events Associated with an Overdose or 
Error in Treatment Administration........................................ 122
5.4
Immediate Reporting Requirements from 
Investigator to Sponsor........................................................ 122
5.4.1
Emergency Medical Contacts.............................................. 123
5.4.2
Reporting Requirements for Serious Adverse 
Events and Adverse Events of Special Interest................... 123
5.4.2.1
Events That Occur prior to Study Treatment 
Initiation ............................................................................... 123
5.4.2.2
Events That Occur after Study Treatment 
Initiation ............................................................................... 123
5.4.3
Reporting Requirements for Pregnancies............................ 124
5.4.3.1
Pregnancies in Female Patients.......................................... 124
5.4.3.2
Pregnancies in Female Partners of Male Patients............... 124
5.4.3.3
Abortions ............................................................................. 125
5.4.3.4
Congenital Anomalies/Birth Defects .................................... 125
5.5
Follow-Up of Patients after Adverse Events ........................ 125
5.5.1
Investigator Follow-Up......................................................... 125
5.5.2
Sponsor Follow-Up .............................................................. 125
5.6
Adverse Events That Occur after the Adverse 
Event Reporting Period........................................................ 125
5.7
Expedited Reporting to Health Authorities, 
Investigators, Institutional Review Boards, and 
Ethics Committees............................................................... 126
6.
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN..................... 126

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6.1
Determination of Sample Size ............................................. 127
6.2
Summaries of Patient Characteristics.................................. 128
6.3
Summaries of Treatment Group Comparability ................... 128
6.4
Safety Analyses................................................................... 128
6.5
Efficacy Analyses ................................................................ 129
6.5.1
Primary Efficacy Endpoint.................................................... 129
6.5.2
Secondary Efficacy Endpoints............................................. 129
6.5.3
Exploratory Efficacy Endpoints............................................ 130
6.6
Pharmacokinetic Analyses................................................... 131
6.7
Immunogenicity Analyses.................................................... 131
6.8
Biomarker Analyses............................................................. 131
6.9
Interim Analyses .................................................................. 131
7.
DATA COLLECTION AND MANAGEMENT ............................................. 132
7.1
Data Quality Assurance....................................................... 132
7.2
Electronic Case Report Forms............................................. 132
7.3
Source Data Documentation................................................ 133
7.4
Use of Computerized Systems ............................................ 133
7.5
Retention of Records........................................................... 134
8.
ETHICAL CONSIDERATIONS.................................................................. 134
8.1
Compliance with Laws and Regulations .............................. 134
8.2
Informed Consent................................................................ 134
8.3
Institutional Review Board or Ethics Committee.................. 135
8.4
Confidentiality...................................................................... 136
8.5
Financial Disclosure ............................................................ 136
9.
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION ................................................................................... 136
9.1
Study Documentation .......................................................... 136
9.2
Protocol Deviations.............................................................. 137
9.3
Site Inspections ................................................................... 137
9.4
Administrative Structure....................................................... 137
9.5
Publication of Data and Protection of Trade 
Secrets ................................................................................ 137
9.6
Protocol Amendments ......................................................... 138

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
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10. REFERENCES ......................................................................................... 139
LIST OF TABLES
Table 1
Induction Treatment.................................................................... 44
Table 2
Post-Induction Treatment............................................................ 45
Table 3
Administration of First and Subsequent Infusions of 
Rituximab.................................................................................... 64
Table 4
Induction Treatment:  Atezo-G-Benda Treatment Group ............ 65
Table 5
Induction Treatment, Safety Run-In Phase:  Atezo-G-CHOP 
Treatment Group......................................................................... 66
Table 6
Induction Treatment, Expansion Phase:  Atezo-R-CHOP........... 67
Table 7
Consolidation Treatment for Patients with DLBCL...................... 67
Table 8
Maintenance Treatment for Patients with FL............................... 68
Table 9
Premedication............................................................................. 69
Table 10
Proposed Non-Inherited Biomarkers........................................... 78
Table 11
Summary of Potentially Overlapping Adverse Events................. 92
Table 12
Guidelines for Management of Hematologic Toxicities during 
Induction Treatment (Except at Administration of 
Obinutuzumab on Day 8 or 15 or Atezolizumab on Day 15)....... 96
Table 13
Guidelines for Management of Hematologic Toxicities during 
Induction Treatment at Administration of Obinutuzumab on 
Day 8 or 15 or Atezolizumab on Day 15 ..................................... 97
Table 14
Guidelines for Management of Non-Hematologic Toxicities........ 98
Table 15
Guidelines for Management of Toxicities That Occur during 
Consolidation or Maintenance Treatment ................................. 111
Table 16
Adverse Event Severity Grading Scale for Events Not 
Specifically Listed in NCI CTCAE ............................................. 116
Table 17
Potential 90% CI for the True Probability of Achieving a 
PET-CTDefined Complete Response at End of Induction ...... 128
LIST OF FIGURES
Figure 1
Study Schema............................................................................. 42
Figure 2
Guidelines for Obinutuzumab Infusions:  First Infusion............... 60
Figure 3
Guidelines for Obinutuzumab Infusions:  Second and 
Subsequent Infusions ................................................................. 61

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LIST OF APPENDICES
Appendix 1
Schedule of Assessments for Patients in the Atezo-G-Benda 
Treatment Group....................................................................... 146
Appendix 2
Schedule of Assessments for Patients with FL in the 
Atezo-G-CHOP Treatment Group............................................. 152
Appendix 3
Schedule of Assessments for Patients with DLBCL in the 
Atezo-R-CHOP Treatment Group ............................................. 158
Appendix 4
Pharmacokinetic and Immunogenicity Sampling Schedule for 
the Atezo-G-Benda Treatment Group....................................... 164
Appendix 5
Pharmacokinetic and Immunogenicity Sampling Schedule for 
the Atezo-G-CHOP Treatment Group....................................... 167
Appendix 6
Pharmacokinetic and Immunogenicity Sampling Schedule for 
with Atezo-R-CHOP Treatment Group...................................... 170
Appendix 7
Lugano Response Criteria for Malignant Lymphoma 
(Cheson et al. 2014) ................................................................. 173
Appendix 8
Summary of Criteria for Tumor Measurements......................... 176
Appendix 9
Eastern Cooperative Oncology Group Performance Status 
Scale......................................................................................... 184
Appendix 10
Ann Arbor Staging..................................................................... 185
Appendix 11
Follicular Lymphoma International Prognostic Index and 
International Prognostic Index................................................... 186
Appendix 12
Anaphylaxis Precautions........................................................... 189
Appendix 13
Preexisting Autoimmune Diseases ........................................... 190
Appendix 14
Calculation of Creatinine Clearance Using the 
Cockcroft-Gault Formula........................................................... 193

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12/Protocol BO29563, Version 6
PROTOCOL AMENDMENT ACCEPTANCE FORM
TITLE:
A PHASE IB/II STUDY EVALUATING THE SAFETY 
AND EFFICACY OF ATEZOLIZUMAB IN 
COMBINATION WITH EITHER OBINUTUZUMAB 
PLUS BENDAMUSTINE OR OBINUTUZUMAB PLUS 
CHOP IN PATIENTS WITH FOLLICULAR 
LYMPHOMA OR RITUXIMAB PLUS CHOP IN 
PATIENTS WITH DIFFUSE LARGE B-CELL 
LYMPHOMA
PROTOCOL NUMBER:
BO29563
VERSION NUMBER:
6
EUDRACT NUMBER:
2015-001364-19
IND NUMBER:
122847
TEST PRODUCTS:
Obinutuzumab (RO5072759)
Rituximab (RO452294)
Atezolizumab (RO5541267)
MEDICAL MONITOR:
, Ph.D.
SPONSOR:
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 as 
instructed by your local study monitor at Covance.

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PROTOCOL SYNOPSIS
TITLE:
A PHASE IB/II STUDY EVALUATING THE SAFETY AND 
EFFICACY OF ATEZOLIZUMAB IN COMBINATION WITH EITHER 
OBINUTUZUMAB PLUS BENDAMUSTINE OR OBINUTUZUMAB 
PLUS CHOP IN PATIENTS WITH FOLLICULAR LYMPHOMA OR 
RITUXIMAB PLUS CHOP IN PATIENTS WITH DIFFUSE LARGE 
B-CELL LYMPHOMA
PROTOCOL NUMBER:
BO29563
VERSION NUMBER:
6
EUDRACT NUMBER:
2015-001364-19
IND NUMBER:
122847
TEST PRODUCTS:
Obinutuzumab (RO5072759)
Rituximab (RO452294)
Atezolizumab (RO5541267)
PHASE:
Phase Ib/II
INDICATION:
Follicular or diffuse large B-cell lymphoma
SPONSOR:
F. Hoffmann-La Roche Ltd
Objectives and Endpoints
This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment 
consisting of atezolizumab in combination with obinutuzumab plus bendamustine (Atezo-G-
benda) in patients with follicular lymphoma (FL), atezolizumab in combination with 
obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) 
(Atezo-G-CHOP) in patients with FL, and atezolizumab in combination with rituximab plus 
CHOP (Atezo-R-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL), followed by 
post-induction treatment consisting of either atezolizumab plus obinutuzumab (Atezo-G) in 
patients with FL who achieve a complete response (CR) or partial response (PR) at end of 
induction (EOI) or atezolizumab alone in patients with DLBCL who achieve a CR at EOI.  
Specific objectives and corresponding endpoints for the study are outlined below.  
In this study, "study treatment" refers to the combination of all study treatment components.
Safety Objective
The safety objective for this study is to evaluate the safety and tolerability of induction treatment 
with either Atezo-G-benda or Atezo-G-CHOP in patients with FL, and Atezo-R-CHOP in patients 
with DLBCL and post-induction treatment with either Atezo-G in patients with FL or 
atezolizumab alone in patients with DLBCL on the basis of the following endpoints:

Nature, frequency, severity, and timing of adverse events

Changes in vital signs, ECGs, and clinical laboratory results during and following study 
treatment administration
Efficacy Objectives
Response will be determined through use of the positron emission tomography (PET) and 
computed tomography (CT)based Lugano Response Criteria for Malignant Lymphoma, 
hereinafter referred to as Lugano 2014 criteria.  Response will also be determined through use 
of the modified version of the Revised Response Criteria for Malignant Lymphoma, hereinafter 

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
14/Protocol BO29563, Version 6
referred to as modified Cheson 2007 criteria, which take into account both PET-CT and CT 
scan results.  Response will be determined by an Independent Review Committee (IRC) and by 
the investigator.
Primary Efficacy Objective
The primary efficacy objective for this study is to evaluate the efficacy of induction treatment 
with either Atezo-G-benda or Atezo-R-CHOP, on the basis of the following endpoint:

CR at EOI, as determined by the IRC using Lugano 2014 criteria 
Secondary Efficacy Objective
The secondary efficacy objective for this study is to evaluate the efficacy of induction treatment 
with either Atezo-G-benda or Atezo-R-CHOP and post-induction treatment with either Atezo-G 
or atezolizumab alone, on the basis of the following endpoints:

CR at EOI, as determined by the investigator using Lugano 2014 criteria

CR at EOI, as determined by the IRC and by the investigator using modified Cheson 2007 
criteria

Objective response (defined as a CR or PR) at EOI, as determined by the IRC and by the 
investigator using Lugano 2014 criteria and modified Cheson 2007 criteria

Best response of CR or PR during the study, as determined by the investigator using 
modified Cheson 2007 criteria
Exploratory Efficacy Objective
The exploratory efficacy objective for this study is to evaluate the long-term efficacy of induction 
treatment with either Atezo-G-benda or Atezo-R-CHOP and post-induction treatment with either 
Atezo-G or atezolizumab alone, on the basis of the following endpoints:

For patients who have positive PET scans at EOI:  CR at 12 months, as determined by the 
IRC and by the investigator using Lugano 2014 criteria

CR at 12, 24, and 30 months in patients with previously untreated FL, as determined by the 
investigator using modified Cheson 2007 criteria

Progression-free survival, defined as the time from initiation of study treatment to first 
occurrence of disease progression or relapse, as determined by the investigator using 
modified Cheson 2007 criteria, or death from any cause

Event-free survival, defined as the time from initiation of study treatment to any treatment 
failure, including disease progression or relapse, as determined by the investigator using 
modified Cheson 2007 criteria, initiation of new anti-lymphoma therapy, or death from any 
cause, whichever occurs first

Disease-free survival, defined, among patients achieving a CR, as the time from the first 
occurrence of a documented CR to relapse, as determined by the investigator using 
modified Cheson 2007 criteria, or death from any cause, whichever occurs first

OS, defined as the time from initiation of study treatment to death from any cause
Pharmacokinetic Objectives
The pharmacokinetic (PK) objectives for this study are to characterize the pharmacokinetics of 
atezolizumab, rituximab, and obinutuzumab when administered as induction treatment 
consisting of either Atezo-G-benda, Atezo-G-CHOP, or Atezo-R-CHOP or post-induction 
treatment consisting of either Atezo-G or atezolizumab alone, on the basis of the following 
endpoints:

Observed serum obinutuzumab concentration at specified timepoints

Observed serum atezolizumab concentration at specified timepoints

Observed serum rituximab concentration at specified timepoints

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Immunogenicity Objectives
The immunogenicity objective for this study is to evaluate the immune response to 
obinutuzumab, to rituximab, and to atezolizumab on the basis of the following endpoints:

Incidence of human anti-human antibodies (HAHAs) to obinutuzumab during the study 
relative to the prevalence of HAHAs at baseline

Incidence of human anti-chimeric antibodies (HACAs) to rituximab during the study relative 
to the prevalence of HACAs at baseline

Incidence of anti-therapeutic antibodies (ATAs) to atezolizumab during the study relative to 
the prevalence of ATAs at baseline
The exploratory immunogenicity objective for this study is to evaluate potential effects of HAHAs, 
HACAs, or ATAs, on the basis of the following endpoint:

Correlation between HAHA, HACA, or ATA status and efficacy, safety, or PK endpoints
Biomarker Objective
The exploratory biomarker objective for this study is to identify non-inherited biomarkers that are 
predictive of response to study treatment (i.e., predictive biomarkers), are associated with 
progression to a more severe disease state (i.e., prognostic biomarkers), are associated with 
acquired resistance to study treatment, are associated with susceptibility to developing adverse 
events, can provide evidence of study treatment activity, can increase the knowledge and 
understanding of lymphoma biology or study treatment mechanism of action, or can contribute 
to improvement of diagnostic assays, on the basis of the following endpoint:

Correlation between non-inherited biomarkers and efficacy, safety, PK, or immunogenicity 
endpoints
Study Design
Description of Study
This Phase Ib/II, open-label, multicenter, non-randomized study will evaluate the safety, efficacy, 
and pharmacokinetics of combination treatment with atezolizumab, obinutuzumab, and 
chemotherapy in patients with FL and atezolizumab, rituximab, and chemotherapy in patients 
with DLBCL.
Study enrollment will take place in two phases:  an initial safety run-in phase followed by an 
expansion phase.
During the safety run-in phase, 12 patients with previously untreated, or relapsed or refractory 
FL are to be enrolled in either the Atezo-G-benda treatment group (n 6) or the Atezo-G-CHOP 
treatment group (n 6) at the discretion of the investigator.  Patients will receive 6 cycles 
(Cycles 16) of induction treatment with either Atezo-G-benda or Atezo-G-CHOP (with 
atezolizumab starting in Cycle 2 for both treatment groups).  Patients who achieve a CR or PR 
at EOI will receive post-induction treatment (referred to as maintenance) with Atezo-G.
During the safety run-in phase, the patients within each treatment group will be closely 
monitored for adverse events during an observation window, defined as Cycles 2 and 3 of 
induction treatment (the first two treatment cycles that contain atezolizumab), to determine if 
any of the stopping criteria have been met.  Patients who discontinue from the study prior to 
completing Cycle 3 for reasons other than toxicity will be replaced.
Number of Patients
Up to 46 patients with FL will be enrolled in the Atezo-G-benda treatment group:  6 patients with 
previously untreated, or relapsed or refractory FL enrolled in the safety run-in phase and 
3440 patients with previously untreated FL enrolled in the expansion phase (depending on the 
number of patients needed to achieve a total enrollment of 40 patients with previously untreated 
FL).  A total of 7 patients with previously untreated, or relapsed or refractory FL were enrolled in 
the Atezo-G-CHOP treatment group during the safety run-in phase.  Per current amendment, , 
further enrollment in the Atezo-G-CHOP treatment group is stopped.  A total of 40 patients with 
previously untreated DLBCL will be enrolled in the Atezo-R-CHOP treatment group.  Therefore, 
enrollment of up to 92 patients is planned for this study.

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Target Population
Inclusion Criteria
Patients must meet the following criteria for study entry:

Signed Informed Consent Form

Age 18 years

Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2

For patients enrolled in the safety run-in phase:  lymphoma classified as either of the 
following:
Relapsed or refractory FL after treatment with at least one prior 
chemoimmunotherapy regimen
Previously untreated Grade 1, 2, or 3a FL that requires treatment, defined as 
meeting at least one of the Groupe d'Etudes des Lymphomes Folliculaires (GELF) 
criteria, as listed below:
Bulky disease, defined as a nodal or extranodal (except spleen) mass 7 cm in 
the greatest diameter
Local symptoms or compromise of normal organ function due to progressive 
nodal disease or extranodal tumor mass
Presence of B symptoms 
Presence of symptomatic extranodal disease (e.g., pleural effusions, peritoneal 
ascites)
Cytopenias due to underlying lymphoma (i.e., ANC 1.0109/L, hemoglobin 
10 g/dL, and/or platelet count 100109/L)
Involvement of 3 nodal sites, each with a diameter of 3 cm

For patients enrolled in the expansion phase:  lymphoma classified as either of the following:
Previously untreated Grade 1, 2, or 3a FL that requires treatment, defined as 
meeting at least one of the GELF criteria (listed above)
Previously untreated advanced DLBCL, defined as Stage III or IV with an 
International Prognostic Index (IPI) 2 or Stage II with bulky disease (defined as at 
least one lesion 7 cm)

Histologically documented CD20-positive lymphoma

Fluorodeoxyglucose-avid lymphoma (i.e., PET-positive lymphoma)

At least one bi-dimensionally measurable lesion (1.5 cm in its largest dimension by 
CT scan or magnetic resonance imaging)

Availability of a representative tumor specimen and the corresponding pathology report for 
retrospective central confirmation of the diagnosis of FL or DLBCL
For patients with FL, if the available biopsy was not done within 12 months, a repeat 
biopsy is strongly recommended.

For women who are not postmenopausal (12 months of non-therapy-induced amenorrhea) 
or surgically sterile (absence of ovaries and/or uterus):  agreement to remain abstinent 
(refrain from heterosexual intercourse) or use contraceptive methods that result in a failure 
rate of 1% per year during the treatment period and for at least 18 months after the last 
dose of study treatment for patients in the Atezo-G-benda and Atezo-G-CHOP treatment 
groups or for at least 12 months after the last dose of study treatment for patients in the 
Atezo-R-CHOP treatment group.
Examples of contraceptive methods with a failure rate of 1% per year include 
bilateral tubal ligation, male sterilization, established, proper use of hormonal 
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), 
and copper IUDs. 

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The reliability of sexual abstinence needs to be evaluated in relation to the duration 
of the clinical trial and the preferred and usual lifestyle of the patient.  Periodic 
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and 
withdrawal are not acceptable methods of contraception.

For men:  agreement to remain abstinent (refrain from heterosexual intercourse) or use 
contraceptive measures and agreement to refrain from donating sperm, as defined below:
With female partners of childbearing potential, men must remain abstinent or use a
condom plus an additional contraceptive method that together result in a failure rate 
of 1% per year during the treatment period and for at least 3 months after the last 
dose of study treatment.  Men must refrain from donating sperm for the same period.
With pregnant female partners, men must remain abstinent or use a condom during 
the treatment period and for at least 3 months after the last dose of study treatment.
The reliability of sexual abstinence needs to be evaluated in relation to the duration 
of the clinical trial and the preferred and usual lifestyle of the patient.  Periodic 
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and 
withdrawal are not acceptable methods of contraception.
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:

Histological evidence of transformation of FL into high-grade B-cell non-Hodgkin's 
lymphoma

Central nervous system lymphoma or leptomeningeal infiltration

For patients with DLBCL:  preplanned consolidative radiotherapy

Treatment with systemic immunosuppressive medications, including, but not limited to, 
prednisone, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor agents 
within 2 weeks prior to Day 1 of Cycle 1
Treatment with inhaled corticosteroids and mineralocorticoids is permitted.
If corticosteroid treatment is urgently required for lymphoma symptom control prior to 
the start of study treatment, 100 mg of prednisone or equivalent can be given for a 
maximum of 5 days, but all tumor assessments must be completed prior to initiation 
of corticosteroid treatment.

For patients with relapsed or refractory FL (enrolled in the safety run-in phase)
Prior allogeneic or autologous stem cell transplantation 
Prior anthracycline therapy (in patients enrolled in the Atezo-G-CHOP treatment 
group)
Treatment with fludarabine or alemtuzumab within 12 months prior to Day 1 of 
Cycle1
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, 
including anti-CTLA4, antiprogrammed death1, and antiprogrammed 
deathligand 1 therapeutic antibodies
Treatment with a monoclonal antibody, radioimmunoconjugate, or antibody-drug 
conjugate within 4 weeks prior to Day 1 of Cycle 1
Radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy 
within 2 weeks prior to Day 1 of Cycle 1
Clinically significant toxicity (other than alopecia) from prior treatment that has not 
resolved to Grade 2 (per National Cancer Institute Common Terminology Criteria in 
Adverse Events v4.0) prior to Day 1 of Cycle 1

History of solid organ transplantation

History of severe allergic or anaphylactic reaction to humanized or murine monoclonal 
antibodies

Known sensitivity or allergy to murine products

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
Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or 
any component of the atezolizumab, obinutuzumab, rituximab, or bendamustine formulation, 
including mannitol

Known history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis 
obliterans), drug-induced pneumonitis, or evidence of active pneumonitis on screening 
chest CT scan
History of radiation pneumonitis in the radiation field (fibrosis) is allowed

Active bacterial, viral, fungal, or other infection or any major episode of infection requiring 
treatment with intravenous (IV) antibiotics within 4 weeks of Day 1 of Cycle 1
Caution should be exercised when considering the use of obinutuzumab and 
rituximab in patients with a history of recurring or chronic infections.

Positive for hepatitis B surface antigen, total hepatitis B core antibody, or hepatitis C virus 
antibody at screening

Known history of HIV positive status
For patients with unknown HIV status, HIV testing will be performed at screening if 
required by local regulations.

History of progressive multifocal leukoencephalopathy

Vaccination with a live virus vaccine within 28 days prior to Day 1 of Cycle 1

History of other malignancy that could affect compliance with the protocol or interpretation 
of results, with the exception of the following:
Curatively treated carcinoma in situ of the cervix, good-prognosis ductal carcinoma 
in situ of the breast, basal- or squamous-cell skin cancer, Stage I melanoma, or 
low-grade, early-stage localized prostate cancer
Any previously treated malignancy that has been in remission without treatment for 
2 years prior to enrollment

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’s 
granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, 
or glomerulonephritis
Patients with a history of autoimmune-related hypothyroidism on a stable dose of 
thyroid replacement hormone may be eligible for this study.
Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be 
eligible for this study.

Evidence of any significant, uncontrolled concomitant disease that could affect compliance 
with the protocol or interpretation of results, including significant cardiovascular disease 
(such as New York Heart Association Class III or IV cardiac disease, myocardial infarction 
within the previous 6 months, unstable arrhythmia, or unstable angina) or significant 
pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)

Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1 
Day 1, or anticipation of a major surgical procedure during the course of the study

For patients who will be receiving CHOP:  left ventricular ejection fraction 50% by 
multiple-gated acquisition scan or echocardiogram

Inadequate hematologic function (unless due to underlying lymphoma), defined as follows:
Hemoglobin 9 g/dL
ANC 1.5 109/L
Platelet count 75 109/L

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
Any of the following abnormal laboratory values (unless due to underlying lymphoma):
Creatinine 1.5 times the upper limit of normal (ULN) (unless creatinine clearance is 
normal) or calculated creatinine clearance 40 mL/min (using the Cockcroft-Gault 
formula)
AST or ALT 2.5 ULN
Serum total bilirubin 1.5 ULN (or 3 ULN for patients with Gilbert syndrome)  
INR or PT 1.5 ULN in the absence of therapeutic anticoagulation
PTT or aPTT 1.5 ULN in the absence of a lupus anticoagulant 

Pregnant or lactating, or intending to become pregnant during the study
Women who are not postmenopausal (12 months of non-therapy-induced 
amenorrhea) or surgically sterile must have a negative serum pregnancy test result 
within 7 days prior to Day 1 of Cycle 1.

Unable to comply with the study protocol, in the investigator’s judgment
End of Study
The end of this study is defined as the time when all enrolled FL patients have completed or 
discontinued study treatment and all enrolled DLBCL patients have been followed for at least 
1 year after they have completed or discontinued study treatment.  
Length of Study
The total length of the study, from screening of the first patient to the end of the study, is 
expected to be approximately 4 years.
Investigational Medicinal Products
Obinutuzumab will be administered IV infusion at an absolute (flat) dose of 1000 mg on Days 1, 
8, and 15 of the first cycle and on Day 1 of each subsequent cycle during induction treatment, 
and on Day 1 of every other cycle (i.e., every 2 months) during maintenance treatment (eligible 
patients with FL only).  No dose modification for obinutuzumab is allowed.
Atezolizumab will be administered at a flat dose consisting of one of the following:  a) 1200 mg 
every 3 weeks (1200 mg on Day 1 of Cycles 2 and beyond, given in 21-day cycles either with 
G-CHOP as induction treatment or alone as consolidation treatment); b) 840 mg every 2 weeks
(840 mg on Days 1 and 15 of Cycles 26, given in 28-day cycles with G-benda as induction 
treatment); or c) 1680 mg every 4 weeks (840 mg on Days 1 and 2 of each month, given with 
obinutuzumab as maintenance treatment).  . No dose modification for atezolizumab is allowed.  
Bendamustine will be administered by IV infusion at a dose of 90 mg/m2 on Days 1 and 2 of 
each 28-day cycle, for up to 6 cycles.  There must be a minimum of 12 hours between each 
bendamustine administration.  
Rituximab will be administered by IV infusion at the dose of 375 mg/m2 on Day 1 of Cycles 1−8.  
No dose modification for rituximab is allowed.
Non-Investigational Medicinal Products
CHOP agents will be administered at the standard dose and schedule, according to the 
standard preparation and infusion procedures of each investigational site.  The CHOP regimen 
consists of cyclophosphamide 750 mg/m2 IV on Day 1, doxorubicin 50 mg/m2 IV on Day 1, 
vincristine 1.4 mg/m2 (maximum, 2 mg) IV on Day 1, and prednisone 40 mg/m2 by mouth on 
Days 15.
Statistical Methods
Primary Analysis
The primary and secondary efficacy analyses will be performed by treatment group, with 
patients grouped according to treatment received. For the Atezo-R-CHOP treatment group, the 
efficacy analyses will include all patients enrolled in the expansion phase. For the 
Atezo-G-benda treatment group, the efficacy analyses will include all patients enrolled in the 
expansion phase as well as patients with previously untreated FL who were enrolled in the 
safety run-in phase.

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Response will be determined through use of the modified Cheson 2007 criteria, which take into 
account both PET-CT and CT scan results, and through use of the PET-CTbased Lugano 
2014 criteria.
Determination of Sample Size  
Data from completed and ongoing studies in similar disease settings will be used as historical 
controls for comparison.  Currently available data indicate that the historical CR rate is 
approximately 40% for first-line treatment of FL and 59% for first-line treatment of DLBCL, as 
assessed by Cheson 2007 criteria.  A sample size of 40 patients is deemed sufficient to provide 
adequate precision for the point estimate and for the lower bound of the two-sided 90% CI to 
rule out a clinically uninteresting probability of response of 40% in FL and 59% in DLBCL, 
assuming an observed PET-CTdefined CR rate of 55% and 72%, respectively.  Updated 
estimates of the proportion of patients expected to achieve a PET-CTdefined CR for each 
histological subtype are expected to be available from ongoing studies by the time of the first 
interim analysis and will be used as reference data.  
Interim Analyses
It is anticipated that at least one interim analysis will be conducted during the expansion phase 
of the study, when at least 15 patients have been evaluated for PET-CT-defined CR at the EOI.  
Additional analyses may be conducted to guide early stopping of enrollment for safety on the 
basis of observed toxicities and the ability to maintain chemotherapy dose intensity.
During the expansion phase, a modified version of the predictive probability design may be 
used to guide early stopping for futility by comparing the observed proportion of patients who 
achieve a PET-CTdefined CR at EOI in each expansion cohort with that in historical controls.  
The earliest interim analysis would occur after at least 15 patients have been evaluated for 
PET-CTdefined CR at EOI.  
If, at any time, an interim analysis suggests that the proportion of patients achieving a 
PET-CTdefined CR for one of the expansion cohorts is lower or higher than expected, the 
Internal Monitoring Committee (IMC) will review the data and decide whether to recommend an 
early decision to stop enrollment in that subgroup.  Interim analysis decision rules will be based 
on the modified version of the predictive probability that the trial will have a positive outcome if 
carried out to completion and will use the historical control data available at the time of analysis.
Additional review of safety and/or efficacy data by the IMC may be requested by and carried out 
at the discretion of the Medical Monitor.  Further details regarding the rules and guidelines of 
data review will be provided in an IMC charter document.

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LIST OF ABBREVIATIONS AND OF TERMS
Abbreviation
Definition
18F-FDG
18F-fluorodeoxyglucose 
ABC
activated B cell–like (subgroup)
ADR
adverse drug reaction
ALP
alkaline phosphatase
ATA
anti-therapeutic antibody
Atezo-G
atezolizumab plus obinutuzumab
Atezo-G-benda
atezolizumab in combination with obinutuzumab plus 
bendamustine
Atezo-G-CHOP
atezolizumab in combination with obinutuzumab plus CHOP
Atezo-R-CHOP
atezolizumab in combination with rituximab plus CHOP
BSA
body surface area
CHOP
cyclophosphamide, doxorubicin, vincristine, and prednisone
CLL
chronic lymphocytic leukemia
CR
complete response
CSR
clinical study report
CT
computed tomography
CTLA-4
cytotoxic T-lymphocyte-associated protein 4
Ctrough
trough concentration
CVP
cyclophosphamide, vincristine, and prednisone
CYP
cytochrome P450
DFS
disease-free survival
DLBCL
diffuse large B-cell lymphoma
DLT
dose-limiting toxicity
EC
Ethics Committee
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic Case Report Form
EDC
electronic data capture
EFS
event-free survival
EOI
end of induction
EORTC
European Organization for Research and Treatment of Cancer
ESMO
European Society for Medical Oncology
FcRIII
Fc gamma receptor type III
FDG
fluorodeoxyglucose
FL
follicular lymphoma
FLIPI, FLIPI2
Follicular Lymphoma International Prognostic Index
Follicular Lymphoma International Prognostic Index 2

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Abbreviation
Definition
G
obinutuzumab (GA101)
G-benda
obinutuzumab plus bendamustine
GCB
germinal-center B cell–like (subgroup)
G-CHOP
obinutuzumab plus CHOP
GClb
G-chlorambucil
GCP
Good Clinical Practice
G-CSF
granulocyte colony-stimulating factor
G-CVP
obinutuzumab plus cyclophosphamide, vincristine, and 
prednisone
GELF
Groupe d'Etudes des Lymphomes Folliculaires
GI
gastrointestinal
HACA
human anti-chimeric antibodies
HAHA
human anti-human antibody
HBcAb
hepatitis B core antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIPAA
Health Insurance Portability and Accountability Act
HR
hazard ratio
IC
immune cell
ICH
International Conference on Harmonisation
IFN-
interferon alpha
IFN-
interferon gamma
Ig
immunoglobulin
IL
interleukin
IMC
Internal Monitoring Committee
IMP
investigational medicinal product
IND
Investigational New Drug
iNHL
indolent non-Hodgkin's lymphoma
IPI
International Prognostic Index
IRB
Institutional Review Board
IRC
Independent Review Committee
IRR
infusion-related reaction
IUD
intrauterine device
IV
intravenous
IxRS
interactive voice or web-based response system
JC
John Cunningham

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Abbreviation
Definition
LFT
liver function test
LMWH
low-molecular-weight heparin
Lugano 2014 criteria
Lugano Response Criteria for Malignant Lymphoma 
LVEF
left ventricular ejection fraction
modified Cheson 2007 
criteria
modified version of the Revised Response Criteria for Malignant 
Lymphoma
MRD
minimal residual disease
MRI
magnetic resonance imaging
MTD
maximum tolerated dose
MUGA
multiple-gated acquisition
NCI CTCAE
National Cancer Institute Common Terminology Criteria in 
Adverse Events
NHL
non-Hodgkin’s lymphoma
NK
natural killer
NSCLC
nonsmall cell lung cancer
ORR
objective response rate
OS
overall survival
PD
pharmacodynamic
PD-1
programmed death1
PD-L1
programmed deathligand 1
PET
positron emission tomography
PFS
progression-free survival
PK
pharmacokinetic
PML
progressive multifocal leukoencephalopathy
PO
by mouth
PR
partial response
q2w
every 2 weeks
q3w
every 3 weeks
q4w
every 4 weeks
R
rituximab
RANKL
Receptor activator of nuclear factor kappa-B ligand 
RCC
renal cell carcinoma
RCR
Roche Clinical Repository
RP2D
recommended Phase II dose
R-CHOP
rituximab plus CHOP chemotherapy
RClb
R-chlorambucil
SCT
stem cell transplantation

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Abbreviation
Definition
Teffs
effector T cells 
TEN
toxic epidermal necrolysis
TFH
helper T cell
TIL
tumor-infiltrating lymphocyte
TLS
tumor lysis syndrome
TP53
tumor protein p53
TSH
thyroid stimulating hormone
UBC
urothelial bladder cancer
UC
urothelial cancer
ULN
upper limit of normal

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1.
BACKGROUND
1.1
BACKGROUND ON NON-HODGKIN'S LYMPHOMA
Non-Hodgkin’s lymphoma (NHL) is the most common hematologic malignancy in adults.  
In 2013, there were an estimated 69,740 new cases and 19,020 deaths due to the 
disease in the United States (Siegel et al. 2013).  In Europe, there were an estimated 
93,400 new cases and 37,900 deaths in 2012 (Ferlay et al. 2013).  NHL is most often of 
B-cell origin, including a wide range of different subtypes of B-cell NHL, broadly divided 
into indolent and aggressive lymphomas, each with unique characteristics.
1.1.1
Follicular Lymphoma
Indolent NHLs (iNHLs) are a heterogeneous group of malignant lymphomas and account 
for approximately one third of all NHLs.  Follicular lymphoma (FL) is the most common 
subtype of iNHL, accounting for about 22% of all newly diagnosed cases of NHL 
(Armitage and Weisenburger 1998).  Approximately 90% of the cases have a t(14;18) 
translocation, which juxtaposes BCL2 gene with the IgH locus and results in deregulated 
expression of BCL2.  
FL remains an incurable disease with the currently available therapies.  The addition of 
rituximab, an anti-CD20 monoclonal antibody, to commonly used induction 
chemotherapy, including cyclophosphamide, doxorubicin, vincristine, and prednisone
(CHOP); cyclophosphamide, vincristine, and prednisone (CVP); fludarabine; or 
bendamustine (Zelenetz et al. 2013; Dreyling et al. 2014), followed by rituximab 
maintenance therapy led to prolonged response and improved patient outcomes.  
Updated results from Study MO18264 confirmed the benefit of 2-year rituximab 
maintenance in patients responding to first-line immunotherapy, with a 6-year 
progression-free survival (PFS) of 59.2% compared with 42.7% in the observation arm 
(p 0.0001) (Salles et al. 2013).
Despite significant therapeutic progress with the use of chemoimmunotherapy as 
first-line treatment, most patients will eventually experience disease relapse.  Relapses 
are characterized by increasing refractoriness and decreasing duration of response to 
subsequent lines of therapy.  Thus, new treatments are needed to improve the outcome 
for these patients.
1.1.2
Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive NHL, 
accounting for approximately 30% of all NHLs diagnosed annually 
(Armitage and Weisenburger 1998).  The use of immunochemotherapy, most commonly 
R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), 
for newly diagnosed DLBCL led to a significant improvement in survival in patients of all 
age groups.  In older patients (60 years), R-CHOP was associated with a 2-year event-
free survival (EFS) rate of 57% and a 10-year survival rate of 43.5% (Coiffier et al. 2010).  
In younger patients (1860 years of age) with favorable prognostic features, R-CHOP 

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demonstrated a 3-year EFS rate of 79% and a survival rate at 3 and 6 years of 93% and 
74.3%, respectively (Pfreundschuh et al. 2011).  However, nearly 40% of patients with 
DLBCL will eventually die of relapsed disease or disease that is refractory to first-line 
treatment.  Patients with a high-risk International Prognostic Index (IPI) have a 5-year 
PFS rate of only 40% following treatment with R-CHOP (Zhou et al. 2014).
Second-line treatments consist of high-dose chemotherapy regimens such as rituximab 
plus ifosfamide, carboplatin, and etoposide or rituximab plus dexamethasone, cytosine 
arabinoside, and cisplatin followed by autologous stem cell transplantation (SCT).  
Approximately half of the patients do not achieve a complete response after salvage 
treatment (Gisselbrecht et al. 2010).  Moreover, elderly patients or patients with 
comorbidities are often deemed ineligible for this aggressive therapy.
Specific molecular subsets of DLBCL are associated with an inferior outcome following 
R-CHOP therapy.  Germinal center B-cell-like (GCB) DLBCL had a better prognosis than 
activated (non-germinal) B-cell-like (ABC) DLBCL, with a 3-year survival rate of 84% 
versus 56%, respectively (p0.001) (Lenz et al. 2008).  Several genetic abnormalities 
predictive of poor outcome have been identified in DLBCL, including MYC 
rearrangement, BCL2 and BCL6 overexpression, and tumor protein p53 (TP53)
mutations.  Rearrangement in MYC (MYC-positive DLBCL) has been reported in 9%17% 
of DLBCL cases and often correlates with the GCB DLBCL phenotype 
(Savage et al. 2009; Barrans et al. 2010).  DLBCL treated with R-CHOP has a markedly 
worse 5-year survival rate in patients with MYC-positive DLBCL compared with 
MYC-negative DLBCL (33% versus 72%) (Savage et al. 2009).  Concurrent MYC and 
IGH-BCL2 rearrangement (“double-hit” DLBCL), observed in 2%11% of DLBCL 
patients, represents a DLBCL subset with an inferior outcome (5-year PFS of 18%; 
5-year survival of 27%) (Savage et al. 2009; Dunleavy et al. 2014).  Mutations in TP53 
have been described in approximately 20% of patients with DLBCL and are strong 
predictor of poor overall survival (OS) (Xu-Monette et al. 2012; Young et al. 2008).
DLBCL remains a high unmet medical need for which novel targeted therapies are 
needed to move the field beyond R-CHOP.
1.2
BACKGROUND ON OBINUTUZUMAB
Obinutuzumab (also known as GA101) is a novel glycoengineered Type II anti-CD20 
antibody.  Compared with rituximab, obinutuzumab is characterized by more potent 
direct B-cell death induction and increased affinity for Fc gamma receptors type III 
(FcRIII) expressed on natural killer (NK) cells, macrophages, and monocytes, resulting 
in enhanced antibody-dependent cellular cytotoxicity and antibody-dependent cellular 
phagocytosis (Beers et al. 2010; Mössner et al. 2010; Herter et al. 2014).  Together, 
these characteristics confer obinutuzumab with enhanced immune effector functions and 
B-cell depleting activity compared with rituximab.

