A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab (Anti-Tigit Antibody) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
Phase: PHASE3
Conditions: Small Cell Lung Cancer
Sponsor: Hoffmann-La Roche

 
Official Title: 
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of 
Atezolizumab Plus Carboplatin and Etoposide With or Without 
Tiragolumab (Anti-TIGIT Antibody) in Patients with Untreated 
Extensive-Stage Small Cell Lung Cancer 
NCT Number: 
NCT04256421 
Document Date: 
Protocol Amendment Version 7: 11-Dec-2023 
 
 
 

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any unpublished data, is the property of F. Hoffmann-La Roche Ltd (or under its control) and therefore 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. 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
Protocol GO41767, Version 7 
PROTOCOL 
PROTOCOL TITLE: 
A PHASE III, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED STUDY OF 
ATEZOLIZUMAB PLUS CARBOPLATIN AND 
ETOPOSIDE WITH OR WITHOUT TIRAGOLUMAB 
(ANTI-TIGIT ANTIBODY) IN PATIENTS WITH 
UNTREATED EXTENSIVE-STAGE SMALL CELL 
LUNG CANCER 
PROTOCOL NUMBER: 
GO41767 
VERSION NUMBER: 
7 
TEST COMPOUND: 
Tiragolumab (RO7092284) 
Atezolizumab (RO5541267) 
STUDY PHASE 
III 
REGULATORY 
AGENCY IDENTIFIER 
NUMBERS: 
IND Number:  129,258 
EU CT Number:  2022-502988-37-00 
EUDRACT Number:  2019-003301-97 
NCT Number:  NCT04256421 
SPONSOR’S NAME 
AND LEGAL 
REGISTERED 
ADDRESS: 
F. Hoffmann-La Roche Ltd
Grenzacherstrasse 124
4070 Basel, Switzerland
APPROVAL: 
See electronic signature and date stamp on the final page 
of this document. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
2/Protocol GO41767, Version 7 
PROTOCOL HISTORY 
Protocol 
Associated Country-Specific Protocols 
Version 
Date Final 
Country and/or Region 
Version 
Date Final 
7 
See electronic date 
stamp on final page 
of this document. 



6 
20 December 2022  



5 
15 November 2021 



4 
9 June 2021 



3 
22 October 2020 



2 
12 May 2020 
VHP 
1 
25 March 2020 
1 
24 September 2019 
 
 
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
3/Protocol GO41767, Version 7 
PROTOCOL AMENDMENT, VERSION 7: 
RATIONALE 
Protocol GO41767 has been amended primarily to follow-up ongoing patients in the 
study for limited information after the final overall survival (OS) analysis is conducted, to 
incorporate changes to update and align study drug risks and adverse event 
management guidelines for atezolizumab with the Atezolizumab Investigator's Brochure 
Version 20 (IB v20), and also to align with Clinical Trials Regulation (CTR) requirements.  
Substantive changes to the protocol, along with a rationale for each change, are 
summarized below: 
 
 
 
 
 
 
 
 
 
 
Updates to the adverse event management guidelines for atezolizumab to align with the 
Atezolizumab IB v20 and the CTR changes are summarized below: 
 
The list of approved indications for atezolizumab has been updated to include 
alveolar soft part sarcoma (Section 1.5). 
 
Personal identifiable information (i.e., name and telephone number) for the Medical 
Monitors has been removed from the protocol.  Medical Monitor contact information 
has been replaced with a sentence indicating that this information will be provided 
separately to sites (Section 5.4.1). 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
4/Protocol GO41767, Version 7 
 
It has been made explicit that expedited safety reports are notified to EudraVigilance 
(Section 5.7). 
 
The adverse event management guidelines have been updated to align with the 
Atezolizumab IB v20 (Appendix 13 and 14). 
 
Additional minor changes and clarifications have been made to improve clarity and 
consistency.  Substantive new information appears in italics.  This amendment 
represents cumulative changes to the original protocol. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
5/Protocol GO41767, Version 7 
 