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Obinutuzumab is approved for use in combination with chlorambucil for the treatment of 
patients with previously untreated chronic lymphocytic leukemia (CLL).  Obinutuzumab is 
also approved for use in combination with bendamustine followed by obinutuzumab 
maintenance for the treatment of patients with FL who did not respond to or who 
progressed during or after treatment with rituximab or a rituximab-containing regimen
and in combination with chemotherapy, followed by obinutuzumab maintenance for the 
treatment of patients with previously untreated follicular lymphoma.
1.2.1
Nonclinical Studies with Obinutuzumab
In nonclinical studies, obinutuzumab demonstrated superior depletion of normal B cells 
(measured as CD19+ depletion) from the blood of healthy volunteers 
(Mössner et al. 2010) as well as malignant B cells from the blood of patients with CLL 
(Patz et al. 2011).  Nonclinical xenograft experiments performed with obinutuzumab as 
monotherapy and in combination with chemotherapy have consistently showed 
promising anti-tumor activity of obinutuzumab (Mössner et al. 2010; Dalle et al. 2011) 
and superiority of obinutuzumab over rituximab (Herting et al. 2014).
For more detailed nonclinical information on obinutuzumab, please refer to the current 
version of the obinutuzumab Investigator’s Brochure.
1.2.2
Clinical Studies with Obinutuzumab
Obinutuzumab is being studied in patients with CLL, iNHL, NHL, DLBCL, B-cell 
lymphoma and solid tumors.  Available efficacy results from the NHL cohorts in these 
studies and available safety results from all patients are summarized below.  
For more detailed clinical information on obinutuzumab, including results in the CLL 
cohorts of the clinical studies, please refer to the obinutuzumab Investigator’s Brochure.
1.2.2.1
Summary of Clinical Efficacy of Obinutuzumab in Patients with 
NHL
In studies of obinutuzumab monotherapy in patients with relapsed or refractory NHL 
(Studies BO20999, BO21003, and JO21900), the proportion of patients who had a 
response (complete response [CR] or partial response [PR]) at the end of treatment 
(as determined on the basis of computed tomography [CT] scans alone) ranged from 
28% to 58%.  The CR rate ranged from 0% to 19%. 
In early studies of obinutuzumab in combination with chemotherapy (e.g., CHOP, 
bendamustine) in patients with previously untreated, or relapsed or refractory NHL 
(BO21000 and GAO4915g), the proportion of patients with a CR or PR at the end of 
induction (EOI) treatment ranged from 82% to 96%.  The CR rate was higher with 
combination therapy (35%39% in previously untreated FL, 39%50% in relapsed or 
refractory FL, and 55% in previously untreated DLBCL) than with monotherapy.

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A Phase III study, GAO4753g, investigated obinutuzumab plus bendamustine (G-benda) 
compared with bendamustine alone in patients with rituximab-refractory iNHL (n396).  
Patients in the G-benda treatment group who had not experienced disease progression 
at the EOI received obinutuzumab monotherapy every 2 months for up to 2 years.  
On the basis of positive results from this study that demonstrated significant 
improvement in PFS in the GB treatment group, with a median PFS of 29 versus 
14 months (hazard ratio [HR]: 0.52; 95% CI: 0.39, 0.70; p 0.0001) (Sehn et al. 2015), 
obinutuzumab was granted approval for use in patients with FL who did not respond or 
who progressed during or up to 6 months after treatment with rituximab or a 
rituximab-containing regimen (see Section 1.2). 
A Phase III study, BO21223, investigated obinutuzumab plus chemotherapy (G-benda,
obinutuzumab plus CVP [G-CVP], G-CHOP) compared with rituximab plus 
chemotherapy in patients with previously untreated iNHL (FL cohort, n1202).  On the 
basis of positive results that demonstrated significant improvement in PFS in the 
obinutuzumab-chemotherapy arm, the Independent Data Monitoring Committee 
recommended that the study be unblinded to the Sponsor at a pre-planned interim 
analysis.  Obinutuzumab was granted approval for use in patients with previously 
untreated FL in European Union, United States, and elsewhere.
A Phase III study, BO21005, investigated obinutuzumab plus CHOP (G-CHOP) 
compared with rituximab plus CHOP (R-CHOP) in patients with previously untreated 
DLBCL.  The study did not meet its primary endpoint of PFS at final analysis.
1.2.2.2
Summary of Clinical Safety of Obinutuzumab
As of 31 October 2017, 4981 patients have received obinutuzumab via clinical trial 
participation.  Patients with NHL (including DLBCL, iNHL, and CLL) have been treated 
with obinutuzumab given as monotherapy or in combination with CHOP, bendamustine, 
fludarabine plus cyclophosphamide, or chlorambucil, at doses ranging from 50 to 
2000 mg.  Overall, the safety of obinutuzumab monotherapy and obinutuzumab 
combination therapy was manageable.
The most frequent causes of death were disease progression and adverse events 
associated with infectious diseases.  This is consistent with the study population and the 
disease under treatment.  The incidence of fatal adverse events was similar across all 
ongoing trials.  In Study GAO4768g (obinutuzumab 1000 versus 2000 mg), the 
incidence of deaths did not increase with increased obinutuzumab dose (7.5% and 
2.6%, respectively).
Of particular interest, a high incidence of infusion-related reactions (IRRs) was observed 
consistently in all obinutuzumab trials.  The reported incidence of IRRs varied across 
studies.  In the CLL population, the incidence ranged from 66% in previously untreated 
patients receiving obinutuzumab plus chlorambucil (Study BO21004) to 100% in 
relapsed or refractory patients receiving obinutuzumab monotherapy (pooled data from 

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Studies BO21003 and BO20999, CLL cohorts).  Anaphylaxis has also been reported in 
patients treated with obinutuzumab.
In the NHL population, the incidence of IRRs in studies of obinutuzumab monotherapy 
was 73%75% (pooled data from Study BO21003 and from high-dose, NHL cohorts 
from Study BO20999).  In studies of obinutuzumab in combination with either CHOP 
(Study GAO4915g) or bendamustine (Study BO21000), the incidence of IRRs 
considered to be related to obinutuzumab was 56%59%.
Other important risks associated or potentially associated with obinutuzumab are tumor 
lysis syndrome (TLS), thrombocytopenia (including acute thrombocytopenia), 
neutropenia (including prolonged and late-onset neutropenia), prolonged B-cell depletion, 
infections (including progressive multifocal leukoencephalopathy [PML] and hepatitis B 
virus [HBV] reactivation), worsening of preexisting cardiac conditions, impaired 
immunization response, gastrointestinal (GI) perforation, immunogenicity, and second 
malignancies.  The important identified risks associated with obinutuzumab are 
presented in detail in Section 5.1.1 of this protocol and in the obinutuzumab 
Investigator's Brochure.
1.3
BACKGROUND ON ATEZOLIZUMAB
Atezolizumab is a humanized immunoglobulin (Ig) G1 monoclonal antibody that targets 
programmed deathligand 1 (PD-L1) and inhibits its interaction with its receptors, 
programmed death1 (PD-1) and B7-1 (also known as CD80).  Both of these 
interactions are reported to provide inhibitory signals to T cells.  Therapeutic blockade of 
PD-L1 binding by atezolizumab is expected to enhance the magnitude and quality of the 
tumor-specific T-cell responses, resulting in improved anti-tumor activity.  Atezolizumab
was engineered to impair its binding to Fc receptors, thus eliminating detectable 
Fc-effector function and associated antibody-mediated clearance of activated effector 
T cells (Teffs).
Atezolizumab is approved for the treatment of patients with locally advanced or 
metastatic urothelial cancer who (1) have disease progression during or following 
platinum-containing chemotherapy or (2) have disease progression within 12 months of 
neoadjudvant or adjuvant treatment with platinum-containing chemotherapy.  
Atezolizumab is also approved for use in patients with metastatic nonsmall cell lung 
cancer that has relapsed after or is refractory to platinum-based chemotherapy.  
Atezolizumab is being investigated as a potential treatment against solid tumors and 
hematologic malignancies in humans.
1.3.1
Nonclinical Studies with Atezolizumab
The safety, pharmacokinetics, and toxicokinetics of atezolizumab were investigated in 
mice and cynomolgus monkeys to support intravenous (IV) administration and to aid 
in projecting the appropriate starting dose in humans.  Given the similar binding of 
atezolizumab for cynomolgus monkey and human PD-L1, the cynomolgus monkey was 

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selected as the primary and relevant nonclinical model for understanding the safety, 
pharmacokinetics, and toxicokinetics of atezolizumab.  Overall, the nonclinical 
pharmacokinetics and toxicokinetics observed for atezolizumab supported entry into 
clinical studies, including providing adequate safety factors for the proposed Phase I 
starting doses.  The results of the toxicology program were consistent with the 
anticipated pharmacologic activity of downmodulating the PD-L1/PD-1 pathway.  
Improved immune responses and the potential to increase immune-associated 
inflammatory lesions were identified as possible safety risks in patients.
The combination of a surrogate anti-mouse PD-L1 antibody with an anti-mouse 
CD20-depleting antibody has been tested using a syngeneic A20 lymphoma model in 
immune-competent mice.  Results from this nonclinical study demonstrated superior 
tumor-growth inhibition and extended time to progression when compared with either 
agent alone.  Combination and single-agent treatments were well tolerated, with no 
significant loss of body weight in any group over the study duration.  Enhanced 
combination efficacy was also observed in a study using A20 cells transfected with 
human CD20 and green fluorescent protein (Genentech data). 
Refer to the Atezolizumab Investigator's Brochure for details on the nonclinical studies.
1.3.2
Clinical Studies with Atezolizumab
Atezolizumab has been tested in multiple Phase I, II, and III studies, both as 
monotherapy and in combination with several anti-cancer therapies; Phase I, II and III 
studies are also on-going in multiple indications.  The majority of the safety and efficacy 
data summarized below are from Phase Ia Study PCD4989g, a multicenter, 
first-in-human, open-label, dose-escalation trial evaluating the safety, tolerability, 
immunogenicity, pharmacokinetics, exploratory pharmacodynamics, and preliminary 
evidence of biologic activity of atezolizumab administered as a single agent by 
IV infusion every 3 weeks (q3w) to patients with locally advanced or metastatic solid or 
hematologic malignancy.
1.3.2.1
Summary of Clinical Safety of Atezolizumab
The safety data for atezolizumab have been derived from Study PCD4989g, in which 
atezolizumab is being used as single-agent therapy in patients with locally advanced or 
metastatic solid tumors or hematologic malignancies.  As of the data cutoff date of 
15 December 2015, the clinical database contained preliminary safety data from 
629 patients who received atezolizumab at doses ranging from 0.01 to 20 mg/kg across 
multiple tumor types.  No dose-limiting toxicities (DLTs) have been observed at any dose 
level, and no maximum tolerated dose (MTD) has been established.  In Study GP28328, 
a Phase Ib multi-arm study, patients with solid tumors were treated with atezolizumab 
1200 mg q3w or 840 mg every 2 weeks (q2w) in combination with commonly used 
chemotherapies (i.e., oxaliplatin, leucovorin, and 5-fluorouracil; carboplatin; paclitaxel;
pemetrexed; nanoparticle albumin-bound paclitaxel) and/or bevacizumab (biologic agent) 
at standard doses.  Preliminary data available for 144 patients show a manageable 

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safety profile without exacerbation of chemotherapy- or bevacizumab-associated 
adverse events.
Summary of Adverse Events
Adverse events were reported in 619 of the 629 (98.4%) safety-evaluable patients.  
Adverse events occurring in 10% of treated patients included fatigue, decreased 
appetite, nausea, pyrexia, constipation, cough, dyspnea, diarrhea, anemia, vomiting, 
asthenia, back pain, headache, arthralgia, pruritus, rash, abdominal pain, insomnia, 
peripheral edema, urinary tract infection, dizziness, and chills.  Grade3 adverse events 
were reported in approximately 43% of patients.
Treatment-related adverse events (per investigator’s assessment of causality) were 
reported in 444 of 629 (70.6%) patients.
Grade 34 treatment-related events were reported in 13.7% of patients, with fatigue and 
asthenia (1.3% each), AST increased and dyspnea (1.1% each), and hyponatremia 
(0.8%) as the most frequently occurring events (0.8% or 5 patients).
Serious adverse events have been reported in 261 of 629 (41.5%) patients in 
Study PCD4989g.  Reported serious adverse events were consistent with the underlying 
disease.  Treatment-related serious adverse events were reported in 9.1% of patients.  
Atezolizumab-related serious adverse events occurring in 2 patients (0.3%) were 
pyrexia (2.1%); dyspnea (0.8%); pneumonitis (0.6%); fatigue, malaise, hypoxia, and 
colitis (0.5% each); and bone pain (0.3%). 
Ten patients (1.6%) had Grade 5 events.  The 3 events assessed by the investigator as 
related to atezolizumab were death (not otherwise specified), hepatic failure, and 
pulmonary hypertension.
Additional details for each case are provided in the Atezolizumab Investigator’s Brochure.
Immune-Related Adverse Events
Given the mechanism of action of atezolizumab, events associated with inflammation or 
immune-related adverse events have been closely monitored during the atezolizumab 
clinical program.  To date immune-related adverse events associated with atezolizumab 
include hepatitis, pneumonitis, colitis, pancreatitis, diabetes mellitus, hypothyroidism, 
hyperthyroidism, adrenal insufficiency, Guillain-Barré syndrome, myasthenic 
syndrome/myasthenia gravis, meningoencephalitis, myocarditis, and hypophysitis.
Guidelines for the management of potential immune-related adverse events are 
described in Section 5.1.7.
Refer to the Atezolizumab Investigator’s Brochure for details on adverse events 
observed in patients treated with atezolizumab. 

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1.3.2.2
Summary of Clinical Activity of Atezolizumab
Patients with multiple tumor types were included in Study PCD4989g, with the largest 
cohorts consisting of patients with nonsmall cell lung cancer (NSCLC), renal cell 
carcinoma (RCC), and urothelial bladder cancer (UBC).  Clinical activity of atezolizumab 
monotherapy was observed in a broad range of malignancies, including NSCLC, RCC, 
melanoma, bladder cancer, colorectal cancer, head and neck cancer, gastric cancer, 
breast cancer, and sarcoma.  Analyses of response by PD-L1 expression status in 
tumor-infiltrating immune cells (ICs) and tumor cells in baseline tumor tissue were also 
conducted. 
Efficacy results, based on a data cutoff date of 15 December 2015, are summarized 
below for the NSCLC, RCC, and UBC cohorts.  See the Atezolizumab Investigator’s 
Brochure for clinical activity in combination studies and for additional details.
Patients with Hematologic Malignancies
Eleven patients with refractory or relapsed hematologic malignancies have been treated 
with atezolizumab in Study PCD4989g.  This includes patients with multiple myeloma 
(n4), FL (n3), cutaneous T-cell lymphoma (n2), DLBCL (n1), and Hodgkin’s 
lymphoma (n1).  Among the 10 patients who were evaluable for response, the best 
response was PR for the 2 patients with cutaneous T-cell lymphoma; stable disease for 
the 3 patients with FL, the 1 patient with Hodgkin’s lymphoma, and 2 patients with 
multiple myeloma; and progressive disease for the remaining 2 patients with multiple 
myeloma. A Phase Ib study (GO29383) of atezolizumab 1200 mg q3w in combination 
with obinutuzumab was performed in patients with relapsed or refractory FL and DLBCL 
(see Section 1.4.3)
Please refer to the Atezolizumab Investigator’s Brochure for details on clinical activity in 
patients treated to date.
1.4
STUDY RATIONALE AND BENEFIT-RISK ASSESSMENT
Despite significant therapeutic progress with the addition of rituximab to chemotherapy 
for first-line treatment of patients with B-cell NHL, FL and DLBCL remain an area of high 
medical need in which novel targeted therapies are required to improve patient outcome 
(see Section 1.1).
1.4.1
PD-L1/PD-1 Pathway in Lymphoma
The PD-L1/PD-1 pathway serves as an immune checkpoint to temporarily dampen 
immune responses in states of chronic antigen stimulation such as chronic infection or 
cancer.  PD-L1 is an extracellular protein that downregulates immune responses through 
binding to its two receptors, PD-1 and B7-1.  PD-1 is an inhibitory receptor expressed on 
T cells following T-cell activation, and expression is sustained in states of chronic 
stimulation (Blank et al. 2005; Keir et al. 2008).  B7-1 is a molecule expressed on 
antigen-presenting cells and activated T cells.  Binding of PD-L1 to PD-1 and B7-1 
inhibits T-cell proliferation and activation, cytokine production, and cytolytic activity, 

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leading to the functional inactivation or exhaustion of T cells (Butte et al. 2007).  
Overexpression of PD-L1 on tumor cells has been reported to impede anti-tumor 
immunity, resulting in immune evasion (Blank and Mackensen 2007).  Therefore, 
interruption of the PD-L1/PD-1 pathway represents an attractive strategy for restoring 
tumor-specific T-cell immunity.
Antibody-mediated PD-1 blockade has already been successfully exploited as a 
therapeutic strategy in solid tumors (Brahmer et al. 2012; Topalian et al. 2012, 
Herbst et al. 2013) and is currently being evaluated in hematologic malignancies 
(see Section 1.4.2).  Increased PD-L1 expression has been reported on tumor cells and 
on immune or microenvironment cells in various lymphoid malignancies.  PD-L1 is highly 
expressed in Hodgkin’s lymphomas, anaplastic large cell lymphoma, and DLBCL, 
particularly the ABC or non-GCB subtypes (Andorsky et al. 2011).  Consistent with 
published data, Sponsor internal data (unpublished) from patients with previously 
untreated DLBCL enrolled in Study AVF4065g showed 67.5% of patients with lymphoma 
that is positive for PD-L1 as assessed by immunohistochemistry (staining 5% of cells), 
including 23% of patients with strong PD-L1 expression (staining in 25% of cells).  
In FL, PD-L1 is expressed on tumor-infiltrating lymphocytes (TILs), macrophages 
peripheral blood T cells, and monocytes but not on tumor cells (Myklebust et al. 2013).
1.4.2
Clinical Experience with PD-L1/PD-1 Pathway Inhibitors in 
Lymphoma
Pidilizumab (CT-011), a humanized IgG-1k monoclonal antibody that targets PD-1, has 
been tested in Phase I and II clinical studies in hematological malignancies.  Pidilizumab 
administered as a single agent after autologous SCT in patients with DLBCL 
(Armand et al. 2013) or in combination with rituximab in patients with relapsed FL 
(Westin et al. 2014) was well tolerated and showed potential clinical benefit.  No 
autoimmune or treatment-related Grade 3 or 4 adverse events have been reported in 
these studies.  Among patients with relapsed FL who received pidilizumab in 
combination with rituximab, responders have been shown to express higher levels of 
PD-L1 on peripheral blood T cells and monocytes at baseline relative to non-responders.  
Additionally, positive correlation with PFS was observed for a T-cell activation signature 
created by gene expression profile studies.  41 genes have been identified to be more 
highly expressed in Teffs as compared with follicular helper T cells (TFH).  Low 
expression of this signature, suggesting more TFH and fewer PD-1+ Teffs within the 
tumor, predicted less tumor shrinkage and shorter PFS:  median of 12.7 months (95% CI: 
6.5, 21.6) for signature-low patients versus not reached (95% CI: NA, NA) for signature-
high patients (Westin et al. 2014).
Nivolumab (BMS-936558), a fully human IgG4 monoclonal antibody that targets PD-1, 
was recently evaluated in a Phase I dose-escalation study that tested doses of 1 and 
3 mg/kg in patients with relapsed or refractory lymphoid malignancies.  Preliminary data 
indicate that 1 patient experienced DLTs of Grade 3 pneumonia and pneumonitis at the 

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1-mg/kg dose and 1 patient experienced DLTs of Grade 3 eosinophilia and diplopia at 
the 3-mg/kg dose (expansion in progress at this dose; Lesokhin et al. 2014).  The overall 
response rate (ORR) and CR rate in patients with B-cell NHL were 28% and 7%, 
respectively, including an ORR of 36% in patients with DLBCL and 40% in patients with 
FL (Armand et al. 2014; Lesokhin et al. 2014).
Atezolizumab is the first-in-class PD-L1 inhibitor being tested in lymphoma.  Eleven 
patients with refractory or relapsed hematologic malignancies have been treated with 
atezolizumab in Study PCD4989g, including 7 patients with lymphoma (see 
Section 1.3.2.2).  Among the 10 patients who were evaluable for response, the best 
response was PR for the 2 patients with cutaneous T-cell lymphoma and stable disease 
for the 3 patients with FL and the 1 patient with Hodgkin’s lymphoma, and 2 patients with 
multiple myeloma.
A Phase Ib study (GO29383) of atezolizumab 1200 mg q3w in combination with 
obinutuzumab was performed in patients with relapsed or refractory FL and DLBCL 
(see Section 1.4.3).
1.4.3
Rationale for Treatment Combination
Prior to the implementation of Protocol Version 3, patients with DLBCL enrolled in the 
expansion phase were to receive Atezo-G-CHOP.  However, results from Study 
BO21005 demonstrated that G-CHOP did not improve PFS compared with the standard 
R-CHOP regimen in patients with previously untreated DLBCL.  Thus, with the 
implementation of Protocol Version 3, patients with DLBCL enrolled in the expansion 
phase will receive atezolizumab in combination with R-CHOP.
Obinutuzumab and atezolizumab, as well as rituximab and atezolizumab, have 
complementary mechanisms of action, acting at different steps of the anti-tumor immune 
response.  Both obinutuzumab and rituximab induce direct tumor-cell killing with 
subsequent release of tumor antigens for immune presentation (immunogenic cell death).  
Additionally, obinutuzumab was engineered to augment antibody-dependent cellular 
cytotoxicity, resulting in enhanced binding to FcRIIIa (CD16).  Thus, obinutuzumab has 
the ability to enhance T-cell priming and IC activation through interactions with dendritic 
cells and NK cells carrying FcRIIIa.  Atezolizumab affects primarily the effector phase of 
the immune response, by restoring cytotoxic T-cell function.
Studies of obinutuzumab plus atezolizumab or rituximab plus atezolizumab have not 
been performed in nonclinical mouse models because there are no suitable models for 
testing the combination. However, synergism was exhibited when the combination of a 
surrogate anti-mouse PD-L1 antibody and an anti-mouse CD20-depleting antibody was 
tested using a syngeneic A20 lymphoma model in immune-competent mice (see 
Section 1.3.1).  Although the anti-CD20 agent used in this study is not completely 
identical to obinutuzumab, the study results provide compelling proof of concept for 
exploring these combinations in clinical trials.

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Clinical data for G-benda or G-CHOP in B-cell NHL are available from a Phase Ib/II 
study in patients with previously untreated and relapsed or refractory FL 
(Study BO21000).  In this study, 81 patients with previously untreated FL received 
induction therapy with G-benda (n41) or G-CHOP (n40), resulting in a CR rate at EOI 
of 37% and 35%, respectively (Dyer et al. 2012).  Both combinations had a manageable 
safety profile, with neutropenia reported as the most common Grade 3 adverse event 
during induction treatment, occurring in 29% of patients in the G-benda arm and 43% of 
patients in the G-CHOP arm.  Grade 3 infections occurred in 10% of patients receiving 
G-benda and 23% of patients receiving G-CHOP.  All events resolved with appropriate 
management.  Seventy-two responders at EOI, including 36 patients in the G-benda 
treatment group and 36 patients in the G-CHOP treatment group, received maintenance 
with obinutuzumab administered every 3 months for up to 2 years.  The CR rate at the 
end of treatment was 61% and 70% in the G-benda and G-CHOP treatment groups, 
respectively (Dyer et al. 2014).  Maintenance treatment with obinutuzumab was 
generally well tolerated.  Clinically relevant neutropenia was reported in 14% of patients 
in the G-benda treatment group but was not observed in the G-CHOP treatment group.  
Grade 3 infections occurred in 17% of patients in the G-benda treatment group and 
14% of patients in the G-CHOP treatment group.  Median IgG, IgA, and IgM levels 
remained within the normal range during maintenance.  In the relapsed or refractory 
cohort of this study, 28 patients received induction therapy with G-CHOP, resulting in a 
CR rate at EOI of 39%.  Neutropenia was the most common Grade 3 adverse event 
occurring in 43% of patients (Radford et al. 2013).
G-CHOP was evaluated in a Phase Ib/II study in 100 patients with previously untreated 
DLBCL (Study GAO4915g).  Data from this study demonstrate encouraging efficacy, 
with a CR rate of 55% per investigator review and 58% per centralized review 
(Zelenetz et al. 2013; GAO4915g clinical study report [CSR]), and a manageable safety 
profile.  Neutropenia was the most common Grade3 adverse event, occurring in 42%
of patients.  Grade3 infections were reported in 21% of patients.  However, these could 
be addressed by prophylactic administration of granulocyte colony-stimulating factor 
(G-CSF) support.  As consistently demonstrated across randomized trials investigating 
obinutuzumab chemotherapy versus rituximab chemotherapy in patients with B-cell 
malignancies, the safety profile of rituximab chemotherapy tended to compare favorably 
with the safety profile of obinutuzumab chemotherapy.  Results from the Phase III study 
(BO21005 [GOYA]) of G-CHOP versus R-CHOP in patients with previously untreated 
DLBCL are supporting the favorable safety profile of R-CHOP when compared with 
G-CHOP (see Table 11).  Results from the Phase III study (BO21223 [GALLIUM]) of 
obinutuzumab chemotherapy (G-benda, G-CVP, G-CHOP) versus rituximab 
chemotherapy, followed by maintenance, as first-line treatment in patients with 
previously untreated iNHL (FL cohort, n1202) demonstrated a higher frequency of 
Grade 35 adverse events (74.6%) and serious adverse events (46.1%) in patients 
treated with obinutuzumab chemotherapy compared with those treated with rituximab 
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chemotherapy treatment group in this study, higher incidence of Grade 35 adverse 
events and serious adverse events was observed in the G-CHOP treatment group (88.5% 
and 39.9%, respectively) compared with the R-CHOP treatment group (75.2% and 
31.5%, respectively) (see CSR 1067980).
Results from the Phase III Study BO21004 (Stage 2), comparing G-chlorambucil (GClb) 
with R-chlorambucil (RClb) in patients with previously untreated CLL (n663), indicated 
that patients exposed to GClb were at higher risk of IRR, TLS, thrombocytopenia, and 
neutropenia than patients exposed to RClb (Goede et al. 2014).
A Phase Ib study (GO29383) of atezolizumab in combination with obinutuzumab in 
patients with relapsed or refractory FL and DLBCL is currently in progress.  Preliminary 
results indicated that atezolizumab combined with obinutuzumab was well tolerated, with 
evidence of clinical activity in this patient population.  A total of 49 patients were enrolled 
and dosed:  26 patients with FL and 23 patients with DLBCL.  The doublet combination 
is consistent with what has been observed with the respective single agents and
manageable in the NHL setting.  As of the 14 June 2017 data cutoff, a review of safety 
data from Study GO29383 in patients with FL (n=26) and DLBCL (n=23) did not reveal 
any new safety signals.  The most commonly reported (>20%) treatment-emergent 
adverse events included the following preferred terms:  fatigue, pyrexia, nausea, 
diarrhea, abdominal pain, cough, and decreased appetite.  The most common 
Grade 34 treatment-related adverse events were neutropenia (8%), diarrhea (8%), and 
pain (8%).  There were no adverse events with fatal outcomes reported in patients with 
NHL treated with atezolizumab + obinutuzumab.  The efficacy data demonstrated 
encouraging signs of response in patients heavily pretreated and refractory with 
relapsed/refractory FL.  The ORR at the end of induction assessment (Lugano 2014 
Response Criteria by positron emission tomography and computed tomography 
[PET-CT]) was 56.5%, with a complete response rate of 26.1%.  The median duration of 
response and median PFS at the time of clinical cutoff were 15.0 and 15.1 months, 
respectively.  In patients with relapsed/refractory DLBCL, the end of induction 
assessment was 11.1% with one patient achieving CR at end of induction.  The median 
duration of response and median PFS at the time of clinical cutoff were 3.5 and 
2.7 months, respectively (Palomba et al. 2017).
Available data and current concepts of immunotherapy suggest that there is a strong 
rationale to expect an improved benefit-risk ratio with the addition of atezolizumab to 
G-benda and R-CHOP in FL and DLBCL, respectively.  The expected benefit may result 
from the strengthened immunotherapy component of the combinations, able to lead to 
robust and long-lasting anti-tumor responses, along with a minimal risk of overlapping 
toxicities, expected to be manageable in the clinical setting (see Section 5.1.6).

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2.
OBJECTIVES AND ENDPOINTS
This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment 
consisting of atezolizumab in combination with obinutuzumab plus bendamustine 
(Atezo-G-benda) in patients with FL, atezolizumab in combination with obinutuzumab 
plus CHOP (Atezo-G-CHOP) in patients with FL, and atezolizumab in combination with 
rituximab plus CHOP (Atezo-R-CHOP) in patients with DLBCL, followed by 
post-induction treatment consisting of either atezolizumab plus obinutuzumab (Atezo-G) 
in patients with FL who achieve a CR or PR at EOI or atezolizumab alone in patients 
with DLBCL who achieve a CR at EOI (see Section 3.1 for details).  Specific objectives 
and corresponding endpoints for the study are outlined below.  
In this study, "study treatment" refers to the combination of all study treatment 
components.
2.1
SAFETY OBJECTIVE 
The safety objective for this study is to evaluate the safety and tolerability of induction 
treatment with either Atezo-G-benda or Atezo-G-CHOP in patients with FL,
Atezo-R-CHOP in patients with DLBCL, and post-induction treatment with either Atezo-G 
in patients with FL or atezolizumab alone in patients with DLBCL on the basis of the 
following endpoints:

Nature, frequency, severity, and timing of adverse events (see Section 3.1.1)

Changes in vital signs, ECGs, and clinical laboratory results during and following 
study treatment administration
2.2
EFFICACY OBJECTIVES
Response will be determined through use of the PET-CTbased Lugano Response 
Criteria for Malignant Lymphoma (Cheson et al. 2014; see Appendix 7), hereinafter 
referred to as Lugano 2014 criteria.  Response will also be determined through use of 
the modified version of the Revised Response Criteria for Malignant Lymphoma 
(Cheson et al. 2007; see Appendix 8), hereinafter referred to as modified Cheson 2007 
criteria, which take into account both PET-CT and CT scan results.  Response will be 
determined by an Independent Review Committee (IRC) and by the investigator.
2.2.1
Primary Efficacy Objective
The primary efficacy objective for this study is to evaluate the efficacy of induction 
treatment with either Atezo-G-benda or Atezo-R-CHOP, on the basis of the following 
endpoint:

CR at EOI, as determined by the IRC using Lugano 2014 criteria 

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2.2.2
Secondary Efficacy Objective
The secondary efficacy objective for this study is to evaluate the efficacy of induction 
treatment with either Atezo-G-benda or Atezo-R-CHOP and post-induction treatment 
with either Atezo-G or atezolizumab alone, on the basis of the following endpoints:

CR at EOI, as determined by the investigator using Lugano 2014 criteria

CR at EOI, as determined by the IRC and by the investigator using modified Cheson 
2007 criteria

Objective response (defined as a CR or PR) at EOI, as determined by the IRC and 
by the investigator using Lugano 2014 criteria and modified Cheson 2007 criteria

Best response of CR or PR during the study, as determined by the investigator 
using modified Cheson 2007 criteria
2.2.3
Exploratory Efficacy Objective
The exploratory efficacy objective for this study is to evaluate the long-term efficacy of 
induction treatment with either Atezo-G-benda or Atezo-R-CHOP and post-induction 
treatment with either Atezo-G or atezolizumab alone, on the basis of the following 
endpoints:

For patients who have positive PET scans at EOI:  CR at 12 months, as determined 
by the IRC and by the investigator using Lugano 2014 criteria

CR at 12, 24, and 30 months in patients with previously untreated FL, as determined 
by the investigator using modified Cheson 2007 criteria

PFS, defined as the time from initiation of study treatment to first occurrence of 
disease progression or relapse, as determined by the investigator using modified 
Cheson 2007 criteria, or death from any cause

EFS, defined as the time from initiation of study treatment to any treatment failure, 
including disease progression or relapse, as determined by the investigator using 
modified Cheson 2007 criteria, initiation of new anti-lymphoma therapy, or death 
from any cause, whichever occurs first

Disease-free survival (DFS), defined, among patients achieving a CR, as the time 
from the first occurrence of a documented CR to relapse, as determined by the
investigator using modified Cheson 2007 criteria, or death from any cause, 
whichever occurs first

OS, defined as the time from initiation of study treatment to death from any cause
2.3
PHARMACOKINETIC OBJECTIVES
The pharmacokinetic (PK) objectives for this study are to characterize the 
pharmacokinetics of atezolizumab, rituximab, and obinutuzumab when administered as 
induction treatment consisting of either Atezo-G-benda, Atezo-G-CHOP, or 
Atezo-R-CHOP or post-induction treatment consisting of either Atezo-G or atezolizumab 
alone, on the basis of the following endpoints:

Observed serum obinutuzumab concentration at specified timepoints

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
Observed serum atezolizumab concentration at specified timepoints

Observed serum rituximab concentration at specified timepoints
2.4
IMMUNOGENICITY OBJECTIVES
The immunogenicity objective for this study is to evaluate the immune response to 
obinutuzumab, to rituximab, and to atezolizumab on the basis of the following endpoints:

Incidence of human anti-human antibodies (HAHAs) to obinutuzumab during the 
study relative to the prevalence of HAHAs at baseline

Incidence of human anti-chimeric antibodies (HACAs) to rituximab during the study 
relative to the prevalence of HACAs at baseline

Incidence of anti-therapeutic antibodies (ATAs) to atezolizumab during the study 
relative to the prevalence of ATAs at baseline
The exploratory immunogenicity objective for this study is to evaluate potential effects of 
HAHAs, HACAs, or ATAs, on the basis of the following endpoint:

Correlation between HAHA, HACA, or ATA status and efficacy, safety, or PK 
endpoints
2.5
BIOMARKER OBJECTIVE
The exploratory biomarker objective for this study is to identify non-inherited biomarkers 
that are predictive of response to study treatment (i.e., predictive biomarkers), are 
associated with progression to a more severe disease state (i.e., prognostic biomarkers), 
are associated with acquired resistance to study treatment, are associated with 
susceptibility to developing adverse events, can provide evidence of study treatment
activity, can increase the knowledge and understanding of lymphoma biology or study 
treatment mechanism of action, or can contribute to improvement of diagnostic assays, 
on the basis of the following endpoint:

Correlation between non-inherited biomarkers (listed in Section 4.5.6) and efficacy, 
safety, PK, or immunogenicity endpoints
3.
STUDY DESIGN
3.1
DESCRIPTION OF STUDY
3.1.1
Overview of Study
This Phase Ib/II, open-label, multicenter, non-randomized study will evaluate the safety, 
efficacy, and pharmacokinetics of combination treatment with atezolizumab, 
obinutuzumab, and chemotherapy in patients with FL and atezolizumab, rituximab, and 
chemotherapy in patients with DLBCL.
Study enrollment will take place in two phases:  an initial safety run-in phase followed by 
an expansion phase.

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During the safety run-in phase, 12 patients with previously untreated, or relapsed or 
refractory FL are to be enrolled in either the Atezo-G-benda treatment group (n6) or 
the Atezo-G-CHOP treatment group (n6) at the discretion of the investigator.  Patients 
will receive 6 cycles (Cycles 16) of induction treatment with either Atezo-G-benda or 
Atezo-G-CHOP (with atezolizumab starting in Cycle 2 for both treatment groups), as 
outlined in Section 3.1.2.  Patients who achieve a CR or PR at EOI will receive 
post--induction treatment (referred to as maintenance) with Atezo-G (see Section 3.1.2
for details).
During the safety run-in phase, the patients within each treatment group will be closely 
monitored for adverse events during an observation window, defined as Cycles 2 and 3 
of induction treatment (the first two treatment cycles that contain atezolizumab), to 
determine if any of the stopping criteria (as defined below) have been met.  Patients who 
discontinue from the study prior to completing Cycle 3 for reasons other than toxicity will 
be replaced.
Stopping Criteria
Stopping criteria will be used to determine whether the study will continue with patient 
enrollment into the expansion phase.  Stopping criteria are defined as any one of the 
following events that occurs during Cycle 2 or 3:

Study treatmentrelated death in at least 1 patient

Any of the following toxicities occurring in at least 2 patients:
Anaphylaxis, acute respiratory distress, or Grade 4 IRR
Hematologic toxicity that is related to study treatment and consists of either of 
the following:
Grade 3 hematologic adverse event that requires study treatment to be 
withheld for 21 days for Atezo-G-benda treatment group and 14 days 
for Atezo-G-CHOP treatment group
Recurrent Grade 4 neutropenia with infection, despite G-CSF support 
and dose modifications
Non-hematologic toxicity that consists of either of the following:
Grade 3 non-hematologic adverse event that has a reasonable 
possibility of being related to study treatment and either is life 
threatening or requires study treatment to be withheld for 21 days for 
Atezo-G-benda treatment group and14 days for AtezoGCHOP 
treatment group
Development of an atezolizumab-related immune-related adverse event 
that is life threatening or requires atezolizumab to be withheld for 
42 days
Note:  The maximum allowed dose delay is 21 days for patients with FL and 14 days 
for patients with DLBCL (see Section 5.1.7 for more details). However, during the 
safety run-in phase, the dose delay associated with the stopping criteria will be 

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restricted to 14 days for FL patients enrolled in the Atezo-G-CHOP treatment 
group. This will allow for a meaningful assessment of dose density maintenance 
under the same dose delay restrictions (i.e., 14 days) that will apply to DLBCL 
patients enrolled in the expansion phase.
During the safety run-in phase, the Medical Monitor will review data on an ongoing basis.  
After 6 patients within a treatment group have either completed Cycle 3 or discontinued 
because of a toxicity, an Internal Monitoring Committee (IMC), as described in 
Section 3.1.3, and the Principal Investigator will perform a formal review of the 
cumulative data and will make appropriate recommendations for further management of 
the study (e.g., proceed with the expansion phase, re-evaluate study treatment dosing 
regimen).
If the stopping criteria (as defined above) are not met during Cycles 2 and 3 among 
patients receiving Atezo-G-benda during the safety run-in phase, approximately 
3440 patients with previously untreated FL will be enrolled in the Atezo-G-benda 
treatment group, depending on the number of patients needed to achieve a total 
enrollment of 40 patients with previously untreated FL in this treatment group.  Patients 
will receive 6 cycles (Cycles 16) of induction treatment with Atezo-G-benda 
(obinutuzumab and bendamustine for Cycles 16 and atezolizumab for Cycles 26), as 
outlined in Section 3.1.2.  Patients who achieve a CR or PR at EOI will receive 
post-induction treatment (referred to as maintenance) with Atezo-G (see Section 3.1.2
for details).
If the stopping criteria (as defined above) are not met during Cycles 2 and 3 among 
patients receiving Atezo-G-CHOP during the safety run-in phase, 40 patients with 
previously untreated DLBCL will be treated with Atezo-R-CHOP.  Patients will receive 
8 cycles (Cycles 18) of induction treatment with Atezo-R-CHOP (rituximab for 
Cycles 18, atezolizumab for Cycles 28, and CHOP for 6 or 8 cycles as determined by 
the investigator), as outlined in Section 3.1.2.  Patients who achieve a CR at EOI will 
receive post-induction treatment (referred to as consolidation) with atezolizumab (see 
Section 3.1.2 for details).
Randomized clinical studies in patients with B-cell malignancies investigating 
obinutuzumab chemotherapy versus rituximab chemotherapy have consistently shown a 
more favorable safety profile of rituximab chemotherapy compared with obinutuzumab 
chemotherapy (see Section 1.4.3). For this reason, no safety run-in will be conducted in 
the Atezo-R-CHOP treatment group; the safety run-in results in the Atezo-G-CHOP 
treatment group are deemed sufficient to enroll patients in the Atezo-R-CHOP treatment 
group during expansion phase.
Patients enrolled in the expansion phase who discontinue from the study after Cycle 1
(i.e., prior to receiving atezolizumab) will be replaced.
A study schema is provided in Figure 1.  Refer to Section 3.1.2 for details on the 
treatment regimens.

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Figure 1
Study Schema
Atezoatezolizumab; bendabendamustine; CHOPcyclophosphamide, doxorubicin, vincristine, and prednisone; CR complete response; 
D1C6Day 1 of Cycle 6; D1C8Day1 of Cycle 8; DLBCLdiffuse large B-cell lymphoma; EOIend of induction; FLfollicular lymphoma; 
Gobinutuzumab; PRpartial response; q2m every 2 months; Rrituximab.
a Patients with DLBCL will receive eight cycles (Cycles 18) of induction treatment with Atezo-R-CHOP (rituximab for Cycles 18, atezolizumab for 
Cycles 28, and six or eight cycles of CHOP as determined by the investigator).

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Overall, it is planned to have 8692 patients enrolled in this study, at approximately 
20 investigative sites around the world.  
All patients will be closely monitored for adverse events throughout the study and for at 
least 90 days after the last dose of study treatment (see Section 5.3.1).  Adverse events 
will be graded according to the National Cancer Institute Common Terminology Criteria 
in Adverse Events, Version 4.0 (NCI CTCAE v4.0).
To characterize the PK properties of atezolizumab, obinutuzumab and rituximab, blood 
samples will be taken at various timepoints before and during dosing (see Appendix 4,
Appendix 5, and Appendix 6).
Response will be determined by the IRC (see Section 3.1.4) and the investigator using 
the Lugano 2014 criteria (see Appendix 7) and the modified Cheson 2007 criteria 
(see Appendix 8).  The primary efficacy endpoint will be based on IRC assessment of 
response through use of the Lugano 2014 criteria.  Refer to Section 4.5.5 for details on 
tumor assessments.
Schedules of assessments are provided in Appendix 1, Appendix 2, and Appendix 3.
3.1.2
Treatment Regimens
All patients (safety run-in phase and expansion phase) will receive induction treatment, 
administered as outlined in Table 1.

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Table 1
Induction Treatment
Atezo-G-benda (FL)
(28-day cycles)
Safety Run-In and Expansion 
Phases
Atezo-G-CHOP (FL)
(21-day cycles)
Safety Run-In Phase
Atezo-R-CHOP (DLBCL)
(21-day cycles)
Expansion Phase
Cycle 1

Obinutuzumab 1000 mg IV on 
Days 1, 8, and 15

Bendamustine 90 mg/m2 IV on 
Days 1 and 2

Obinutuzumab 1000 mg IV on Days 1, 8, 
and 15

CHOP:
– Cyclophosphamide 750 mg/m2 IV on Day 1
– Doxorubicin 50 mg/m2 IV on Day 1
– Vincristine 1.4 mg/m2 (max. 2 mg) IV on 
Day 1
– Prednisone a 40 mg/m2 PO on Days 15

Rituximab 375 mg/m2 IV on Day 1

CHOP:
– Cyclophosphamide 750 mg/m2 IV on Day 1
– Doxorubicin 50 mg/m2 IV on Day 1
– Vincristine 1.4 mg/m2 (max. 2 mg) IV on 
Day 1
– Prednisone a 40 mg/m2 PO on Days 15
Cycles 
26/8 b

Obinutuzumab 1000 mg IV on 
Day 1

Bendamustine 90 mg/m2 IV on 
Days 1 and 2

Atezolizumab 840 mg IV on 
Days 1 and 15

Obinutuzumab 1000 mg IV on Day 1 b

CHOP b:
– Cyclophosphamide 750 mg/m2 IV on Day 1
– Doxorubicin 50 mg/m2 IV on Day 1
– Vincristine 1.4 mg/m2 (max. 2 mg) IV on 
Day 1
– Prednisone a 40 mg/m2 PO on Days 15

Atezolizumab 1200 mg IV on Day 1 b

Rituximab 375 mg/m2 IV on Day 1

CHOP b:
– Cyclophosphamide 750 mg/m2 IV on Day 1
– Doxorubicin 50 mg/m2 IV on Day 1
– Vincristine 1.4 mg/m2 (max. 2 mg) IV on 
Day 1
– Prednisone a 40 mg/m2 PO on Days 15

Atezolizumab 1200 mg IV on Day 1 b
Atezoatezolizumab;bendabendamustine; CHOPcyclophosphamide, doxorubicin, vincristine, and prednisone; DLBCLdiffuse large B-cell 
lymphoma; FLfollicular lymphoma; Gobinutuzumab; IVintravenous; max.maximum; POby mouth; Rrituximab.
a Prednisolone may be given if prednisone is unavailable.  The 40 mg/m2 dose of prednisone on Day 1 will be replaced by oral corticosteroids 
given as premedication on Day 1 of Cycle 1 (and subsequent cycles as indicated) (see details on premedication in Section 4.3.2.9).
b All patients treated with Atezo-G-benda and Atezo-G-CHOP during the safety run-in phase (i.e., patients with FL) will receive induction treatment 
for 6 cycles.  Patients treated with Atezo-R-CHOP during the expansion phase (i.e., patients with DLBCL) will receive eight cycles (Cycles 18) 
of induction treatment with Atezo-R-CHOP (rituximab for Cycles 18, atezolizumab for Cycles 28, and six or eight cycles of CHOP as 
determined by the investigator).

 
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Patients with DLBCL who achieve a CR at EOI will receive post-induction treatment 
(referred to as consolidation) with atezolizumab, and patients with FL who achieve a CR 
or PR at EOI will receive post-induction treatment (referred to as maintenance) with 
Atezo-G, as outlined in Table 2.  Post-induction treatment should start 8 weeks ( 1 week) 
after Day 1 of the final cycle of induction and will continue until disease progression or 
unacceptable toxicity for up to 1 year for consolidation treatment or 2 years for 
maintenance treatment.  
Table 2 
Post-Induction Treatment 
Patients 
with DLBCL  
Consolidation treatment consisting of the following, administered in 21-day cycles 
for 17 cycles: 
 Atezolizumab 1200 mg IV on Day 1 of Cycles 9 to 25 
Patients 
with FL 
Maintenance treatment consisting of the following, administered for 24 months (from 
Month 1 to Month 24): 
 Atezolizumab 840 mg IV on Days 1 and 2 of each month, starting with Month 1 
 Obinutuzumab 1000 mg IV on Day 1 of every other month (i.e., every 
2 months), starting with Month 1 
DLBCL  diffuse large B-cell lymphoma; FL  follicular lymphoma; IV  intravenous. 
 
3.1.3 
Internal Monitoring Committee  
An IMC will monitor patient safety throughout the study.  The IMC will include Sponsor’s 
representatives from Clinical Science, Clinical Drug Safety and Biostatistics, 
independent of the study.  In addition to the ongoing assessment of the incidence and 
nature of adverse events (particularly Grade  3 events), serious adverse events, deaths, 
and laboratory abnormalities performed by the investigator and the Medical Monitor, 
the IMC will review all necessary cumulative data at regular intervals during the study.  
Significant attention will be focused on the maintenance of dose intensity of 
chemotherapy in DLBCL.  At the time of each review, the IMC will make appropriate 
recommendations (e.g., the study should continue as planned, additional analyses 
should be performed, enrollment should be held pending further safety evaluations).  
Decisions will be made in consideration of the totality of the available data.  Ad hoc 
meetings may be called in addition to scheduled meetings, as necessary, to 
provide recommendations on management of any potential new safety signals.  
At the time when all patients have completed/discontinued study treatment 
(maintenance/consolidation), regular IMC assessments will no longer take place.  
Ad hoc meetings may be called at the discretion of the Medical Monitor in case of newly 
identified safety signals.  Specific operational details such as the committee's 
composition, frequency and timing of meetings, and members' roles and responsibilities 
will be detailed in an IMC Charter. 
3.1.4 
Independent Review Committee  
An IRC will assess all patients for response on the basis of imaging results, bone 
marrow biopsy results, and relevant clinical data.  The review will consist of two parts:  

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a radiology review and an oncology review.  The IRC will consist of radiologists, nuclear 
medicine experts, and a board-certified oncologist with experience in malignant 
lymphoma.  Specific methodological and operational details will be specified in the IRC 
charter.
3.1.5
Post-Treatment Follow-Up and Survival Follow-Up
Patients who complete treatment or discontinue treatment for reasons other than 
disease progression will undergo assessments every 3 months during the post-treatment 
follow-up period, which will continue until disease progression, the start of new 
anti-lymphoma treatment, or the end of the study (as defined below), whichever occurs 
first.  Patients who experience disease progression will undergo limited assessments
every 3 months during the survival follow-up period, which will continue until the end of 
the study. 
3.2
END OF STUDY AND LENGTH OF STUDY
The end of this study is defined as the time when all enrolled FL patients have 
completed or discontinued study treatment and all enrolled DLBCL patients have been 
followed for at least 1 year after they have completed or discontinued study 
treatment. The total length of the study, from screening of the first patient to the end of 
the study, is expected to be approximately 4 years.
3.3
RATIONALE FOR STUDY DESIGN
3.3.1
Rationale for Patient Population
As discussed in Section 1.1.1, despite significant therapeutic progress with the use of 
chemoimmunotherapy as first-line treatment, FL remains essentially an incurable 
disease for which more effective treatments are needed.  G-benda has been shown to 
be effective and well tolerated in patients with previously untreated FL (see 
Section 1.4.3).  Based on a preclinical and clinical rationale presented in Section 1.4.1
and Section 1.4.2, atezolizumab is expected to be active in FL and to provide an 
improved immunochemotherapy regimen when combined with G-benda.  The risk of 
overlapping toxicities associated with combining atezolizumab with G-benda is expected 
to be minimal, and any such toxicities are expected to be manageable in the clinical 
setting (see Section 5.1.6).  The expected benefit and minimal risk provide a rationale for 
testing Atezo-G-benda as first-line treatment in patients with FL.  However, the 
combination will first be investigated in a safety run-in phase in which patients with 
relapsed or refractory FL can also be enrolled. 
Although approximately 60% of patients with DLBCL have long-term responses with 
R-CHOP as first-line treatment, patients with advanced DLBCL have a lower chance of 
being cured.  More effective treatments are needed for these patients.  On the basis of a 
compelling biologic and clinical rationale, as presented in Section 1.4, the combination of 
atezolizumab with R-CHOP is a promising approach to expand the number of patients 
with DLBCL who achieve a cure.  For ethical reasons related to the curative potential of 

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chemoimmunotherapy as first-line treatment for DLBCL, the Atezo-G-CHOP regimen will 
first be investigated in a safety run-in phase in which 6 patients with previously untreated, 
or relapsed or refractory FL will be enrolled.  
The risk of overlapping toxicities associated with the addition of atezolizumab to 
R-CHOP is expected to be minimal.  Additionally, preliminary data from the safety run-in 
phase prior to the implementation of Protocol Version 3 indicated that the combination of 
atezolizumab with G-CHOP was well tolerated.  A total of 7 patients with FL (6 patients 
with previously untreated and 1 patient with relapsed or refractory disease) were 
enrolled and completed at least three cycles of induction treatment.  None of the 
stopping criteria defined for the safety run-in phase of the study were met.  There were 
no treatment-related Grade 3 and 4 adverse events during Cycles 2 and 3 (i.e., safety 
observation window).  No treatment delays or treatment discontinuations due to adverse 
events were observed. 
Consistently across randomized clinical trials in patients with B-cell malignancies 
investigating obinutuzumab chemotherapy versus rituximab chemotherapy, the safety 
profile of rituximab chemotherapy tended to compare favorably with the safety profile of 
obinutuzumab chemotherapy (see Section 1.4.3).
Thus, the expected benefit and acceptable risk provide the rationale for testing 
Atezo-R-CHOP as first-line treatment in patients with DLBCL.  As presented in 
Section 3.1.3, patients will be monitored on a regular basis for safety, including the 
ability to maintain dose intensity of the CHOP chemotherapy.
3.3.2
Rationale for Dose and Schedule
3.3.2.1
Rationale for Atezolizumab Dose and Schedule
Atezolizumab will be administered at a flat dose consisting of one of the following:  
a) 1200 mg q3w (1200 mg on Day 1 of Cycles 2 and beyond, given in 21-day cycles
either with G-CHOP as induction treatment or alone as consolidation treatment); 
b) 840 mg q2w (840 mg on Days 1 and 15 of Cycles 26, given in 28-day cycles with 
G-benda as induction treatment); or c) 1680 mg every 4 weeks (q4w) (840 mg on Days 1 
and 2 of each month, given with obinutuzumab as maintenance treatment).  All three 
dosages are equivalent to an average body weightbased dose of 15 mg/kg q3w. 
The dosage of 15 mg/kg q3w was selected as recommended Phase II dose (RP2D) on 
the basis of both nonclinical studies and available clinical data from Study PCD4989g, 
as described below.
The target exposure for atezolizumab was projected on the basis of clinical and 
nonclinical parameters, including nonclinical tissue distribution data in tumor-bearing 
mice, target-receptor occupancy in the tumor, and the observed atezolizumab interim 
pharmacokinetics in humans.  The target trough concentration (Ctrough) was projected to 
be 6 g/mL on the basis of several assumptions, including the following:  1) 95% 

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tumor-receptor saturation is needed for efficacy and 2) the tumor interstitial 
concentrationto-plasma ratio is 0.30 on the basis of tissue distribution data in 
tumor-bearing mice.
In Study PCD4989g, the first-in-human study in patients with advanced solid tumors and 
hematologic malignancies, 30 patients were treated with atezolizumab at doses ranging 
from 0.01 mg/kg to 20 mg/kg q3w during the dose-escalation stage and 247 patients 
were treated with atezolizumab at doses of 10, 15, or 20 mg/kg q3w in the 
dose-expansion stage.  Anti-tumor activity has been observed across all dose cohorts.  
atezolizumab was safely administered to 11 patients with various hematologic 
malignancies (including 7 patients with lymphoma) at a dose of 15 mg/kg q3w (n1) and 
20 mg/kg q3w (n10).  There was no evidence of dose-dependent toxicity in this study.  
The MTD of atezolizumab was not reached, and no DLTs were observed at any dose.  
ATAs to atezolizumab were associated with changes in pharmacokinetics for some 
patients in the lower dose cohorts (0.3, 1, and 3 mg/kg), but patients treated at 10, 15, 
and 20 mg/kg maintained the expected target trough levels of drug despite the detection 
of ATAs.  To date, no relationship has been observed between the development of 
measurable ATAs and safety or efficacy.  After review of available PK and ATA data for 
a range of doses, 15 mg/kg q3w was identified as the lowest atezolizumab dosing 
regimen that would maintain Ctrough at 6 g/mL while further safeguarding against 
interpatient variability and the potential effect of ATAs that could lead to subtherapeutic 
levels of atezolizumab.
Simulations (Bai et al. 2012) do not suggest any clinically meaningful differences in 
exposure following a fixed dose compared with a body weightadjusted dose.  
On the basis of this analysis, a fixed dose of 1200 mg q3w (equivalent to a weight-based 
dose of 15 mg/kg q3w) was defined as the RP2D.  Atezolizumab 1200 mg q3w is 
currently being evaluated in combination with obinutuzumab in an ongoing Phase Ib 
study (GO29383) in patients with relapsed or refractory DLBCL or FL.  The combination 
has been safely administered in the first 3 patients who were evaluable for DLTs.  
Atezolizumab is added to obinutuzumab starting with Cycle 2, in an attempt to mitigate 
the risk of increased IRRs during the first infusion of obinutuzumab.  The incidence and 
severity of IRRs related to obinutuzumab decrease substantially with the second and 
subsequent infusions.  
For the q2w dosing interval, the fixed dose of 840 mg q2w is the equivalent of a 
weight-based dose of 15 mg/kg q3w.  This dosing schedule is currently being evaluated 
in patients with advanced solid tumors in combination with chemotherapy or biologic 
agents (see Section 1.3.2.1).
For the q4w dosing interval, the fixed dose of 1680 mg q4w is the equivalent of a 
weight-based dose of 15 mg/kg q3w.  Population PK modeling suggests that the area 
under the curve would be comparable to that of 1200 mg q3w (Genentech data).  The 

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total dose of 1680 mg will be administered as 840 mg on Day 1 and Day 2 of a 28-day 
cycle.  The total dose is split into two daily doses to minimize the risk of exceeding safe 
limits for manufacturing processderived impurities such as host cell DNA and 
endotoxins.  The manufacturing processes for atezolizumab are capable of clearing such 
impurities to safe levels, and tests for impurities are performed as a part of the 
manufacturing processes. However, splitting of the atezolizumab dose is being 
implemented at this stage of clinical development to further minimize the potential risk.
Consistent with the dosing schedule used in Study GO29383, in this study, atezolizumab 
will be added to G-benda and G-CHOP starting with Cycle 2. 
3.3.2.2
Rationale for Obinutuzumab, Bendamustine, Rituximab, and 
CHOP Dose and Schedule
In two recent Phase III trials testing the combination of bendamustine and rituximab in 
previously untreated patients with iNHL (Rummel et al. 2013; Flinn et al. 2014), 
bendamustine was safely administered and active at a dose of 90 mg/m2 on Days 1 
and 2 of each 28 day-cycle.  The dose of 90 mg/m2 is also the dose of bendamustine 
recommended at a consensus conference of hematologists when used in combination 
with rituximab (Cheson et al. 2010). 
G-benda was shown to be active and safe in 41 patients with previously untreated FL in 
Study BO21000 and in 2 Phase III studies in patients with previously untreated iNHL 
(Study BO21223) and rituximab-refractory iNHL (Study GAO4753g). In all three studies, 
treatment has been given in 28-day cycles.  For induction therapy, obinutuzumab has 
been administered at a flat dose of 1000 mg on Days 1, 8, and 15 of Cycle 1 and on 
Day 1 of each subsequent cycle (Cycles 26), and bendamustine has been administered 
at a dose of 90 mg/m2 on 2 consecutive days of each cycle.  In patients achieving a CR 
or PR at EOI, obinutuzumab has been administered as maintenance therapy at a dose 
of 1000 mg every 2 months for 2 years.  On the basis of available clinical data and to 
maintain consistency with the ongoing trials, the same obinutuzumab and bendamustine 
dosing regimens will be administered in this study.
G-CHOP was shown to be active and safe in 100 patients with previously untreated 
DLBCL in Study GAO4915g and in 40 patients with previously untreated FL in 
Study BO21000.  G-CHOP has also been evaluated in Study BO21005, a Phase III 
study in patients with previously untreated DLBCL.  In all three studies of G-CHOP, 
treatment is given in 21-day cycles, with obinutuzumab administered at a flat dose of 
1000 mg on Days 1, 8, and 15 of Cycle 1 and on Day 1 of each subsequent cycle 
(Cycles 26 or 28) and CHOP administered at standard doses during each cycle.  
On the basis of clinical experience to date, and to maintain consistency with the ongoing 
trial, the same obinutuzumab and CHOP dosing regimens have been administered to 
patients with FL enrolled in the safety run-in phase.

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R-CHOP is approved for treatment of DLBCL in the United States and in the European 
Union, as well as in many other countries and regions worldwide, on the basis of the 
results from three randomized, prospective studies of approximately 2000 previously 
untreated patients with advanced DLBCL (Coiffier et al 2002; Habermann et al. 2006; 
Pfreundschuh et al. 2006).  On the basis of these studies, a dosing regimen of up to 
eight cycles of rituximab (375 mg/m2 on Day 1 of each cycle) combined with six or eight
cycles of CHOP is considered to be the standard of care for patients with advanced 
DLBCL (NCCN Guidelines2016) and will be used in this study.
3.3.2.3
Rationale for Treatment Duration
The objective of post-induction treatment is to improve the response to induction 
therapy, not only by converting a PR to a CR, but also by eradicating minimal residual 
disease (MRD) to achieve a molecular response in patients with a clinical CR after 
induction treatment, thus reducing the relapse risk for responders. 
Despite recent improvements in therapy for FL, including demonstrated benefit from 
2-year rituximab maintenance in patients responding to first-line immunochemotherapy 
(Study MO18264), FL is still not considered curable, with a 6-year PFS of 59.2% 
(Salles et al. 2013).  Final results from the maintenance phase of the Phase Ib study, 
BO21000, demonstrated that maintenance treatment with obinutuzumab monotherapy 
after obinutuzumab plus chemotherapy induction is active and generally well tolerated 
(Section 1.4.3).  A Phase III study, BO21223, is currently investigating obinutuzumab 
versus rituximab as chemoimmunotherapy induction, followed by immunotherapy 
maintenance, in patients with untreated iNHL, including FL.  Under the assumption that 
Study BO21223 will demonstrate greater clinical benefit with obinutuzumab- compared 
with rituximab-containing regimens, potentially altering the standard of care in FL, it 
appears important to investigate the combination of obinutuzumab with new targeted 
drugs in this setting.  On the basis of a compelling nonclinical rationale (presented in 
Section 1.4.3), it is hypothesized that the addition of atezolizumab to obinutuzumab may 
enhance and prolong the anti-tumor immune response and provide significant clinical 
benefit to patients.  Building on the obinutuzumab dosing schedule tested in the ongoing 
Phase III study (i.e., every 2 months for 2 years' duration), atezolizumab will be 
administered on a monthly basis for the same treatment period of 2 years.
Although most patients with DLBCL achieve complete metabolic response with first-line 
therapy, up to 40% ultimately relapse.  Relapses most likely originate from MRD that is 
undetectable by radiologic examination.  Although no therapy has been demonstrated to 
be effective in DLBCL after standard rituximab-based immunochemotherapy, PD-L1 
blockade in patients achieving a CR at EOI may prevent PD-L1driven exhaustion of 
anti-tumor lymphocytes and maintain activated Teffs, leading to eradication of residual 
disease and improvement in patients’ outcome. 
The risk of relapse is higher in patients with advanced DLBCL, which represents the 
patient population in this study.  Relapses occur mostly during the first 2 years following 

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first-line treatment (Coiffier et al. 2010).  Thus, 12 months of consolidation treatment with 
atezolizumab, for a total treatment duration of approximately 18 months, is considered to 
be a reasonable exploratory therapeutic approach with an anticipated positive 
benefit-risk ratio.  During consolidation treatment, MRD will be measured to allow for 
analysis of the benefit of 12 months of consolidation treatment.  T-cell receptor repertoire 
will also be assessed during treatment and after discontinuation of atezolizumab to 
evaluate the kinetics of atezolizumab-induced immune responses.
3.3.3
Rationale for PET-CTBased Complete Response as the 
Primary Efficacy Endpoint
In DLBCL, the prognostic value of the post-treatment fluorodeoxyglucose (18F-FDG) 
PET-CT scan has been well documented (Thomas et al. 2010; Vitolo et al. 2010).  
PET-CT scans have been implemented in the Lugano 2014 criteria (Cheson et al. 2014) 
and are commonly used to assess efficacy in medical practice and clinical trials in 
lymphoma.  More recently, the value of post-induction PET-CT status has been 
investigated as a prognostic marker for long-term outcome in patients with FL.  In the 
first-line setting, results from a pooled analysis of 246 patients enrolled in three studies 
and having PET-CT scans available at the end of chemoimmunotherapy showed, with a 
median follow-up of 55 months, a 4-year PFS in PET-CTpositive and PET-CTnegative 
patients of 23.2% (95% CI: 11.1%, 37.9%) versus 63.4% (95% CI: 55.9%, 70.0%; 
p0.001), respectively, and a 4-year survival of 87.2% (95% CI: 71.9%, 94.5%) versus 
97.1% (95% CI: 93.2%, 98.8%; p0.0001), respectively (Trotman et al. 2014).  In the 
relapsed FL setting, results from a preliminary analysis of Phase II study (BO21003) 
comparing obinutuzumab versus rituximab monotherapy demonstrated that the 
post-induction PET-CT status is strongly prognostic of PFS.  With a median follow-up of 
32.1 months, the risk of disease progression was significantly reduced in 
PET-CTnegative compared with PET-CTpositive patients, regardless of the 
assessment criteria, either International Harmonization Project criteria (HR, 0.25; 
95% CI: 0.191, 0.807; p0.0083) or European Organization for Research and Treatment 
of Cancer (EORTC) criteria (HR, 0.39; 95% CI: 0.191, 0.807; p0.0083)
(Kostakoglu et al. 2014).
In response to developments involving PET-CT status, the 11th International Conference 
of Malignant Lymphoma imaging group provided an updated guidance for the use of 
PET-CT scan results for lymphoma staging and response assessment (Lugano 2014 
criteria; Cheson et al. 2014).  
3.3.4
Rationale for Biomarker Assessments
3.3.4.1
Rationale for Analysis of DLBCL Subtype, BCL2, and MYC
DLBCL cell-of-origin prognostic subgroups (ABC and GCB), defined using gene 
expression profiling, have been associated with different clinical outcomes in patients 
receiving R-CHOP for DLBCL, with GCB subgroups demonstrating a better prognosis 
than ABC groups (3-year survival rate of 84% versus 56%, respectively; p0.001) 

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(Lenz et al. 2008).  Bcl-2 overexpression has been shown to have prognostic value in 
DLBCL (Iqbal et al. 2006).  Next-generation sequencing studies have also shown that 
BCL2 is the most mutated gene in patients with GCB DLBCL, observed in up to 35% of 
cases (Schuetz et al. 2012).  Approximately 9%17% of patients with newly diagnosed 
DLBCL harbor an underlying MYC rearrangement, and these patients are at high risk of 
treatment failure with R-CHOP (Savage et al. 2009).  A subset of patients with 
MYC-positive DLBCL also harbors an additional BCL2 rearrangement.  These 
“double-hit” lymphomas are associated with a very poor outcome (Savage et al. 2009; 
Dunleavy et al. 2014).  Overexpression of BCL-2 and MYC in DLBCL has also been 
observed in the absence of translocation.  This “double-positive” DLBCL status is also 
associated with worse prognosis (Green et al. 2012; Johnson et al. 2012; Hu et al. 2013).
Correlative investigations are essential to understand mechanisms of both sensitivity 
and resistance to therapy in patients with mutational profiles that predict poor response 
to standard treatment.  
3.3.4.2
Rationale for Assessment of Immune-Related Biomarkers
Over the last decade, tumor microenvironment and host immunity have emerged as 
critical determinants of cancer development and response to therapy.  There is an 
increasing body of evidence regarding the prognostic value of TILs in B-cell NHL.  
CD8-positive cytotoxic T-cell infiltrate has been identified as a biomarker of poor 
prognosis in DLBCL (Galand et al. 2012).  More recently, analysis of peripheral T-cell 
receptor repertoire demonstrated impaired T-cell diversity in B-cell NHL, with expansion 
of oligoclonal clusters of CD8-positive T cells and expansion of T-regulatory cells 
associated with an increased degree of skewing observed within the CDR3 region 
(Fozza et al. 2014).  A recent study of 12 melanoma patients treated with ipilimumab, a 
blocker of the immunologic checkpoint cytotoxic T-lymphocyte-associated protein 4 
(CTLA-4), showed a correlation between T-cell receptor diversity in the peripheral blood 
at baseline and patient outcomes (Postow et al. 2014).  
This study will investigate the potential correlation of TIL signature and the status of 
peripheral T-cell receptor repertoire (diversity and quantity of receptors) with response to 
study treatment.  
Increase in T-cell activation biomarkers has been observed in peripheral blood following 
atezolizumab administration in cancer patients (Herbst et al. 2014).  Cytokines that are 
characteristic of activated T-cells (e.g., interleukin [IL]-18, interferon gamma [IFN-) and 
potential correlation with response to treatment will be assessed in this study.
A recent publication (Rosille et al. 2014) described the prognostic effect of soluble PD-L1 
in DLBCL.  The prognostic value of soluble PD-L1 levels at baseline will also be 
assessed in this study.  Any effect on PK parameters may also be examined.

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3.3.4.3
Rationale for Assessment of Minimal Residual Disease
MRD measurement is an increasingly recognized tool for response assessment in B-cell 
malignancies.  Circulating lymphoma cells and/or tumor DNA can be detected and 
quantified at low levels as MRD to assess treatment dynamics and monitor patients after 
treatment.  However, there is no scientific proof that MRD is a reliable measure of 
clinical outcome in NHL, and technical validation of novel technologies for MRD 
assessment that have clinical utility is still pending. 
In FL, MRD at end of treatment is likely to be prognostic (Ladetto et al. 2013).  In DLBCL, 
serum MRD was shown to predict early and late progression after first-line treatment 
(Roschewski et al. 2014).  In addition, MRD assessment may complement the response 
assessment, particularly in immune treatmentbased regimens, and mitigate potential 
false positive FDG-PET results caused by infiltration of metabolically active ICs into the 
tumor.
In this study, MRD will be quantified by circulating lymphoma cells and cell-free 
circulating tumor DNA as an exploratory endpoint.
4.
MATERIALS AND METHODS
4.1
PATIENTS
This study will enroll patients with FL and DLBCL who meet the eligibility criteria 
presented below.
4.1.1
Inclusion Criteria
Patients must meet the following criteria for study entry:

Signed Informed Consent Form

Age 18 years

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 
(see Appendix 9)

For patients enrolled in the safety run-in phase:  lymphoma classified as either of 
the following:
Relapsed or refractory FL after treatment with at least one prior 
chemoimmunotherapy regimen
Previously untreated Grade 1, 2, or 3a FL that requires treatment, defined as 
meeting at least one of the Groupe d'Etudes des Lymphomes Folliculaires 
(GELF) criteria, as listed below:
Bulky disease, defined as a nodal or extranodal (except spleen) 
mass 7 cm in the greatest diameter
Local symptoms or compromise of normal organ function due to 
progressive nodal disease or extranodal tumor mass
Presence of B symptoms 

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Presence of symptomatic extranodal disease (e.g., pleural effusions, 
peritoneal ascites)
Cytopenias due to underlying lymphoma (i.e., ANC 1.0109/L, 
hemoglobin 10 g/dL, and/or platelet count 100109/L)
Involvement of 3 nodal sites, each with a diameter of 3 cm

For patients enrolled in the expansion phase:  lymphoma classified as either of the 
following:
Previously untreated Grade 1, 2, or 3a FL that requires treatment, defined as 
meeting at least one of the GELF criteria (listed above)
Previously untreated advanced DLBCL, defined as Stage III or IV with an IPI 2 
or Stage II with bulky disease (defined as at least one lesion 7 cm)

Histologically documented CD20-positive lymphoma, as determined by the local 
laboratory

FDG-avid lymphoma (i.e., PET-positive lymphoma)

At least one bi-dimensionally measurable lesion (1.5 cm in its largest dimension by 
CT scan or magnetic resonance imaging [MRI])

Availability of a representative tumor specimen and the corresponding pathology 
report for retrospective central confirmation of the diagnosis of FL or DLBCL
If archival tissue is unavailable or unacceptable according to above criteria, a 
pretreatment core-needle, excisional, or incisional tumor biopsy is required.  
Cytological or fine-needle aspiration samples are not acceptable.  
For patients with FL, if the available biopsy was not done within 12 months, a 
repeat biopsy is strongly recommended.
Further details are provided in Section 4.5.6.

For women who are not postmenopausal (12 consecutive months of 
non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or 
uterus):  agreement to remain abstinent (refrain from heterosexual intercourse) or 
use contraceptive methods that result in a failure rate of 1% per year during the
treatment period and for at least 18 months after the last dose of study treatment for 
patients in the Atezo-G-benda and Atezo-G-CHOP treatment groups or for at least 
12 months after the last dose of study treatment for patients in the Atezo-R-CHOP 
treatment group.  
Examples of non-hormonal contraceptive methods with a failure rate of 1% 
per year include bilateral tubal ligation, male sterilization, established, proper 
use of progestogen-only hormonal contraceptives that inhibit ovulation, 
hormone-releasing intrauterine devices (IUDs), and copper IUDs. 
The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the patient.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not acceptable methods of contraception.  

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Barrier methods must always be supplemented with the use of a spermicide.

For men:  agreement to remain abstinent (refrain from heterosexual intercourse) or 
use contraceptive measures and agreement to refrain from donating sperm, as 
defined below:
With female partners of childbearing potential, men must remain abstinent or 
use a condom plus an additional contraceptive method that together result in a 
failure rate of 1% per year during the treatment period and for at least 
3 months after the last dose of study treatment.  Men must refrain from 
donating sperm for the same period.
With pregnant female partners, men must remain abstinent or use a condom 
during the treatment period and for at least 3 months after the last dose of study 
treatment.
The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the patient.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not acceptable methods of contraception.
4.1.2
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:

Histological evidence of transformation of FL into high-grade B-cell NHL

Central nervous system lymphoma or leptomeningeal infiltration

For patients with DLBCL:  preplanned consolidative radiotherapy

Treatment with systemic immunosuppressive medications, including, but not limited 
to, prednisone, azathioprine, methotrexate, thalidomide, and antitumor necrosis 
factor agents within 2 weeks prior to Day 1 of Cycle 1
Treatment with inhaled corticosteroids and mineralocorticoids is permitted.
If corticosteroid treatment is urgently required for lymphoma symptom control 
prior to the start of study treatment, 100 mg of prednisone or equivalent can be 
given for a maximum of 5 days, but all tumor assessments must be completed 
prior to initiation of corticosteroid treatment.

For patients with relapsed or refractory FL (enrolled in the safety run-in phase)
Prior allogeneic or autologous SCT
Prior anthracycline therapy (patients enrolled in the Atezo-G-CHOP treatment 
group)
Treatment with fludarabine or alemtuzumab within 12 months prior to Day 1 of 
Cycle 1
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, 
including anti-CTLA-4, antiPD-1, and antiPD-L1 therapeutic antibodies
Treatment with a monoclonal antibody, radioimmunoconjugate, or 
antibody-drug conjugate within 4 weeks prior to Day 1 of Cycle 1

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Radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule 
therapy within 2 weeks prior to Day 1 of Cycle 1
Clinically significant toxicity (other than alopecia) from prior treatment that has 
not resolved to Grade 2 (per NCI CTCAE v4.0) prior to Day 1 of Cycle 1

History of solid organ transplantation

History of severe allergic or anaphylactic reaction to humanized, chimeric, or murine 
monoclonal antibodies

Known sensitivity or allergy to murine products

Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary 
cells or any component of the atezolizumab, obinutuzumab, rituximab, or 
bendamustine formulation, including mannitol

Known history of idiopathic pulmonary fibrosis, organizing pneumonia 
(e.g., bronchiolitis obliterans), drug-induced pneumonitis, or evidence of active 
pneumonitis on screening chest CT scan
History of radiation pneumonitis in the radiation field (fibrosis) is allowed

Active bacterial, viral, fungal, or other infection or any major episode of infection 
requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1
Caution should be exercised when considering the use of obinutuzumab and 
rituximab in patients with a history of recurring or chronic infections.

Positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody 
(HBcAb), or hepatitis C virus (HCV) antibody at screening

Known history of HIV positive status
For patients with unknown HIV status, HIV testing will be performed at 
screening if required by local regulations.

History of PML

Vaccination with a live virus vaccine within 28 days prior to Day 1 of Cycle 1 or 
anticipation that such a live, attenuated vaccine will be required during the study

History of other malignancy that could affect compliance with the protocol or 
interpretation of results, with the exception of the following:
Curatively treated carcinoma in situ of the cervix, good-prognosis ductal 
carcinoma in situ of the breast, basal- or squamous-cell skin cancer, Stage I 
melanoma, or low-grade, early-stage localized prostate cancer
Any previously treated malignancy that has been in remission without treatment 
for 2 years prior to enrollment

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’s granulomatosis, Sjögren’s syndrome, Guillain-Barré 
syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix 13 for 
a comprehensive list of autoimmune diseases)

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Patients with a history of autoimmune-related hypothyroidism on a stable dose 
of thyroid replacement hormone may be eligible for this study.
Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen 
may be eligible for this study.

Evidence of any significant, uncontrolled concomitant disease that could affect 
compliance with the protocol or interpretation of results, including significant 
cardiovascular disease (such as New York Heart Association Class III or IV cardiac 
disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or 
unstable angina) or significant pulmonary disease (such as obstructive pulmonary
disease or history of bronchospasm)

Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of 
Cycle 1, Day 1, or anticipation of a major surgical procedure during the course of the 
study

For patients who will be receiving CHOP:  left ventricular ejection fraction (LVEF) 
50% by multiple-gated acquisition (MUGA) scan or echocardiogram

Inadequate hematologic function (unless due to underlying lymphoma), defined as 
follows:
Hemoglobin 9 g/dL
ANC 1.5109/L
Platelet count 75109/L

Any of the following abnormal laboratory values (unless due to underlying 
lymphoma):
Creatinine 1.5 times the upper limit of normal (ULN) (unless creatinine 
clearance is normal) or calculated creatinine clearance 40 mL/min (using the 
Cockcroft-Gault formula; see Appendix 14)
AST or ALT 2.5ULN
Serum total bilirubin 1.5ULN (or 3ULN for patients with Gilbert syndrome)  
INR or PT 1.5ULN in the absence of therapeutic anticoagulation
PTT or aPTT 1.5ULN in the absence of a lupus anticoagulant 

Pregnant or lactating, or intending to become pregnant during the study
Women who are not postmenopausal (12 months of non-therapy-induced 
amenorrhea) or surgically sterile must have a negative serum pregnancy test 
result within 7 days prior to Day 1 of Cycle 1.

Unable to comply with the study protocol, in the investigator’s judgment
4.2
METHOD OF TREATMENT ASSIGNMENT
During the safety run-in phase, patients with FL will be assigned to the Atezo-G-benda 
or Atezo-G-CHOP induction treatment group at the discretion of the investigator.  During 
the expansion phase, induction treatment will be assigned on the basis of lymphoma 
histology.  Patients with FL will receive Atezo-G-benda induction treatment, and patients 

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with DLBCL will receive Atezo-R-CHOP induction treatment.  Post-induction treatment 
(for eligible patients only) will also depend on lymphoma histology.  Patients with FL will 
receive Atezo-G maintenance treatment, and patients with DLBCL will receive 
atezolizumab consolidation treatment (see Section 3.1.2 for details).
Enrollment tracking will be performed through use of an interactive voice or web-based 
response system (IxRS).  Prior to initiating screening, the study site should confirm via 
the IxRS that slots within the planned treatment group are available for enrollment.  After 
written informed consent has been obtained and preliminary eligibility has been 
established, the study site will submit documentation supporting eligibility to the Sponsor 
and obtain the Sponsor’s approval to enroll the patient.  Once the Sponsor reviews and 
approves the patient for enrollment, the patient number will be assigned and the patient 
will be enrolled via the IxRS.  The Sponsor will communicate to the sites impending 
closure of screening for a particular treatment group.
4.3
STUDY TREATMENT
4.3.1
Formulation, Packaging, and Handling
4.3.1.1
Obinutuzumab
Obinutuzumab will be supplied by the Sponsor as an investigational medicinal product 
(IMP).  Obinutuzumab will be provided as a single-dose, sterile liquid formulation in a 
50-mL glass vial containing 1000 mg of obinutuzumab.  For information on the 
formulation and handling of obinutuzumab, see the obinutuzumab Investigator's 
Brochure and Pharmacy Manual.
4.3.1.2
Atezolizumab
Atezolizumab will be supplied by the Sponsor as an IMP.  The atezolizumab drug 
product is provided in a single-use, 20-mL USP/European Pharmacopoeia Type 1 glass 
vial as a colorless to slightly yellow, sterile, preservative-free clear liquid solution 
intended for IV administration.  The vial is designed to deliver 20 mL (1200 mg) of 
atezolizumab solution but may contain more than the stated volume to enable delivery 
of the entire 20 mL volume.  For information on the formulation and handling of 
atezolizumab, see the Atezolizumab Investigator’s Brochure and Pharmacy Manual.
4.3.1.3
CHOP
CHOP agents will be administered according to the standard preparation and infusion 
procedures at each investigational site.  Refer to the local prescribing information for 
each agent for information on the formulation, packaging, and handling. 
4.3.1.4
Bendamustine
Bendamustine will be supplied by the Sponsor as an IMP.  For information on the 
formulation, packaging, and handling of bendamustine, see the summary of 
product characteristics for bendamustine.  