TABLE OF CONTENTS 
PROTOCOL AMENDMENT ACCEPTANCE FORM .......................................... 14 
PROTOCOL SYNOPSIS .................................................................................... 15 
1. 
BACKGROUND ............................................................................ 23 
1.1 
Background on Lung Cancer ................................................... 23 
1.1.1 
First-Line Treatment for Extensive-Stage Small Cell Lung 
Cancer ..................................................................................... 23 
1.2 
TIGIT Pathway in Cancer as Potential Anti-Cancer 
Therapy ................................................................................... 24 
1.3 
Combined Inhibition of the TIGIT and PD-L1/PD-1 
Pathways as Potential Anti-Cancer Therapy ........................... 25 
1.4 
Background on Tiragolumab .................................................... 25 
1.4.1 
Summary of Nonclinical Data with Tiragolumab ...................... 26 
1.4.2 
Clinical Experience with Tiragolumab ...................................... 27 
1.4.2.1 
Ongoing Clinical Studies with Tiragolumab ............................. 27 
1.4.2.2 
Clinical Safety of Tiragolumab ................................................. 28 
1.4.2.3 
Clinical Activity of Tiragolumab Plus Atezolizumab .................. 30 
1.4.2.4 
Clinical Pharmacokinetics and Immunogenicity of 
Tiragolumab and Atezolizumab ............................................... 32 
1.5 
Background on Atezolizumab .................................................. 33 
1.6 
Study Rationale and BenefitRisk Assessment ....................... 33 
1.6.1 
Rationale for Testing Tiragolumab in Combination with 
Atezolizumab and Carboplatin and Etoposide in First-Line 
Extensive-Stage Small Cell Lung Cancer ................................ 33 
1.6.2 
Study Rationale ....................................................................... 34 
1.6.3 
BenefitRisk Assessment ........................................................ 35 
2. 
OBJECTIVES AND ENDPOINTS ................................................. 38 
2.1 
Efficacy Objectives .................................................................. 38 
2.1.1 
Primary Efficacy Objective ....................................................... 38 
2.1.2 
Secondary Efficacy Objective .................................................. 38 
 ................................................. 39 
2.2 
Safety Objectives ..................................................................... 39 
2.3 
Pharmacokinetic Objectives..................................................... 39 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
6/Protocol GO41767, Version 7 
2.4 
Immunogenicity Objectives ...................................................... 40 
............................................................. 40 
2.6 
Health Status Utility Objective .................................................. 40 
3. 
STUDY DESIGN ........................................................................... 40 
3.1 
Description of the Study ........................................................... 40 
3.1.1 
Overview of Study Design........................................................ 40 
3.1.2 
Treatment after Disease Progression ...................................... 44 
3.1.3 
Independent Data Monitoring Committee ................................ 45 
3.2 
End of Study and Length of Study ........................................... 45 
3.3 
Duration of Participation .......................................................... 45 
3.4 
Rationale for Study Design ...................................................... 46 
3.4.1 
Rationale for Tiragolumab Dose and Schedule ....................... 46 
3.4.2 
Rationale for Control Arm ........................................................ 46 
3.4.3 
Rationale for Evaluation of Patients Without Brain 
Metastases at Baseline (Primary Analysis Set for 
Statistical Analysis) .................................................................. 46 
3.4.4 
Rationale for Progression-Free Survival and Overall 
Survival as Co-Primary Endpoints ........................................... 47 
3.4.5 
Rationale for Tiragolumab and/or Atezolizumab Treatment 
Beyond Initial Radiographic Disease Progression ................... 48 
3.4.6 
Rationale for Patient-Reported Outcome Assessments ........... 48 
........ 49 
........ 49 
........ 49 
4. 
MATERIALS AND METHODS ...................................................... 49 
4.1 
Patients .................................................................................... 49 
4.1.1 
Inclusion Criteria ...................................................................... 50 
4.1.2 
Exclusion Criteria ..................................................................... 52 
4.2 
Method of Treatment Assignment and Blinding ....................... 56 
4.2.1 
Treatment Assignment ............................................................. 56 
4.2.2 
Blinding .................................................................................... 56 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
7/Protocol GO41767, Version 7 
4.3 
Study Treatment and Other Treatments Relevant to the 
Study Design ........................................................................... 58 
4.3.1 
Study Treatment Formulation, Packaging, and Handling ......... 58 
4.3.1.1 
Tiragolumab and Placebo ........................................................ 58 
4.3.1.2 
Atezolizumab ........................................................................... 58 
4.3.1.3 
Carboplatin and Etoposide....................................................... 58 
4.3.2 
Study Treatment Dosage, Administration, and Compliance .... 58 
4.3.2.1 
Atezolizumab ........................................................................... 59 
4.3.2.2 
Tiragolumab/Placebo ............................................................... 60 
4.3.2.3 
Atezolizumab and Tiragolumab/Placebo ................................. 62 
4.3.2.4 
Carboplatin  Etoposide .......................................................... 63 
4.3.3 
Investigational Medicinal Product Accountability ..................... 64 
4.3.4 
Continued Access to Tiragolumab and/or Atezolizumab ......... 65 
4.4 
Concomitant Therapy .............................................................. 65 
4.4.1 
Permitted Therapy ................................................................... 65 
4.4.2 
Cautionary Therapy for Tiragolumab- and/or 
Atezolizumab-Treated Patients ................................................ 66 
4.4.2.1 
Corticosteroids, Immunosuppressive Medications, and 
Tumor Necrosis Factor- Inhibitors ......................................... 66 
4.4.2.2 
Herbal Therapies ..................................................................... 67 
4.4.3 
Prohibited Therapy .................................................................. 67 
4.5 
Study Assessments ................................................................. 67 
4.5.1 
Informed Consent Forms and Screening Log .......................... 68 
4.5.2 
Medical History, Baseline Conditions, Concomitant 
Medication, and Demographic Data ......................................... 68 
4.5.3 
Physical Examinations ............................................................. 69 
4.5.4 
Vital Signs ................................................................................ 69 
4.5.5 
Performance Status ................................................................. 69 
4.5.6 
Tumor and Response Evaluations ........................................... 69 
4.5.7 
Laboratory, Biomarker, and Other Biological Samples ............ 72 
4.5.8 
Optional Tumor Biopsies ......................................................... 75 
4.5.9 
Electrocardiograms .................................................................. 75 
4.5.10 
Clinical Outcome Assessments ............................................... 75 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
8/Protocol GO41767, Version 7 
4.5.11 
Blood Samples for Whole Genome Sequencing or Whole 
Exome Sequencing (Patients at Participating Sites) ................ 78 
4.5.12 
Optional Samples for Research Biosample Repository ........... 79 
4.5.12.1 
Overview of the Research Biosample Repository .................... 79 
4.5.12.2 
Approval by the Institutional Review Board or Ethics 
Committee ............................................................................... 79 
4.5.12.3 
Sample Collection .................................................................... 79 
4.5.12.4 
Confidentiality .......................................................................... 80 
4.5.12.5 
Consent to Participate in the Research Biosample 
Repository................................................................................ 81 
4.5.12.6 
Withdrawal from the Research Biosample Repository ............. 81 
4.5.12.7 
Monitoring and Oversight ......................................................... 81 
4.6 
Patient, Treatment, Study, and Site Discontinuation ................ 82 
4.6.1 
Study Treatment Discontinuation ............................................. 82 
4.6.2 
Patient Discontinuation from the Study .................................... 83 
4.6.3 
Study Discontinuation .............................................................. 84 
4.6.4 
Site Discontinuation ................................................................. 84 
5. 
ASSESSMENT OF SAFETY ......................................................... 84 
5.1 
Safety Plan .............................................................................. 84 
5.1.1 