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4.3.1.5
Rituximab
Rituximab will be supplied by the Sponsor as an IMP.  Rituximab is packaged in 10-mL 
(100-mg) and 50-mL (500-mg) single-dose, pharmaceutical-grade glass vials at a 
concentration of 10 mg/mL of protein.  The antibody is formulated for IV injection as a 
sterile product in a solution of sodium chloride (pH 6.5) containing polysorbate 80 and 
sodium citrate. For information on the formulation and handling of rituximab, see the 
Rituximab Investigator's Brochure and the Rituximab Pharmacy Manual.
4.3.2
Dosage, Administration, and Compliance
The treatment regimens are summarized in Table 4Table 8 (see Sections 4.3.2.6, 
4.3.2.7, and 4.3.2.8).
Guidelines for dosage modification and treatment delays or discontinuation are provided 
in Section 5.1.
Any overdose or incorrect administration of any of the study treatments should be noted 
on the Study Drug Administration electronic Case Report Form (eCRF).  Adverse events 
associated with an overdose or incorrect administration of any of the study treatments 
should be recorded on the Adverse Event eCRF.
4.3.2.1
Obinutuzumab
Obinutuzumab will be administered by IV infusion at an absolute (flat) dose of 1000 mg 
on Days 1, 8, and 15 of the first cycle and on Day 1 of each subsequent cycle during 
induction treatment, and on Day 1 of every other month (i.e., every 2 months) during 
maintenance treatment (eligible patients with FL only).
Obinutuzumab should be administered as an IV infusion through a dedicated line in an 
environment in which full resuscitation facilities are immediately available and under the 
close supervision of an experienced physician.  Obinutuzumab infusions will be 
administered per the instructions outlined in Figure 2 and Figure 3.  For patients with 
bulky lymphadenopathy, the infusion may be given extremely slowly over a longer period 
of time, or the dose may be split and given over more than 1 day.
No dose modification for obinutuzumab is allowed.  Guidelines for treatment delays or 
discontinuation are provided in Section 5.1.
Premedication with a corticosteroid, analgesic/antipyretic, and antihistamine, as outlined 
in Section 4.3.2.9 (see Table 9), is required to reduce the incidence and severity of IRRs.  
For anaphylaxis precautions, see Appendix 12.

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Figure 2
Guidelines for Obinutuzumab Infusions:  First Infusion
IRR infusion-related reaction.
a
All patients should receive full premedication with an oral corticosteroid, oral analgesic/anti-pyretic, antihistamine, and anti-emetic prior to the first obinutuzumab 
infusion.  Refer to Section 4.3.2.9 for details.
b Supportive treatment should include acetaminophen/paracetamol and an antihistamine such as diphenhydramine, if not administered within the previous 4 hours.  
intravenous saline may be indicated.  For bronchospasm, urticaria, or dyspnea, patients may require antihistamines, oxygen, corticosteroids (e.g., 100 mg oral 
prednisone or equivalent), and/or bronchodilators.  For anaphylaxis precautions, see Appendix 12.

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Figure 3
Guidelines for Obinutuzumab Infusions:  Second and Subsequent Infusions
IRR infusion-related reaction.
a
Patients should receive full premedication with an oral corticosteroid, oral analgesic/anti-pyretic, and antihistamine prior to the obinutuzumab infusion.  Refer to 
Section 4.3.2.9  for details.
b
Patients who experience wheezing, urticaria, or other symptoms of anaphylaxis must receive full premedication prior to all subsequent doses.

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4.3.2.2
Atezolizumab
Atezolizumab will be administered at a flat dose consisting of one of the following:  
a) 1200 mg q3w (1200 mg on Day 1 of Cycles 2 and beyond, given in 21-day cycles
either with G-CHOP as induction treatment or alone as consolidation treatment); 
b) 840 mg q2w (840 mg on Days 1 and 15 of Cycles 26, given in 28-day cycles with 
G-benda as induction treatment); or c) 1680 mg q4w (840 mg on Days 1 and 2 of each 
month, given with obinutuzumab as maintenance treatment).  Detailed atezolizumab 
dosing regimens are provided in Table 4 and Table 5 for induction treatment and in 
Table 7 and Table 8 for post-induction treatment (see Sections 4.3.2.6, 4.3.2.7, and 
4.3.2.8).
Atezolizumab infusions will be administered as follows: 

The initial dose of atezolizumab will be delivered over 60 (15) minutes.  If the first 
infusion is tolerated without infusion-associated adverse events, the second infusion 
may be delivered over 30 (10) minutes.  If the 30-minute infusion is well tolerated, 
all subsequent infusions may be delivered over 30 (10) minutes.

In the event that a patient experiences a mild (NCI CTCAE Grade 1) IRR, the 
infusion rate should be reduced to half the rate being given at the time of event 
onset.  Once the event has resolved, the investigator should wait for 30 minutes 
while delivering the infusion at the reduced rate.  If tolerated, the infusion rate may 
then be increased to the original rate.  

In the event that a patient experiences a moderate (NCI CTCAE Grade 2) IRR or 
flushing, fever, or throat pain, the infusion should be immediately interrupted and the 
patient should receive aggressive symptomatic treatment.  The infusion should be 
restarted only after the symptoms have adequately resolved.  The infusion rate at 
restart should be half of the infusion rate being given at the time of event onset.

In the event of a severe or life-threatening (NCI CTCAE Grade 3 or 4) IRR, the 
infusion should be stopped immediately, aggressive resuscitation and supportive 
measures should be initiated, and atezolizumab should be permanently 
discontinued.
For anaphylaxis precautions, see Appendix 12.
No dose modification for atezolizumab is allowed.  Guidelines for treatment delays or 
discontinuation are provided in Section 5.1.
4.3.2.3
CHOP
Each CHOP agent will be administered at the standard dose and schedule, according to 
the standard preparation and infusion procedures of each investigational site (see 
Section 4.3.2.7 for details).

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4.3.2.4
Bendamustine
For the Atezo-G-benda treatment group, bendamustine will be administered by IV 
infusion at a dose of 90 mg/m2 on Days 1 and 2 of each 28-day cycle, for up to 6 cycles.  
There must be a minimum of 12 hours between each bendamustine administration.  
Body surface area (BSA) will be determined at screening and should be used to 
calculate the dose of bendamustine throughout the study unless the patient’s weight 
increases or decreases by 10% from screening, in which case BSA should be 
recalculated and used for subsequent dosing.  In obese patients (defined as body mass 
index 30 kg/m2), there is no BSA cap and actual body weight, not adjusted weight, is 
recommended.  Empiric dose adjustment for obese patients may be implemented per 
institutional guidelines.
4.3.2.5
Rituximab
Rituximab will be administered by IV infusion at the dose of 375 mg/m2 on Day 1 of 
Cycles 1−8.  BSA will be determined at screening and used as described in 
Section 4.3.2.4.
The infusion of rituximab may be split over 2 days if the patient is at increased risk for an 
IRR (high tumor burden or high peripheral lymphocyte count).  Administration of 
rituximab may be continued on the following day, if needed, for patients who experience 
an adverse event during the rituximab infusion. 
If a dose of rituximab is split over 2 days, both infusions must occur with appropriate 
premedication (see Section 4.3.2.9) and at the first infusion rate (see Table 3).
Rituximab infusions will be administered according to the instructions in Table 3.  If a 
patient tolerates the first three cycles of study treatment without significant infusion 
reactions, rituximab may be administered as a rapid infusion in accordance with local 
institutional guidelines.
During the treatment period, rituximab must be administered to patients in a setting 
where full emergency resuscitation facilities are immediately available.  Patients should 
be under close supervision of the investigator at all times. 
Rituximab should be administered as a slow IV infusion through a dedicated line.  After 
the end of the first infusion, the IV line or central venous catheter should remain in place 
for 2 hours in order to administer IV drugs, if necessary.  If no adverse events occur 
after 2 hours, the IV line may be removed or the central venous catheter may be 
de-accessed.  For subsequent infusions, the IV line or central venous catheter should 
remain in place for at least 1 hour after the end of the infusion.  If no adverse events 
occur after 1 hour, the IV line may be removed or the central venous catheter may be 
de-accessed.

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Table 3
Administration of First and Subsequent Infusions of Rituximab
First Infusion (Day 1 of Cycle 1)
Subsequent Infusions
Begin infusion at an initial rate of 
50 mg/hr.
If no infusion-related or 
hypersensitivity reaction occurs, 
increase the infusion rate in 50-mg/hr 
increments every 30 minutes to a 
maximum of 400 mg/hr.
If a reaction develops, stop or slow the 
infusion.  Administer medications and 
supportive care in accordance with 
institutional guidelines.  If the reaction 
has resolved, resume the infusion at a 
50% reduction in rate (i.e., 50% of rate 
being used at the time when the 
reaction occurred).
If the patient experienced an infusion-related or 
hypersensitivity reaction during the prior infusion, 
use full premedication, including 100 mg of 
prednisone/prednisolone or 80 mg of 
methylprednisolone or equivalent (until no further 
IRR occurs); begin infusion at an initial rate of 
50 mg/hr; and follow instructions for first infusion.
If the patient tolerated the prior infusion well 
(defined by an absence of Grade 2 reactions 
during a final infusion rate of 100 mg/hr), begin 
infusion at a rate of 100 mg/hr.
If no reaction occurs, increase the infusion rate 
in 100-mg/hr increments every 30 minutes to a 
maximum of 400 mg/hr.
If a reaction develops, stop or slow the infusion.  
Administer medications and supportive care in 
accordance with institutional guidelines.  If the 
reaction has resolved, resume the infusion at a 
50% reduction in rate (i.e., 50% of rate being 
used at the time when the reaction occurred).
No dose modification for rituximab is allowed.  Guidelines for treatment delays or 
discontinuation are provided in Section 5.1.7.
Premedication with a corticosteroid, analgesic/antipyretic, and antihistamine, as outlined 
in Section 4.3.2.9, is required to reduce the incidence and severity of IRRs.  For 
anaphylaxis precautions, see Appendix 12.
4.3.2.6
Induction Treatment with Atezo-G-Benda
Patients in the Atezo-G-benda treatment group will receive induction treatment, 
administered in 28-day cycles, as follows:

Patients will receive 6 cycles of induction treatment consisting of obinutuzumab and 
bendamustine for Cycles 16 and for Cycles 26, as outlined in Table 5.
Premedication should be administered as described in Section 4.3.2.9.
Obinutuzumab will be administered first, followed by a line flush (unless there is a central 
line with more than one line/port), after which atezolizumab will be administered.  
Bendamustine will be administered at least 30 minutes after atezolizumab infusion.  If it 
is the strong preference of the investigator or the site (e.g., for logistical reasons), the 
administration of bendamustine prior to obinutuzumab is allowed. In this case, 
obinutuzumab should be administered within 30 minutes after bendamustine infusion.

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For patients at increased risk for IRRs (high tumor burden), the obinutuzumab infusion 
may be split and administered over 2 days.  
For patients who experience an adverse event during obinutuzumab infusion, 
administration of atezolizumab and bendamustine may be delayed by 1 day if clinically 
required.  If bendamustine is delayed, subsequent bendamustine infusions should be 
delayed by the same number of days to maintain the regular bendamustine cycle interval 
of 28 days.  
Table 4
Induction Treatment:  Atezo-G-Benda Treatment Group
Regimen (28-day cycles)
Treatment
Dose
Route
Cycle 1
Cycles 26
Obinutuzumab
1000 mg
IV
Days 1, 8, and 15
Day 1
Bendamustine
90 mg/m2
IV
Days 1 and 2
Days 1 and 2
Atezolizumab
840 mg
IV

Days 1 and 15
Atezoatezolizumab; Bendabendamustine; Gobinutuzumab; IVintravenous.
4.3.2.7
Induction Treatment with Atezo-G-CHOP or Atezo-R-CHOP 
Patients will receive induction treatment, administered in 21-day cycles, as follows:

Patients enrolled in the safety run-in phase (i.e., patients with FL) will receive 
6 cycles of induction treatment consisting of obinutuzumab and CHOP for 
Cycles 16 and atezolizumab for Cycles 26, as outlined in Table 5.

Patients enrolled in the expansion phase (i.e., patients with DLBCL) will receive 
8 cycles of induction treatment consisting of rituximab for Cycles 18, atezolizumab 
for Cycles 28, and CHOP for either Cycles 16 or Cycles 18 as determined by the 
investigator, as outlined in Table 5.
Premedication should be administered as described in Section 4.3.2.9.
Oral prednisone (or prednisolone, if prednisone is unavailable) should be administered 
first, at least 60 minutes prior to commencing study treatment infusions.  Obinutuzumab 
or rituximab will be administered second, followed by a line flush (unless there is a 
central line with more than one line/port). Then atezolizumab will be administered
followed by a line flush.  Finally, chemotherapy components will be administered.  The 
order of administration of cyclophosphamide, doxorubicin, and vincristine will be 
determined by local institutional practice.
The 40 mg/m2 dose of prednisone on Day 1 will be replaced by oral corticosteroids given 
as premedication on Day 1 of Cycle 1 (and subsequent cycles as indicated).  Details on 
corticosteroid premedication are provided in Section 4.3.2.9.

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For patients at increased risk for IRRs (high tumor burden), the obinutuzumab and 
rituximab infusions may be split and administered over 2 days.  
For patients who experience an adverse event during obinutuzumab or rituximab 
infusion, administration of atezolizumab and CHOP may be delayed by 1 day if clinically 
required.  If CHOP is delayed, subsequent CHOP administration should be delayed by 
the same number of days to maintain the regular CHOP cycle interval of 21 days.
Table 5
Induction Treatment, Safety Run-In Phase:  Atezo-G-CHOP 
Treatment Group
Regimen (21-day cycles)
Treatment
Dose
Route
Cycle 1
Cycles 26
Obinutuzumab
1000 mg
IV
Days 1, 8, and 15
Day 1
Cyclophosphamide
750 mg/m2
IV
Day 1
Day 1
Doxorubicin
50 mg/m2
IV
Day 1
Day 1
Vincristine 
1.4 mg/m2
(maximum, 2 mg)
IV
Day 1
Day 1
Prednisone a
40 mg/m2
Oral
Days 15
Days 15
Atezolizumab
1200 mg
IV

Day 1
Atezoatezolizumab; CHOPcyclophosphamide, doxorubicin, vincristine, and prednisone; 
Gobinutuzumab; IVintravenous.
a Prednisolone may be given if prednisone is unavailable.  The 40 mg/m2 dose of prednisone on 
Day 1 will be replaced by oral corticosteroids given as premedication on Day 1 of Cycle 1 (and 
subsequent cycles as indicated) (see details on premedication in Section 4.3.2.9).

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Table 6
Induction Treatment, Expansion Phase:  Atezo-R-CHOP
Regimen (21-day cycles)
Treatment
Dose
Route
Cycle 1
Cycles 26/8 a
Rituximab
375 mg/m2
IV
Day 1
Day 1
Cyclophosphamide
750 mg/m2
IV
Day 1
Day 1
Doxorubicin
50 mg/m2
IV
Day 1
Day 1
Vincristine 
1.4 mg/m2
(maximum, 
2 mg)
IV
Day 1
Day 1
Prednisone b
40 mg/m2
Oral
Days 15
Days 15
Atezolizumab
1200 mg
IV

Day 1
Atezoatezolizumab; CHOPcyclophosphamide, doxorubicin, vincristine, and prednisone; 
IVintravenous; Rrituximab.
a Patients will receive eight cycles of induction treatment consisting of rituximab for 
Cycles 18, atezolizumab for Cycles 28, and CHOP for either Cycles 16 or Cycles 18, as 
determined by the investigator.
b Prednisolone may be given if prednisone is unavailable.  The 40 mg/m2 dose of prednisone 
on Day 1 will be replaced by oral corticosteroids given as premedication on Day 1 of Cycle 1 
(and subsequent cycles as indicated) (see details on premedication in Section 4.3.2.9).
4.3.2.8
Post-Induction Treatment
Patients with DLBCL (i.e., patients treated with Atezo-R-CHOP during the expansion 
phase) who achieve a CR at EOI will receive post-induction treatment (referred to as 
consolidation) with atezolizumab, administered in 21-day cycles for 17 cycles, as 
outlined in Table 7.  Patients with FL who achieve a CR or PR at EOI will receive 
post-induction treatment (referred to as maintenance) with atezolizumab and 
obinutuzumab for approximately 24 months, as outlined in Table 8.  Obinutuzumab will 
be administered first, followed by a line flush (unless there is a central line with more 
than one line/port), after which atezolizumab will be administered.  Post-induction 
treatment should start 8 weeks (1 week) after Day 1 of the final cycle of induction and 
will continue until disease progression or unacceptable toxicity for up to 1 year for 
consolidation treatment or 2 years for maintenance treatment. 
Table 7
Consolidation Treatment for Patients with DLBCL
Treatment
Dose
Route
Regimen (21-day cycles)
Atezolizumab
1200 mg
IV
Day 1 of Cycles 925
DLBCLdiffuse large B-cell lymphoma; IVintravenous.

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Table 8
Maintenance Treatment for Patients with FL
Treatment
Dose
Route
Regimen (total of 24 monthsa)
Obinutuzumab
1000 mg
IV
Day 1 of every other month (starting with Month 1)
Atezolizumab
840 mg
IV
Days 1 and 2 of each month
FLfollicular lymphoma; IVintravenous.
a
1 month28 days.
4.3.2.9
Premedication
Patients should receive premedication as outlined in Table 9 below.

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Table 9
Premedication
Timepoint
Patients Requiring 
Premedication
Premedication
Administration
Cycle 1, 
Day 1
All patients
Oral corticosteroid a
Complete 1 hour prior to obinutuzumab or rituximab 
infusion.
All patients 
Oral analgesic/anti-pyretic b
Antihistamine drug c
Administer 30 minutes prior to obinutuzumab or 
rituximab infusion.
All patients
Serotonin (5-HT3) antagonist 
(e.g., dolasetron, ondansetron) 
or another anti-emetic
Administer 30 minutes prior to initiation of study 
treatment, on Day 1 for patients receiving CHOP and on 
Days 1 and 2 for patients receiving bendamustine.
Patients at risk for TLS 
(e.g., because of bulky 
disease or renal impairment 
(creatinine clearance 
70 mL/min)
Allopurinol or suitable alternative 
such as rasburicase, along with 
adequate hydration
Administer prior to obinutuzumab or rituximab infusion.  
For patients in Atezo-G-benda treatment group, 
allopurinol should be started 72 hours prior to 
bendamustine infusion and stopped 24 hours prior to 
bendamustine infusion.
Cycle 1, 
Days 8 and 15
Cycles 2 and 
Beyond,
Day 1
Patients with no IRR or with 
Grade 1 or 2 IRR during the 
previous infusion
Antihistamine drug b
Oral analgesic/anti-pyretic c
Administer at least 30 minutes prior to obinutuzumab 
infusion.  For patients receiving rituximab who do not 
experience any IRR with their previous infusion, 
premedication may be omitted at the investigator’s 
discretion.
Patients with Grade 3 IRR, 
wheezing, urticaria, or other 
symptoms of anaphylaxis 
during the previous infusion
Patients with bulky disease
Oral corticosteroid a
Complete 1 hour prior to obinutuzumab or rituximab 
infusion.
Antihistamine drug b
Oral analgesic/anti-pyretic c
Administer at least 30 minutes prior to obinutuzumab or 
rituximab infusion.
Patients still at risk for TLS
Allopurinol or suitable alternative 
such as rasburicase, along with 
adequate hydration
Administer prior to obinutuzumab or rituximab infusion.  
For patients in Atezo-G-benda treatment group, 
allopurinol should be started 72 hours prior to 
bendamustine infusion and stopped 24 hours prior to 
bendamustine infusion.

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Table 9
Premedication (cont.)
Timepoint
Patients Requiring 
Premedication
Premedication
Administration
Cycles 26/8 
All patients receiving 
chemotherapy
Serotonin (5-HT3) antagonist 
(e.g., dolasetron, ondansetron) 
or another anti-emetic
Administer 30 minutes prior to initiation of study 
treatment, on Day 1 for patients receiving CHOP and on 
Days 1 and 2 for patients receiving bendamustine.
Atezo-G-bendaatezolizumab in combination with obinutuzumab plus bendamustine; CHOP cyclophosphamide, doxorubicin, vincristine, and 
prednisone; IRRinfusion-related reaction; TLStumor lysis syndrome.
a Treat with 100 mg of prednisone or prednisolone, 20 mg of dexamethasone, or 80 mg of methylprednisolone.  Hydrocortisone should not be 
used, as it has not been effective in reducing rates of IRR.  On Day 1, the premedication oral corticosteroid dose (100 mg of prednisone or 
prednisolone, or 80 mg of methylprednisolone) will be given in place of the 40-mg/m2 prednisone dose for patients treated with 
Atezo-G-CHOP or Atezo-R-CHOP.
b For example, 1000 mg of acetaminophen/paracetamol.
c For example, 50 mg of diphenhydramine.

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4.3.3
Investigational Medicinal Product Accountability
All IMPs required for completion of this study (obinutuzumab, rituximab, atezolizumab, 
and bendamustine) will be provided by the Sponsor.  The study site will acknowledge 
receipt of IMPs using the IxRS to confirm the shipment condition and content.  Any 
damaged shipments will be replaced.
IMPs will either be disposed of at the study site according to the study site’s institutional 
standard operating procedure or returned to the Sponsor with the appropriate 
documentation.  The site's method of IMP destruction must be agreed to by the Sponsor.  
The site must obtain written authorization from the Sponsor before any IMP is destroyed, 
and IMP destruction must be documented on the appropriate form.
Accurate records of all IMPs received at, dispensed from, returned to, and disposed of by 
the study site should be recorded on the Drug Inventory Log.
4.3.4
Post-Trial Access to Obinutuzumab, Rituximab, Atezolizumab, 
and Bendamustine
Patients may continue to receive study treatment and undergo scheduled assessments 
as part of an extension study.  Currently, the Sponsor does not have any plans to 
provide post-trial access to any IMP or interventions to patients who do not qualify for 
the extension study. The Roche Global Policy on Continued Access to Investigational 
Medicinal Product is available at the following Web site:
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
4.4
CONCOMITANT THERAPY
Concomitant therapy includes any medication (e.g., prescription drugs, over-the-counter 
drugs, herbal or homeopathic remedies, nutritional supplements) used by a patient from 
7 days prior to screening to the treatment completion/discontinuation visit.  All such 
medications should be reported to the investigator and recorded on the Concomitant 
Medications eCRF.  
4.4.1
Permitted Therapy 
Premedication should be administered as described in Section 4.3.2.9.
Patients who use oral contraceptives, hormone-replacement therapy, or other 
maintenance therapy should continue their use.
Primary prophylaxis with G-CSF is recommended according to American Society of 
Clinical Oncology, EORTC, and European Society for Medical Oncology guidelines 
(Smith et al. 2015), or per each site’s institutional standards.  Additionally, G-CSF 
prophylaxis is strongly recommended in Cycle 1 for all patients in the Atezo-G-CHOP 
and Atezo-G-benda treatment groups, given the expected myelosuppressive effect of 
these combinations.

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Patients receiving concomitant medication that could possibly worsen 
thrombocytopeniarelated events (e.g., platelet inhibitors and anticoagulants) may be at 
greater risk of bleeding.  When possible, replace prior vitamin K antagonist therapy with 
low-molecular-weight heparin (LMWH) prior to Day 1 of Cycle 1.
Prophylactic treatment with antibiotics should be administered as per standard practice.
Necessary supportive measures for optimal medical care will be given throughout the 
study according to institutional standards.  
4.4.2
Prohibited Therapy
Use of the following therapies (excluding protocol-specified treatments) is prohibited 
during the study:

Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor (denosumab) 
for a period of 10 weeks after the last dose of atezolizumab
RANKL inhibition could potentially alter the activity and safety of atezolizumab.  
Thus, patients receiving a RANKL inhibitor prior to enrollment must be willing 
and eligible to receive a bisphosphonate instead of a RANKL inhibitor.

Any anti-cancer therapy, approved or investigational, other than intrathecal central 
nervous system prophylaxis

Hormonal therapy other than contraceptives, stable hormone-replacement therapy, 
or megestrol acetate

Biologic agents other than hematopoietic growth factors (as described in 
Section 4.4.1)

Immunostimulatory agents, including, but not limited to, interferon alpha (IFN-, 
IFN-, or IL-2
Immunostimulatory agents, in combination with atezolizumab, could potentially 
increase the risk for autoimmune conditions.  Patients should not receive other 
immunostimulatory agents for 10 weeks after the last dose of atezolizumab.

Vaccines, as outlined below:
Any live, attenuated vaccine (e.g., FluMist) is prohibited while the patient is 
receiving atezolizumab and for a period of 5 months after discontinuation of 
atezolizumab.  Inactivated influenza vaccines are allowed only during flu season. 
Vaccination with live vaccines is not recommended during treatment with 
obinutuzumab and until B-cell recovery. 
4.5
STUDY ASSESSMENTS 
See Appendix 1, Appendix 2, and Appendix 3 for the schedules of assessments 
performed during the study.

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4.5.1
Informed Consent Forms and Screening Log
Written informed consent for participation in the study must be obtained before 
performing any study-related procedures.  Informed Consent Forms for enrolled patients 
and for patients who are not subsequently enrolled will be maintained at the study site.
All screening evaluations must be completed and reviewed to confirm that patients meet 
all eligibility criteria before enrollment.  The investigator will maintain a screening log to 
record details of all patients screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Results of standard-of-care tests or examinations performed prior to obtaining informed 
consent, and within the defined window, may be used as screening and baseline 
assessments (see Appendix 1, Appendix 2, and Appendix 3); such tests do not need to 
be repeated for screening purposes (e.g., screening tumor assessment).  
Study treatment should be initiated within 28 days after the Informed Consent Form has 
been signed.
4.5.2
Medical History and Demographic Data
Medical history includes clinically significant diseases, surgeries, reproductive status, 
smoking history, and alcohol and drug abuse.  In addition, all medications 
(e.g., prescription drugs, over-the-counter drugs, herbal or homeopathic remedies, 
nutritional supplements) used by the patient within 7 days prior to the screening visit will 
be recorded.
Demographic data will include age, sex, and self-reported race/ethnicity.
The following clinical parameters relative to disease history, diagnosis, and prognostic 
indices will be recorded at screening: 

Date of initial diagnosis

ECOG performance status (see Appendix 9)

B symptoms (unexplained fever 38C, night sweats, unexplained weight loss 10% 
of body weight over 6 months) 

Ann Arbor staging (see Appendix 10)

For patients with FL: Follicular Lymphoma International Prognostic Index (FLIP)I 
and FLIPI2 (see Appendix 11)

For patients with DLBCL:  IPI (see Appendix 11) 

For patients with relapsed or refractory FL:  prior anti-lymphoma treatment as well 
as response to prior treatment, date of disease progression in relation to start date 
of prior treatment, and date of last dose of prior treatment

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4.5.3
Physical Examinations
A complete physical examination should be performed at screening and should include 
an evaluation of the head, eyes, ears, nose, and throat, and the cardiovascular, 
dermatological, musculoskeletal, respiratory, GI, genitourinary, and neurological systems.  
Any abnormality identified at baseline should be recorded on the General Medical 
History and Baseline Conditions eCRF.
As part of tumor assessment, the physical examination should include evaluation for the 
presence of enlarged nodes, palpable hepatomegaly, and splenomegaly.  This 
information will be recorded on the appropriate tumor assessment eCRF.
At subsequent visits (or as clinically indicated), targeted (limited, symptom-directed) 
physical examinations should be performed.  Targeted physical examinations should be 
limited to systems of primary relevance (e.g., cardiovascular and respiratory systems), 
systems associated with symptoms (newly emergent or monitored from baseline), and 
areas associated with tumor assessment (lymph nodes, liver, spleen, and any other 
areas identified at baseline) (see Section 4.5.5).  
Changes from baseline abnormalities should be recorded in patient notes.  New or 
worsened clinically significant abnormalities should be recorded as adverse events on 
the Adverse Event eCRF.
4.5.4
Vital Signs 
Vital signs will include measurements of respiratory rate, pulse rate, body temperature, 
and systolic and diastolic blood pressures while the patient is in a seated position.  Vital 
sign measurements will be performed as outlined in the schedules of assessments (see 
Appendix 1, Appendix 2, and Appendix 3), but the associated data, other than the data 
collected at screening, do not need to be recorded on the eCRF (except in the case of 
an adverse event as described in Section 5.3.5.6).
4.5.5
Tumor and Response Evaluations 
All evaluable or measurable disease must be documented at screening and re-assessed 
at each subsequent tumor evaluation.  Response will be assessed by the IRC and the 
investigator on the basis of physical examinations (see Section 4.5.3), PET and CT 
scans, and bone marrow examinations using the Lugano 2014 criteria (see Appendix 7). 
and the modified Cheson 2007 criteria (see Appendix 8).  In this study, the Lugano 2014 
criteria for a PET-CTbased CR and PR have been modified, as outlined below.

A designation of PET-CTbased CR requires normal bone marrow by morphology 
for patients with bone marrow involvement at baseline.  If indeterminate by 
morphology, immunohistochemistry should be negative.

A designation of PET-CTbased PR requires that CT-based response criteria for a 
CR or PR be met in addition to the PET-CTbased response criteria for a PR.

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4.5.5.1
Radiographic Assessments
PET scans should include skull-base to mid-thigh.  Full body PET scans should be 
performed when clinically appropriate.
CT scans with oral and IV contrast should include chest, abdomen, and pelvic scans.  
CT scans of the neck should be included if clinically indicated (i.e., if evidence of disease 
upon physical examination) and must be repeated throughout the study if there is 
disease involvement at baseline.  
PET-CT scans and diagnostic CT scans should be acquired according to a standardized 
imaging manual, which will be provided to all sites.
If contrast is medically contraindicated (e.g., patients with contrast allergy or impaired 
renal clearance), MRI scans of the chest, abdomen, and pelvis (and neck, if clinically 
indicated) and a non-contrast CT scan of the chest may be performed.  If MRI scans 
cannot be obtained, CT scans without contrast are permitted as long as this allows 
consistent and precise measurement of the targeted lesions during the study treatment 
period.  
The same radiographic assessment modality must be used for all response evaluations 
to ensure consistency across different timepoints (including unscheduled assessments).
A full tumor assessment, including radiographic assessment, must be performed any 
time disease progression or relapse is suspected.
Additional details regarding imaging procedures will be provided in the Imaging Manual.
4.5.5.2
Bone Marrow Assessments
Bone marrow examinations are required at screening for staging purposes in all patients 
and should be performed within approximately 3 months prior to Day 1 of Cycle 1.  
If bone marrow infiltration is present at screening, a bone marrow biopsy is required at 
the EOI response assessment for all patients who may have achieved a CR.  In patients 
with a PR and continued bone marrow involvement, a subsequent bone marrow 
examination may be required to confirm a CR at a later timepoint.
Any additional (unscheduled) bone marrow examinations performed during the study will 
be at the discretion of the investigator.  

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4.5.6
Laboratory, Biomarker, and Other Biological Samples
Local Laboratory Assessments
Samples for the following laboratory tests will be analyzed at the study site's local 
laboratory for analysis:

Hematology:  hemoglobin, hematocrit, platelet count, RBC count, WBC count, 
percent or absolute WBC differential count (neutrophils, eosinophils, basophils, 
monocytes, lymphocytes, other cells) 

Serum chemistry:  sodium, potassium, glucose, BUN or urea, creatinine, calculated 
creatinine clearance, calcium, total bilirubin, direct bilirubin, total protein, albumin, 
ALT, AST, alkaline phosphatase (ALP), amylase, lipase, LDH, uric acid

Thyroid-stimulating hormone (TSH), triiodothyronine, thyroxine (T4)

2 microglobulin

Coagulation:  INR, aPTT (or PTT), PT

Pregnancy test
All women who are not postmenopausal (12 months of non-therapy-induced 
amenorrhea) or surgically sterile will have a serum pregnancy test at screening 
(within 7 days of Day 1 of Cycle 1) and at the end of treatment.

Viral serology 
Hepatitis B testing includes HBsAg and total HBcAb.  
Hepatitis C testing includes HCV antibody.

Quantitative immunogloblulins: IgA, IgG, IgM
Central Laboratory Assessments
The following samples will be sent to one or several Sponsor-designated central 
laboratories or to the Sponsor for analysis:

Serum samples for obinutuzumab PK analysis using a validated assay

Serum samples for atezolizumab (MPDL3280A) PK analysis using a validated 
assay

Serum samples for rituximab PK analysis using a validated assay

Serum samples for assessment of HACAs to rituximab using a validated assay

Serum samples for assessment of HAHAs to obinutuzumab using a validated assay

Serum samples for assessment of ATAs to atezolizumab (MPDL3280A) using 
validated assays

Tumor tissue samples and the corresponding pathology report for retrospective 
central confirmation of the diagnosis of FL or DLBCL, and for exploratory research 
on candidate biomarkers (see Table 10)
The specimen must contain adequate evaluable tumor cells (20% for 
excisional biopsy and50% for core biopsy).  

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Formalin-fixed paraffin-embedded tissue blocks are preferred over slides.  
Tissue blocks that are not formalin fixed will be accepted in countries that use a 
fixative other than paraformaldehyde, but information on the type of fixative 
should be included.  If a tissue block is not available, 1520 serial, freshly-cut, 
unstained slides accompanied by a punch biopsy may be sent.  A tumor block 
or punch biopsy is required for construction of a tissue microarray.  If fewer than 
1520 unstained, serial slides are available, the study site should consult the 
Sponsor (or delegate) regarding the acceptability of a fewer number of slides. 
If archival tissue is unavailable or unacceptable according to above criteria, a 
pretreatment core-needle, excisional, or incisional tumor biopsy is required.  
Cytological or fine-needle aspiration samples are not acceptable.  
The sample should be shipped according to instructions provided in the 
laboratory manual.  The remainder of the tissue blocks will be returned to the 
local pathology laboratory, according to country-specific procedures.
Analysis methods will be detailed in the Biomarker Analysis Plan.

Tumor biopsy samples obtained prior to the start of Cycle 2 and at the time of 
progression (unless no adequate tumor site is accessible) for exploratory research 
on candidate biomarkers (see Table 10)

Serum samples for exploratory research on candidate biomarkers (see Table 10)

Whole blood samples for exploratory research on candidate biomarkers (see 
Table 10)

Whole blood samples for isolation of peripheral blood mononuclear cells for 
exploratory research on candidate biomarkers (see Table 10)
Exploratory biomarker research may include, but will not be limited to, the biomarkers 
listed in Table 10.

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Table 10 Proposed Non-Inherited Biomarkers
Sample Type
Timing
Proposed 
Non-Inherited Biomarkers
Archival or fresh tumor 
tissue 
Prior to study (archival) or 
baseline (fresh)
For DLBCL patients only:  DLBCL 
cell-of-origin subtype (ABC vs. GCB), 
BCL2, MYC, Epstein-Barr virus status
Lymphoma-related genetic changes 
(DNA) and gene expression (mRNA)
PD-L1, HLA-1
CD8 and other biomarkers of T-cell 
subpopulations
Biomarkers of other immune cells (such 
as macrophages)
Tumor tissue biopsy
Prior to the start of Cycle 2 
and at the time of 
progression (unless no 
adequate tumor site is 
accessible)
PD-L1
CD8 and other biomarkers of T-cell 
subpopulations
Plasma
Baseline
Soluble PD-L1
Plasma
Baseline and subsequent 
timepoints during treatment
Cytokines characteristic of T-cell 
activation (e.g., IL-18, IFN-)
Whole blood 
(separated into PBMCs 
and plasma)
Baseline and subsequent 
timepoints during treatment
Detection of minimal residual disease:
Cell-free circulating tumor DNA in 
plasma
Circulating lymphoma cells in PBMCs
PBMCs isolated from 
whole blood
Baseline and subsequent 
timepoints during treatment
T-cell receptor repertoire
Whole blood
Baseline and subsequent 
timepoints during and after 
treatment
Lymphocyte immunophenotyping, 
including B-cell counts (CD19), T-cell 
counts (CD3, CD4, and CD8), and 
NK-cell counts (CD16 and CD56)
ABCactivated B cell–like; BCL2B-cell lymphoma 2 gene; DBLCLdiffuse large B-cell 
lymphoma; GCBgerminal-center B-cell–like; HLA-1human lymphocyte antigen;
IFN-interferon gamma; ILinterleukin; NKnatural killer; PBMCs peripheral blood 
mononuclear cells; PD-L1programmed death-ligand 1.
Note:  Exploratory biomarker research may include, but will not be limited to, the biomarkers 
listed in this table.
Samples collected for PK and immunogenicity analyses may be used for assay 
development purposes, and additional safety and immunogenicity assessments, as 
appropriate.
Biological samples will be destroyed when the final clinical study report has been 
completed, unless the patient gives specific consent for the leftover samples to be stored 
for optional exploratory research (see Section 4.5.9).

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4.5.7
Electrocardiograms 
Single, resting, 12-lead ECG recordings will be obtained at specified timepoints, as 
outlined in the schedules of assessments (see Appendix 1, Appendix 2, and Appendix 3), 
and may be obtained at unscheduled timepoints as clinically indicated.  ECGs for each 
patient should be obtained using the same machine wherever possible.  Interpretation of 
the ECG should be performed by the investigator.
4.5.8
Echocardiogram or MUGA
For patients receiving CHOP, LVEF will be assessed by echocardiography or MUGA 
scan at specified timepoints, as outlined in the schedules of assessments (see 
Appendix 1, Appendix 2, and Appendix 3).
4.5.9
Samples for Roche Clinical Repository 
4.5.9.1
Overview of the Roche Clinical Repository
The Roche Clinical Repository (RCR) is a centrally administered group of facilities used 
for the long-term storage of human biologic specimens, including body fluids, solid 
tissues, and derivatives thereof (e.g., DNA, RNA, proteins, peptides).  The collection and 
analysis of RCR specimens will facilitate the rational design of new pharmaceutical 
agents and the development of diagnostic tests, which may allow for individualized 
therapy for patients in the future.
Specimens for the RCR will be collected from patients who give specific consent to 
participate in this optional research.  RCR specimens will be used to achieve the 
following objectives:

To study the association of biomarkers with efficacy, adverse events, or disease 
progression

To increase knowledge and understanding of disease biology

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
4.5.9.2
Approval by the Institutional Review Board or Ethics 
Committee
Collection and submission of biological samples to the RCR is contingent upon the 
review and approval of the exploratory research and the RCR portion of the Informed 
Consent Form by each site's Institutional Review Board or Ethics Committee (IRB/EC) 
and, if applicable, an appropriate regulatory body.  If a site has not been granted 
approval for RCR sampling, this section of the protocol (Section 4.5.9) will not be 
applicable at that site.

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4.5.9.3
Sample Collection
The following samples will be collected for research purposes, including, but not limited 
to, research on dynamic (non-inherited) biomarkers related to obinutuzumab, 
atezolizumab, or NHL:

Peripheral blood (i.e., whole blood, plasma, and serum)

Leftover tumor tissue from lymph node biopsy (archival and/or fresh biopsy)

Leftover peripheral blood
For all samples, dates of consent and specimen collection should be recorded on the 
associated RCR page of the eCRF.  For sampling procedures, storage conditions, and 
shipment instructions, see the laboratory manual.  
RCR specimens will be destroyed no later than 15 years after the date of final closure of 
the associated clinical database.  The RCR storage period will be in accordance with the 
IRB/EC-approved Informed Consent Form and applicable laws (e.g., health authority 
requirements).
4.5.9.4
Confidentiality
Confidentiality for All RCR Specimens
Specimens and associated data will be labeled with a unique patient identification 
number.
Patient medical information associated with RCR specimens is confidential and may be 
disclosed to third parties only as permitted by the Informed Consent Form (or separate 
authorization for use and disclosure of personal health information) signed by the patient, 
unless permitted or required by law.
Data generated from RCR specimens must be available for inspection upon request by 
representatives of national and local health authorities, and the Sponsor’s monitors, 
representatives, and collaborators, as appropriate.
Data derived from RCR specimen analysis on individual patients will generally not be 
provided to study investigators unless a request for research use is granted.  The 
aggregate results of any research conducted using RCR specimens will be available in 
accordance with the effective Sponsor policy on study data publication.
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of the RCR data will become and remain the exclusive and unburdened property 
of the Sponsor, except where agreed otherwise.
Additional Confidentiality for Specimens Used for Genetic Research
Given the sensitive nature of genetic data, the Sponsor has implemented additional 
processes to ensure patient confidentiality for RCR specimens collected for genetic 
research.  Upon receipt by the RCR, specimens for genetic research are "double-coded" 

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by replacing the patient identification number with a new independent number.  Data 
generated from the use of these specimens and all clinical data transferred from the 
clinical database and considered relevant are also labeled with this same independent 
number.  A "linking key" between the patient identification number and this new 
independent number is stored in a secure database system.  Access to the linking key is 
restricted to authorized individuals and is monitored by audit trail.  Legitimate operational 
reasons for accessing the linking key are documented in a standard operating procedure.  
Access to the linking key for any other reason requires written approval from the Pharma 
Repository Governance Committee and the Sponsor’s Legal Department, as applicable.
4.5.9.5
Consent to Participate in the Roche Clinical Repository
The Informed Consent Form will contain a separate section that addresses participation 
in the RCR.  The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential hazards of participation in the RCR.  Patients will be 
told that they are free to refuse to participate and may withdraw their specimens at any 
time and for any reason during the storage period.  A separate, specific signature will be 
required to document a patient's agreement to provide optional RCR specimens.  
Patients who decline to participate will not provide a separate signature.
The investigator should document whether or not the patient has given consent to 
participate by completing the RCR Research Sample Informed Consent eCRF.
In the event of an RCR participant's death or loss of competence, the participant's 
specimens and data will continue to be used as part of the RCR research.
4.5.9.6
Withdrawal from the Roche Clinical Repository
Patients who give consent to provide RCR specimens have the right to withdraw their 
specimens from the RCR at any time for any reason.  If a patient wishes to withdraw 
consent to the testing of his or her specimens, the investigator must inform the Medical 
Monitor in writing of the patient's wishes through use of the RCR Subject Withdrawal 
Form and, if the trial is ongoing, must enter the date of withdrawal on the RCR Research 
Sample Withdrawal of Informed Consent eCRF.  The patient will be provided with 
instructions on how to withdraw consent after the trial is closed.  A patient's withdrawal 
from Study BO29563 does not, by itself, constitute withdrawal of specimens from the 
RCR.  Likewise, a patient's withdrawal from the RCR does not constitute withdrawal from 
Study BO29563.
4.5.9.7
Monitoring and Oversight
RCR specimens will be tracked in a manner consistent with Good Clinical Practice (GCP) 
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 specimens as specified in this protocol and in the 
Informed Consent Form.  The Sponsor’s monitors and auditors will have direct access to 
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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 RCR samples.
4.6
PATIENT, TREATMENT, STUDY, AND SITE DISCONTINUATION
4.6.1
Patient Discontinuation
Patients have the right to voluntarily withdraw from the study at any time for any reason.  
In addition, the investigator has the right to withdraw a patient from the study at any time.  
Reasons for withdrawal from the study may include, but are not limited to, the following:

Patient withdrawal of consent at any time

Any medical condition that the investigator or Sponsor determines may jeopardize 
the patient’s safety if he or she continues in the study

Investigator or Sponsor determines it is in the best interest of the patient

Patient non-compliance (e.g., consistent failure to show up for scheduled visits)
Every effort should be made to obtain information on patients who withdraw from the 
study.  The primary reason for withdrawal from the study should be documented on the 
appropriate eCRF.  However, patients will not be followed for any reason after consent 
has been withdrawn.
If a patient withdraws consent, this request must be documented in the source 
documents and signed by the investigator.  Study personnel may use a public 
information source (e.g., county records) to obtain information about survival status.
4.6.2
Study Treatment Discontinuation
Study treatment should be permanently discontinued in patients who experience any of 
the following:

Anaphylaxis, acute respiratory distress, or Grade 4 IRR
If a Grade 3 IRR is recurrent during the second and subsequent cycles, study 
treatment may be discontinued at the discretion of the investigator, following an 
individual benefit-risk assessment.  

Hematologic toxicity that is related to study treatment and consists of either of the 
following:
Grade 3 hematologic adverse event that requires study treatment to be 
withheld 21 days in patients with FL and14 days in patients with DLBCL
Recurrent Grade 4 neutropenia with infection, despite G-CSF support and dose 
modifications

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
Non-hematologic toxicity that consists of either of the following:
Grade 3 non-hematologic adverse event that has a reasonable possibility of 
being related to study treatment and either is life threatening or requires study 
treatment to be withheld for 21 days in patients with FL and14 days in 
patients with DLBCL
Development of an atezolizumab-related immune-related adverse event that is 
life threatening or requires atezolizumab to be withheld for 42 days, unless 
approved by the Medical Monitor

Disease progression
Cases of apparent radiographic progression (pseudoprogression/tumor immune 
infiltration), including the appearance of new lesions have been described in 
patients with solid tumors treated with immunotherapies (Wolchok et al. 2009).  
In case of CT- findings suggestive for pseudoprogression in patients with 
persistent clinical benefit, the investigator should contact the Medical Monitor to 
discuss further patient management. Patients who continue to receive study 
treatment should have a CT scan repeated 48 weeks later.

Pregnancy
The primary reason for study treatment discontinuation should be documented on the 
appropriate eCRF.
Patients who discontinue study treatment will not be replaced, except as outlined below:

During the safety run-in phase, patients who discontinue study treatment prior to 
completing Cycle 3 for reasons other than toxicity will be replaced.

During the expansion phase, patients who discontinue from the study after Cycle 1 
(i.e., prior to receiving atezolizumab) will be replaced.
4.6.3
Study and Site Discontinuation
The Sponsor has the right to terminate this study at any time.  Reasons for terminating 
the study may include, but are not limited to, the following:

The incidence or severity of adverse events in this or other studies indicates a 
potential health hazard to patients.

Patient enrollment is unsatisfactory.
The Sponsor will notify the investigator if the Sponsor decides to discontinue the study.  
The Sponsor has the right to close a site at any time.  Reasons for closing a site may 
include, but are not limited to, the following:

Excessively slow recruitment

Poor protocol adherence

Inaccurate or incomplete data recording

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
Non-compliance with the International Conference on Harmonisation (ICH) guideline 
for GCP

No study activity (i.e., all patients have completed the study and all obligations have 
been fulfilled)
5.
ASSESSMENT OF SAFETY
5.1
SAFETY PLAN
The safety plan for patients in this study is based on clinical experience with study 
treatment components in completed and ongoing studies.  The anticipated important 
safety risks of IMPs in this study (i.e., obinutuzumab, atezolizumab, and bendamustine) 
are outlined below.  
Several measures will be taken to ensure the safety of patients participating in this trial.  
Eligibility criteria have been designed to exclude patients at higher risk for toxicities 
(see Section 4.1).  In addition, patients will undergo adequate safety monitoring during 
the study, as described in this section and in Section 4.5.  Finally, guidelines for 
managing adverse events, including criteria for dosage modification and treatment 
delays or discontinuation, have been provided (see Section 5.1.7).
5.1.1
Risks Associated with Obinutuzumab
The following adverse events are considered to be important risks associated or 
potentially associated with obinutuzumab:  IRRs and hypersensitivity reactions, TLS, 
thrombocytopenia (including acute thrombocytopenia), neutropenia (including prolonged 
and late onset neutropenia), infections (including PML and HBV reactivation), prolonged 
B-cell depletion, impaired immunization response, worsening of preexisting cardiac 
conditions, GI perforation, immunogenicity, and second malignancies.  These events, 
with the exception of prolonged B-cell depletion, immunogenicity, and second 
malignancies, are described below.
5.1.1.1
Infusion-Related Reactions and Hypersensitivity Reactions
IRRs have been reported predominantly during the first infusion of obinutuzumab.  The 
incidence and severity of IRRs decreased substantially with the second and subsequent 
infusions.  In the majority of patients, IRRs were mild or moderate and resolved with the 
slowing or interruption of the infusion and supportive care.  The commonly experienced 
IRRs have been characterized by hypotension, fever, chills, dyspnea, flushing, nausea, 
vomiting, hypertension, fatigue, headache, tachycardia, dizziness, diarrhea, and other 
symptoms.  
IRRs may be clinically indistinguishable from IgE-mediated allergic or anaphylactic 
reactions; anaphylaxis has been reported in patients treated with obinutuzumab.  
Hypotension may occur during obinutuzumab IV infusions.  Therefore, withholding of 
anti-hypertensive treatments should be considered for 12 hours prior to and throughout 

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each obinutuzumab infusion and for the first hour after administration.  Patients at acute 
risk of hypertensive crisis should be evaluated for the benefits and risks of withholding 
their anti-hypertensive medication.
Patients who have preexisting cardiac or pulmonary conditions should be monitored 
carefully throughout the infusion and the postinfusion period.
Guidelines for medical management of IRRs and anaphylaxis are provided in 
Section 5.1.7.3 and Appendix 12.
Hypersensitivity reactions with immediate (e.g., anaphylaxis) and delayed onset 
(e.g., serum sickness) have been reported in patients treated with obinutuzumab.  
Hypersensitivity reactions typically occur after previous exposure and very rarely with the 
first infusion.  In the case a hypersensitivity reaction is suspected during or after an 
infusion, the infusion should be stopped and treatment permanently discontinued.
5.1.1.2
Tumor Lysis Syndrome
TLS, including fatal events, has been reported with obinutuzumab administration.  
Patients at risk for TLS (e.g., because of bulky disease or renal insufficiency) should 
receive adequate hydration and premedication with allopurinol or an alternative 
uricostatic agent as indicated in Section 4.3.2.9 (see Table 9).  Additional guidelines for 
management of TLS in this study are provided in Section 5.1.7.2 (see Table 14).
5.1.1.3
Neutropenia
Grade 3 or 4 neutropenia, including febrile neutropenia, has been reported with 
obinutuzumab administration.  Neutropenia resolved spontaneously or with use of 
hematopoietic growth factors.  Patients who experience Grade 3 or 4 neutropenia 
should be closely monitored until neutrophil values return to at least Grade 2.  Cases of 
late-onset neutropenia (ANC1000 cells/L occurring28 days after obinutuzumab 
treatment has been completed or stopped) or prolonged neutropenia 
(ANC1000 cells/L that does not resolve after 28 days without obinutuzumab treatment) 
have also been reported.  The use of G-CSF is allowed for treatment of neutropenia in 
this study.  Prophylactic treatment with antibiotics should be administered as per 
standard practice.  Guidelines for primary prophylaxis with G-CSF are provided in 
Section 4.4.1.  
5.1.1.4
Thrombocytopenia
Severe and life-threatening thrombocytopenia, including acute thrombocytopenia 
(occurring within 24 hours after the infusion), has been observed during treatment with 
obinutuzumab.  In CLL patients exposed to obinutuzumab, fatal hemorrhagic events 
have also been reported in Cycle 1.  A clear relationship between thrombocytopenia and 
hemorrhagic events has not been established.  Patients receiving concomitant 
medication that could possibly worsen thrombocytopenia related events (e.g., platelet 
inhibitors and anticoagulants) may be at greater risk of bleeding.  When possible, 

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replace prior vitamin K antagonist therapy with LMWH prior to Day 1 of Cycle 1.  
Patients should be closely monitored for thrombocytopenia, especially during the first 
cycle.  For patients who experience thrombocytopenia, regular laboratory tests should 
be performed until the event resolves, and dose delays should be considered in case of 
severe or life-threatening thrombocytopenia.  Transfusion of blood products (i.e., platelet 
transfusion) may be performed at the discretion of the treating physician, according to 
institutional practice.  
5.1.1.5
Infections
On the basis of its mechanism of action, resulting in profound B-cell depletion, 
obinutuzumab may be associated with an increased risk of infections.  Obinutuzumab 
should not be administered to patients with active infection, and caution should be 
exercised when including patients with a history of recurrent or chronic infections.  
Serious bacterial, fungal, and new or reactivated viral infections can occur during and 
following the completion of obinutuzumab therapy.  Fatal infections have been reported.
In the FL studies, a high incidence of infections was observed in all phases of the 
studies, including follow-up, with the highest incidence seen during maintenance.  
Details are provided in the Obinutuzumab Investigator’s Brochure.
Reactivation of hepatitis B in patients with chronic hepatitis (HBsAg positive) with 
evidence of prior hepatitis B exposure, or in patients who are carriers (HBsAg negative 
and HBcAb positive) has been reported with other anti-CD20 antibodies.  The risk is 
increased particularly when anti-CD20 antibodies are administered with 
immunosuppressive therapies, such as steroids or chemotherapy.  Patients positive for 
HBsAg and HBcAb are not eligible for this study.
John Cunningham (JC) viral infection resulting in PML has been reported in patients 
treated with obinutuzumab.  The diagnosis of PML should be considered in any patient 
presenting with new-onset neurologic manifestations.  The symptoms of PML are 
unspecific and can vary depending on the affected region of the brain.  Motor symptoms 
with corticospinal tract findings (e.g., muscular weakness, paralysis, and sensory 
disturbances), sensory abnormalities, cerebellar symptoms, and visual field defects are 
common.  Some signs or symptoms regarded as “cortical” (e.g., aphasia or visual-spatial 
disorientation) may occur.  Evaluation of PML includes, but is not limited to, consultation 
with a neurologist, brain MRI, and lumbar puncture (cerebrospinal fluid testing for 
JC viral DNA).  Additional guidelines for medical management of PML in this study are 
provided in Table 13.
5.1.1.6
Immunizations
The safety of immunization with live virus vaccines following obinutuzumab therapy has 
not been studied.  Thus, vaccination with live virus vaccines is not recommended during 
treatment and until B-cell recovery.

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5.1.1.7
Worsening of Preexisting Cardiac Condition
In patients with underlying cardiac disease and treated with obinutuzumab, adverse 
events such as angina pectoris, acute coronary syndrome, myocardial infarction, heart 
failure, and arrhythmias, including atrial fibrillation and tachyarrhythmia, have been 
observed.  These events may occur as part of an IRR and can be fatal.  Therefore, 
patients with a history of cardiac disease should be monitored closely.  In addition, these 
patients should be hydrated with caution to prevent a potential fluid overload.
5.1.1.8
Gastrointestinal Perforation
GI perforation has been reported in patients treated with obinutuzumab, mainly in NHL, 
including fatal events.  Patients with GI involvement should be monitored for signs of 
GI perforation.
5.1.2
Risks Associated with Rituximab
The following adverse events are considered to be important risks associated or 
potentially associated with rituximab:  IRRs, infections (including PML and HBV 
reactivation), neutropenia (including prolonged), rTLS, impaired immunization response, 
GI perforation, and severe mucotanous reactions.  Details for some of these risks are 
provided below; refer to Rituximab Investigator’s Brochure for full information.
5.1.2.1
Infusion-Related Reactions
Acute IRRs are very common in patients receiving rituximab (occurring in 10% of 
patients) based on clinical trial experience. However, serious IRRs are uncommonly 
reported (occurring in 1/1,000 and 1/100 patients) and are rarely fatal (occurring in 
1/10,000 and 1/1,000 patients). Most IRRs occur with the first administration of 
rituximab. Rituximab-induced IRRs consist of a cluster of symptoms and signs occurring 
during or within 24 hours of a rituximab infusion. These are related to cytokine release,
and these acute IRRs overlap with “cytokine release syndrome”. Anaphylactic and other 
hypersensitivity reactions also occur following rituximab administration, and clinical 
manifestations of these reactions are similar to cytokine release syndrome. In contrast 
to cytokine release syndrome, true hypersensitivity reactions typically occur within 
minutes of starting the rituximab infusion.
5.1.2.2
Infections (Including Serious Infections)
Serious infections, including fatal bacterial, fungal, and new or reactivated viral 
infections, can occur during and up to 1 year following completion of rituximab-based 
therapy.  New or reactivated viral infections include cytomegalovirus, herpes simplex 
virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis B and C 
viruses.
5.1.2.3
Neutropenia
Neutropenia is very common in patients receiving rituximab (occurring in 10% of 
patients) based on clinical trial experience. However, delayed onset neutropenia is very 
rare (occurring in 1/10,000 patients), and the incidence of prolonged neutropenia is 

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unknown. Neutropenia may lead to serious or overwhelming infection, especially if 
profound (Grade 3/4), prolonged, associated with breaches in natural mucosal barriers 
(e.g., diarrhea and/or mucositis), and/or other immunological defects (e.g., lymphopenia, 
hypogammaglobulinemia, acquired immunodeficiency syndrome). Despite an increase 
in incidence of neutropenia and Grade 3/4 neutropenia associated with rituximab, most 
studies have not reported a significant increase in serious neutropenic infections.
5.1.2.4
Tumor Lysis Syndrome
Patients treated with rituximab may be at risk for TLS.  Severe tumor TLS is very rare in 
patients receiving rituximab (occurring in 1/10,000 patients), based on postmarketing 
experience. Signs and symptoms (e.g. hyperuricemia, hyperkalemia, hypocalcemia, 
hyperphosphatemia, acute renal failure, and elevated LDH) that are consistent with TLS 
have been reported to occur after the first MabThera/Rituxan IV infusion in patients with 
high numbers of circulating malignant lymphocytes.  A high number of circulating 
malignant cells (25,000/mm3) or high tumor burden confers a greater risk of TLS.  For 
patients with evidence of TLS, rituximab should be discontinued, and the patient should 
be treated as clinically indicated.
5.1.2.5
Hepatitis B Reactivation
Reactivation of hepatitis B ranges from asymptomatic reactivations (detected by 
changes in laboratory parameters only) to fulminant liver failure and death. Patients with 
chronic hepatitis B (HBsAg positive) viral infection are at risk for reactivation and will be 
excluded from the study.  Patients with evidence of prior hepatitis B exposure or who are 
carriers (defined as HBsAg negative and anti-HBcAb positive) are at a lower risk for 
reactivation.  Patients who demonstrate evidence of reactivation while receiving an 
appropriate anti-viral therapy will be discontinued from study treatment.
5.1.2.6
Progressive Multifocal Leukoencephalopathy
Rare cases of PML have also been reported in patients treated with rituximab alone or in 
combination with other immunosuppressive medications (Goldberg et al. 2002; 
Calabrese et al. 2007; Carson and Bennett 2009).  In a review of 57 patients who 
developed PML after rituximab administration, all patients had received prior therapies 
with alkylating agents, corticosteroids, purine analogs, or drugs to prevent allogeneic 
stem cell or solid-organ graft rejection.  The diagnosis of PML in any patient treated with 
rituximab is rare, but it should be suspected in any patient who develops new-onset 
neurologic manifestations.  The majority of patients with hematologic malignancies 
diagnosed with PML received rituximab in combination with chemotherapy or as part of a 
hematopoietic SCT.  Most cases of PML were diagnosed within 12 months of the 
patients’ last infusion of rituximab.
5.1.2.7
Severe Mucocutaneous Reactions
Severe reactions, including fatal mucocutaneous reactions, can occur in patients 
receiving rituximab.  These reactions include paraneoplastic pemphigus, 
Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic 

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epidermal necrolysis (TEN).  The onset of these reactions in patients treated with 
rituximab has varied from 113 weeks following rituximab exposure.
5.1.2.8
Gastrointestinal Perforation
Abdominal pain, bowel obstruction, and perforation, in some cases leading to death, 
can occur in patients receiving rituximab in combination with chemotherapy. 
In postmarketing reports of rituximab, the mean time to documented GI perforation was 
6 days (range:  177 days) in patients with NHL.
5.1.3
Risks Associated with Atezolizumab
Atezolizumab has been associated with risks such as the following:  IRRs and 
immune-related hepatitis, pneumonitis, colitis, pancreatitis, diabetes mellitus, 
hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, Guillain-Barré
syndrome, myasthenic syndrome or myasthenia gravis, meningoencephalitis, 
myocarditis, and nephritis. In addition, systemic immune activation is a potential risk 
when atezolizumab is given in combination with other immunomodulating agents.  Refer 
to Section 6 of the Atezolizumab Investigator's Brochure for a detailed description of 
anticipated safety risks for atezolizumab.
Guidelines for management of atezolizumab-associated non-hematologic toxicity are 
provided in Table 14 and Table 15.
5.1.4
Risks Associated with Bendamustine
5.1.4.1
Myelosuppression
Bendamustine caused severe myelosuppression (Grade3) in 98% of patients in the two 
bendamustine single-agent studies (Friedberg et al. 2008; Kahl et al. 2010).  
Hematologic nadirs were observed predominantly in the third week of therapy.  Patients 
who experience Grade 3 or 4 neutropenia or thrombocytopenia should be monitored 
until neutrophil and platelet values return to at least Grade 2.  The use of G-CSF for 
primary prophylaxis and treatment of neutropenia is permitted in this study.  
Myelosuppression may require dose delays and/or subsequent dose reductions if 
recovery to the recommended values has not occurred by the first day of the next 
scheduled cycle.  Guidelines for management of hematologic toxicities are provided in 
Section 5.1.7.2.
5.1.4.2
Infection
Infection, including pneumonia and sepsis, has been reported with bendamustine 
administration.  Patients with myelosuppression after treatment with bendamustine are 
more susceptible to infections.  The study physician will treat patients with clinical 
evidence of infection appropriately.

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5.1.4.3
Infusion-Related Reactions and Anaphylaxis
Infusion reactions to bendamustine have occurred commonly in clinical trials.  Symptoms 
include fever, chills, pruritus, and rash.  In rare instances, severe anaphylaxis and 
anaphylactoid reactions have occurred, particularly in the second and subsequent cycles 
of therapy.  
5.1.4.4
Tumor Lysis Syndrome
TLS has been reported in association with bendamustine treatment in clinical trials and 
in postmarketing reports.  The onset tends to be within the first treatment cycle of 
bendamustine and, without intervention, may lead to acute renal failure and death.  
Patients at risk for TLS (e.g., because of bulky disease or renal insufficiency) should 
receive adequate hydration and premedication with allopurinol or an alternative 
uricostatic agent as indicated in Section 4.3.2.9 (see Table 9).  Additional guidelines for 
management of TLS in this study are provided in Section 5.1.7.3 (see Table 15).
5.1.4.5
Skin Reactions
Skin reactions have been reported with bendamustine treatment, including rash, toxic 
skin reactions, and bullous exanthema.  In a study of bendamustine in combination with 
rituximab, one case of TEN occurred.  Cases of Stevens−Johnson syndrome and TEN, 
some fatal, have been reported when bendamustine was administered concomitantly 
with allopurinol and other medications known to cause these syndromes.  The 
relationship to bendamustine cannot be determined.  Patients with skin reactions should 
be monitored closely.  If skin reactions are severe or progressive, bendamustine should 
be withheld.
5.1.4.6
Long-Term Stem-Cell Toxicity
There are reports of premalignant and malignant diseases that have developed in 
patients treated with bendamustine, including myelodysplastic syndrome, 
myeloproliferative disorders, acute myeloid leukemia, and bronchial carcinoma.  The 
association with bendamustine therapy has not been determined.
5.1.4.7
Extravasation Injury
Bendamustine extravasations have been reported, resulting in hospitalizations from 
erythema, marked swelling, and pain.  Precautions should be taken to avoid
extravasation, including monitoring of the IV infusion site for redness, swelling, pain, 
infections, and necrosis during and after administration of bendamustine.
5.1.4.8
Drug Interactions
Certain medications may interact with bendamustine.  Caution should be used or 
alternative treatments should be considered if concomitant treatment with cytochrome 
P450 (CYP)1A2 inhibitors or inducers is needed.  CYP1A2 inhibitors and inducers are 
not contraindicated.

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During treatment with bendamustine, patients will be provided with a card to keep with 
them that provides notification to other health care providers that the patient is taking 
bendamustine as a participant in a clinical study (see Appendix 13).
5.1.5
Risks Associated with CHOP
Refer to prescribing information for doxorubicin, cyclophosphamide, vincristine, and 
prednisone for risks related to CHOP chemotherapy.
5.1.6
Risk of Overlapping Toxicities
The anticipated toxicities from the combined administration of atezolizumab and 
obinutuzumab, with either CHOP or bendamustine, and of atezolizumab with rituximab 
and CHOP are expected to be manageable in this clinical trial.  A summary of 
anticipated overlapping toxicities is presented in Table 11.
Obinutuzumab was safely combined with CHOP in patients with previously untreated 
DLBCL (n 100) or relapsed or refractory FL (n38), and with bendamustine in patients 
with previously untreated FL (n 37).  Neutropenia and infections (mainly neutropenic 
infections) appeared to be the most important adverse events associated with these 
combinations but were manageable with prophylactic administration of G-CSF and 
appropriate management of infections (Dyer et al. 2012; Zelenetz et al. 2013).  
Rituximab in combination with CHOP is the standard of care in previously untreated 
DLBCL and is generally well tolerated, with the main toxicities being myelosuppression 
and infections.
There is no anticipated risk of overlapping hematologic toxicity when combining 
atezolizumab with G-CHOP, R-CHOP, or G-benda.  Thus, the Atezo-G-CHOP, 
Atezo-R-CHOP, and Atezo-G-benda regimens will likely be associated with a 
manageable risk of myelosuppression and infections in the clinical setting.  In addition to 
the standard hematologic monitoring, patients enrolled in this study will be closely 
monitored for evidence of infections. 
Atezolizumab has a minimal risk of overlapping non-hematologic toxicity with G-CHOP, 
R-CHOP, and G-benda, limited to potentially increased risk of IRRs, GI toxicity (nausea, 
vomiting, and diarrhea), dermatologic reactions, and impaired liver function.  These risks 
will be addressed by standard monitoring for IRRs, premedication for nausea/vomiting, 
and close clinical monitoring for any evidence of skin reactions, diarrhea, or hepatic 
abnormalities.  The potential risk of increased liver toxicity is substantially mitigated by 
excluding patients who are positive for HBV and HCV from enrollment in the study.

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Table 11 Summary of Potentially Overlapping Adverse Events
Event
Atezolizumab a
Obinutuzumab b,c
Rituximab b
G-CHOP d
R-CHOP d
G-Benda e
Hematologic Toxicity
Neutropenia, Grade 3 or 4
0
5%14%
7%
46.2%
38.1%
29%
Febrile neutropenia
0
2%5%
1%
17.5%
15.2%
5.3%
Thrombocytopenia, Grade 3 or 4
0
5%8%
0
4.4% 
1.4%
10%
Anemia, Grade 3 or 4
4.6%
3%
1%
7.2%
7.5%
7%
Non-Hematologic Toxicity
IRRs
All grades
1.2% 
73%75%
51%
36%
23.5%
59%
Grade 3 or 4
0
11%
5%
2.8%
0.6%
10%
Infections
All grades
0
5%41%
49%
53.8%
44%
15%
Grade 3 or 4
0
3%10%
6%
19.2% f
15.5% f
10%
Rash
All grades
13%
7% 
3%
2.3%
6.4%
12%
Grade 3 or 4
0
0
0
0.1%
0.1%
Diarrhea
All grades
22.4% g
5%8%
8%
16%
13%
34%
Grade 3 or 4
0
0
0
2.1%
1.3%
2%
Vomiting
All grades
19.7%
5%
3%
14.6%
10.5%
15%
Grade 3 or 4
0.2%
0
0
1%
0.3%
0

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Table 11 Summary of Potentially Overlapping Adverse Events (cont.)
Event
Atezolizumab a
Obinutuzumab b,c
Rituximab b
G-CHOP d
R-CHOP d
G-Benda e
Nausea
All grades
27.8%
5%9%
8%
29.4%
28.3%
56%
Grade 3 or 4
0.2%
0
0
1.8%
0.3%
5%
SGOT/SGPT 
increase
Grade 3 or 4
1.7% g
3%
1%
1%
1%
0
G-Bendaobinutuzumab plus bendamustine; G-CHOP obinutuzumab plus CHOP chemotherapy; R-CHOPrituximab plus CHOP 
chemotherapy.
a Atezolizumab Investigator’s Brochure, Version 9, August 2016.
b BO21003 CSR (No. 1056428).
c BO20999 CSR (No. 1036614) (high dose, NHL cohorts).
d Study BO21005/Outputs dated 14 July 2016.
e BO21000 CSR (No. 1051870) (adverse events during induction).
f
The most frequent Grade 34 infection was pneumonia (4%).
g Grade 2 immune colitis and Grade 3 or 4 immune hepatitis were documented in 0.4% and 0.7% of patients, respectively.

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5.1.7
Management of Specific Adverse Events
Patients should be assessed clinically before each study treatment administration.  
Guidelines for management of toxicities are based on laboratory values obtained within 
72 hours prior to Day 1 of each cycle or within 24 hours prior to Days 8 and 15 of 
Cycle 1.  Dosing will occur only if a patient’s clinical assessment and laboratory test 
values are acceptable.  
There will be no dose reductions of obinutuzumab, rituximab, or atezolizumab.  Study 
treatment may be delayed for toxicity for a maximum amount of time, as specified in the 
tables below.  If study treatment is delayed for longer than the specified maximum, study 
treatment will be permanently discontinued.  Treatment delays apply to all toxicities 
described below; dose modifications apply only to toxicities that are considered to be 
related to any of the study treatment components.  Toxicities that occur during the cycle 
and subside prior to the next cycle should not trigger the suggested dose modifications.
Guidelines for management of toxicities during induction treatment are provided in 
Section 5.1.7.2.  Guidelines for management of toxicities during consolidation or 
maintenance treatment are provided in Section 5.1.7.3.
5.1.7.1
Systemic Immune Activation
Systemic immune activation is a rare condition characterized by an excessive immune 
response. Given the mechanism of action of atezolizumab, this condition is considered 
a potential risk when given in combination with other immunomodulating agents.  
Systemic immune activation should be included in the differential diagnosis for patients 
who, in the absence of an alternative etiology, develop a sepsis-like syndrome after 
administration of atezolizumab, and the initial evaluation should include the following:

CBC with peripheral smear

PT, PTT, fibrinogen, and D-dimer

Ferritin

Triglycerides

AST, ALT, and total bilirubin

LDH

Complete neurologic and abdominal examination (assess for hepatosplenomegaly)
If systemic immune activation is still suspected after the initial evaluation, contact the 
Medical Monitor for additional recommendations.
5.1.7.2
Toxicities during Induction Treatment
Hematologic Toxicities during Induction Treatment
Table 12 provides guidelines for management of hematologic toxicities that occur during 
induction treatment, with the exception of toxicities identified or ongoing at administration 
of obinutuzumab on Day 8 or 15 or atezolizumab on Day 15.  Table 13 provides 

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guidelines for management of hematologic toxicities that are identified or ongoing at 
administration of obinutuzumab on Day 8 or 15 or atezolizumab on Day 15 when 
patients are to receive treatment with obinutuzumab or atezolizumab only.  Hematologic 
toxicity is defined as neutropenia, anemia, or thrombocytopenia.  Lymphopenia is not 
considered hematologic toxicity, but an expected outcome of therapy.  

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Table 12 Guidelines for Management of Hematologic Toxicities during 
Induction Treatment (Except at Administration of Obinutuzumab 
on Day 8 or 15 or Atezolizumab on Day 15)
Event
Action to Be Taken
Grade 3 or 4 
hematologic 
toxicity a,b,c
For patients who have had one or no prior chemotherapy dose reductions:

Withhold study treatment. a

Administer RBCs or platelets as required.

If patient has not already initiated G-CSF, initiate prophylactic G-CSF for 
current and subsequent cycles.

For patients who develop platelet count of 20,000/L while receiving LMWH, 
reduce the dose of LMWH.  For patients who develop platelet count 
of 20,000/L while receiving platelet inhibitors, consider temporarily 
withholding platelet inhibitors.

If improvement to Grade2 or baseline within 7 days after the scheduled date 
for the next cycle in patients with DLBCL or within 13 days after the scheduled 
date for the next cycle in patients with FL, resume obinutuzumab/rituximab and 
atezolizumab at full dose and resume chemotherapy components at current 
dose.

If improvement to Grade2 or baseline 814 days after the scheduled date for 
the next cycle in patients with DLBCL or 1421 days after the scheduled date 
for the next cycle in patients with FL, resume obinutuzumab/rituximab and 
atezolizumab at full dose and resume chemotherapy components at a reduced 
dose a,b for current and subsequent cycles as outlined below:
First reduction
–
Atezo-G-CHOP or Atezo-R-CHOP:  Decrease cyclophosphamide dose to 
500 mg/m2 and doxorubicin dose to 35 mg/m2.
–
Atezo-G-benda:  Decrease bendamustine dose to 70 mg/m2.
Second reduction
–
Atezo-G-CHOP or Atezo-R-CHOP:  Decrease cyclophosphamide dose to 
375 mg/m2 and doxorubicin dose to 25 mg/m2.
–
Atezo-G-benda:  Decrease bendamustine dose to 50 mg/m2.
No more than two dose reductions of chemotherapy are allowed.

If study treatment is withheld for 14 days in patients with DLBCL or for 
21 days in patients with FL, permanently discontinue study treatment.
For patients who have had two prior chemotherapy dose reductions:

Permanently discontinue study treatment.
Atezoatezolizumab; bendabendamustine; CHOPcyclophosphamide, doxorubicin, 
vincristine, and prednisone; DBLCLdiffuse large B-cell lymphoma; FLfollicular lymphoma; 
Gobinutuzumab; G-CSFgranulocyte colony-stimulating factor; LMWHlow-molecular-weight 
heparin NHLnon-Hodgkin's lymphoma; Rrituximab.
a Treatment delays apply to all toxicities; dose modifications apply only to toxicities that are 
considered to be related to any of the study treatment components.  Toxicities that occur 
during the cycle and subside prior to the next cycle should not trigger the suggested dose 
modifications.
b If cytopenia is thought to be caused mainly by NHL infiltration of the bone marrow, the 
investigator may decide not to reduce the chemotherapy doses.

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Table 13 Guidelines for Management of Hematologic Toxicities during 
Induction Treatment at Administration of Obinutuzumab on Day 8 
or 15 or Atezolizumab on Day 15
Event
Action to Be Taken
Febrile 
neutropenia or 
neutropenia with 
infection

Withhold obinutuzumab and atezolizumab until resolution of fever and 
infection (as applicable).

If the event is ongoing on Day 1 of the subsequent cycle, follow 
instructions in Table 12.
Note:  Obinutuzumab and atezolizumab should not be withheld for 
asymptomatic neutropenia.
Severe 
thrombocytopenia a
or bleeding

Withhold obinutuzumab and atezolizumab until platelet count 50,000/μL 
and resolution of bleeding.

If receiving LMWH, reduce the dose.

If receiving platelet inhibitors, consider temporarily withholding platelet 
inhibitors.

If the event is ongoing on Day 1 of the subsequent cycle, follow 
instructions in Table 12.
LMWHlow-molecular-weight heparin.
a Severe thrombocytopenia is defined as a platelet count10,000/L for patients who are not 
receiving concomitant anticoagulants or platelet inhibitors and20,000/L for patients who are 
receiving concomitant anticoagulants or platelet inhibitors.
Non-Hematologic Toxicities during Induction Treatment
Table 14 provides guidelines for management of non-hematologic toxicities that occur 
during induction treatment.

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Table 14 Guidelines for Management of Non-Hematologic Toxicities
Event
Action to Be Taken
General guidance for treatment 
delays and discontinuation

For patients receiving obinutuzumab, if toxicity occurs before Cycle 1 Day 8 or Cycle 1 Day 15, these doses 
of obinutuzumab will not be skipped but given after resolution of toxicity.

If study treatment is withheld for 21 days in patients with FL and > 14 days in patients with DLBCL because 
of a toxicity that is attributable to obinutuzumab/rituximab and/or chemotherapy, permanently discontinue all 
study treatment.

When a treatment cycle is delayed because of toxicity resulting from any component of the regimen, all study 
treatment should generally be held and resumed together to remain synchronized.  However, if it is 
anticipated that atezolizumab will be delayed by 21 days in patients with FL and > 14 days in patients with 
DLBCL, obinutuzumab/rituximab and chemotherapy should be given without atezolizumab if there is no 
contraindication. 

Toxicities associated or possibly associated with atezolizumab treatment should be managed according to 
standard medical practice.  Additional tests, such as autoimmune serology or biopsies, should be used to 
evaluate for a possible immunogenic etiology.  For detailed information regarding management of adverse 
events associated with atezolizumab, please refer to the Atezolizumab Investigator’s Brochure.

If a life-threatening immune-related toxicity occurs, or if atezolizumab is withheld for 42 days because of an 
immune-related toxicity, permanently discontinue atezolizumab, unless approval for continued treatment is 
granted by the Medical Monitor.

If atezolizumab is permanently discontinued because of toxicity solely attributable to atezolizumab, 
obinutuzumab/rituximab and chemotherapy may be continued at the investigator's discretion if agreed to by 
the Medical Monitor.
IRRs and anaphylaxis

Guidelines for the management of IRRs are provided in Section 4.3.2.1 for obinutuzumab and rituximab and 
Section 4.3.2.2 for atezolizumab.  Anaphylaxis precautions are provided in Appendix 12. 

Metamizole (dipyrone) is prohibited in treating atezolizumab-associated IRRs because of its potential for 
causing agranulocytosis.

In case of anaphylaxis, study treatment should be permanently discontinued.
Systemic immune activation

Follow guidance in Section 5.1.7.1 and Atezolizumab Investigator’s Brochure
TLS

Withhold study treatment.

Perform chemistry panel on a regular bases during the first week a

Correct electrolyte abnormalities, monitor renal function, cardiac function and fluid balance, and administer 
supportive care, including dialysis as indicated.  Rasburicase therapy (if approved by the local health 
authority) may be administered as needed to reduce hyperuricemia.

If symptoms have resolved completely, resume obinutuzumab/rituximab and atezolizumab at full dose and 
resume chemotherapy components at current dose.

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Table 14 Guidelines for Management of Non-Hematologic Toxicities (cont.)
Event
Action to Be Taken
Hemorrhagic cystitis

Withhold Atezo-G-CHOP or Atezo-R-CHOP a

If improvement to Grade1, resume Atezo-G-CHOP or Atezo-R-CHOP with the cyclophosphamide dose 
decreased to 500 mg/m2 (no modifications for other treatment components). a  Mesna and hydration during 
the next administration of cyclophosphamide is recommended.

If symptoms do not recur, cyclophosphamide dose may be increased to 750 mg/m2 for subsequent cycles.
Peripheral 
neuropathy
Grade 4 or 
Myasthenia gravis 
(any grade) or 
Guillain-Barre (any 
grade)

Permanently discontinue study treatment.
Grade 2 or 3

Withhold Atezo-G-CHOP or Atezo-R-CHOP. a

If improvement to Grade 1 or baseline, resume Atezo-G-CHOP or Atezo-R-CHOP with the vincristine dose 
decreased to 0.7 mg/m2 (maximum, 1 mg) for current and subsequent cycles (no modifications for other 
treatment components). a

Permanently discontinue atezolizumab for life-threatening immune-related neuropathy.
New-onset neurologic 
manifestations suggestive of PML

Withhold study treatment. a

Consult with a neurologist if PML is suspected (refer to Section 5.1.1.5 for guidance on investigations).

If PML is ruled out, resume obinutuzumab and atezolizumab or atezolizumab and rituximab at full dose and 
resume chemotherapy components at current dose. 

If PML is confirmed, permanently discontinue study treatment. 
Immune-related 
meningoencephalitis

Withhold study treatment.

Refer patient to neurologist.

Initiate treatment with 12 mg/kg/day IV methylprednisolone or equivalent and convert to 12 mg/kg/day oral 
prednisone or equivalent upon improvement.  If event does not improve within 48 hours after initiating 
corticosteroids, consider adding an immunosuppressive agent.

If event resolves to Grade 1:
–Resume obinutuzumab/rituximab at full dose and chemotherapy components at current dose.
–
Taper corticosteroids over 1 month.  Contact the Medical Monitor before resuming atezolizumab.

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Table 14 Guidelines for Management of Non-Hematologic Toxicities (cont.)
Event
Action to Be Taken
AST, ALT, or 
bilirubin 
increase
Grade 3 
(or10ULN for 
patients with 
liver 
involvement)

Withhold study treatment a and monitor liver enzymes at least every 7 days.

Investigate etiology.  Consult with a hepatologist if immune etiology is suspected (refer to the Atezolizumab 
Investigator's Brochure for guidance in case of suspected immune-related hepatitis).

For immune-related hepatopathy:
–Treat with corticosteroids following guidance provided in the Atezolizumab Investigator’s Brochure
–Permanently discontinue atezolizumab
–Obinutuzumab/rituximab may be resumed at full dose and chemotherapy components at reduced dose for 
current and subsequent cycles as specified below, at investigator’s discretion and after approval by the 
Medical Monitor. 