Risks Associated with Tiragolumab ......................................... 85 
5.1.1.1 
Infusion-Related Reactions ...................................................... 85 
5.1.1.2 
................................................... 86 
5.1.1.3 
Immune-Mediated Adverse Events .......................................... 86 
5.1.1.4 
Lymphopenia ........................................................................... 86 
5.1.1.5 
Embryofetal Toxicity ................................................................ 87 
5.1.2 
Risks Associated with Atezolizumab ........................................ 87 
5.1.3 
Risks Associated with Combination Use of Tiragolumab 
and Atezolizumab .................................................................... 87 
5.1.4 
Risks Associated with Etoposide ............................................. 88 
5.1.5 
Risks Associated with Carboplatin ........................................... 88 
5.1.6 
Management of Adverse Events .............................................. 88 
5.1.6.1 
Dose Modification .................................................................... 88 
5.1.6.2 
Tiragolumab and/or Atezolizumab Dose Modification, 
Treatment Interruption, or Treatment Discontinuation ............. 89 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
9/Protocol GO41767, Version 7 
5.1.6.3 
Chemotherapy Dose Modifications, Treatment Delays, or 
Treatment Discontinuation and Management of Specific 
Adverse Events ........................................................................ 91 
5.1.7 
Potential Overlapping Toxicities ............................................... 91 
5.2 
Safety Parameters and Definitions .......................................... 92 
5.2.1 
Adverse Events ........................................................................ 92 
5.2.2 
Serious Adverse Events (Immediately Reportable to the 
Sponsor) .................................................................................. 93 
5.2.3 
Adverse Events of Special Interest (Immediately 
Reportable to the Sponsor) ...................................................... 93 
5.3 
Methods and Timing for Capturing and Assessing 
Safety Parameters ................................................................... 94 
5.3.1 
Adverse Event Reporting Period .............................................. 95 
5.3.2 
Eliciting Adverse Event Information ......................................... 95 
5.3.3 
Assessment of Severity of Adverse Events ............................. 95 
5.3.4 
Assessment of Causality of Adverse Events............................ 97 
5.3.5 
Procedures for Recording Adverse Events .............................. 98 
................ 98 
5.3.5.2 
Diagnosis Versus Signs and Symptoms .................................. 99 
5.3.5.3 
Adverse Events that are Secondary to Other Events ............... 99 
5.3.5.4 
Persistent or Recurrent Adverse Events ................................ 100 
5.3.5.5 
Abnormal Laboratory Values ................................................. 100 
5.3.5.6 
Abnormal Vital Sign Values ................................................... 101 
5.3.5.7 
Abnormal Liver Function Tests .............................................. 101 
5.3.5.8 
Deaths ................................................................................... 102 
5.3.5.9 
Preexisting Medical Conditions .............................................. 102 
5.3.5.10 
Lack of Efficacy or Worsening of Small Cell Lung Cancer ..... 102 
5.3.5.11 
Hospitalization or Prolonged Hospitalization .......................... 103 
5.3.5.12 
Cases of Accidental Overdose or Medication Error ............... 103 
5.3.5.13 
Patient-Reported Outcome Data ............................................ 104 
5.4 
Immediate Reporting Requirements from Investigator to 
Sponsor ................................................................................. 104 
5.4.1 
Emergency Medical Contacts ................................................ 105 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
10/Protocol GO41767, Version 7 
5.4.2 
Reporting Requirements for Serious Adverse Events and 
Adverse Events of Special Interest ........................................ 105 
5.4.2.1 
Events that Occur Prior to Study Treatment Initiation ............ 105 
5.4.2.2 
Events that Occur After Study Treatment Initiation ................ 106 
5.4.3 
Reporting Requirements for Pregnancies .............................. 106 
5.4.3.1 
Pregnancies in Female Patients ............................................ 106 
5.4.3.2 
Pregnancies in Female Partners of Male Patients ................. 106 
5.4.3.3 
Abortions................................................................................ 107 
5.4.3.4 
Congenital Anomalies/Birth Defects ...................................... 107 
5.5 
Follow-Up of Patients After Adverse Events .......................... 107 
5.5.1 
Investigator Follow-Up ........................................................... 107 
5.5.2 
Sponsor Follow-Up ................................................................ 108 
5.6 
Adverse Events that Occur After the Adverse Event 
Reporting Period .................................................................... 108 
5.7 
Expedited Reporting to Health Authorities, Investigators, 
Institutional Review Boards, and Ethics Committees ............. 108 
6. 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN ....... 109 
6.1 
Determination of Sample Size ............................................... 110 
.............................................................. 110 
6.1.2 
Co-Primary Endpoint:  Progression-Free Survival in the 
Primary Analysis Set .............................................................. 110 
6.1.3 
Co-Primary Endpoint:  Overall Survival in the Primary 
Analysis Set ........................................................................... 111 
6.2 
Summaries of Conduct of Study ............................................ 112 
6.3 
Summaries of Treatment Group Comparability ...................... 112 
6.4 
Efficacy Analyses ................................................................... 112 
6.4.1 
Co-Primary Efficacy Endpoints .............................................. 112 
6.4.2 
Secondary Efficacy Endpoints ............................................... 113 
6.4.2.1 
Progression-Free Survival and Overall Survival in the Full 
Analysis Set ........................................................................... 113 
6.4.2.2 
Confirmed Objective Response Rate ..................................... 113 
6.4.2.3 
Duration of Response ............................................................ 114 
6.4.2.4 
Landmark Analysis on Progression-Free Survival and 
Overall Survival ...................................................................... 114 
6.4.2.5 
Patient-Reported Outcomes .................................................. 114 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
11/Protocol GO41767, Version 7 
6.5 
Safety Analyses ..................................................................... 115 
6.6 
Pharmacokinetic Analyses ..................................................... 116 
6.7 
Immunogenicity Analyses ...................................................... 116 
..................... 116 
..................... 117 
..................... 117 
..................... 117 
..................... 117 
6.10.1 
Progression-Free Survival ..................................................... 117 
6.10.2 
Overall Survival ...................................................................... 117 
6.10.3 
Safety Monitoring ................................................................... 118 
7. 
DATA COLLECTION AND MANAGEMENT ............................... 118 
7.1 
Data Quality Assurance ......................................................... 118 
7.2 
Electronic Case Report Forms ............................................... 119 
7.3 
Source Data Documentation .................................................. 119 
7.4 
Use of Computerized Systems .............................................. 120 
7.5 
Retention of Records ............................................................. 120 
8. 
ETHICAL CONSIDERATIONS .................................................... 120 
8.1 
Compliance with Laws and Regulations ................................ 120 
8.2 
Informed Consent .................................................................. 120 
8.3 
Institutional Review Board or Ethics Committee .................... 122 
8.4 
Confidentiality ........................................................................ 122 
8.5 
Financial Disclosure ............................................................... 123 
9. 
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION ..................................................................... 123 
9.1 
Study Documentation ............................................................ 123 
9.2 
Protocol Deviations ................................................................ 123 
9.3 
Management of Study Quality ................................................ 124 
9.4 
Site Inspections ..................................................................... 124 
9.5 
Administrative Structure ......................................................... 124 
9.6 
Dissemination of Data and Protection of Trade Secrets ........ 124 
9.7 
Protocol Amendments ........................................................... 126 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
12/Protocol GO41767, Version 7 
10. 
REFERENCES............................................................................ 127 
 