If immune etiology is unlikely and there is improvement to Grade1, resume obinutuzumab/rituximab and 
atezolizumab at full dose and resume chemotherapy components at a reduced dose a for current and 
subsequent cycles as outlined below:
–Atezo-G-CHOP or Atezo-R-CHOP:  Decrease cyclophosphamide dose to 500 mg/m2 and doxorubicin dose 
to 35 mg/m2.
–Atezo-G-benda:  Decrease bendamustine dose to 70 mg/m2.

Permanently discontinue study treatment for life-threatening liver toxicity.
Grade 2 lasting
57 days

Withhold atezolizumab.

If immune etiology is suspected, treat with corticosteroids according to guidance provided in the 
Atezolizumab Investigator’s Brochure.

If there is improvement to Grade 1, resume atezolizumab after corticosteroids have been tapered over 
1 month to 10 mg/day of oral prednisone or equivalent.  Contact Medical Monitor before resuming 
atezolizumab.

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Table 14 Guidelines for Management of Non-Hematologic Toxicities (cont.)
Event
Action to Be Taken
Amylase or 
lipase increase 
Grade 3 with 
or without 
abdominal pain
Grade 3

Withhold study treatment. a

Investigate etiology.  Consult with a gastroenterologist if immune etiology is suspected.

In cases of isolated increase of lipase or amylase that is asymptomatic and considered related to 
atezolizumab, obinutuzumab/rituximab and chemotherapy components treatment may be continued at 
current dose at the investigator’s discretion and in discussion with the Medical Monitor.

Treat with corticosteroids following guidance provided in the Atezolizumab Investigator’s Brochure. 

If improvement to Grade 2 and patient is asymptomatic, resume obinutuzumab/rituximab at full dose and 
resume chemotherapy components at current dose.  Atezolizumab may be resumed if approved by the 
Medical Monitor.
Note:  If pancreatitis is treated with corticosteroids, atezolizumab should not be resumed until the 
corticosteroids have been tapered to10 mg/day of prednisone or equivalent.

Permanently discontinue atezolizumab for recurrent Grade 4 amylase/lipase elevations. For recurrent 
Grade 3 lipase or amylase increase that is isolated and asymptomatic, atezolizumab may be resumed 
following an individual benefit/risk assessment and in discussion with the Medical Monitor.
Grade 2 long 
lasting 
(e.g., > 3 weeks)

Continue study treatment.

Consider oral prednisone 10 mg daily or equivalent.
Ocular toxicity 
Grade 3 or 4

Withhold study treatment. a

Investigate etiology.  Consult with an ophthalmologist.

Treat immune-related toxicity attributable to atezolizumab with systemic corticosteroids following guidance 
provided in the Atezolizumab Investigator’s Brochure. 

If improvement to Grade 1, resume obinutuzumab/rituximab at full dose and chemotherapy components at 
current dose.

Permanently discontinue atezolizumab.
Grades 1 or 2

Consult with an ophthalmologist.

Treat with topical corticosteroid eye drops.  Topical immunosuppressive therapy may also be considered.

Discontinue atezolizumab if symptoms persist.

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Table 14 Guidelines for Management of Non-Hematologic Toxicities (cont.)
Event
Action to Be Taken
Diarrhea/Colitis
Grade 4

Permanently discontinue study treatment.

Investigate etiology.  Consult with a gastroenterologist (refer to the Atezolizumab Investigator's Brochure for 
guidance on investigations in case of suspected immune-related colitis).

Treat with corticosteroids following guidance provided in the Atezolizumab Investigator’s Brochure.
Grade 2 or 3

Withhold study treatment. a

Investigate etiology.  Consult with a gastroenterologist if immune etiology is suspected (refer to the 
Atezolizumab Investigator's Brochure for guidance in case of suspected immune-related colitis).

Treat immune diarrhea/colitis with corticosteroids following guidance provided in the Atezolizumab 
Investigator’s Brochure.

If diarrhea improves to Grade 1, resume obinutuzumab/rituximab at full dose and resume chemotherapy 
components at a reduced dose a for current and subsequent cycles as outlined below:
–Atezo-G-CHOP or Atezo-R-CHOP:  Decrease cyclophosphamide dose to 500 mg/m2 and doxorubicin dose 
to 35 mg/m2.
–
Atezo-G-benda:  Decrease bendamustine dose to 70 mg/m2.

If immune-related diarrhea/colitis improves to Grade 1 and any colitis has cleared as confirmed by 
sigmoidoscopy (or colonoscopy, if appropriate) with colonic biopsy, resume atezolizumab at full dose.  
Discuss with Medical Monitor before resuming atezolizumab.
Note:  If colitis is treated with corticosteroids, atezolizumab should not be resumed until the corticosteroids 
have been tapered to 10 mg/day of prednisone or equivalent.

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Table 14 Guidelines for Management of Non-Hematologic Toxicities (cont.)
Pulmonary 
event 
Grades 3 or 4

Permanently discontinue atezolizumab and contact Medical Monitor.

Bronchoscopy or BAL is recommended.

Initiate treatment with 12 mg/kg/day oral prednisone or equivalent.

If event does not improve within 48 hours after initiating corticosteroids, consider adding a 
immunosuppressive agent.

If event resolves to Grade 1 or better, taper corticosteroids over 1 month.
Grade 2

Withhold atezolizumab for up to 12 weeks after event onset. b

Refer patient to pulmonary and infectious disease specialists and consider bronchoscopy or BAL.

Initiate treatment with 12 mg/kg/day oral prednisone or equivalent.

If event resolves to Grade 1 or better, resume atezolizumab. c

If event does not resolve to Grade 1 or better while withholding atezolizumab, permanently discontinue 
atezolizumab and contact Medical Monitor. d

For recurrent events, treat as a Grade 3 or 4 event.
Grade 1

Continue atezolizumab and monitor closely.

Re-evaluate on serial imaging.

Consider patient referral to pulmonary specialist.

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Table 14 Guidelines for Management of Non-Hematologic Toxicities (cont.)
Event
Action to Be Taken
Dermatologic 
toxicity:
Grade 4

Permanently discontinue study treatment.
Grade 3
First occurrence:

Withhold study treatment. a  Permanently discontinue rituximab in the event of Stevens-Johnson syndrome or 
toxic epidermal necrolysis.

Investigate etiology.  Consult with a dermatologist.  A biopsy should be considered, unless contraindicated.

Administer oral prednisone 10 mg or equivalent.  If event is unresolved after 4872 hours, administer oral 
prednisone 60 mg or equivalent.

If improvement to Grade 1, resume obinutuzumab/rituximab at full dose and resume chemotherapy 
components at a reduced dose a for current and subsequent cycles as outlined below:
–
Atezo-G-benda:  Decrease bendamustine dose to 70 mg/m2.
Atezolizumab may be resumed at full dose if rash is resolved and systemic corticosteroids dose is 
10 mg/day of oral prednisone or equivalent.  Discuss with the Medical Monitor before resuming 
atezolizumab.
Second occurrence:

Permanently discontinue study treatment.
Grade 1 or 2

Continue study treatment.

Administer symptomatic therapy with antihistamines as needed.

If immune-related toxicity related to atezolizumab is suspected, consider topical steroids and, for Grade 2, 
higher potency topical steroids if rash unresolved.

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Table 14 Guidelines for Management of Non-Hematologic Toxicities (cont.)
Event
Action to Be Taken
Hypothyroidism

Investigate etiology.  Consult with an endocrinologist (refer to the Atezolizumab Investigator's Brochure for 
guidance).

Start thyroid replacement hormone.

Monitor TSH weekly.
Asymptomatic elevation of TSH

Continue study treatment.
Symptomatic elevation of TSH

Withhold study treatment. a

If symptoms are controlled and TSH levels are decreasing, resume obinutuzumab/rituximab and 
atezolizumab at full dose and resume chemotherapy components at current dose.

Permanently discontinue atezolizumab for Grade 3 hypothyroidism.
Hypophysitis 
(panhypopituitarism)
Grade 4

Permanently discontinue atezolizumab and contact Medical Monitor.

Refer patient to endocrinologist.

Perform brain MRI (pituitary protocol).

Initiate treatment with 12 mg/kg/day IV methylprednisolone or equivalent and convert to 12 mg/kg/day oral 
prednisone or equivalent upon improvement.

Initiate hormone replacement if clinically indicated.
Grade 2 or 3 
Withhold atezolizumab.

Refer patient to endocrinologist.

Perform brain MRI (pituitary protocol).

Initiate treatment with 12 mg/kg/day IV methylprednisolone or equivalent and convert to 12 mg/kg/day oral 
prednisone or equivalent upon improvement.

Initiate hormone replacement if clinically indicated.

Resume atezolizumab if event resolves to Grade 1 or better, and patient is stable on replacement therapy 
(if required) within 12 weeks.

If event does not resolve to Grade 1 or better while withholding atezolizumab, permanently discontinue 
atezolizumab and contact Medical Monitor.

For recurrent hypophysitis, treat as a Grade 4 event.

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Table 14 Guidelines for Management of Non-Hematologic Toxicities (cont.)
Event
Action to Be Taken
Hyperthyroidism
For asymptomatic patients with TSH 0.5 mU/L:

Perform TSH, free T4, and T3 tests every 4 weeks.
For asymptomatic patients with TSH 0.5 mU/L or symptomatic patients

Withhold atezolizumab.

Consider consultation with an endocrinologist 

Administer methimazole as needed.

Resume atezolizumab when symptoms are controlled by thyroid hormone replacement.

Permanently discontinue atezolizumab for life-threatening hyperthyroidism.
Hyperglycemia
Grade 34

Withhold atezolizumab.

Initiate treatment with insulin.

Monitor for glucose control.

Resume atezolizumab when symptoms resolve and glucose levels are stable.
Symptomatic 
adrenal 
insufficiency
Grade 24

Withhold atezolizumab.

Refer patient to endocrinologist.

Perform appropriate imaging.

Initiate treatment with 12 mg/kg/day intravenous methylprednisolone or equivalent and convert to 
12 mg/kg/day oral prednisone or equivalent upon improvement.

Resume atezolizumab if event resolves to Grade 1 and patient is stable on replacement therapy 
(if required) within 12 weeks.  If corticosteroids have been initiated, they must be tapered over 1 month to 
10 mg/day oral prednisone or equivalent before atezolizumab can be resumed.  Contact the Medical 
Monitor before resuming atezolizumab.

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Table 14 Guidelines for Management of Non-Hematologic Toxicities (cont.)
Event
Action to Be Taken
Immune-related 
nephritis
Grade 3 or 4

Permanently discontinue study treatment and contact Medical Monitor.

Refer patient to renal specialist.

Consider renal biopsy and supportive measures as indicated.

Corticosteroids and/or additional immunosuppressive agents should be administered as clinically 
indicated.

If event resolves to Grade 1 or better, taper corticosteroids over 1 month.
Grade 2

Withhold atezolizumab for up to 12 weeks after event onset.b  Contact Medical Monitor.

Refer patient to renal specialist.

Consider renal biopsy and supportive measures as indicated.

Corticosteroids and/or additional immunosuppressive agents should be administered as clinically 
indicated.

If event resolves to Grade 1 or better, resume atezolizumab. c

If event does not resolve to Grade 1 or better while withholding atezolizumab, permanently discontinue 
atezolizumab and contact Medical Monitor. d
Grade 1

Continue study treatment.

Monitor kidney function, including creatinine, closely until values resolve to within normal limits or to 
baseline values.

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Table 14 Guidelines for Management of Non-Hematologic Toxicities (cont.)
Event
Action to Be Taken
Immune-related 
myocarditis
Grade 34

Permanently discontinue study treatment and contact Medical Monitor.

Refer patient to cardiologist.

Initiate treatment as per institutional guidelines and consider antiarrhythmic drugs, temporary pacemaker, 
ECMO, or VAD as appropriate.

Initiate treatment with 12 mg/kg/day IV methylprednisolone or equivalent and convert to 12 mg/kg/day 
oral prednisone or equivalent upon improvement.

If event does not improve within 48 hours after initiating corticosteroids, consider adding an 
immunosuppressive agent.

If event resolves to Grade 1 or better, taper corticosteroids over 1 month.
Grade 2

Withhold study treatment.

Initiate treatment as per institutional guidelines and consider antiarrhythmic drugs, temporary pacemaker, 
ECMO, or VAD as appropriate.

Consider treatment with 12 mg/kg/day IV methylprednisolone or equivalent and convert to 12 mg/kg/day 
oral prednisone or equivalent upon improvement.

If event resolves to Grade 1 or better, resume study treatment.

If event does not resolve to Grade 1 or better while withholding atezolizumab, permanently discontinue 
atezolizumab and contact Medical Monitor.
Grade 1

Refer patient to cardiologist.

Initiate treatment as per institutional guidelines.

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Table 14 Guidelines for Management of Non-Hematologic Toxicities (cont.)
Event
Action to Be Taken
Other 
non-hematologic and 
non-immune-related 
toxicities (i.e., not 
described above), 
excluding alopecia, 
nausea, and vomiting 
Grade 3 
or 4
For patients who have had no prior chemotherapy dose reductions:

Withhold study treatment . a

If improvement to Grade1 or baseline, resume obinutuzumab/rituximab and atezolizumab at full dose and 
resume chemotherapy components at a reduced dose a for current and subsequent cycles as outlined below:
–
Atezo-G-CHOP or Atezo-R-CHOP:  Decrease cyclophosphamide dose to 500 mg/m2 and doxorubicin 
dose to 35 mg/m2.
–
Atezo-G-benda:  Decrease bendamustine dose to 70 mg/m2.
For patients who have had one prior chemotherapy dose reduction:
Grade 4 events

Permanently discontinue study treatment.
Grade 3 events

Withhold study treatment. a

If improvement to Grade1 or baseline, resume obinutuzumab/rituximab and atezolizumab at full dose and 
resume chemotherapy components at a reduced dose a for subsequent cycles as outlined below:
–
Atezo-G-CHOP or Atezo-R-CHOP:  Decrease cyclophosphamide dose to 375 mg/m2 and doxorubicin 
dose to 25 mg/m2.
–
Atezo-G-benda:  Decrease bendamustine dose to 50 mg/m2.
No more than two dose reductions of chemotherapy are allowed.
For patients who have had two prior chemotherapy dose reductions:

Permanently discontinue study treatment.
Grade 2

Withhold study treatment. a

If there is improvement to Grade1 or baseline, resume obinutuzumab/rituximab and atezolizumab at full 
dose and resume chemotherapy components at current dose.

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Table 14 Guidelines for Management of Non-Hematologic Toxicities (cont.)
Atezoatezolizumab; bendabendamustine; BALbronchoscopic alveolar lavage; CHOPcyclophosphamide, doxorubicin, vincristine, and 
prednisone; CT computed tomography; DBLCLdiffuse large B-cell lymphoma; ECMOextracorporeal membrane oxygenation; FLfollicular 
lymphoma; Gobinutuzumab; G-CSFgranulocyte colony-stimulating factor; IRR infusion-related reaction; LMWHlow-molecular-weight heparin; 
MRImagnetic resonance imaging; NHLnon-Hodgkin's lymphoma; PMLprogressive multifocal leukoencephalopathy; Rrituximab; 
TSHthyroid-stimulating hormone; VADventricular assist device.
a Treatment delays apply to all events; dose modifications apply only to events that are considered to be related to any of the study treatment 
components.  Toxicities that occur during the cycle and subside prior to the next cycle should not trigger the suggested dose modifications.
For Grade 3 laboratory abnormalities that are isolated, asymptomatic and considered not clinically significant, study treatment may be either 
continued or resumed at the current dose upon improvement to Grade 2, at the investigator’s discretion, following an individual benefit/risk 
assessment. For Grade 2 isolated and asymptomatic laboratory abnormalities, study treatment may be continued at the current dose.
b Atezolizumab may be withheld for a longer period of time (i.e., 12 weeks after event onset) to allow for corticosteroids (if initiated) to be reduced 
to 10 mg/day oral prednisone or equivalent.  The acceptable length of the extended period of time must be agreed upon by the investigator and 
the Medical Monitor.
c If corticosteroids have been initiated, they must be tapered over 1 month to 10 mg/day oral prednisone or equivalent before atezolizumab can 
be resumed.
d Resumption of atezolizumab may be considered in patients who are deriving benefit and have fully recovered from the immune-related event.  
Patients can be re-challenged with atezolizumab only after approval has been documented by both the investigator (or an appropriate delegate) 
and the Medical Monitor.

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5.1.7.3
Toxicities during Consolidation or Maintenance Treatment
Table 15 provides guidelines for management of toxicities that occur during 
consolidation or maintenance treatment.
Table 15 Guidelines for Management of Toxicities That Occur during 
Consolidation or Maintenance Treatment
Event
Action to Be Taken
Hematologic toxicity:
Grade 3 or 4
For all patients:

Atezolizumab may be continued at the discretion of the 
investigator.

Administer G-CSF for neutropenia per institutional guidelines.

Administer RBCs or platelets as required.
For patients receiving obinutuzumab:

Withhold obinutuzumab. a

If improvement to Grade2, resume obinutuzumab at full dose.

If obinutuzumab is withheld for 42 days, permanently discontinue 
study treatment. 
Non-hematologic toxicity:
Grade2
For Atezolizumab-related toxicities with possible immune 
etiology:

Follow guidelines presented in Table 14 for the management of 
atezolizumab-related toxicities with possible immune etiology 
(i.e., autoimmune colitis, hepatitis, pancreatitis, hypothyroidism, 
pneumopathy, skin, toxicity, or ocular toxicity).
For all other non-hematologic toxicities:

Withhold study treatment. a

If improvement to Grade1 or baseline, administer study treatment 
at full dose.

If study treatment is withheld for 42 days, permanently 
discontinue study treatment.
G-CSFgranulocyte colony-stimulating factor.
a Treatment delays apply to all events; dose modifications apply only to events that are 
considered to be related to any of the study treatment components.  Toxicities that occur 
during the cycle and subside prior to the next cycle should not trigger the suggested dose 
modifications.
5.2
SAFETY PARAMETERS AND DEFINITIONS
Safety assessments will consist of monitoring and recording adverse events, including 
serious adverse events and adverse events of special interest, performing 
protocol-specified safety laboratory assessments, measuring protocol-specified vital 
signs, and conducting other protocol-specified tests that are deemed critical to the safety 
evaluation of the study.
Certain types of events require immediate reporting to the Sponsor, as outlined in 
Section 5.4.

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5.2.1
Adverse Events
According to the ICH guideline for GCP, an adverse event is any untoward medical 
occurrence in a clinical investigation subject administered a pharmaceutical product, 
regardless of causal attribution.  An adverse event can therefore be any of the following:

Any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product

Any new disease or exacerbation of an existing disease (a worsening in the 
character, frequency, or severity of a known condition), except as described in 
Section 5.3.5.10

Recurrence of an intermittent medical condition (e.g., headache) not present at 
baseline

Any deterioration in a laboratory value or other clinical test (e.g., ECG, X-ray) that is 
associated with symptoms or leads to a change in study treatment or concomitant 
treatment or discontinuation from study treatment.

Adverse events that are related to a protocol-mandated intervention, including those 
that occur prior to assignment of study treatment (e.g., screening invasive 
procedures such as biopsies)
5.2.2
Serious Adverse Events (Immediately Reportable to the 
Sponsor)
A serious adverse event is any adverse event that meets any of the following criteria:

Is fatal (i.e., the adverse event actually causes or leads to death)

Is life threatening (i.e., the adverse event, in the view of the investigator, places the 
patient at immediate risk of death)
This does not include any adverse event that had it occurred in a more severe 
form or was allowed to continue might have caused death.

Requires or prolongs inpatient hospitalization (see Section 5.3.5.11 )

Results in persistent or significant disability/incapacity (i.e., the adverse event 
results in substantial disruption of the patient’s ability to conduct normal life 
functions)

Is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to 
study treatment

Is a significant medical event in the investigator's judgment (e.g., may jeopardize the 
patient or may require medical/surgical intervention to prevent one of the outcomes 
listed above)
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 NCI CTCAE 
criteria; see Section 5.3.3); the event itself may be of relatively minor medical 
significance (such as severe headache without any further findings).

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Severity and seriousness need to be independently assessed for each adverse event 
recorded on the eCRF.
Serious adverse events are required to be reported by the investigator to the Sponsor 
immediately (i.e., no more than 24 hours after learning of the event; see Section 5.4.2 for 
reporting instructions).
5.2.3
Adverse Events of Special Interest (Immediately Reportable to 
the Sponsor)
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 learning of the event; see 
Section 5.4.2 for reporting instructions).  Adverse events of special interest for this study 
include the adverse events of special interest listed below.
Adverse events of special interest to any study drug 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 5.3.5.7)

Suspected transmission of an infectious agent by the 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 a patient exposed to a medicinal product.  This term applies only
when a contamination of any of the study treatment components is suspected.
Adverse events of special interest to obinutuzumab are as follows:

TLS of any grade, irrespective of causality

Second malignancies
Adverse events of special interest to atezolizumab are as follows:

Pneumonitis

Colitis

Endocrinopathies: diabetes mellitus, pancreatitis, adrenal insufficiency,
hyperthyroidism, and hypophysitis

Hepatitis, including AST or ALT > 10 x ULN

Systemic lupus erythematosus

Neurological disorders: Guillain-Barré syndrome, myasthenic syndrome or
myasthenia gravis, and meningoencephalitis

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
Events suggestive of hypersensitivity, infusion-related reactions, cytokine-release
syndrome, influenza-like illness, systemic inflammatory response syndrome, and
systemic immune activation

Nephritis

Ocular toxicities (e.g., uveitis, retinitis)

Myositis

Myopathies, including rhabdomyolysis

Grade 2 cardiac disorders (e.g., atrial fibrillation, myocarditis, pericarditis)

Vasculitis
5.2.4
Selected Adverse Events
Adverse events of special interest are listed in Section 5.2.3. Selected adverse events 
in this study are defined as adverse events for which additional data collection or 
analyses will be performed.  Selected adverse events do not require immediate reporting 
if they are not serious (except for TLS and second malignancies).
The following adverse events are considered selected adverse events:

Thrombocytopenia, including acute thrombocytopenia (events occurring during and 
within 24 hours following obinutuzumab infusion)

Hepatitis B reactivation

Cardiac events

IRRs

All infections, including PML

Neutropenia, including prolonged neutropenia (neutropenia 1000 cells/L that does 
not resolve after 28 days without obinutuzumab treatment) and late-onset 
neutropenia (neutropenia 1000 cells/L occurring28 days after obinutuzumab 
treatment has been completed or stopped) 

GI perforation
Events for which additional data collection will be required are PML, and hepatitis B 
reactivation.
5.3
METHODS AND TIMING FOR CAPTURING AND ASSESSING 
SAFETY PARAMETERS
The investigator is responsible for ensuring that all adverse events (see Section 5.2.1 for 
definition) are recorded on the Adverse Event eCRF and reported to the Sponsor in 
accordance with instructions provided in this section and in Sections 5.45.6.
For each adverse event recorded on the Adverse Event eCRF, the investigator will make 
an assessment of seriousness (see Section 5.2.2 for seriousness criteria), severity (see 
Section 5.3.3), and causality (see Section 5.3.4).  

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5.3.1
Adverse Event Reporting Period
Investigators will seek information on adverse events at each patient contact.  All 
adverse events, whether reported by the patient or noted by study personnel, will be 
recorded in the patient’s medical record and on the Adverse Event eCRF.
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., invasive 
procedures such as biopsies, discontinuation of medications) should be reported 
(see Section 5.4.2 for instructions for reporting serious adverse events).
After initiation of study treatment, all adverse events will be reported until 90 days 
after the last dose of study treatment.  After this period, the investigator should report 
any serious adverse events that are believed to be related to prior study treatment 
(see Section 5.6).
An exception is made for Grade 3–4 infections (related and unrelated to study treatment), 
which should be reported until up to 2 years after the last dose of obinutuzumab (in the 
Atezo-G-benda and Atezo-G-CHOP treatment groups).
Similarly, second malignancies (related and unrelated to study treatment) will be 
reported indefinitely (even if the study has been closed) for patients who received 
obinutuzumab (see Section 5.6).
5.3.2
Eliciting Adverse Event Information
A consistent methodology of non-directive questioning should be adopted for eliciting 
adverse event information at all patient evaluation timepoints.  Examples of non-directive 
questions include the following:
"How have you felt since your last clinic visit?"
"Have you had any new or changed health problems since you were last here?" 
5.3.3
Assessment of Severity of Adverse Events
The adverse event severity grading scale for the NCI CTCAE v4.0 will be used for 
assessing adverse event severity.  Table 16 will be used for assessing severity for 
adverse events that are not specifically listed in the NCI CTCAE.

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Table 16 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
NCI CTCAENational Cancer Institute Common Terminology Criteria for Adverse Events.
Note:  Based on the most recent version of NCI CTCAE (v4.0), which can be found at:  
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm
a Instrumental activities of daily living refer to 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 patients 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 5.4.2 for reporting instructions), per the definition of serious 
adverse event in Section 5.2.2.
d Grade 4 and 5 events must be reported as serious adverse events (see Section 5.4.2 for 
reporting instructions), per the definition of serious adverse event in Section 5.2.2.
5.3.4
Assessment of Causality of Adverse Events
Investigators should use their knowledge of the patient, the circumstances surrounding 
the event, and an evaluation of any potential alternative causes to determine whether or 
not an adverse event is considered to be related to any of the study treatment 
components, indicating "yes" or "no" accordingly.  The following guidance should be 
taken into consideration:

Temporal relationship of event onset to the initiation of study treatment

Course of the event, considering especially the effects of study treatment 
modifications or discontinuation, or reintroduction of study treatment (as applicable)

Known association of the event with the study treatment or with similar treatments

Known association of the event with the disease under study

Presence of risk factors in the patient or use of concomitant medications known to 
increase the occurrence of the event

Presence of nontreatment-related factors that are known to be associated with the 
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For patients receiving combination therapy, causality will be assessed individually for 
each protocol-mandated therapy.
5.3.5
Procedures for Recording Adverse Events
Investigators should use correct medical terminology/concepts when recording adverse 
events on the Adverse Event eCRF.  Avoid colloquialisms and abbreviations.
Only one adverse event term should be recorded in the event field on the Adverse Event 
eCRF.
5.3.5.1
Infusion-Related Reactions 
Adverse events that occur during or within 24 hours after the end of study treatment 
infusion and are judged to be related to infusion of any of the study treatment 
components should be captured as a diagnosis (e.g., "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 Infusion-Related 
Reaction eCRF.  If a patient experiences both a local and systemic reaction to the same 
dose of study treatment, each reaction should be recorded separately on the Adverse 
Event eCRF, with signs and symptoms also recorded separately on the dedicated 
Infusion-Related Reaction eCRF.
5.3.5.2
Diagnosis versus Signs and Symptoms
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.
5.3.5.3
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 
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.

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
If a severe GI hemorrhage leads to renal failure, both events should be reported 
separately on the eCRF.

If dizziness leads to a fall and consequent fracture, all three 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.
5.3.5.4
Persistent or Recurrent Adverse Events
A persistent adverse event is one that extends continuously, without resolution, between 
patient 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.  Details regarding any increases or decrease in severity will be captured on the 
Adverse Event Intensity or Grade Changes eCRF.  If the event becomes serious, it 
should be reported to the Sponsor immediately (i.e., no more than 24 hours after 
learning that the event became serious; see Section 5.4.2 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 patient evaluation timepoints 
and subsequently recurs.  Each recurrence of an adverse event should be recorded as a 
separate event on the Adverse Event eCRF.
5.3.5.5
Abnormal Laboratory Values
Not every laboratory abnormality qualifies as an adverse event.  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.
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.

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If a clinically significant laboratory abnormality is a sign of a disease or syndrome 
(e.g., ALP and bilirubin 5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 if 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 5.3.5.4 for 
details on recording persistent adverse events).
5.3.5.6
Abnormal Vital Sign Values
Not every vital sign abnormality qualifies as an adverse event.  A vital sign 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 or a change in concomitant therapy

Is clinically significant in the investigator’s judgment 
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 (i.e., 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 5.3.5.4 for 
details on recording persistent adverse events).

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5.3.5.7
Abnormal Liver Function Tests
The finding of an elevated ALT or AST (3baseline value) 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baseline value in combination with total 
bilirubin 2 ULN (of which35% is direct bilirubin)

Treatment-emergent ALT or AST 3baseline value 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 5.3.5.2) 
and reported to the Sponsor immediately (i.e., no more than 24 hours after learning of 
the event), either as a serious adverse event or an adverse event of special interest
(see Section 5.4.2).
5.3.5.8
Deaths
For this protocol, mortality is an efficacy endpoint.  Deaths that occur during the 
protocol-specified adverse event reporting period (see Section 5.3.1) that are attributed 
by the investigator solely to progression of lymphoma should be recorded only on the 
Study Completion/Early Discontinuation eCRF.  All other on-study deaths, regardless of 
relationship to study treatment, must be recorded on the Adverse Event eCRF and 
immediately reported to the Sponsor (see Section 5.4.2).  An IMC will monitor the 
frequency of deaths from all causes.
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 
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").
During survival follow-up, deaths attributed to progression of lymphoma should be 
recorded only on the Study Completion/Early Discontinuation eCRF.
5.3.5.9
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.

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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").
5.3.5.10
Lack of Efficacy or 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 the Lugano 2014 criteria (see Appendix 7) and the modified 
Cheson 2007 criteria (see Appendix 8).  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.
5.3.5.11
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 
event (per the definition of serious adverse event in Section 5.2.2), 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 required by the protocol (e.g., for study treatment 
administration or insertion of access device for study treatment administration) 

Hospitalization for a preexisting condition, provided that all of the following criteria 
are met:
The hospitalization was planned prior to the study or was scheduled during the 
study when elective surgery became necessary because of the expected 
normal progression of the disease
The patient 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 patient requirement for outpatient 
care outside of normal outpatient clinic operating hours

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5.3.5.12
Adverse Events Associated with an Overdose or Error in 
Treatment Administration
An overdose is the accidental or intentional use of a drug in an amount higher than the 
dose being studied.  An overdose or incorrect administration of study treatment is not 
itself an adverse event, but it may result in an adverse event.  Additionally, all adverse 
events associated with an overdose or incorrect administration of study treatment should 
be recorded on the Adverse Event eCRF.  If the associated adverse event fulfills 
seriousness criteria, the event should be reported to the Sponsor immediately (i.e., no 
more than 24 hours after learning of the event; see Section 5.4.2).
No experience with overdosage is available from human clinical trials.  In clinical trials 
with obinutuzumab doses ranging from 50 mg up to and including 2000 mg per infusion 
have been administered.  The incidence and intensity of adverse reactions reported in 
these studies did not appear to be dose-dependent.
Patients who experience overdose should have immediate interruption or reduction of 
their infusion and should be closely supervised.  Consideration should be given to the 
need for regular monitoring of blood cell count and for increased risk of infections while 
patients are B cell-depleted.
5.4
IMMEDIATE REPORTING REQUIREMENTS FROM 
INVESTIGATOR TO SPONSOR
Certain events require immediate reporting to allow the Sponsor to take appropriate 
measures to address potential new risks in a clinical trial.  The investigator must report 
such events to the Sponsor immediately; under no circumstances should reporting take 
place more than 24 hours after the investigator learns of the event.  The following is a list 
of events that the investigator must report to the Sponsor within 24 hours after learning 
of the event, regardless of relationship to any of the study treatments:

Serious adverse events (see Section 5.4.2 for further details)

Adverse events of special interest (see Section 5.4.2 for further details)

Pregnancies (see Section 5.4.3 for further details)
The investigator must report new significant follow-up information for these events to the 
Sponsor immediately (i.e., no more than 24 hours after becoming 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

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Investigators must also comply with local requirements for reporting serious adverse 
events to the local health authority and IRB/EC.
5.4.1
Emergency Medical Contacts
Medical Monitor Contact Information for all sites
Medical Monitor:
, Ph.D.
Mobile Telephone No.:
To ensure the safety of study patients, an Emergency Medical Call Center Help Desk will 
access the Roche Medical Emergency List, escalate emergency medical calls, provide 
medical translation service (if necessary), connect the investigator with a Roche Medical 
Responsible (listed above and/or on the Roche Medical Emergency List), and track all 
calls.  The Emergency Medical Call Center Help Desk will be available 24 hours per day, 
7 days per week.  Toll-free numbers for the Help Desk, as well as Medical Monitor and 
Medical Responsible contact information, will be distributed to all investigators.  
5.4.2
Reporting Requirements for Serious Adverse Events and 
Adverse Events of Special Interest
5.4.2.1
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 should be reported.  
The Serious Adverse Event/Adverse Event of Special Interest Reporting 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 emailing the form using the fax number or email address provided to 
investigators.
5.4.2.2
Events That Occur after Study Treatment Initiation
After initiation of study treatment, all adverse events will be reported until 90 days after 
the last dose of study treatment.  Investigators should record all case details that can be 
gathered immediately (i.e., within 24 hours after learning 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 Serious Adverse Event/Adverse 
Event of Special Interest Reporting 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 emailing the form using 
the fax number or email 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 post-study adverse events are provided in Section 5.6.

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5.4.3
Reporting Requirements for Pregnancies
5.4.3.1
Pregnancies in Female Patients
Female patients of childbearing potential will be instructed to immediately inform the 
investigator if they become pregnant during the study and for at least 18 months after 
the last dose of study treatment for patients in the Atezo-G-benda and Atezo-G-CHOP 
treatment groups and for at least 12 months after the last dose of study treatment for 
patients in the Atezo-R-CHOP treatment group.  
A 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 learning of the 
pregnancy), either by faxing or by scanning and emailing the form using the fax number 
or email address provided to investigators.  Pregnancy should not be recorded on the 
Adverse Event eCRF.  The investigator should discontinue study treatment immediately 
and counsel the patient, discussing the risks of the pregnancy and the possible effects 
on the fetus.  
Monitoring of the patient 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/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.
5.4.3.2
Pregnancies in Female Partners of Male Patients
Male patients will be instructed through the Informed Consent Form to immediately 
inform the investigator if their partner becomes pregnant during the study or within 
3 months after the last dose of study treatment.  A 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 learning of the pregnancy) either by faxing or by 
scanning and emailing the form using the fax number or email 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 patient exposed to study treatment.  
The pregnant partner will need to sign an Authorization for Use and Disclosure of 
Pregnancy Health Information to allow for follow-up on her pregnancy.  After the 
authorization has been signed, the investigator will submit a Clinical Trial Pregnancy 
Reporting Form when updated information on the course and outcome of the pregnancy 
becomes available.  An investigator who is contacted by the male patient 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.

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5.4.3.3
Abortions
Any 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 learning of the 
event; see Section 5.4.2).  
5.4.3.4
Congenital Anomalies/Birth Defects
Any congenital anomaly/birth defect in a child born to a female patient exposed to study 
treatment or the female partner of a male patient exposed to study treatment 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 learning of the 
event; see Section 5.4.2).
5.5
FOLLOW-UP OF PATIENTS AFTER ADVERSE EVENTS
5.5.1
Investigator Follow-Up
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 patient is lost to 
follow-up, or the patient withdraws consent.  Every effort should be made to follow all 
serious adverse events considered to be related to study treatment or trial-related 
procedures until a final outcome can be reported.
During the study period, resolution of adverse events (with dates) should be documented 
on the Adverse Event eCRF and in the patient’s medical record to facilitate source data 
verification.
All pregnancies reported during the study should be followed until pregnancy outcome.  
5.5.2
Sponsor Follow-Up
For serious adverse events, adverse events of special interest, and pregnancies, the 
Sponsor or a designee may follow up by telephone, fax, electronic 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.
5.6
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 last 
dose of study treatment), all deaths, regardless of cause, should be reported through 
use of the Long-Term Survival Follow-Up eCRF.
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.

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An exception is made for Grade 3–4 infections (related and unrelated), which should be 
reported until up to 2 years after the last dose of study treatment.
The Sponsor should also be notified of events of second malignancies indefinitely 
(related and unrelated, even if the Atezo-G-benda treatment group or the overall study 
has been closed) for patients who received obinutuzumab.
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 emailing the paper 
Clinical Trial Serious Adverse Event/Adverse Event of Special Interest Reporting Form 
using the fax number or email address provided to investigators.
5.7
EXPEDITED REPORTING TO HEALTH AUTHORITIES, 
INVESTIGATORS, INSTITUTIONAL REVIEW BOARDS, AND 
ETHICS COMMITTEES
The Sponsor will promptly evaluate all serious adverse events and adverse events of 
special interest against cumulative product experience to identify and expeditiously 
communicate possible new safety findings to investigators, IRBs, ECs, and applicable 
health authorities based on applicable legislation.
To determine reporting requirements for single adverse event cases, the Sponsor will 
assess the expectedness of these events using the following reference document:

Obinutuzumab Investigator's Brochure 

Atezolizumab Investigator’s Brochure

Rituximab Investigator’s Brochure

Bendamustine Summary of Product Characteristics
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.
6.
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN
The study will include an initial safety run-in phase followed by an expansion phase.  
During the safety run-in phase, 6 patients with previously untreated, or relapsed or 
refractory FL are to be enrolled within each treatment group (Atezo-G-CHOP or 
Atezo-G-benda).  If the stopping criteria are not met during the safety run-in phase within 
a treatment group, enrollment will continue in the expansion phase, as follows: 

Additional patients with previously untreated FL will be enrolled in the 
Atezo-G-benda treatment group. 

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
Patients with previously untreated DLBCL will be enrolled in the Atezo-R-CHOP 
treatment group.
Enrollment in the Atezo-G-CHOP treatment group was stopped after the safety run-in 
phase was completed.
6.1
DETERMINATION OF SAMPLE SIZE
Up to 46 patients with FL will be enrolled in the Atezo-G-benda treatment group:  
6 patients with previously untreated, or relapsed or refractory FL enrolled in the safety 
run-in phase and 3440 patients with previously untreated FL enrolled in the expansion 
phase (depending on the number of patients needed to achieve a total enrollment of 
40 patients with previously untreated FL).  A total of 7 patients with previously untreated 
or relapsed or refractory FL were enrolled in the Atezo-G-CHOP treatment group during 
the safety run-in phase.  Per current amendment, , further enrollment in the 
Atezo-G-CHOP treatment group is stopped.  A total of 40 patients with previously 
untreated DLBCL will be enrolled in the Atezo-R-CHOP treatment group.  Therefore, 
enrollment of up to 92 patients is planned for this study.
The primary efficacy analysis will be the estimation of the true proportion of patients 
expected to obtain a PET-CTdefined CR at EOI.
Data from completed and ongoing studies in similar disease settings will be used as 
historical controls for comparison.  Currently available data indicate that the historical 
CR rate is approximately 40% for first-line treatment of FL (Dyer et al. 2012; 
Rummel et al. 2013) and 59% for first-line treatment of DLBCL (Study BO21005/GOYA), 
as assessed by Cheson 2007 criteria.  A sample size of 40 patients is deemed sufficient 
to provide adequate precision for the point estimate and for the lower bound of the 
two-sided 90% CI to rule out a clinically uninteresting probability of response of 40% in 
FL and 59% in DLBCL, assuming an observed PET-CTdefined CR rate of 55% and 
72%, respectively.  Updated estimates of the proportion of patients expected to achieve 
a PET-CTdefined CR for each histological subtype are expected to be available from 
ongoing studies by the time of the first interim analysis and will be used as reference 
data.  
Table 17 lists the two-sided 90% Clopper-Pearson exact CI for the true probability of 
achieving a PET-CTdefined CR at EOI for a range of observed proportions based on a 
sample of 40 patients.  