 
LIST OF TABLES 
Table 1 
Study GO41767 Treatment Arms ................................................ 42 
Table 2 
Administration of First and Subsequent Atezolizumab and 
Tiragolumab/Placebo Infusions ................................................... 60 
Table 3 
Adverse Event Severity Grading Scale for Events Not 
Specifically Listed in NCI CTCAE ............................................... 96 
............................................... 96 
Table 5 
Causal Attribution Guidance ....................................................... 98 
Table 6 
Analysis Timing for Overall Survival .......................................... 112 
Table 7 
Analysis Timing and Stopping Boundary of Overall Survival 
in the Primary Analysis Set ....................................................... 118 
 
 
LIST OF FIGURES 
Figure 1 
Study Schema ............................................................................. 41 
Figure 2 
Progression Free Survival and Overall Survival Analysis 
Hierarchy, -Allocation, and -Recycling .................................. 110 
 
 
LIST OF APPENDICES 
Appendix 1 
 Schedule of Activities ............................................................... 132 
.............. 139 
Appendix 3 
 Veterans Administration Lung Study Group (VALG) Staging 
System for SCLC ...................................................................... 142 
Appendix 4 
 Response Evaluation Criteria in Solid Tumors, Version 1.1 
(RECIST v1.1) ........................................................................... 143 
.................................................................. 152 
.................................................................. 154 
.................................................................. 155 
Appendix 8 
 EuroQol EQ-5D-5L ................................................................... 156 
Appendix 9 
 Eastern Cooperative Oncology Group Performance Status 
Scale ......................................................................................... 159 
Appendix 10 
 Anaphylaxis Precautions .......................................................... 160 
Appendix 11 
 Preexisting Autoimmune Diseases and Immune Deficiencies . 161 
Appendix 12 
 Investigational Medicinal Product and Non-Investigational 
Medicinal Product Designations (for Use in European 
Economic Area and United Kingdom) ....................................... 162 
Appendix 13 
 Overall Guidelines for Management of Patients Who 
Experience Adverse Events ...................................................... 164 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
13/Protocol GO41767, Version 7 
Appendix 14 
 Risks Associated with Tiragolumab or Atezolizumab and 
Guidelines for Management of Adverse Events Associated 
with Tiragolumab or Atezolizumab ............................................ 167 
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
14/Protocol GO41767, Version 7 
PROTOCOL AMENDMENT ACCEPTANCE FORM 
TITLE: 
A PHASE III, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED STUDY OF 
ATEZOLIZUMAB PLUS CARBOPLATIN AND 
ETOPOSIDE WITH OR WITHOUT TIRAGOLUMAB 
(ANTI-TIGIT ANTIBODY) IN PATIENTS WITH 
UNTREATED EXTENSIVE-STAGE SMALL CELL 
LUNG CANCER 
PROTOCOL NUMBER: GO41767 
VERSION NUMBER: 
7 
TEST COMPOUND (S): Tiragolumab (RO7092284) 
Atezolizumab (RO5541267) 
SPONSOR NAME: 
F. Hoffmann-La Roche Ltd 
I agree to conduct the study in accordance with the current protocol. 
 
 
 
Principal Investigator’s Name (print) 
 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
Please retain the signed original of this form for your study files.  Please return a copy of 
the signed form as instructed by your local study monitor. 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
15/Protocol GO41767, Version 7 
PROTOCOL SYNOPSIS 
TITLE: 
A PHASE III, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED STUDY OF ATEZOLIZUMAB PLUS 
CARBOPLATIN AND ETOPOSIDE WITH OR WITHOUT 
TIRAGOLUMAB (ANTI-TIGIT ANTIBODY) IN PATIENTS WITH 
UNTREATED EXTENSIVE-STAGE SMALL CELL LUNG CANCER 
REGULATORY 
AGENCY IDENTIFIER 
NUMBERS: 
IND Number:  129,258 
EU CT Number:  2022-502988-37-00 
EUDRACT NUMBER:2019-003301-97 
NCT Number:  NCT04256421 
STUDY RATIONALE 
The purpose of this study is to evaluate the safety and efficacy of tiragolumab in combination 
with atezolizumab and carboplatin and etoposide (CE) compared with treatment with placebo in 
combination with atezolizumab and CE in patients who are chemotherapy-naive 
extensive‑stage small cell lung cancer (ES-SCLC).  The current standard first-line treatment for 
patients with ES-SCLC is the PD-L1 inhibitor atezolizumab given with platinum-based 
chemotherapy consisting of CE as induction therapy for 4 cycles, followed by atezolizumab 
maintenance therapy.  Despite the improved efficacy observed with first-line atezolizumab plus 
CE, most patients with ES-SCLC experienced disease progression, and upon relapse, their 
prognosis is poor.  Therefore, novel strategies are needed to deliver better long-term survival.  
The addition of complementary immunomodulatory agents to the current treatment backbone is 
an appealing strategy to further improve the prognosis of patients with advanced small cell lung 
cancer. 
OBJECTIVES AND ENDPOINTS 
Primary Efficacy Objective 
Corresponding Endpoint  
To evaluate the efficacy of tiragolumab 
plus atezolizumab and CE compared 
with placebo plus atezolizumab and 
CE in patients with untreated 
ES-SCLC 
 PFS after randomization, defined as the time from 
randomization to the first occurrence of disease 
progression as determined by the investigator 
according to RECIST v1.1 or death from any 
cause, whichever occurs first in patients who are 
randomly assigned without presence or history of 
brain metastases at baseline (PAS) 
 OS after randomization, defined as the time from 
randomization to death from any cause in the PAS 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
17/Protocol GO41767, Version 7 
ADAs  anti-drug antibodies;
CE  carboplatin and etoposide; CR  complete response; CRS  cytokine-release syndrome; 
DOR  duration of response; ES‑SCLC  extensive-stage small cell lung cancer; 
EORTC  European Organisation for the Research and Treatment of Cancer; FAS  full analysis 
set; GHS  global health status; NCI CTCAE  National Cancer Institute Common Terminology 
Criteria for Adverse Events; ORR  objective response rate; OS  Overall survival; PAS  primary 
analysis set; PFS  progression-free survival; PK  pharmacokinetic; PR  partial response; 
QLQ-C30  Quality of Life-Core 30 Questionnaire; QoL  quality of life; RECIST  Response 
Evaluation Criteria in Solid Tumors; TTCD  time to confirmed deterioration. 
 
OVERALL DESIGN AND STUDY POPULATION 
This is a randomized, Phase III, global, multicenter, double-blinded, placebo-controlled study 
designed to evaluate the safety and efficacy of tiragolumab in combination with atezolizumab 
and CE compared with treatment with placebo in combination with atezolizumab and CE in 
patients who are chemotherapy-naive ES-SCLC.   
Several key aspects of the study design and study population are summarized below. 
Phase: 
Phase III 
Population Type: 
Adult patients 
Control Method: 
Active Comparator, 
Placebo 
Population Diagnosis 
or Condition: 
Extensive-stage small 
cell lung cancer 
Interventional 
Model: 
Parallel group 
Population Age: 
 18 years 
Test Compounds: 
tiragolumab 
Site Distribution: 
Multi-site 
Active Comparator: 
atezolizumab and 
carboplatin and 
etoposide 
Study Intervention 
Assignment Method: 
Randomization 
Number of Arms: 
2 
Number of Participants 
to Be Enrolled: 
Approximately 470 
patients 
 
STUDY TREATMENT 
Eligible patients will be stratified by Eastern Cooperative Oncology Group Performance Status 
(0 vs. 1), LDH ( upper limit of normal [ULN] vs.  ULN), and presence or history of brain 
metastasis (yes vs. no) and randomly assigned in a 1:1 ratio to receive one of the following 
treatment regimens during the induction phase:  
 
Arm A:  tiragolumab plus atezolizumab plus CE 
 
Arm B:  placebo plus atezolizumab plus CE 
 
The induction phase of the study will consist of four cycles of atezolizumab plus 
tiragolumab/placebo plus chemotherapy, with each cycle being 21 days in duration.  On Day 1 
of each cycle, all eligible patients will be administered study drug infusions in the following 
order: 
Arm A:  atezolizumab  tiragolumab  carboplatin  etoposide  
Arm B:  atezolizumab  placebo  carboplatin  etoposide 
During the induction phase, study treatment should be administered in the following manner on 
Day 1: 
Atezolizumab 1200 mg administered intravenously over 60 ( 15) minutes (for the first infusion 
and shortening to 30 [ 10] minutes for subsequent infusions), followed by tiragolumab/placebo 
600 mg administered intravenously over
 minutes (for the first infusion and shortening 
to
minutes for subsequent infusions), followed by carboplatin administered 
intravenously over 3060 minutes to achieve an initial target area under the concentrationtime 
curve (AUC) of
mg/mL/min (Calvert formula dosing), followed by etoposide (100 mg/m2) 
administered intravenously over 60 minutes. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
18/Protocol GO41767, Version 7 
During the induction phase, etoposide (100 mg/m2) will be also administered intravenously over 
60 minutes on Days 2 and 3. 
Cycles in which no chemotherapy is given do not count toward the total number of induction 
chemotherapy cycles. 
After the induction phase, patients will begin maintenance therapy with atezolizumab plus 
tiragolumab/placebo.  
The suggested infusion times for CE may be adapted in accordance with local standard of care. 
Following the induction phase, patients will continue maintenance therapy with either 
atezolizumab plus tiragolumab (Arm A) or atezolizumab plus placebo (Arm B).   
Treatment will be continued until radiographic disease progression according to Response 
Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), or as long as patients are 
experiencing clinical benefit, as assessed by the investigator, in the absence of unacceptable 
toxicity or symptomatic deterioration attributed to disease progression after an integrated 
assessment of radiographic data, biopsy results (if available), and clinical status.  Patients who 
meet the criteria for disease progression per RECIST v1.1 will be permitted to continue study 
treatment (tiragolumab plus atezolizumab or placebo plus atezolizumab) if they meet all criteria 
and provide written consent. 
There will be no dose modifications for tiragolumab/placebo and/or atezolizumab in this study. 
Dose modifications for carboplatin and etoposide are permitted for toxicity according to the 
prescribing information and local standard of care.   
Dose modification guidelines are provided below.  Once reduced, the dose cannot be increased 
back to 100%.   
Treatment with carboplatin or etoposide should be discontinued if a patient experiences any 
hematologic or non-hematologic Grade 3 or 4 toxicity after two dose reductions or treatment is 
delayed for more than
days due to toxicities.  
Hematologic Toxicity 
At the start of each cycle, the ANC should be  1500/L and the platelet count should be 
 100,000/L.  Treatment could be delayed for up to
days to allow sufficient time for 
recovery.  Growth factors may be used in accordance with American Society of Clinical 
Oncology and National Comprehensive Cancer Network (NCCN) guidelines (Smith et al. 2015; 
NCCN 2019).  Upon recovery, dose adjustments at the start of a subsequent cycle will be made 
on the basis of the lowest platelet and neutrophil values from the previous cycle (see table 
below). 
In the event that dose adjustments are needed for both ANC and platelets, patients are to 
receive the lower dose. 
 
Chemotherapy Dose Modification for Hematologic Toxicities 
Toxicity a 
Dose 
ANC  500/L and platelets  50,000/L 
75% of previous dose 
Platelets  25,000/L, regardless of ANC 
75% of previous dose 
Platelets  50,000/L with Grade  2 bleeding, regardless of ANC 
50% of previous dose 
ANC  1000/L plus fever of  38.5°C 
75% of previous dose 
a Nadir of prior cycle. 
 
Investigators should be vigilant and alert to early and overt signs of myelosuppression, infection, 
or febrile neutropenia so that these complications can be promptly and appropriately managed.  
Patients should be made aware of these signs and encouraged to seek medical attention at the 
earliest opportunity. 
If chemotherapy is withheld because of hematologic toxicity, full blood counts (including 
differential WBC) should be obtained weekly until the counts reach the lower limits for treatment 
as outlined.  The treatment can then be resumed. 
No dose reductions are recommended for anemia.  Patients should be supported per the 
investigator’s institution’s guidelines. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
19/Protocol GO41767, Version 7 
Non-Hematologic Toxicity 
For a non-hematologic toxicity (see table below), treatment should be delayed for up to
days 
until resolution to less than or equal to the patient’s baseline value (or Grade  1 if the patient 
did not have that toxicity at baseline).  Dose reductions at the start of the subsequent cycle 
should be made on the basis of non-hematologic toxicities from the dose administered in the 
preceding cycle.  The table below provides recommended dose modifications for 
non‑hematologic toxicities. 
 
Dose Modifications or Treatment Discontinuation for Non-Hematologic Toxicities  
Toxicity 
Adjusted Dose as % 
of Previous Dose a 
Diarrhea 
Grade 3 or 4 b 
75% 
Nausea/vomiting 
Grade 3 or 4 c 
75% 
Neurotoxicity 
Grade 2  
75% 
 
Grade 3 or 4 
50% or permanent 
discontinuation 
Transaminase elevation 
Grade 3 
75% 
 
Grade 4 
Discontinue 
Other  
Grade 3 or 4 
75% 
AUC  area under the concentrationtime curve. 
a If deemed appropriate by the investigator, adjust carboplatin dose to the 
specified percentage of the previous AUC. 
b Grade 3 or 4 diarrhea that occurs on adequate anti-diarrhea medication or 
any grade of diarrhea requiring hospitalization. 
c Despite the use of anti-emetics. 
 
Diarrhea should be controlled with adequate anti-diarrhea medication.  Nausea and/or vomiting 
may be controlled with adequate anti-emetics.  For Grade 3 or 4 neurotoxicity chemotherapy 
should be resumed at 50% of the previous dose upon improvement or discontinued immediately 
(based on investigator’s clinical judgment). 
Suggested recommendations for dose modification of etoposide for renal impairment are 
provided in the table below.  
Etoposide Dose Modification for Renal Impairment 
Creatinine clearance 
(mL/min) 
Etoposide Dose 
 50 
100% 
1550 
75% of dose 
 