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Table 17 Potential 90% CI for the True Probability of Achieving a 
PET-CTDefined Complete Response at End of Induction
Observed Proportion of Patients
Achieving a PET-CTDefined CR at EOI
Two-Sided 90% Clopper-Pearson CI a for 
True Population PET-CTDefined CR
0.50
(0.36, 0.64)
0.55
(0.40. 0.68)
0.60
(0.46, 0.73)
0.65
(0.51, 0.77)
0.70
(0.56, 0.82)
0.72
(0.58, 0.83)
0.75
(0.61, 0.86)
0.80
(0.66, 0.89)
0.85
(0.72, 0.93)
CRcomplete response; CTcomputed tomography; EOIend of induction; PET positron 
emission tomography.
a Note that the lower limit of a two-sided 90% CI is equivalent to a one-sided 95% CI.
6.2
SUMMARIES OF PATIENT CHARACTERISTICS
Summaries of patient characteristics will be performed by treatment group.  Enrollment, 
major protocol violations, and discontinuations from the study will be listed.  The 
incidence of treatment discontinuation for reasons other than disease progression will be 
tabulated.  
Data related to the administration of study treatment components will be listed, and any 
dose modifications will be flagged.  The number of doses, treatment cycles, average 
dose received, and relative dose intensity for each treatment component will be 
summarized for each treatment group using descriptive statistics (mean, standard 
deviation, median, and range).
6.3
SUMMARIES OF TREATMENT GROUP COMPARABILITY
Demographic and baseline characteristics, such as age, sex, race, and duration of 
malignancy, will be summarized using descriptive statistics (mean, standard deviation, 
median, and range) for continuous variables and frequencies and percentages for 
categorical variables.
6.4
SAFETY ANALYSES
The safety analyses will be performed by treatment group, separately for each treatment 
phase (i.e., safety run-in and expansion), and will include all treated patients 
(i.e., patients who received any amount of study treatment), with patients grouped 
according to treatment received.

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Safety will be assessed through summaries of adverse events, changes from baseline in 
laboratory test results, laboratory data with values outside of the normal ranges, ECGs, 
and vital signs.
All adverse events occurring on or after first study treatment will be summarized by 
mapped term, appropriate thesaurus levels, and NCI CTCAE v4.0 grade.  All serious 
adverse events and adverse events of special interest will be summarized and listed.  
Deaths reported during the treatment period and during post-treatment follow-up will be 
listed.
Relevant laboratory and vital sign (temperature, heart rate, respiratory rate, and blood 
pressure) data will be displayed by time, with Grade 3 and 4 values identified as 
appropriate.
6.5
EFFICACY ANALYSES
The primary and secondary efficacy analyses will be performed by treatment group, with 
patients grouped according to treatment received. For the Atezo-R-CHOP treatment 
group, the efficacy analyses will include all patients enrolled in the expansion 
phase. For the Atezo-G-benda treatment group, the efficacy analyses will include all 
patients enrolled in the expansion phase as well as patients with previously untreated FL 
who were enrolled in the safety run-in phase.
Response will be determined through use of the modified Cheson 2007 criteria 
(Cheson et al. 2007; see Appendix 8), which take into account both PET-CT and CT 
scan results, and through use of the PET-CTbased Lugano 2014 criteria
(Cheson et al. 2014; see Appendix 7).
6.5.1
Primary Efficacy Endpoint
The primary efficacy analysis will be estimation of the proportion of patients achieving a 
CR at EOI, as determined by the IRC through use of the PET-CTbased Lugano 2014 
criteria.  Point estimates will be presented, along with the corresponding two-sided 90% 
Clopper-Pearson exact CIs.  The primary efficacy analysis will include patients who 
received at least one dose of atezolizumab.  Patients without a post-baseline tumor 
assessment will be considered non-responders.
6.5.2
Secondary Efficacy Endpoints
The secondary efficacy analyses will be estimation of the proportion of patients 
achieving each of the following endpoints: 

CR at EOI, as determined by the investigator using Lugano 2014 criteria

CR at EOI, as determined by the IRC and by the investigator using modified Cheson 
2007 criteria

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
Objective response (defined as a CR or PR) at EOI, as determined by the IRC and 
by the investigator using Lugano 2014 criteria and modified Cheson 2007 criteria

Objective response (defined as a CR or PR) during the study, as determined by the 
investigator using modified Cheson 2007 criteria
Point estimates will be presented, along with the corresponding two-sided 90% 
Clopper-Pearson exact CIs.  Patients without a post-baseline tumor assessment will be 
considered non-responders.
6.5.3
Exploratory Efficacy Endpoints
Exploratory efficacy analyses will include estimation of the proportion of patients 
achieving each of the following endpoints: 

For patients who have positive PET scans at EOI:  CR at 12 months, as determined 
by the IRC and by the investigator using Lugano 2014 criteria

CR at 12, 24, and 30 months in patients with previously untreated FL, as determined 
by the investigator using modified Cheson 2007 criteria
Point estimates will be presented, along with the corresponding two-sided 90% 
Clopper-Pearson exact CIs.  Patients without a post-baseline tumor assessment will be 
considered non-responders.
Exploratory efficacy analyses will also be performed on the following endpoints: 

PFS

EFS

DFS

OS
PFS, EFS, DFS, and OS will be summarized descriptively using the Kaplan-Meier 
method (Kaplan and Meier 1958).  For the PFS, EFS, and DFS analyses, data for 
patients without an event of interest will be censored at the date of the last tumor 
assessment.  For patients without post-baseline tumor assessments, data will be 
censored at the date of initiation of study treatment plus 1.  For the OS analysis, data for 
patients who have not died will be censored at the date the patient was last known to be 
alive.  Where medians are reached, the corresponding estimated median will be 
provided, along with the 95% CI using the method of Brookmeyer and Crowley (1982).  
In addition, landmark estimates of the proportion of patients who are event free at 
6 months, 9 months, 1 year, and 2 years will be provided, along with 95% asymptotic CIs 
using Greenwood’s formula for standard errors.  No formal comparison of time-to-event 
outcomes by treatment group will be conducted. 

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6.6
PHARMACOKINETIC ANALYSES
Individual and mean serum concentrations of obinutuzumab-, rituximab-, and 
atezolizumab-versus-time data will be tabulated and plotted, after appropriate grouping.  
After appropriate grouping, summary statistics of concentration data will be computed for 
each scheduled sampling time for each analyte, and interpatient variability and drug 
accumulation after multiple doses will be evaluated.  Compartmental, 
non-compartmental, and/or population approaches will be considered as appropriate, 
including potential pooled analyses across studies.  Potential drug interactions may be 
assessed by comparison of pharmacokinetics in the current study with historical data.  
Potential correlations between PK variability and demographic and pathophysiological 
covariates may be explored by population PK analysis.  Potential correlations between 
PK variability and pharmacodynamic (PD), efficacy, and safety endpoints may be 
explored by exploratory graphical analysis and PK/PD modeling.  The assessment of PK 
parameters and related analyses will be performed per the Sponsor’s discretion, taking 
into consideration the appropriateness of the PK data collected and the trial outcome.  
Compartmental and/or population PK/PD analyses may be reported separately from 
CSR.
6.7
IMMUNOGENICITY ANALYSES
The numbers and proportions of HAHA-, HACA-, or ATA-positive patients HAHA-, 
HACA-, or ATA-negative patients during both the treatment and follow-up periods will be 
summarized by treatment group.
The relationship between HAHA, HACA, or ATA status and safety, efficacy, and PK 
endpoints will be explored as appropriate.
6.8
BIOMARKER ANALYSES
Exploratory analyses of biomarkers related to tumor biology and study treatment 
mechanisms of action will be conducted.  Analyses will assess the prognostic and/or 
predictive value of candidate biomarkers for each treatment group with respect to both 
IRC- and investigator-assessed outcomes.  Specifically, the association between 
candidate biomarkers and PET-CTdefined CR rate and OR rate, and potentially other 
measures of efficacy and safety, will be explored to assess potential prognostic or 
predictive value.  These analyses may not be included in the final study report because 
of their exploratory nature.  In addition to analysis in the context of this study, data will 
also be explored in aggregate with data from other studies.  
6.9
INTERIM ANALYSES
It is anticipated that at least one interim analysis will be conducted during the expansion 
phase of the study, when at least 15patients have been evaluated for PET-CT-defined 
CR at the EOI.  Additional analyses may be conducted to guide early stopping of 
enrollment for safety on the basis of observed toxicities and the ability to maintain 
chemotherapy dose intensity.

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During the expansion phase, a modified version of the predictive probability design 
(Lee and Liu 2008) may be used to guide early stopping for futility by comparing the 
observed proportion of patients who achieve a PET-CTdefined CR at EOI in each 
expansion cohort with that in historical controls.  The earliest interim analysis would 
occur after at least 15 patients have been evaluated for PET-CTdefined CR at EOI.
If, at any time, an interim analysis suggests that the proportion of patients achieving a 
PET-CTdefined CR for one of the expansion cohorts is lower or higher than expected, 
the IMC will review the data and decide whether to recommend an early decision to stop 
enrollment in that subgroup.  Interim analysis decision rules will be based on the 
modified version of the predictive probability that the trial will have a positive outcome if 
carried out to completion and will use the historical control data available at the time of 
analysis.
Additional review of safety and/or efficacy data by the IMC may be requested by and 
carried out at the discretion of the Medical Monitor.  Further details regarding the rules 
and guidelines of data review will be provided in an IMC charter document.
7.
DATA COLLECTION AND MANAGEMENT
7.1
DATA QUALITY ASSURANCE
The Sponsor will be responsible for data management of this study, including quality 
checking of the data.  Data entered manually will be collected via EDC through use of 
eCRFs.  Sites will be responsible for data entry into the EDC system.  In the event of 
discrepant data, the Sponsor will request data clarification from the sites, which the sites 
will resolve electronically in the EDC system.
The Sponsor will produce an EDC Study Specification document that describes the 
quality checking to be performed on the data.  Central laboratory data and any other 
externally-generated electronic study data will be sent directly to the Sponsor, using the 
Sponsor’s standard procedures to handle and process the electronic transfer of these 
data.
eCRFs and correction documentation will be maintained in the EDC system’s audit trail.  
System backups for data stored by the Sponsor and records retention for the study data 
will be consistent with the Sponsor’s standard procedures.
7.2
ELECTRONIC CASE REPORT FORMS 
eCRFs are to be completed through use of a Sponsor-designated EDC system.  Sites 
will receive training and have access to a manual for appropriate eCRF completion.  
eCRFs will be submitted electronically to the Sponsor and should be handled in 
accordance with instructions from the Sponsor.

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All eCRFs should be completed by designated, trained site staff.  eCRFs should be 
reviewed and electronically signed and dated by the investigator or a designee.
At the end of the study, the investigator will receive patient data for his or her site in a 
readable format on a compact disc that must be kept with the study records.  
Acknowledgement of receipt of the compact disc is required.
7.3
SOURCE DATA DOCUMENTATION
Study monitors will perform ongoing source data verification to confirm that critical 
protocol data (i.e., source data) entered into the eCRFs by authorized site personnel are 
accurate, complete, and verifiable from source documents.  
Source documents (paper or electronic) are those in which patient data are recorded 
and documented for the first time.  They include, but are not limited to, hospital records, 
clinical and office charts, laboratory notes, memoranda, patient-reported outcomes, 
evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies of transcriptions that are certified after verification as being accurate 
and complete, microfiche, photographic negatives, microfilm or magnetic media, X-rays, 
patient files, and records kept at pharmacies, laboratories, and medico-technical 
departments involved in a clinical trial.
Before study initiation, the types of source documents that are to be generated will be 
clearly defined in the Trial Monitoring Plan.  This includes any protocol data to be 
entered directly into the eCRFs (i.e., no prior written or electronic record of the data) and 
considered source data.
Source documents that are required to verify the validity and completeness of data 
entered into the eCRFs must not be obliterated or destroyed and must be retained per 
the policy for retention of records described in Section 7.5.
To facilitate source data verification, the investigators and institutions must provide the 
Sponsor direct access to applicable source documents and reports for trial-related 
monitoring, Sponsor audits, and IRB/EC review.  The study site must also allow 
inspection by applicable health authorities.
7.4
USE OF COMPUTERIZED SYSTEMS
When clinical observations are entered directly into a study site’s computerized medical 
record system (i.e., in lieu of original hardcopy records), the electronic record can serve 
as the source document if the system has been validated in accordance with health 
authority requirements pertaining to computerized systems used in clinical research.  
An acceptable computerized data collection system allows preservation of the original 
entry of data.  If original data are modified, the system should maintain a viewable audit 
trail that shows the original data as well as the reason for the change, name of the 
person making the change, and date of the change.

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7.5
RETENTION OF RECORDS
Records and documents pertaining to the conduct of this study and the distribution of 
IMP, including eCRFs, ePRO data (if applicable), Informed Consent Forms, laboratory 
test results, and medication inventory records, must be retained by the Principal 
Investigator for at least 15 years after completion or discontinuation of the study, or for 
the length of time required by relevant national or local health authorities, whichever is 
longer.  After that period of time, the documents may be destroyed, subject to local 
regulations.  
No records may be disposed of without the written approval of the Sponsor.  Written 
notification should be provided to the Sponsor prior to transferring any records to 
another party or moving them to another location.
8.
ETHICAL CONSIDERATIONS
8.1
COMPLIANCE WITH LAWS AND REGULATIONS
This study will be conducted in full conformance with the ICH E6 guideline for GCP and 
the principles of the Declaration of Helsinki, or the laws and regulations of the country in 
which the research is conducted, whichever affords the greater protection to the 
individual.  The study will comply with the requirements of the ICH E2A guideline 
(Clinical Safety Data Management:  Definitions and Standards for Expedited Reporting).  
Studies conducted in the United States or under a U.S. Investigational New Drug (IND) 
application will comply with U.S. Food and Drug Administration regulations and 
applicable local, state, and federal laws.  Studies conducted in the European Union or 
European Economic Area will comply with the E.U. Clinical Trial Directive (2001/20/EC).
8.2
INFORMED CONSENT
The Sponsor’s sample Informed Consent Form (and ancillary sample Informed Consent 
Forms such as a Child’s Informed Assent Form or Home Nursing Informed Consent 
Form, if applicable) will be provided to each site.  If applicable, it will be provided in a 
certified translation of the local language.  The Sponsor or its designee must review and 
approve any proposed deviations from the Sponsor's sample Informed Consent Forms 
or any alternate consent forms proposed by the site (collectively, the "Consent Forms") 
before IRB/EC submission.  The final IRB/ECapproved Consent Forms must be 
provided to the Sponsor for health authority submission purposes according to local 
requirements.
If applicable, the Informed Consent Form will contain separate sections for any optional 
procedures.  The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential risks associated with each optional procedure.  
Patients will be told that they are free to refuse to participate and may withdraw their 
consent at any time for any reason.  A separate, specific signature will be required to 
document a patient's agreement to participate in optional procedures.  Patients who 
decline to participate will not provide a separate signature.

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The Consent Forms must be signed and dated by the patient or the patient’s legally 
authorized representative before his or her participation in the study.  The case history or 
clinical records for each patient shall document the informed consent process and that 
written informed consent was obtained prior to participation in the study.
The Consent Forms should be revised whenever there are changes to study procedures 
or when new information becomes available that may affect the willingness of the patient 
to participate.  The final revised IRB/EC-approved Consent Forms must be provided to 
the Sponsor for health authority submission purposes.
Patients must be re-consented to the most current version of the Consent Forms (or to a 
significant new information/findings addendum in accordance with applicable laws and 
IRB/EC policy) during their participation in the study.  For any updated or revised 
Consent Forms, the case history or clinical records for each patient shall document the 
informed consent process and that written informed consent was obtained using the 
updated/revised Consent Forms for continued participation in the study.
A copy of each signed Consent Form must be provided to the patient or the patient’s 
legally authorized representative.  All signed and dated Consent Forms must remain in 
each patient’s study file or in the site file and must be available for verification by study 
monitors at any time.
For sites in the United States, each Consent Form may also include patient authorization 
to allow use and disclosure of personal health information in compliance with the U.S. 
Health Insurance Portability and Accountability Act of 1996 (HIPAA).  If the site utilizes a 
separate Authorization Form for patient authorization for use and disclosure of personal 
health information under the HIPAA regulations, the review, approval, and other 
processes outlined above apply except that IRB review and approval may not be 
required per study site policies.
8.3
INSTITUTIONAL REVIEW BOARD OR ETHICS COMMITTEE
This protocol, the Informed Consent Forms, any information to be given to the patient, 
and relevant supporting information must be submitted to the IRB/EC by the Principal 
Investigator and reviewed and approved by the IRB/EC before the study is initiated.  
In addition, any patient recruitment materials must be approved by the IRB/EC.  
The Principal Investigator is responsible for 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.  Investigators are also responsible 
for promptly informing the IRB/EC of any protocol amendments (see Section 9.6).
In addition to the requirements for reporting all adverse events to the Sponsor, 
investigators must comply with requirements for reporting serious adverse events to the 
local health authority and IRB/EC.  Investigators may receive written IND safety reports 

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
136/Protocol BO29563, Version 6
or other safety-related communications from the Sponsor.  Investigators are responsible 
for ensuring that such reports are reviewed and processed in accordance with health 
authority requirements and the policies and procedures established by their IRB/EC, and 
archived in the site’s study file.  
8.4
CONFIDENTIALITY
The Sponsor maintains confidentiality standards by coding each patient enrolled in the 
study through assignment of a unique patient identification number.  This means that 
patient names are not included in data sets that are transmitted to any Sponsor location.
Patient medical information obtained by this study is confidential and may be disclosed 
to third parties only as permitted by the Informed Consent Form (or separate 
authorization for use and disclosure of personal health information) signed by the patient, 
unless permitted or required by law.
Medical information may be given to a patient’s personal physician or other appropriate 
medical personnel responsible for the patient’s welfare, for treatment purposes.
Data generated by this study must be available for inspection upon request by 
representatives of national and local health authorities, Sponsor monitors, 
representatives, and collaborators, and the IRB/EC for each study site, as appropriate.
8.5
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 (defined as the time 
when all enrolled FL patients have completed or discontinued study treatment and all 
enrolled DLBCL patients have been followed for at least 1 year after they have 
completed or discontinued study treatment).
9.
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION
9.1
STUDY DOCUMENTATION
The investigator must maintain adequate and accurate records to enable the conduct 
of the study to be fully documented, including, but not limited to, the protocol, protocol 
amendments, Informed Consent Forms, and documentation of IRB/EC and 
governmental approval.  In addition, at the end of the study, the investigator will receive 
the patient data, including an audit trail containing a complete record of all changes to 
data.

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
137/Protocol BO29563, Version 6
9.2
PROTOCOL DEVIATIONS
The investigator should document and explain any protocol deviations.  The investigator 
should promptly report any deviations that might have an impact on patient 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.
9.3
SITE INSPECTIONS
Site visits will be conducted by the Sponsor or an authorized representative for 
inspection of study data, patients’ medical records, and eCRFs.  The investigator will 
permit national and local health authorities, Sponsor monitors, representatives, and 
collaborators, and the IRBs/ECs to inspect facilities and records relevant to this study.
9.4
ADMINISTRATIVE STRUCTURE
This trial will be sponsored and managed by Roche.
Electronic data capture will be used for this study.  An IxRS will be used to assign patient 
numbers.  A central laboratory will be used for a subset of laboratory assessments as 
specified in Section 4.5.6; otherwise, local laboratories will be used.  A central 
independent review facility will be used to collect PET-CT and CT scans, and the IRC 
will perform independent assessments of response for all patients enrolled in the study 
(separate IRC Charter will contain all details).  Data from this study will be shared with 
an Expert Scientific Committee that will provide scientific input for the benefit-risk 
assessment for each combination.
9.5
PUBLICATION OF DATA AND PROTECTION OF TRADE 
SECRETS
Regardless of the outcome of a trial, the Sponsor is dedicated to openly providing 
information on the trial to healthcare professionals and to the public, both at scientific 
congresses and in peer-reviewed journals.  The Sponsor will comply with all 
requirements for publication of study results.  For more information, refer to the Roche 
Global Policy on Sharing of Clinical Trials Data at the following Web site:
http://www.roche.com/roche_global_policy_on_sharing_of_clinical_study_information.pdf
The results of this study may be published or presented at scientific congresses.  For all 
clinical trials in patients involving an IMP for which a marketing authorization application 
has been filed or approved in any country, the Sponsor aims to submit a journal 
manuscript reporting primary clinical trial results within 6 months after the availability of 
the respective clinical study report.  In addition, for all clinical trials in patients involving 
an IMP for which a marketing authorization application has been filed or approved in any 

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
138/Protocol BO29563, Version 6
country, the Sponsor aims to publish results from analyses of additional endpoints and 
exploratory data that are clinically meaningful and statistically sound.
The investigator must agree to submit all manuscripts or abstracts to the Sponsor prior 
to submission for publication or presentation.  This allows the Sponsor to protect 
proprietary information and to provide comments based on information from other 
studies that may not yet be available to the investigator.
In accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of multicenter trials only in their entirety and not as individual center 
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.  Any formal publication 
of the study in which contribution of Sponsor personnel exceeded that of conventional 
monitoring will be considered as a joint publication by the investigator and the 
appropriate Sponsor personnel.
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of data from this study will become and remain the exclusive and unburdened 
property of the Sponsor, except where agreed otherwise.
9.6
PROTOCOL AMENDMENTS
Any protocol amendments will be prepared by the Sponsor.  Protocol amendments will 
be submitted to the IRB/EC and to regulatory authorities in accordance with local 
regulatory requirements.
Approval must be obtained from the IRB/EC and regulatory authorities (as locally 
required) before implementation of any changes, except for changes necessary to 
eliminate an immediate hazard to patients or changes that involve logistical or 
administrative aspects only (e.g., change in Medical Monitor or contact information).

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
139/Protocol BO29563, Version 6
10.
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Appendix 1
Schedule of Assessments for Patients in the Atezo-G-Benda Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
147/Protocol BO29563, Version 6
Screening a
Induction (6 months; 28-day cycles)
EOI
Maint. (24 months)
EOM c
Post-
Treatment
FU Period 
(q3m) d
Survival 
FU 
Period 
(q3m) d
D28 
to 
D1
D14 
to 
D1
Cycle 1 
(1 d)
Cycle 2 
(2 d)
Cycles 36
(2 d)
After last 
induction 
dose b
Monthly
Every 
2 months
35 days
after last 
dose
(1 wk)
D1
D8 D15 D1 D15
D1
D15
D1
D1
Hepatitis B and C testing t
x
Quantitative IgA, IgG, IgM
x
x
x l
x
x u
TSH, T3, T4
x
Every 3 months
HAHA sample for obinutuzumab
x v
ATA sample for atezolizumab
x v
PK sample for obinutuzumab
x v
PK sample for atezolizumab
x v
Serum for soluble PD-L1
x
Whole blood for MRD w
x q
x
x l
Whole blood for lymphocyte 
immunophenotyping x
x q
x q
x q
x q
x
x l
x
x u
Whole blood for T-cell receptor 
repertoire in PBMCs
x q
x q
x q, y
x
x z
Serum for cytokine analysis
x q
x q
x q, y
Optional peripheral blood sample 
for RCR aa
x

Appendix 1
Schedule of Assessments for Patients in the Atezo-G-Benda Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
148/Protocol BO29563, Version 6
Screening a
Induction (6 months; 28-day cycles)
EOI
Maint. (24 months)
EOM c
Post-
Treatment
FU Period 
(q3m) d
Survival 
FU 
Period 
(q3m) d
D28 
to 
D1
D14 
to 
D1
Cycle 1 
(1 d)
Cycle 2 
(2 d)
Cycles 36
(2 d)
After last 
induction 
dose b
Monthly
Every 
2 months
35 days
after last 
dose
(1 wk)
D1
D8 D15 D1 D15
D1
D15
D1
D1
Tumor tissue specimen (leftover 
tissue may be used for optional 
RCR specimen aa)
x bb
x cc
x cc
Concomitant medications
x
To be recorded continually until end of treatment
Adverse events dd
x
To be assessed continually dd
PET-CT scan
x ee
x ff
x gg
CT scan hh
x hh
x ff
x ii
x m
x n
Bone marrow biopsy and aspirate 
x jj
x ff, kk
x kk
x m, kk
Study treatment 
administration
Obinutuzumab ll
x
x
x
x
x
x
Atezolizumab ll
D1, D15
D1, D15
D1, D2
Bendamustine ll
D1, D2
D1, D2
D1, D2
New anti-lymphoma treatment
x
x
Survival follow-up
x
ATAanti-therapeutic antibody; Atezo-G-bendaatezolizumab in combination with obinutuzumab plus bendamustine; CT computed tomography; 
Dday; Discont.discontinuation; ECOG Eastern Cooperative Oncology Group; eCRF electronic Case Report Form; EOIend of induction; 
EOMend of maintenance; FLIPIFollicular Lymphoma International Prognostic Index; FU follow-up; HAHA human anti-human antibody;
Igimmunoglobulin; Maint. maintenance; MRDminimal residual disease; MRImagnetic resonance imaging; NKnatural killer; 
PBMCperipheral blood mononuclear cell; PD-L1programmed deathligand 1; PET positron emission tomography; PKpharmacokinetic;
q3m every 3 months; RCRRoche Clinical Repository; wk week.
Notes:  On treatment days, all assessments should be performed prior to dosing, unless otherwise specified.

Appendix 1
Schedule of Assessments for Patients in the Atezo-G-Benda Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
149/Protocol BO29563, Version 6
Assessments shaded in gray should be performed as scheduled, but the associated data do not need to be recorded on the eCRF (except in the 
case of an adverse event).  
a The screening period starts with the signing of the Informed Consent Form.  Results of standard-of-care tests or examinations performed prior to 
obtaining informed consent and within the defined window may be used as screening and baseline assessments; such tests do not need to be 
repeated for screening purposes.
b EOI assessments should be performed 68 weeks after Day 1 of the last induction cycle.  As an exception, patients who discontinue induction 
treatment prematurely because of an adverse event may undergo EOI assessments 48 weeks after their last dose of study treatment.
c Patients who complete maintenance treatment or discontinue maintenance treatment prematurely will undergo assessments at EOM.
d Patients who complete treatment or discontinue treatment for reasons other than disease progression will undergo assessments every 3 months 
during the post-treatment FU period, which will continue until disease progression, the start of new anti-lymphoma treatment, or the end of the 
study, whichever occurs first.  The first post-treatment FU visit is 3 months after the EOI visit for patients who do not receive maintenance 
treatment and 3 months after the last dose for patients who receive maintenance treatment.  Patients who experience disease progression will 
undergo limited assessments every 3 months during the survival FU period, which will continue until the end of the study.  The end of the study is 
defined as the time when all enrolled FL patients have completed or discontinued study treatment and all enrolled DLBCL patients have been 
followed for at least 1 year after they have completed or discontinued study treatment. 
e Informed consent must be documented before any study-specific screening procedure is performed.
f
Vital signs include respiratory rate, pulse rate, body temperature, and systolic and diastolic blood pressures while the patient is in a seated 
position.  For obinutuzumab infusions:  For the first cycle and for patients who experience an infusion-related reaction, vital signs will be 
measured prior to the infusion, every 15 (5) minutes for the first 90 minutes of the infusion, and then every 30 ( 10) minutes until 1 hour after 
completion of the infusion.  For the second and subsequent cycles, vital signs will be measured every 30 minutes during the infusion, except in 
patients who had experienced an infusion-related reaction during a prior infusion.  For atezolizumab infusions:  Vital signs should be determined 
up to 60 (15) minutes before each atezolizumab infusion. Vital signs should also be obtained during or after the atezolizumab infusion if 
clinically indicated.
g Perform only in patients who will not be receiving maintenance treatment.
h Includes evaluation of the head, eyes, ears, nose, and throat, and the cardiovascular, dermatological, musculoskeletal, respiratory, 
gastrointestinal, genitourinary, and neurological systems.  Record abnormalities observed at baseline on the General Medical History and 
Baseline Conditions eCRF.
i
As part of tumor assessment, the physical examination should include evaluation for the presence of enlarged nodes, palpable hepatomegaly, 
and splenomegaly.  This information will be recorded on the appropriate tumor assessment eCRF.

Appendix 1
Schedule of Assessments for Patients in the Atezo-G-Benda Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
150/Protocol BO29563, Version 6
j
Includes systems of primary relevance (e.g., cardiovascular and respiratory systems), systems associated with symptoms (newly emergent or 
monitored from baseline), and areas associated with tumor assessment (lymph nodes, liver, spleen, and any other areas identified at baseline).  
Record new or worsened clinically significant abnormalities on the Adverse Event eCRF.
k Unexplained fever 38C, night sweats, unexplained weight loss 10% of body weight over 6 months.
l
Perform at the same time as tumor assessments at 12, 18, and 24 months after initiation of induction treatment.
m Perform only if not done within the previous 3 months.
n Perform every 6 months.
o Includes hemoglobin, hematocrit, platelet count, RBC count, WBC count, and percent or absolute WBC differential count (neutrophils, 
eosinophils, basophils, monocytes, lymphocytes, other cells).
p Screening laboratory assessments may be used for Day 1 of Cycle 1 if performed within 72 hours prior to Day 1 of Cycle 1.
q Perform hematology and chemistry tests within 72 hours prior to Day 1 of each cycle, and within 24 hours prior to Days 8 and 15 of Cycle 1.  
Samples for exploratory biomarker research should be collected at the same time as hematology and chemistry samples.
r
Includes sodium, potassium, glucose, BUN or urea, creatinine, calculated creatinine clearance, calcium, total bilirubin, direct bilirubin, 
total protein, albumin, ALT, AST, alkaline phosphatase, amylase, lipase, LDH, and uric acid.
s All women who are not postmenopausal (12 months of non-therapy-induced amenorrhea) or surgically sterile will have a serum pregnancy test 
at screening within 7 days prior to Day 1 of Cycle 1.
t
Includes hepatitis B surface antigen, total hepatitis B core antibody, and hepatitis C virus antibody.
u Perform every 3 months until disease progression, or the start of new anti-lymphoma treatment, whichever occurs first.
v See Appendix 4 for detailed schedule.
w Includes circulating lymphoma cells and/or cell-free circulating tumor DNA.
x Includes B-cell counts (CD19), T-cell counts (CD3, CD4, and CD8), and NK-cell counts (CD16 and CD56).
y Cycle 3 only.
z Perform at the same time as tumor assessments at 12 and 18 months after initiation of induction treatment.
aa Requires separate patient consent for RCR participation.  Not applicable for a site that has not been granted approval for RCR sampling.
bb Availability of adequate archival or freshly biopsied tumor tissue samples should be confirmed at screening (see Section 4.5.6 for details).
cc A tumor biopsy sample will be collected prior to the start of Cycle 2 and at the time of progression unless no adequate tumor site is accessible.

Appendix 1
Schedule of Assessments for Patients in the Atezo-G-Benda Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
151/Protocol BO29563, Version 6
dd After informed consent has been obtained but prior to initiation of study treatment, only serious adverse events caused by a protocol-mandated 
intervention should be reported.  After initiation of study treatment, all adverse events will be reported until 90 days after the last dose of study 
treatment.  After this period, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be 
related to prior study treatment (see Section 5.6).  An exception is made for Grade 3–4 infections (related and unrelated), which should be 
reported until up to 2 years after the last dose of obinutuzumab.  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 patient is lost to follow-up, or the patient withdraws consent.  
Every effort should be made to follow all serious adverse events considered to be related to any of the study treatment components or 
trial-related procedures until a final outcome can be reported.
ee The screening PET-CT scan must be performed within 35 days prior to Day 1 of Cycle 1.
ff Perform only for patients who have received at least two cycles of induction treatment.
gg If PET-CT scan is positive at EOI, perform at 12 months after initiation of induction treatment, within 14 days prior to treatment administration.
hh CT scan of the neck (if clinically indicated), chest, abdomen and pelvis.  If contrast is medically contraindicated (e.g., patients with contrast allergy 
or impaired renal clearance), MRI scans of the chest, abdomen, and pelvis (and neck, if clinically indicated) and a non-contrast CT scan of the 
chest may be performed.  Combined PET/CT scanners may be used to collect diagnostic CT scans, but only according to the technical guidelines 
in the imaging manual.  Screening CT scan must be performed within 35 days prior to Day 1 of Cycle 1.
ii Perform at 12, 18, and 24 months after initiation of induction treatment, within 14 days prior to treatment administration.  
jj Bone marrow biopsy and aspirate must be performed within approximately 3 months prior to Day 1 of Cycle 1.
kk For patients with bone marrow involvement at screening, a repeat assessment will be performed at EOI if there is radiologic evidence of a 
complete response, and during maintenance or at EOM if there is radiologic evidence of a complete response or if clinically indicated 
(e.g., if there is clinical suspicion of progressive disease in the bone marrow with no radiologic evidence of progression).
ll Refer to Sections 4.3.2.6 and 4.3.2.8 for details on dosing and schedule.
mm
Patient may be assessed every 2 months if atezolizumab has been discontinued and maintenance treatment is continued with obinutuzumab 
single agent.

Appendix 2
Schedule of Assessments for Patients with FL in the Atezo-G-CHOP Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
153/Protocol BO29563, Version 6
Screening a
Induction (4 months; 21-day cycles)
EOI
Maint. (24 months)
EOM c
35 days
after last 
dose
Post-
Treatment
FU Period 
(q3m) d
Survival 
FU 
Period 
(q3m) d
D28 
to 
D1
D14 
to 
D1
Cycle 1 
(1 d)
Cycle 2 
(2 d)
Cycles 36
(2 d)
After last 
induction 
dose b
Monthly
Every 
2 months
(1 wk)
D1
D8
D15
D1
D1
D1
D1
Coagulation (INR, aPTT [or PTT], 
and PT)
x
Pregnancy test s
x
x g
x
Hepatitis B and C testing t
x
Quantitative IgA, IgG, IgM
x
x
x l
x
x u
TSH, T3, T4
x
Every 3 months
HAHA sample for obinutuzumab
x v
ATA sample for atezolizumab 
(MPDL3280A)
x v
PK sample for obinutuzumab
x v
PK sample for atezolizumab 
(MPDL3280A)
x v
Serum for soluble PD-L1
x
Whole blood for MRD w
x q
x
x l
Whole blood for lymphocyte 
immunophenotyping x
x q
x q
x q
x q
x
x l
x
x u
Whole blood for T-cell receptor 
repertoire in PBMCs
x q
x q
x q,y
x
x z
Serum for cytokine analysis
x q
x q
x q,y
Optional peripheral blood sample 
for RCR aa
x

Appendix 2
Schedule of Assessments for Patients with FL in the Atezo-G-CHOP Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
154/Protocol BO29563, Version 6
Screening a
Induction (4 months; 21-day cycles)
EOI
Maint. (24 months)
EOM c
Post-
Treatment
FU Period 
(q3m) d
Survival 
FU 
Period 
(q3m) d
D28 
to 
D1
D14 
to 
D1
Cycle 1 
(1 d)
Cycle 2 
(2 d)
Cycles 36
(2 d)
After last 
induction 
dose b
Monthly
Every 
2 months
35 days
after last 
dose
(1 wk)
D1
D8
D15
D1
D1
D1
D1
Tumor tissue specimen (leftover 
tissue may be used for optional 
RCR specimen aa)
x bb
x cc
x cc
Concomitant medications
x
To be recorded continually until end of treatment
Adverse events dd
x
To be assessed continually dd
PET-CT scan
x ee
x ff
x gg
CT scan hh
x hh
x ff
x ii
x m
x n
Bone marrow biopsy and aspirate 
x jj
x ff,kk
x kk
x m,kk
Study 
treatment 
administration
Obinutuzumab ll
x
x
x
x
x
x
Atezolizumab ll
x
x
D1, D2
CHOP ll
D15 of Cycles 16
New anti-lymphoma treatment
x
x
Survival follow-up
x
ATAanti-therapeutic antibody; Atezo-G-CHOPatezolizumab in combination with obinutuzumab plus CHOP; CHOPcyclophosphamide, 
doxorubicin, vincristine, and prednisone; CT computed tomography; Dday; Discont. discontinuation; ECOG Eastern Cooperative Oncology 
Group; eCRFelectronic Case Report Form; EOIend of induction; EOMend of maintenance; FLIPIFollicular Lymphoma International 
Prognostic Index; FU follow-up; HAHAhuman anti-human antibody; LVEFleft ventricular ejection fraction; Maint. maintenance; MRDminimal 
residual disease; MRImagnetic resonance imaging; MUGAmultiple-gated acquisition; NKnatural killer; PBMCperipheral blood mononuclear 
cell; PD-L1programmed deathligand 1; PET positron emission tomography; PKpharmacokinetic; q3m every 3 months; RCRRoche Clinical 
Repository; wk week.
Notes:  On treatment days, all assessments should be performed prior to dosing, unless otherwise specified.
Assessments shaded in gray should be performed as scheduled, but the associated data do not need to be recorded on the eCRF (except in the 
case of an adverse event).  

Appendix 2
Schedule of Assessments for Patients with FL in the Atezo-G-CHOP Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
155/Protocol BO29563, Version 6
a The screening period starts with the signing of the Informed Consent Form.  Results of standard-of-care tests or examinations performed prior to 
obtaining informed consent and within the defined window may be used as screening and baseline assessments; such tests do not need to be 
repeated for screening purposes.
b EOI assessments should be performed 68 weeks after Day 1 of the last induction cycle.  As an exception, patients who discontinue induction 
treatment prematurely because of an adverse event may undergo EOI assessments 48 weeks after their last dose of study treatment.
c Patients who complete maintenance treatment or discontinue maintenance treatment prematurely will undergo assessments at EOM.
d Patients who complete treatment or discontinue treatment for reasons other than disease progression will undergo assessments every 3 months 
during the post-treatment FU period, which will continue until disease progression, the start of new anti-lymphoma treatment, or the end of the 
study, whichever occurs first.  The first post-treatment FU visit is 3 months after the EOI visit for patients who do not receive maintenance 
treatment and 3 months after the last dose for patients who receive maintenance treatment.  Patients who experience disease progression will 
undergo limited assessments every 3 months during the survival FU period, which will continue until the end of the study.  The end of the study is 
defined as the time when all enrolled FL patients have completed or discontinued study treatment and all enrolled DLBCL patients have been 
followed for at least 1 year after they have completed or discontinued study treatment. 
e Informed consent must be documented before any study-specific screening procedure is performed.  
f
Vital signs include respiratory rate, pulse rate, body temperature, and systolic and diastolic blood pressures while the patient is in a seated 
position.  For obinutuzumab infusions:  For the first cycle and for patients who experience an infusion-related reaction, vital signs will be 
measured prior to the infusion, every 15 (5) minutes for the first 90 minutes of the infusion, and then every 30 (10) minutes until 1 hour after 
completion of the infusion.  For the second and subsequent cycles, vital signs will be measured every 30 minutes during the infusion, except in 
patients who had experienced an infusion-related reaction during a prior infusion.  For atezolizumab infusions:  Vital signs should be determined 
up to 60 (15) minutes before each atezolizumab infusion. Vital signs should also be obtained during or after the atezolizumab infusion if 
clinically indicated. 
g Perform only in patients who will not be receiving maintenance treatment.
h Includes evaluation of the head, eyes, ears, nose, and throat, and the cardiovascular, dermatological, musculoskeletal, respiratory, 
gastrointestinal, genitourinary, and neurological systems.  Record abnormalities observed at baseline on the General Medical History and 
Baseline Conditions eCRF.
i
As part of tumor assessment, the physical examination should include evaluation for the presence of enlarged nodes, palpable hepatomegaly, 
and splenomegaly.  This information will be recorded on the appropriate tumor assessment eCRF.
j
Includes systems of primary relevance (e.g., cardiovascular and respiratory systems), systems associated with symptoms (newly emergent or 
monitored from baseline), and areas associated with tumor assessment (lymph nodes, liver, spleen, and any other areas identified at baseline).  
Record new or worsened clinically significant abnormalities on the Adverse Event eCRF.
k Unexplained fever 38C, night sweats, unexplained weight loss 10% of body weight over 6 months.