DURATION OF PARTICIPATION 
The total duration of study participation for each individual is expected to be up to approximately 
72 months. 
COMMITTEES 
Independent Committees: Independent Data Monitoring Committee 
Other Committees: 
Not applicable 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
20/Protocol GO41767, Version 7 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
ADA 
anti-drug antibody 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
AUC 
area under the concentrationtime curve 
CD 
cluster of differentiation 
CE 
carboplatin and etoposide 
CHO 
Chinese hamster ovary 
CIT 
cancer immunotherapy 
COPD 
chronic obstructive pulmonary disease 
COVID-19 
coronavirus disease 2019 
CR 
complete response 
CRCL 
creatinine clearance 
CRS 
cytokine-release syndrome 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
dose-limiting toxicity 
DOR 
duration of response 
EAE 
experimental autoimmune encephalitis  
EC 
Ethics Committee 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic Case Report Form 
EDC 
electronic data capture 
EORTC 
European Organisation for Research and Treatment of Cancer 
EQ-5D-5L 
EuroQol 5-Dimension, 5-Level Questionnaire 
ES-SCLC 
extensive-stage small cell lung cancer 
FACS 
fluorescence-activated cell sorting 
FAS 
full analysis set 
Fc 
fragment crystallizable 
FDA 
U.S. Food and Drug Administration 
FFPE 
formalin-fixed, paraffin-embedded 
GFR 
glomerular filtration rate 
GHS 
global health status 
HIPAA 
Health Insurance Portability and Accountability Act 
HLH 
hemophagocytic lymphohistiocytosis 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
22/Protocol GO41767, Version 7 
Abbreviation 
Definition 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SCLC 
small cell lung cancer 
SITC 
Society for Immunotherapy of Cancer 
TC 
tumor cell 
TIGIT 
T-cell immunoreceptor with Ig and ITIM domains 
TNF 
tumor necrosis factor 
TPS 
tumor proportion score 
TTCD 
time to confirmed deterioration 
TTE 
transthoracic echocardiogram 
ULN 
upper limit of normal 
VALG 
Veterans Administration Lung Study Group 
VCA 
viral capsid antigen 
WES 
whole exome sequencing 
WGS 
whole genome sequencing 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
23/Protocol GO41767, Version 7 
1. 
BACKGROUND 
1.1 
BACKGROUND ON LUNG CANCER 
Lung cancer remains the leading cause of cancer deaths worldwide.  In the 
United States, it was estimated that there will be 228,150 new cases of lung cancer in 
2019 (116,440 in men and 111,710 in women) and 142,670 lung cancer deaths 
(Siegel et al. 2019).  Similar data from Europe estimate that in 2018, there were 
387,900 lung cancer deaths (267,300 in men and 120,600 in women) 
(Ferlay et al. 2019). 
Nonsmall cell lung cancer (NSCLC) accounts for approximately 85% of all cases of 
lung cancer (Molina et al. 2008; Howlader et al. 2014).  Small cell lung cancer (SCLC) 
accounts for approximately 15% of all cases and is distinguished from NSCLC by its 
rapid growth rate and early development of metastatic disease (Govindan et al. 2006).  
Nearly all cases of SCLC are attributable to cigarette smoking (Pesch et al. 2012).  Poor 
prognostic factors for survival in patients with SCLC include extensive-stage disease, 
poor performance status, weight loss, and markers associated with excessive bulk of 
disease, such as lactate dehydrogenase (LDH) (Yip and Harper 2000; 
Foster et al. 2009).  
Patients with limited-stage SCLC can be treated with chemotherapy and radiation with 
the potential for long-term survival (Stinchcombe and Gore 2010), although a majority 
will relapse.  The majority (approximately 70%) of patients with SCLC are diagnosed 
with extensive-stage small cell lung cancer (ES-SCLC), which has poor survival 
prospects (median overall survival [OS] approximately 1012 months) 
(Socinski et al. 2009; Horn et al. 2018).  Chemotherapy alone can palliate symptoms and 
prolong survival for patients with ES-SCLC; however, long-term survival is rare 
(Johnson and Janne 2004; Demedts et al. 2010).  
1.1.1 
First-Line Treatment for Extensive-Stage Small Cell Lung 
Cancer 
The current standard first-line treatment for patients with ES-SCLC is the PD-L1 inhibitor 
atezolizumab given with platinum-based chemotherapy consisting of carboplatin and 
etoposide (CE) as induction therapy for 4 cycles, followed by atezolizumab maintenance 
therapy (National Comprehensive Cancer Network [NCCN] 2019).  In the randomized 
Phase III Study GO30081 (IMpower133), a total of 201 patients were randomly assigned 
to the atezolizumab plus CE group, and 202 patients assigned to the placebo plus CE 
group.  At a median follow-up of 13.9 months, the hazard ratio [HR] for death was 
0.70 (95% CI: 0.54 to 0.91; p  0.007) with a median OS of 12.3 months in the 
atezolizumab plus CE group and 10.3 months in the placebo plus CE group.  The HR for 
progression-free survival (PFS) was 0.77 (95% CI: 0.62 to 0.96; p  0.02) with a median 
PFS of 5.2 months and 4.3 months for atezolizumab plus CE and placebo plus CE, 
respectively.  The safety profile of atezolizumab plus CE was consistent with the 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
24/Protocol GO41767, Version 7 
previously reported safety profile of the individual agents, with no new findings observed 
(Horn et al. 2018). 
Despite the improved efficacy observed with first-line atezolizumab plus CE, most 
patients with ES-SCLC experienced disease progression, and upon relapse, their 
prognosis is poor.  Therefore, novel strategies are needed to deliver better long-term 
survival.  The addition of complementary immunomodulatory agents to the current 
treatment backbone is an appealing strategy to further improve the prognosis of patients 
with advanced SCLC. 
1.2 
TIGIT PATHWAY IN CANCER AS POTENTIAL ANTI-CANCER 
THERAPY 
T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is a novel immune inhibitory 
receptor that is a member of the immunoglobulin superfamily (Yu et al. 2009; 
Manieri et al. 2017).  T-cell immunoreceptor with Ig and ITIM domains is expressed on 
the surface of activated T-cell and natural killer (NK)-cell subsets and interacts with high 
affinity with cluster of differentiation [CD] 155 (also known as poliovirus receptor [PVR]) 
(Yu et al. 2009).  Genetic ablation of TIGIT in T cells in mice results in exacerbated 
T-cell responses in nonclinical models of autoimmune diseases and viral infections, 
demonstrating the role of TIGIT in inhibiting T-cell responses (Joller et al. 2011; 
Johnston et al. 2014).  T-cell immunoreceptor with Ig and ITIM domains expression is 
observed in the tumor microenvironment in many human tumors, is coordinately 
expressed with other checkpoint immune-receptors such as PD-1, and is associated with 
impaired T-cell function and anti-tumor immunity (Johnston et al. 2014).  Activation of 
TIGIT on T cells and NK cells limits cellular proliferation, effector cytokine production, 
and killing of target tumor cells (TCs) (Stanietsky et al. 2009; Yu et al. 2009; Johnston et 
al. 2014; Wang et al. 2015; Manieri et al. 2017). 
T-cell immunoreceptor with Ig and ITIM domains is expressed in a wide variety of human 
tumors and is highly correlated with T-cell infiltration and PD-1 expression 
(Johnston et al. 2014).  Fluorescence-activated cell sorting (FACS) analysis on fresh 
tumor samples showed that TIGIT and PD-1 are also co-expressed on NSCLC 
tumor-infiltrating T cells.  T-cell immunoreceptor with Ig and ITIM domains expression 
ranges from 30%80% and 50%80% on tumor-infiltrating CD4   and CD8   T cells, 
respectively (Johnston et al. 2014).  Similarly, TIGIT and PD-1 are expressed on 
CD8   tumor-infiltrating lymphocytes in SCLC (Xu et al. 2019).  The TIGIT ligand PVR is 
broadly expressed in SCLC cell lines and tumor samples (Yu et al. 2018a, 2018b; 
Xu et al. 2019).  Poliovirus receptor is predominantly present on the membrane of tumor 
cells, and 79% of SCLC patients express PVR with a  50% tumor positivity score 
(Yu et al. 2018a).  
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
25/Protocol GO41767, Version 7 
 
 
  Together, these data support the 
hypothesis that anti-TIGIT treatment in combination with antiPD-L1 treatment may 
reactivate anti-tumor immunity in SCLC, which may lead to clinical benefit for patients 
(see Section 1.3).  
1.3 
COMBINED INHIBITION OF THE TIGIT AND PD-L1/PD-1 
PATHWAYS AS POTENTIAL ANTI-CANCER THERAPY 
The inhibitory immunoreceptor TIGIT has been shown to limit the effector function of 
tumor-associated lymphocytes.  Activation of TIGIT on T cells and NK cells limits 
proliferation, effector cytokine production, and killing of target TCs.  Therefore, in the 
context of the tumor microenvironment, TIGIT acts to limit anti-tumor immune responses.  
Interference with the TIGIT/PVR interaction may enhance the magnitude and quality of 
tumor-specific T-cell responses through increased expansion of T cells as well as 
improved T-cell priming and/or effector function.  Because TIGIT and PD-1 are 
coordinately expressed by tumor-infiltrating T cells in several human tumors, inhibition of 
the TIGIT/PVR pathway may complement and potentiate the anti-tumor activity of a 
PD-L1 pathway inhibitor, such as atezolizumab (Johnston et al. 2014). 
In nonclinical models, concomitant blockade of both TIGIT and PD-L1/PD-1 pathways 
demonstrated superior efficacy over the respective single-agent treatments.  In one such 
nonclinical model, tumor-infiltrating T cells demonstrate increased interferon-gamma 
(IFN-) expression (a hallmark of activation and anti-tumor activity of T cells) only when 
both TIGIT and PD-1 are blocked concurrently and not when each individual pathway is 
blocked by the respective single-agent treatments.  Notably, co-inhibition of TIGIT and 
PD-L1 in this syngeneic tumor model was not associated with body weight loss or any 
other observable adverse responses (Johnston et al. 2014).   
1.4 
BACKGROUND ON TIRAGOLUMAB 
Tiragolumab is a fully human IgG1/kappa monoclonal antibody (MAb) that binds TIGIT 
and prevents its interaction with PVR.  The recombinant antibody is produced in Chinese 
hamster ovary (CHO) cells and consists of two heavy chains (456 amino acid residues 
each) and two light chains (220 amino acid residues each).  There are two N-linked 
glycosylation sites (Asn306) in the fragment crystallizable (Fc) domain.  The predicted 
molecular weight of tiragolumab is 148,409 Da (peptide chains only, without heavy chain 
C-terminal lysine residue). 
Therapeutic blockade of TIGIT by tiragolumab represents an attractive strategy for 
cancer therapy and is expected to enhance the magnitude and quality of the 
tumor-specific T-cell responses, which may result in improved meaningful anti-tumor 
activity when tiragolumab is used as a single agent or in combination with other cancer 
immunotherapies (CITs). 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
27/Protocol GO41767, Version 7 
Please refer to the Tiragolumab Investigator’s Brochure for additional details on 
nonclinical studies. 
1.4.2 
Clinical Experience with Tiragolumab 
Please refer to the Tiragolumab Investigator’s Brochure for additional details on clinical 
studies conducted to date. 
1.4.2.1 
Ongoing Clinical Studies with Tiragolumab 
Tiragolumab has been tested in a Phase I study (GO30103), a combined 
Phase Ia/Phase Ib multicenter, first-in-human, open-label, dose-escalation study 
evaluating the safety, tolerability, immunogenicity, pharmacokinetics, exploratory 
pharmacodynamics, and preliminary evidence of biologic activity of tiragolumab 
administered as a single agent by IV infusion every 21 days (Phase Ia) or in combination 
with atezolizumab at 1200 mg administered by IV infusion every 21 days (Phase Ib) to 
patients with locally advanced or metastatic malignancies (please see the Tiragolumab 
Investigator’s Brochure for a full study description).  
 
 
  Refer to the Tiragolumab Investigator’s 
Brochure for further details. 
The combination of tiragolumab plus atezolizumab is being investigated further in 
Study GO40290 (CITYSCAPE), an ongoing Phase II, global, multicenter, randomized, 
blinded, placebo-controlled trial.  This study was designed to evaluate the safety and 
efficacy of tiragolumab plus atezolizumab compared with placebo plus atezolizumab in 
patients with previously untreated, locally advanced, unresectable or metastatic 
PD-L1selected (tumor proportion score [TPS]  1%) NSCLC (please see the 
Tiragolumab Investigator’s Brochure for a full study description).  The co-primary 
endpoints for the study are objective response rate (ORR) and PFS.  Secondary 
endpoints include duration of response (DOR), OS, safety, pharmacokinetics, and 
immunogenicity. 
Patients were eligible if they were  18 years old with an Eastern Cooperative Oncology 
Group (ECOG) Performance Status of 0 or 1 and had previously untreated, locally 
advanced unresectable or metastatic PD-L1selected NSCLC without a sensitizing 
epidermal growth factor receptor mutation or anaplastic lymphoma rearrangement. 
For the purposes of PD-L1 selection, formalin-fixed tumor samples were assessed 
locally by the commercially available PD-L1 immunohistochemistry (IHC) 22C3 pharmDx 
assays (Dako) or, when unavailable, patients were prospectively tested for PD-L1 
expression by central testing using the same assay.  Programmed 
death-ligand 1selected tumors were defined as tumors with a TPS  1% by the PD-L1 
IHC 22C3 pharmDx assay. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
28/Protocol GO41767, Version 7 
Eligible patients were stratified by the PD-L1 IHC 22C3 pharmDx assay result 
(TPS 1%49% vs. TPS  50%), tumor histology (non-squamous vs. squamous), and 
patient’s history of tobacco use (yes vs. no). 
Patients for this study were enrolled at 39 sites in France, Spain, Serbia, South Korea, 
Taiwan, and the United States between August 2018 and March 2019.  As of the primary 
analysis data cutoff date of 30 June 2019, a total of 135 patients with a PD-L1 
TPS  1% (22C3) by local analysis were included in the intent-to-treat (ITT) population 
and were randomly assigned to tiragolumab plus atezolizumab (n  67) or placebo plus 
atezolizumab (n  68).  Of the enrolled patients, 43% of patients had a TPS of  50% 
versus 57% of patients with a TPS 1%49%; 59.3% had non-squamous histology versus 
40.7% of patients who had squamous histology; and 10.4% of patients were 
never-smokers versus 89.6% who had smoked.  These three stratification factors were 
well balanced between treatment groups.  Demographics were generally well balanced 
between treatment groups as well, with a median age of 68 years in both the 
tiragolumab plus atezolizumab and placebo plus atezolizumab groups.  There were 
more females (41.8% vs. 29.4%) and more White patients (62.7% vs. 58.8%) in the 
tiragolumab plus atezolizumab group compared with the placebo plus atezolizumab 
group. 
At the primary analysis, in the ITT population, 47.8% of patients in the tiragolumab plus 
atezolizumab group versus 27.9% of patients in the placebo plus atezolizumab group 
were still receiving study treatment.  In the TPS  50% population, 65.5% of patients in 
the tiragolumab plus atezolizumab group versus 24.1% of patients in the placebo plus 
atezolizumab group were still receiving study treatment. 
Available single agent and combination safety and preliminary efficacy data from 
Study GO30103 and combination safety data and efficacy data from Study GO40290 are 
summarized below. 
1.4.2.2 
Clinical Safety of Tiragolumab 
 