Appendix 2
Schedule of Assessments for Patients with FL in the Atezo-G-CHOP Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
156/Protocol BO29563, Version 6
l
Perform at the same time as tumor assessments at 12, 18, and 24 months after initiation of induction treatment.
m Perform only if not done within the previous 3 months.
n Perform every 6 months.
o Includes hemoglobin, hematocrit, platelet count, RBC count, WBC count, and percent or absolute WBC differential count (neutrophils, 
eosinophils, basophils, monocytes, lymphocytes, other cells).
p Screening laboratory assessments may be used for Day 1 of Cycle 1 if performed within 72 hours prior to Day 1 of Cycle 1.
q Perform hematology and chemistry tests within 72 hours prior to Day 1 of each cycle, and within 24 hours prior to Days 8 and 15 of Cycle 1.  
Samples for exploratory biomarker research should be collected at the same time as hematology and chemistry samples.
r
Includes sodium, potassium, glucose, BUN or urea, creatinine, calculated creatinine clearance, calcium, total bilirubin, direct bilirubin, 
total protein, albumin, ALT, AST, alkaline phosphatase, amylase, lipase, LDH, and uric acid.
s All women who are not postmenopausal (12 months of non-therapy-induced amenorrhea) or surgically sterile will have a serum pregnancy test 
at screening within 7 days prior to Day 1 of Cycle 1.
t
Includes hepatitis B surface antigen, total hepatitis B core antibody, and hepatitis C virus antibody.
u Perform every 3 months until disease progression, or the start of new anti-lymphoma treatment, whichever occurs first.
v See Appendix 5 for detailed schedule.
w Includes circulating lymphoma cells and/or cell-free circulating tumor DNA.
x Includes B-cell counts (CD19), T-cell counts (CD3, CD4, and CD8), and NK-cell counts (CD16 and CD56).
y Cycle 3 only.
z Perform at the same time as tumor assessments at 12 and 18 months after initiation of induction treatment.
aa Requires separate patient consent for RCR participation.  Not applicable for a site that has not been granted approval for RCR sampling.
bb Availability of adequate archival or freshly biopsied tumor tissue samples should be confirmed at screening (see Section 4.5.6 for details).
cc A tumor biopsy sample will be collected prior to the start of Cycle 2 and at the time of progression unless no adequate tumor site is accessible. 
dd After informed consent has been obtained but prior to initiation of study treatment, only serious adverse events caused by a protocol-mandated 
intervention should be reported.  After initiation of study treatment, all adverse events will be reported until 90 days after the last dose of study 
treatment.  After this period, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be 
related to prior study treatment (see Section 5.6).  An exception is made for Grade 3–4 infections (related and unrelated), which should be 
reported until up to 2 years after the last dose of obinutuzumab.  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 patient is lost to follow-up, or the patient withdraws consent.  
Every effort should be made to follow all serious adverse events considered to be related to any of the study treatment components or 
trial-related procedures until a final outcome can be reported.
ee The screening PET-CT scan must be performed within 35 days prior to Day 1 of Cycle 1.

Appendix 2
Schedule of Assessments for Patients with FL in the Atezo-G-CHOP Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
157/Protocol BO29563, Version 6
ff Perform only for patients who have received at least two cycles of induction treatment.
gg If PET-CT scan is positive at EOI, perform at 12 months after initiation of induction treatment, within 14 days prior to treatment administration.
hh CT scan of the neck (if clinically indicated), chest, abdomen and pelvis.  If contrast is medically contraindicated (e.g., patients with contrast allergy 
or impaired renal clearance), MRI scans of the chest, abdomen, and pelvis (and neck, if clinically indicated) and a non-contrast CT scan of the 
chest may be performed.  Combined PET/CT scanners may be used to collect diagnostic CT scans, but only according to the technical guidelines 
in the imaging manual.  Screening CT scan must be performed within 35 days prior to Day 1 of Cycle 1.
ii Perform at 12, 18, and 24 months after initiation of induction treatment, within 14 days prior to treatment administration.  
jj Bone marrow biopsy and aspirate must be performed within approximately 3 months prior to Day 1 of Cycle 1.
kk For patients with bone marrow involvement at screening, a repeat assessment will be performed at EOI if there is radiologic evidence of a 
complete response, and during maintenance or at EOM if there is radiologic evidence of a complete response or if clinically indicated (e.g., if 
there is clinical suspicion of progressive disease in the bone marrow with no radiologic evidence of progression).
ll Refer to Sections 4.3.2.7 and 4.3.2.8 for details on dosing and schedule.
mm 
Patient may be assessed every 2 month if atezolizumab has been discontinued and maintenance treatment is continued with obinutuzumab 
single agent.

Appendix 3
Schedule of Assessments for Patients with DLBCL in the Atezo-R-CHOP Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
159/Protocol BO29563, Version 6
Screening a
Induction 
(6 months; 21-day cycles)
EOI
Consolidation
(21-day cycles)
EOC c
Post-
Treatment
FU Period 
(q3m) d
Survival 
FU 
Period 
(q3m) d
D28 
to 
D1
D14 
to 
D1
Cycle 1 
(1 d)
Cycle 2 
(2 d)
Cycles 38
(2 d)
After last 
induction 
dose b
Cycles 925 
(3 days)
35 days
after last 
dose
D1
D1
D1
D1
Coagulation (INR, aPTT [or 
PTT], and PT)
x
Pregnancy test r
x
x g
x
Hepatitis B and C testing s
x
Quantitative IgA, IgG, IgM
x
x
x
x
TSH, T3, T4
x
Every 3 months
HACA sample for rituximab
x t
ATA sample for atezolizumab 
(MPDL3280A)
x t
PK sample for rituximab
x t
PK sample for atezolizumab 
(MPDL3280A)
x t
Serum for soluble PD-L1
x
Whole blood for MRD u
x p
x
Within 1 week 
prior to C17
x
x
Whole blood for lymphocyte 
immunophenotyping v
x p
x p
x p
x
Within 1 week 
prior to C17
x
x
Whole blood for T-cell receptor 
repertoire in PBMCs
x p
x p
x p, w
x
Within 1 week 
prior to C17
x
x

Appendix 3
Schedule of Assessments for Patients with DLBCL in the Atezo-R-CHOP Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
160/Protocol BO29563, Version 6
Screening a
Induction 
(6 months; 21-day cycles)
EOI
Consolidation
(21-day cycles)
EOC c
Post-
Treatment
FU Period 
(q3m) d
Survival 
FU 
Period 
(q3m) d
D28 
to 
D1
D14 
to 
D1
Cycle 1 
(1 d)
Cycle 2 
(2 d)
Cycles 38
(2 d)
After last 
induction 
dose b
Cycles 925 
(3 days)
35 days
after last 
dose
D1
D1
D1
D1
Serum for cytokine analysis
x p
x p
x p, w
Optional peripheral blood 
sample for RCR x
x
Tumor tissue specimen (leftover 
tissue may be used for optional 
RCR specimen x)
x y
x z
x z
Concomitant medications
x
To be recorded continually until end of treatment
Adverse events aa
x
To be recorded continually aa
PET-CT scan
x bb
x cc
CT scan dd
x dd
x cc
Within 1 week 
prior to C17
x l
x m
Bone marrow biopsy and 
aspirate 
x ee
x cc, ff
x ff
x l, ff
Study 
treatment 
administration
Rituximab gg
x
x
x
Atezolizumab gg
x
x
x
CHOP gg
D15
D15 of Cycles 26/8
New anti-lymphoma treatment
x
x
Survival follow-up
x

Appendix 3
Schedule of Assessments for Patients with DLBCL in the Atezo-R-CHOP Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
161/Protocol BO29563, Version 6
ATAanti-therapeutic antibody; Atezo-R-CHOPatezolizumab in combination with rituximab plus CHOP; Ccycle; CHOPcyclophosphamide, 
doxorubicin, vincristine, and prednisone; CT computed tomography; Dday; Discont. discontinuation; DLBCLdiffuse large B-cell lymphoma; 
ECOGEastern Cooperative Oncology Group; eCRF electronic Case Report Form; EOCend of consolidation; EOIend of induction; 
FU follow-up; HAHAhuman anti-human antibody; IPIInternational Prognostic Index; LVEF left ventricular ejection fraction; MRDminimal 
residual disease; MRImagnetic resonance imaging; MUGAmultiple-gated acquisition; NKnatural killer; PBMCperipheral blood mononuclear 
cell; PD-L1programmed deathligand 1; PET positron emission tomography; PKpharmacokinetic; q3m every 3 months; RCRRoche Clinical 
Repository; wk week.
Notes:  On treatment days, all assessments should be performed prior to dosing, unless otherwise specified.
Assessments shaded in gray should be performed as scheduled, but the associated data do not need to be recorded on the eCRF (except in the 
case of an adverse event).  
a The screening period starts with the signing of the Informed Consent Form.  Results of standard-of-care tests or examinations performed prior to 
obtaining informed consent and within the defined window may be used as screening and baseline assessments; such tests do not need to be 
repeated for screening purposes.
b EOI assessments should be performed 68 weeks after Day 1 of the last induction cycle.  As an exception, patients who discontinue induction 
treatment prematurely because of an adverse event may undergo EOI assessments 48 weeks after their last dose of study treatment.
c Patients who complete consolidation treatment or discontinue consolidation treatment prematurely will undergo assessments at EOC.
d Patients who complete treatment or discontinue treatment for reasons other than disease progression will undergo assessments every 3 months 
during the post-treatment FU period, which will continue until disease progression, the start of new anti-lymphoma treatment, or the end of the 
study, whichever occurs first.  The first post-treatment FU visit is 3 months after the EOI visit for patients who do not receive consolidation 
treatment and 3 months after the last dose for patients who receive consolidation treatment.  Patients who experience disease progression will 
undergo limited assessments every 3 months during the survival FU period, which will continue until the end of the study.  The end of the study is 
defined as the time when all enrolled FL patients have completed or discontinued study treatment and all enrolled DLBCL patients have been 
followed for at least 1 year after they have completed or discontinued study treatment. 
e Informed consent must be documented before any study-specific screening procedure is performed.  
f
Vital signs include respiratory rate, pulse rate, body temperature, and systolic and diastolic blood pressures while the patient is in a seated 
position.  For rituximab infusions:  Vital signs monitoring during infusion should be determined as per local label.  For atezolizumab infusions:  
Vital signs should be determined up to 60 (15) minutes before each atezolizumab infusion. Vital signs should also be obtained during or after 
the atezolizumab infusion if clinically indicated.
g Perform only in patients who will not be receiving consolidation treatment.

Appendix 3
Schedule of Assessments for Patients with DLBCL in the Atezo-R-CHOP Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
162/Protocol BO29563, Version 6
h Includes evaluation of the head, eyes, ears, nose, and throat, and the cardiovascular, dermatological, musculoskeletal, respiratory, 
gastrointestinal, genitourinary, and neurological systems.  Record abnormalities observed at baseline on the General Medical History and 
Baseline Conditions eCRF.
i
As part of tumor assessment, the physical examination should include evaluation for the presence of enlarged nodes, palpable hepatomegaly, 
and splenomegaly.  This information will be recorded on the appropriate tumor assessment eCRF.
j
Includes systems of primary relevance (e.g., cardiovascular and respiratory systems), systems associated with symptoms (newly emergent or 
monitored from baseline), and areas associated with tumor assessment (lymph nodes, liver, spleen, and any other areas identified at baseline).  
Record new or worsened clinically significant abnormalities on the Adverse Event eCRF.
k Unexplained fever 38C, night sweats, unexplained weight loss 10% of body weight over 6 months.
l
Perform only if not done within the previous 3 months.
m Perform every 6 months.
n Includes hemoglobin, hematocrit, platelet count, RBC count, WBC count, and percent or absolute WBC differential count (neutrophils, 
eosinophils, basophils, monocytes, lymphocytes, other cells).
o Screening laboratory assessments may be used for Day 1 of Cycle 1 if performed within 72 hours prior to Day 1 of Cycle 1.
p Perform hematology and chemistry tests within 72 hours prior to Day 1 of each cycle and within 24 hours prior to other timepoints during 
induction treatment.  Samples for exploratory biomarker research should be collected at the same time as hematology and chemistry samples.
q Includes sodium, potassium, glucose, BUN or urea, creatinine, calculated creatinine clearance, calcium, total bilirubin, direct bilirubin, 
total protein, albumin, ALT, AST, alkaline phosphatase, amylase, lipase, LDH, and uric acid.
r
All women who are not postmenopausal (12 months of non-therapy-induced amenorrhea) or surgically sterile will have a serum pregnancy test 
at screening within 7 days prior to Day 1 of Cycle 1.
s Includes hepatitis B surface antigen, total hepatitis B core antibody, and hepatitis C virus antibody.
t
See Appendix 6 for detailed schedule.
u Includes circulating lymphoma cells and/or cell-free circulating tumor DNA.
v Includes B-cell counts (CD19), T-cell counts (CD3, CD4, and CD8), and NK-cell counts (CD16 and CD56).
w Cycle 3 only.
x Requires separate patient consent for RCR participation.  Not applicable for a site that has not been granted approval for RCR sampling.
y Availability of adequate archival or freshly biopsied tumor tissue samples should be confirmed at screening (see Section 4.5.6 for details).
z A tumor biopsy sample will be collected prior to the start of Cycle 2 and at the time of progression unless no adequate tumor site is accessible.

Appendix 3
Schedule of Assessments for Patients with DLBCL in the Atezo-R-CHOP Treatment Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
163/Protocol BO29563, Version 6
aa After informed consent has been obtained but prior to initiation of study treatment, only serious adverse events caused by a protocol-mandated 
intervention should be reported.  After initiation of study treatment, all adverse events will be reported until 90 days after the last dose of study 
treatment.  After this period, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be 
related to prior study treatment (see Section 5.6).  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 patient is lost to follow-up, or the patient withdraws consent.  Every effort 
should be made to follow all serious adverse events considered to be related to any of the study treatment components or trial-related procedures 
until a final outcome can be reported.
bb The screening PET-CT scan must be performed within 35 days prior to Day 1 of Cycle 1.
cc Perform only for patients who have received at least two cycles of induction treatment.
dd CT scan of the neck (if clinically indicated), chest, abdomen and pelvis.  If contrast is medically contraindicated (e.g., patients with contrast allergy 
or impaired renal clearance), MRI scans of the chest, abdomen, and pelvis (and neck, if clinically indicated) and a non-contrast CT scan of the 
chest may be performed.  Combined PET/CT scanners may be used to collect diagnostic CT scans, but only according to the technical guidelines 
in the imaging manual.  Screening CT scan must be performed within 35 days prior to Day 1 of Cycle 1.
ee Bone marrow biopsy and aspirate must be performed within 3 approximately months prior to Day 1 of Cycle 1.
ff For patients with bone marrow involvement at screening, a repeat assessment will be performed at EOI if there is radiologic evidence of a 
complete response, and during consolidation and at EOC if clinically indicated (e.g., if there is clinical suspicion of progressive disease in the 
bone marrow with no radiologic evidence of progression).
gg Refer to Sections 4.3.2.7 and 4.3.2.8 for details on dosing and schedule.

Appendix 4
Pharmacokinetic and Immunogenicity Sampling Schedule for the Atezo-G-Benda Treatment 
Group (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
166/Protocol BO29563, Version 6
Study Visit
Serum Obinutuzumab 
Pharmacokinetic Sample a
Serum Atezolizumab 
Pharmacokinetic Sample
Serum Obinutuzumab 
HAHA Sample
Serum Atezolizumab 
ATA Sample
Months 7, 15, 
and 23
Day 1
Prior to obinutuzumab infusion
(within 5 hr prior to dose);
After obinutuzumab infusion
(30 min [10 min] after end of 
infusion)
Prior to atezolizumab infusion
(within 5 hr prior to dose)

Prior to atezolizumab 
infusion (any time prior 
to dose)
Treatment discontinuation
x
x
x
x
120 days (30 days) after 
last dose of obinutuzumab 
and last dose of 
atezolizumab (as appropriate 
for sample) 
x
x
x
x
1 year after the last dose of 
obinutuzumab and last dose 
of atezolizumab (as 
appropriate for sample)
x
x
x
x
ATAanti-therapeutic antibody; Atezo-G-bendaatezolizumab in combination with obinutuzumab plus bendamustine; FLfollicular lymphoma; 
HAHAhuman anti-human antibody.
a Following analysis of the serum pharmacokinetic sample for obinutuzumab quantitation, the remaining sample may be used for HAHA 
analysis (if HAHA analysis is not already planned at that timepoint) at the discretion of the clinical pharmacologist and/or the clinical scientist, 
should there be any unusual results in the obinutuzumab concentrations.
b If the Cycle 1, Day 1 dose of obinutuzumab is split over 2 days, take the “30 minutes after the end of infusion obinutuzumab” PK sample 
relative to the end of the infusion on Day 2, and ensure that the date and time of the PK collection are accurately recorded.

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
173/Protocol BO29563, Version 6
Appendix 7
Lugano Response Criteria for Malignant Lymphoma
(Cheson et al. 2014)
In this study, only positron emission tomography and computed tomography 
(PET-CT)based response criteria will be used with the following modifications:  

If the bone marrow was involved by lymphoma before treatment, the designation 
of a complete response (CR) requires normal bone marrow by morphology.  
If indeterminate by morphology, immunohistochemistry should be negative.

The designation of PET-CT-based partial response (PR) requires that CT-based 
response criteria for a CR or PR be met in addition to the PET-CT-based response 
criteria for a PR

Appendix 7
Lugano Response Criteria for Malignant Lymphoma
(Cheson et al. 2014) (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
174/Protocol BO29563, Version 6

Appendix 7
Lugano Response Criteria for Malignant Lymphoma
(Cheson et al. 2014) (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
175/Protocol BO29563, Version 6
REFERENCE
Cheson B, Fisher R, Barrington S, et al. Recommendations for initial evaluation, staging 
and response assessment of Hodgkin and nonHodgkin lymphoma: The Lugano 
Classification. J Clin Oncol 2014;32:305969.

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
176/Protocol BO29563, Version 6
Appendix 8
Summary of Criteria for Tumor Measurements
Summary of Criteria for Tumor Measurements
Criteria for tumor measurements, which are based on the modified Cheson 2007 criteria, 
are presented below.
Selection of Target Lesions at Baseline
Up to six of the largest dominant nodes or tumor masses (extranodal) should be 
selected according to all of the following:

Lesions should be clearly measurable in at least two perpendicular dimensions.

All nodal lesions must measure either 1.5 cm in long axis regardless of short axis 
measurement or 1.0 cm in short axis with a long axis of 1.1 to 1.5 cm.

Measurable extranodal disease should be assessed in a manner similar to that used 
for nodal disease.  All measurable extranodal lesions must be 1.0 cm in the long 
axis and twice the reconstruction interval of the scan.  Extranodal lesions within the 
liver or spleen must be at least 1.0 cm in two perpendicular dimensions

If possible, the lesions should be from disparate regions of the body.

Lesions should include mediastinal and retroperitoneal areas of disease whenever 
these sites are involved.
Selection of Non-Target Lesions
Non-target lesions will be qualitatively assessed at each subsequent timepoint.  All of the 
sites of disease present at baseline and not classified as target lesions will be classified 
as non-target lesions, including nodal and extranodal (any measurable lesions that were 
not chosen as target lesions), and assessable disease.  Examples of non-target lesions 
include the following:

All bone lesions, irrespective of the modality used to assess them

Lymphangitis of the skin or lung

Cystic lesions

Splenomegaly and hepatomegaly

Measurable lesions beyond the maximum number of six

Groups of lesions that are small and numerous

Pleural/pericardial effusions and/or ascites

Appendix 8
Summary of Criteria for Tumor Measurements (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
177/Protocol BO29563, Version 6
For this study, a significant increase in existing pleural effusions, ascites, or other fluid 
collections will be considered sufficient evidence of progression and will not require 
cytological proof of malignancy.  Effusions, ascites, or other fluid collections will be 
followed as non-target lesions as outlined below:

Existing effusions/ascites:  Effusions, ascites, or other fluid collections will be 
followed as non-target lesions.  At each timepoint, radiologists will check for the 
presence or absence of effusions/ascites.  If there is a significant volume increase in 
the absence of a benign etiology, progression can be assessed.

New effusions/ascites:  Significant new effusions, ascites, or other fluid collections 
that are radiographically suggestive of malignancy should be recorded as new 
lesions.
Reporting Conventions
Unable to Evaluate Lesion Category
The unable to evaluate (UE) lesion category is reserved for target and non-target lesions 
that are deemed unevaluable because 1) subsequent (post-baseline) examinations had not 
been performed, 2) lesions could not be evaluated because of poor radiographic technique 
or poorly defined margins, or 3) lesions identified at baseline were not measurable at a 
subsequent timepoint.
Examples of UE lesions are a lung lesion in the hilum obstructing the bronchus and 
causing atelectasis of the lobe, or a hypodense liver lesion that becomes surrounded by 
fatty infiltration.  In both examples, the boundaries of the lesion can be difficult to 
distinguish.  Every effort should be made to assign measurements to lesions that develop 
less distinct margins because they become much smaller.  Another example is the instance 
when lesions identified at baseline were not imaged at a subsequent timepoint unless the 
lesions are not imaged because of complete resolution.  Lesions that cannot be measured 
or evaluated will be classified for that timepoint as UE.
If a target lesion is classified as UE after baseline, the sum of the product of the diameters 
(SPD) of the target lesions cannot accurately be determined for that timepoint, a response 
of complete response (CR), partial response (PR), or stable disease (SD) cannot be 
assigned for that timepoint, and the response assessment will be UE unless unequivocal 
progression is determined on the basis of non-target or new lesions, or the evaluable 
target lesions.
Progressive disease can be determined without evaluation of all sites of disease based 
on the SPD for target lesions, evaluation of unequivocal progression in non-target 
lesions, or observation of a new lesion within the available radiographic or clinical 
assessments.

Appendix 8
Summary of Criteria for Tumor Measurements (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
178/Protocol BO29563, Version 6
Too Small to Measure Lesion Category
In this trial, an average threshold of detection limit is set at 5 mm.  Any target lesion 
findings identified on baseline images that decrease in size to 5 mm in any dimension 
at a subsequent timepoint should be categorized as too small to measure.  The lesion, 
node, or mass should be assigned measurements of 5 5 mm (for the long axis and the 
short axis) on the source document for the purpose of calculating the area.  If that lesion 
increases in size to 5 mm in any dimension afterwards, its true size (long axis and 
short axis) should be recorded.  The purpose of the assigned value for the measurement 
is the acknowledgment that small findings are not accurately measured.

Appendix 8
Summary of Criteria for Tumor Measurements (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
179/Protocol BO29563, Version 6
Timepoint Radiological Response
Target Lesions
Non-Target Lesions
New Lesion a
Timepoint Response
CR
CR
No
CR
CR
SD
No
PR
CR
UE
No
UE
PR
UE
No
UE
PR
CR
No
PR
PR
SD
No
PR
SD
UE
No
UE
SD
CR
No
SD
SD
SD
No
SD
PD
Any
Yes/No
PD
Any
PD
Yes/No
PD
Any
Any
Yes
PD
UE
Non-PD
No
UE
UE
UE
No
UE
CR
NA b
No
CR
PR
NA b
No
PR
SD
NA b
No
SD
NA c
SD
No
SD
NA c
CR
No
CR
NA c
UE
No
UE
NA c
NA b
No
UE
CRcomplete response; NAnot applicable; PDprogressive disease; PRpartial 
response; SDstable disease; UEunable to evaluate.
a Identification of new lesions at a post-baseline timepoint will result in a response 
assessment of PD.  If an identified new lesion subsequently becomes UE, the timepoint 
response will be recorded as PD unless the new lesion has proven to have resolved.  
b No non-target lesions identified at baseline.
c No target lesions identified at baseline.
Adapted from:
Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant 
lymphoma. J Clin Oncol 2007;25:579–86.

Appendix 8
Summary of Criteria for Tumor Measurements (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
180/Protocol BO29563, Version 6
Response should be determined on the basis of computed tomography (CT) scan and 
confirmed with positron emission tomography (PET)-CT using the modified Cheson 2007
criteria.  The modified Cheson 2007 criteria are presented below, with slight 
modifications for consistency with the protocol.
Assessment of positive PET scans should follow the criteria described by Consensus of 
the Imaging Subcommittee of International Harmonization Project in Lymphoma
(Juweid et al. 2007).  A positive focal or diffuse fluorodeoxyglucose (FDG)-PET scan is 
defined as follows:  FDG uptake above background in a location incompatible with 
normal anatomy or physiology, without a specific standardized uptake value cutoff.
Complete Response
Based on CT imaging, the designation of CR requires all of the following:

Complete disappearance of all detectable clinical evidence of disease 
and disease-related symptoms if present prior to therapy must be demonstrated.

The spleen and/or liver, if considered enlarged prior to therapy on the basis of 
a physical examination or CT scan, should not be palpable on physical examination 
and should be considered normal in size by imaging studies, and nodules related to 
lymphoma should disappear.  However, determination of splenic involvement is not
always reliable because a spleen considered normal in size may still contain 
lymphoma, whereas an enlarged spleen may reflect variations in anatomy, blood 
volume, the use of hematopoietic growth factors, or causes other than lymphoma.

If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must 
have cleared on repeat bone marrow biopsy.  The biopsy sample on which this 
determination is made must be adequate (20 mm unilateral core).  If the sample 
is indeterminate by morphology, it should be negative by immunohistochemistry.  
A sample that is negative by immunohistochemistry but demonstrating a small 
population of clonal lymphocytes by flow cytometry will be considered a CR until 
data become available demonstrating a clear difference in patient outcome. 
Based on PET-CT imaging, the designation of CR requires the following: 

For patients with a positive PET scan before treatment:  Post-treatment residual 
masses of any size must be PET negative.

Appendix 8
Summary of Criteria for Tumor Measurements (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
181/Protocol BO29563, Version 6
Partial Response
Based on CT imaging, the designation of PR requires all of the following: 

A 50% decrease in the SPD of up to six of the largest dominant nodes or nodal 
masses must be demonstrated.  These nodes or masses should be selected 
according to all of the following:  (a) they should be clearly measurable in at least 
two perpendicular dimensions; (b) if possible, they should be from disparate regions 
of the body; and (c) they should include mediastinal and retroperitoneal areas of 
disease whenever these sites are involved.

No increase in the size of the other nodes, liver, or spleen should be observed.

Splenic and hepatic nodules must regress by 50% in their SPD or, for single 
nodules, in the long axis.

With the exception of splenic and hepatic nodules, involvement of other organs 
is usually assessable and no measurable disease should be present.

Bone marrow assessment is irrelevant for determination of a PR if the sample was 
positive prior to treatment.  However, if positive, the cell type should be specified 
(e.g., large-cell lymphoma or small neoplastic B cells).  Patients who achieve a CR 
by the above criteria, but who have persistent morphologic bone marrow 
involvement, will be considered partial responders.

No new sites of disease should be observed (e.g., nodes 1.5 cm in any axis).
Based on PET-CT imaging, the designation of PR requires the following: 

For patients with a positive PET scan before treatment:  The post-treatment PET 
should be positive in at least one previously involved site. 
Stable Disease
Based on CT imaging, SD is defined as the following:  

The patient does not meet the criteria needed for a CR or PR and does not meet the 
criteria for progressive disease (see below).
Based on PET-CT imaging, SD is defined as the following:

For patients with a positive PET scan before treatment:  The PET scan should be 
positive at prior sites of disease with no new areas of involvement on the 
post-treatment CT or PET-CT scan.  

Appendix 8
Summary of Criteria for Tumor Measurements (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
182/Protocol BO29563, Version 6
Progressive Disease
Lymph nodes should be considered abnormal if the long axis is 1.5 cm, regardless of 
the short axis.  If a lymph node has a long axis of 1.11.5 cm, it should only be 
considered abnormal if its short axis is 1.0.  Lymph nodes 1.01.0 cm will not be 
considered as abnormal for relapsed or progressive disease.
Based on CT imaging, the designation of progressive disease (PD) requires any of the 
following: 

Appearance of any new lesion 1.5 cm in any axis during or at the end of therapy is 
demonstrated, even if other lesions are decreasing in size.

There is a 50% increase from the nadir in the SPD of any previously involved 
nodes, or in a single involved node, or the size of other lesions (e.g., splenic or 
hepatic nodules).  To be considered progressive disease, a lymph node with a 
diameter of the short axis of 1.0 cm must increase by 50% and to a size 
of 1.51.5 cm, or 1.5 cm in the long axis.

There is a 50% increase in the long axis of any single previously identified node 
with a short axis 1 cm.
Based on PET-CT imaging, the designation of PD requires any of the following: 

For patients with a positive PET scan before treatment:  Lesions should be PET 
positive, unless the lesion is too small to be detected with current PET system 
(1.5 cm in its long axis by CT). 
Increased FDG uptake in a previously unaffected site should only be 
considered progressive disease after confirmation with other modalities.
Additional Response Assessment Guidelines
If a small increase is seen in only one lesion, a new evaluation after some weeks may be 
necessary to determine whether there was true progression in that lesion.
Because the potential for tumor flares with immunotherapies increases the risk of false 
positive PET-CT scans in lymphoma, caution must be exercised to avoid confusing the 
possible tumor flare with progressive disease.  In the event of residual metabolically 
active tissue, it is recommended that either a biopsy be performed or the lesion be 
reassessed in at least 2 weeks; if there is continued evidence of tumor progression, the 
date of progressive disease should be the date of the previous evaluation.

Appendix 8
Summary of Criteria for Tumor Measurements (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
183/Protocol BO29563, Version 6
REFERENCES
Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant 
lymphoma. J Clin Oncol 2007;25:57986.
Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for 
response assessment of lymphoma: consensus of the imaging subcommittee of 
international harmonization project in lymphoma. J Clin Oncol 2007;25:5718.

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
184/Protocol BO29563, Version 6
Appendix 9
Eastern Cooperative Oncology Group 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.

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
185/Protocol BO29563, Version 6
Appendix 10
Ann Arbor Staging
Grade
Description
Stage I
Involvement of a single lymph node region (I) or of a single 
extralymphatic organ or site (IE) a
Stage II
Involvement of two or more lymph node regions or lymphatic 
structures on the same side of the diaphragm alone (II) or with 
involvement of limited, contiguous extralymphatic organ or tissue 
(IIE)
Stage III
Involvement of lymph node regions on both sides of the diaphragm 
(III), which may include the spleen (IIIS) or limited, contiguous 
extralymphatic organ or site (IIIE), or both (IIIES)
Stage IV b
Diffuse or disseminated foci of involvement of one or more 
extralymphatic organs or tissues, with or without associated 
lymphatic involvement
Note:  All cases are subclassified to indicate the absence (A) or presence (B) of the systemic 
B symptoms of significant unexplained fever (38C), night sweats, or unexplained weight loss 
exceeding 10% of body weight during the 6 months prior to diagnosis.
a The designation “E” generally refers to extranodal contiguous extension (i.e., proximal or 
contiguous extranodal disease) that can be encompassed within an irradiation field appropriate 
for nodal disease of the same anatomic extent.  A single extralymphatic site as the only site of 
disease should be classified as IE, rather than Stage IV.
b Involvement of bone marrow at screening will always qualify for Ann Arbor Stage IV and 
should be recorded as extranodal involvement.
Adapted from:
Carbone PP, Kaplan HS, Musshoff K, et al. Report of the committee on Hodgkin’s disease 
staging classification. Cancer Res 1971;31:18601.
Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the 
evaluation and staging of patients with Hodgkin’s disease: Cotswolds Meeting. J Clin Oncol 
1989;7:16306.

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
186/Protocol BO29563, Version 6
Appendix 11
Follicular Lymphoma International Prognostic Index and 
International Prognostic Index
Table 1
Follicular Lymphoma International Prognostic Index
FLIPI Risk Factor
Ann Arbor Stage III or IV
Age 60 years
Serum LDH 1ULN
Anemia (hemoglobin 120 g/L)
Involved nodal areas 4
FLIPI Risk Group
Number of FLIPI Risk Factors
Low
0 or 1
Intermediate
2
High
3 to 5
FDGfluorodeoxyglucose; FLIPIFollicular Lymphoma International Prognostic Index; 
PET positron emission tomography; ULNupper limit of normal.
Note:  The results of FDG-PET should not be taken into account for calculation of FLIPI since this 
prognostic score was established without FDG-PET.
Adapted from:
Solal-Celigny P, Roy P, Colombat P, et al. Follicular lymphoma international prognostic index. 
Blood 2004;104:1258–64.

Appendix 11
Follicular Lymphoma International Prognostic Index and 
International Prognostic Index (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
187/Protocol BO29563, Version 6
Table 2
Follicular Lymphoma International Prognostic Index 2
FLIPI2 Risk Factor
Bone marrow involvement
Age 60 years
2 microglobulin 1ULN
Anemia (hemoglobin 120 g/L)
Longest diameter of largest involved node 6 cm
FLIPI2 Risk Group
Number of FLIPI2 Risk Factors
Low
0 
Intermediate
1 or 2
High
3 to 5
FDGfluorodeoxyglucose; FLIPI2Follicular Lymphoma International Prognostic Index 2; 
PET positron emission tomography; ULNupper limit of normal.
Note:  The results of FDG-PET should not be taken into account for calculation of FLIPI2 since 
this prognostic score was established without FDG-PET.
Adapted from:
Federico M, Bellei M, Marcheselli L, et al. Follicular Lymphoma International Prognostic Index 2: 
a new prognostic index for follicular lymphoma developed by the International Follicular 
Lymphoma Prognostic Factor Project. J Clin Oncol 2009;27:455562.

Appendix 11
Follicular Lymphoma International Prognostic Index and 
International Prognostic Index (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
188/Protocol BO29563, Version 6
Table 3
International Prognostic Index
IPI Risk Factor
Ann Arbor Stage III or IV
Age 60 years
Serum LDH 1ULN
ECOG Performance Status 2
Extranodal involvement 2
IPI Risk Group
Number of IPI Risk Factors
Low
0 or 1
LowIntermediate
2
HighIntermediate
3
High
4 or 5
ECOGEastern Cooperative Oncology Group; FDGfluorodeoxyglucose; IPIInternational 
Prognostic Index; PET positron emission tomography; ULNupper limit of normal.
Note:  The results of FDG-PET should not be taken into account for calculation of IPI since this 
prognostic score was established without FDG-PET.
Adapted from:  
Shipp MA, Harrington DP, Anderson JR, et al. A predictive model for aggressive non-Hodgkin’s 
lymphoma. N Engl J Med 1993;329:98794.

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
189/Protocol BO29563, Version 6
Appendix 12
Anaphylaxis Precautions
EQUIPMENT NEEDED

Tourniquet

Oxygen

Epinephrine for subcutaneous, intravenous (IV), and/or endotracheal use in 
accordance with standard practice 

Antihistamines

Corticosteroids

IV infusion solutions, tubing, catheters, and tape
PROCEDURES
In the event of a suspected anaphylactic reaction during study treatment infusion, the 
following procedures should be performed:

Stop the study treatment infusion.

Apply a tourniquet proximal to the injection site to slow systemic absorption of study 
treatment.  Do not obstruct arterial flow in the limb.

Maintain an adequate airway.

Administer glucocorticoids, antihistamines, epinephrine, or other medications as 
required by patient status and directed by the physician in charge.

Continue to observe the patient and document observations.

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
190/Protocol BO29563, Version 6
Appendix 13
Preexisting Autoimmune Diseases
Patients should be carefully questioned regarding their history of acquired or congenital 
immune deficiencies or autoimmune disease.  Patients with any history of immune 
deficiencies or autoimmune disease listed in the table below will be excluded from 
participating in the study.  Possible exceptions to this exclusion could be patients with a 
medical history of such entities as atopic disease or childhood arthralgias where the 
clinical suspicion of autoimmune disease is low.  Patients with a history of 
autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone 
may be eligible for this study.  In addition, patients with transient autoimmune 
manifestations of an acute infectious disease that resolved upon treatment of the 
infectious agent are not excluded (e.g., acute Lyme arthritis).  Please contact the 
Medical Monitor regarding any uncertainty over autoimmune exclusions.
Acute disseminated
encephalomyelitis
Addison’s disease
Ankylosing spondylitis
Antiphospholipid antibody
syndrome
Aplastic anemia
Autoimmune hemolytic anemia
Autoimmune hepatitis
Autoimmune
hypoparathyroidism
Autoimmune hypophysitis
Autoimmune myocarditis
Autoimmune oophoritis
Autoimmune orchitis
Autoimmune 
thrombocytopenic
purpura
Behcet’s disease
Bullous pemphigold
Chronic inflammatory
demyelinating
polyneuropathy
Chung-Strauss syndrome
Crohn’s disease 
Dermatomyositis
Diabetes mellitus type 1
Dysautonomia
Epidermolysis bullosa acquista
Gestational pemphigoid
Giant cell arteritis
Goodpasture’s syndrome
Graves’ disease
Guillain-Barré syndrome
Hashimoto’s disease
IgA nephropathy
Inflammatory bowel disease
Interstitial cystitis
Kawasaki’s disease
Lambert-Eaton myasthenia
syndrome
Lupus erythematosus
Lyme disease - chronic
Meniere’s syndrome
Mooren’s ulcer
Morphea
Multiple sclerosis
Myasthenia gravis
Myasthenia gravis
Neuromyotonia
Opsoclonus myoclonus
syndrome
Optic neuritis
Ord’s thyroiditis
Pemphigus
Pernicious anemia
Polyarteritis nodusa
Polyarthritis
Polyglandular autoimmune
syndrome
Primary biliary cirrhosis
Psoriasis
Reiter’s syndrome
Rheumatoid arthritis
Sarcoidosis
Scleroderma
Sjögren’s syndrome
Stiff-Person syndrome
Takayasu’s arteritis
Ulcerative colitis
Vitiligo
Vogt-Kovanagi-Harada 
disease
Wegener’s granulomatosis

Appendix 13
Preexisting Autoimmune Diseases (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
191/Protocol BO29563, Version 6
COMMONLY USED CYP1A2 INHIBITORS AND INDUCERS
Based on the product information for bendamustine, no formal clinical assessments of 
pharmacokinetic drug–drug interactions between bendamustine and other drugs have 
been conducted.  Bendamustine's active metabolites, gamma-hydroxy bendamustine 
(M3) and N-desmethyl-bendamustine (M4), are formed via cytochrome P450 (CYP)1A2.  
Inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) have potential to increase plasma 
concentrations of bendamustine and decrease plasma concentrations of active 
metabolites.  Inducers of CYP1A2 (e.g., omeprazole, smoking) have potential to 
decrease plasma concentrations of bendamustine and increase plasma concentrations 
of its active metabolites.  The medications listed below are not contraindicated; however, 
caution should be used, or alternative treatments with medications that are not CYP1A2 
inhibitors or inducers should be considered if concomitant treatment with CYP1A2 
inhibitors or inducers is needed for the patient's medical condition.  This list is not 
exhaustive (adapted from ctep.cancer.gov/protocolDevelopment/docs/cyp1a2.doc).
CYP1A2 Inhibitors
CYP1A2 Inhibitors (continued)
Amiodarone 
Amitriptyline 
Amlodipine 
Anastrozole 
Caffeine 
Cimetidine
Ciprofloxacin
Citalopram nifedipine
Clarithromycin 
Clotrimazole 
Clozapine 
Diclofenac 
Diltiazem 
Echinacea 
Ethinyl estradiol 
Fluoroquinolones 
Fluconazole
Fluvoxamine
Gemfibrozil
Ginseng
Imipramine
Isoniazid
Ketoconazole 
Lidocaine 
Losartan 
Erythromycin 
Estrogens 
Mexiletine 
Modafenil 
Olanzapine 
Omeprazole 
Ondansetron 
Paroxetinee 
Propafenone 
Propanolol 
Ranitidine 
Sertraline

Appendix 13
Preexisting Autoimmune Diseases (cont.)
Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
192/Protocol BO29563, Version 6
CYP1A2 Inducers
Barbiturates (e.g., phenobarbital)
Cruciferous vegetables (broccoli, cauliflower, arugula, brussel sprouts, cabbage, kale, chard,
turnips, radishes, wasabi, bok choy, watercress, collard greens)
Char-grilled meat
Carbamazepine
Primidone
Rifampin
Smoking
Triamterene
Zolmitriptan
Below is a sample card to be handed to patients in the BO29563 study.  This card may 
be adapted to comply with local guidelines.

Obinutuzumab, Rituximab, and Atezolizumab—F. Hoffmann-La Roche Ltd
193/Protocol BO29563, Version 6
Appendix 14
Calculation of Creatinine Clearance Using the 
Cockcroft-Gault Formula
Creatinine clearance (men)(140Age)Lean Body Weight (kg)
Serum Creatinine (mg/dL)72
Creatinine clearance (women)0.85(140Age)Lean Body Weight (kg)
Serum Creatinine (mg/dL)72
Adapted from:  Gault MH, Longerich LL, Harnett JD, et al. Predicting glomerular function from 
adjusted serum creatinine [editorial]. Nephron 1992;62:24956.