 
 
 
 
 
. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
29/Protocol GO41767, Version 7 
Clinical Safety of Single-Agent Tiragolumab:  Study GO30103 
 
 
  
Clinical Safety of Tiragolumab plus Atezolizumab:  Study GO30103 
 
 
 
 
 
Clinical Safety of Tiragolumab plus Atezolizumab in Patients with 
NonSmall Cell Lung Cancer:  Study GO40290 
In the Phase II, randomized, double-blinded Study GO40290, as of 30 June 2019, a total 
of 135 patients had been enrolled.  A total of 67 patients received tiragolumab (600 mg) 
in combination with atezolizumab (1200 mg) every 3 weeks (Q3W), and 68 patients 
received placebo in combination with atezolizumab Q3W.  The safety profile was 
comparable between the tiragolumab plus atezolizumab arm and the placebo plus 
atezolizumab arm for all grades of adverse events (98.5% vs. 95.6%), 
Grade 35 adverse events (41.8% vs. 44.1%), Grade 5 adverse events (3.0% vs. 7.4%), 
serious adverse events (34.3% vs. 35.3%), and adverse events leading to study 
treatment withdrawal (7.5% vs. 10.3%).  Study treatmentrelated adverse events 
occurred at a higher frequency in the tiragolumab plus atezolizumab arm (80.6%) 
compared with the placebo plus atezolizumab arm (72.1%).  
Adverse events (MedDRA terms) that occurred at a higher frequency ( 5% difference 
between arms) in the tiragolumab plus atezolizumab arm were infusion-related reaction 
(IRR) (28.4% vs. 10.3%), fatigue (22.4% vs. 13.2%), pruritus (19.4% vs. 11.8%), 
rash (19.4% vs. 8.8%), arthralgia (16.4% vs. 8.8%), edema peripheral (10.4% vs. 4.4%), 
rash maculo-papular (9.0% vs. 2.9%), pleural effusion (9.0% vs. 2.9%), and back pain 
(9.0% vs. 2.9%).  Adverse events that occurred at a higher frequency in the placebo plus 
atezolizumab arm included dyspnea (13.4% vs. 20.6%), productive 
cough (4.5% vs. 10.3%), ALT increased (4.5% vs. 10.3%), respiratory tract infection 
(3.0% vs. 8.8%), and hypercalcemia (0% vs. 5.9%).  Grade  3 adverse 
events ( 2% difference between arms) that occurred at a higher frequency in the 
tiragolumab plus atezolizumab arm were pneumonia (9.0% vs. 4.4%), 
pleural effusion (6.0% vs.1.5%), lipase increased (6.0% vs. 2.9%), and 
hypokalemia (3.0% vs. 0%); Grade  3 adverse events that occurred at a higher 
frequency in the placebo plus atezolizumab arm were 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
30/Protocol GO41767, Version 7 
pulmonary embolism (0% vs. 2.9%), amylase increased (0% vs. 2.9%), and asthenia 
(0% vs. 2.9%). 
Grade 5 adverse events in Study GO40290 that occurred in the tiragolumab plus 
atezolizumab arm were Epstein-Barr virus (EBV) infection and pyrexia (reported for 
1 patient each), and Grade 5 adverse events in the placebo plus atezolizumab arm were 
cardiorespiratory arrest, cerebrovascular accident, multiple-organ dysfunction syndrome, 
pneumonia, and pulmonary embolism (1 patient each). 
 
 
 
 
 
 
Please refer to the Tiragolumab Investigator’s Brochure for further details and the most 
current information on the adverse events observed in patients treated with tiragolumab 
plus atezolizumab.  
Clinical Safety of Tiragolumab plus Atezolizumab and Chemotherapy 
The safety profiles resulting from combining PD-1/PD-L1 inhibitors and chemotherapy 
have generally been consistent with the known toxic effects of each agent as observed 
in multiple clinical trials of advanced solid tumors (Gandhi et al. 2018; Horn et al. 2018; 
Paz-Ares et al. 2018; Schmid et al. 2018). 
 
 
 
 
 
 
  
Please refer to the Tiragolumab Investigator’s Brochure for further details and the 
current information on the safety of tiragolumab. 
1.4.2.3 
Clinical Activity of Tiragolumab Plus Atezolizumab 
Clinical Activity of Single-Agent Tiragolumab:  Study GO30103 
 
 
  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
31/Protocol GO41767, Version 7 
 
 
Clinical Activity of Tiragolumab Plus Atezolizumab:  Study GO30103 
 
Clinical Activity of Tiragolumab Plus Atezolizumab in Patients with 
NonSmall Cell Lung Cancer:  Study GO40290 
As of the primary clinical cutoff date of 30 June 2019, a total of 135 patients with a 
PD-L1 TPS  1% were included in the ITT population and were randomly assigned to 
receive tiragolumab plus atezolizumab (n  67) or placebo plus atezolizumab (n  68).  Of 
the enrolled patients, 43.0% of patients had a TPS  50% relative to 57.0% of patients 
with a TPS 1%49%, 59.3% had non-squamous histology compared with 40.7% of 
patients who had squamous histology, and 10.4% of patients were never-smokers 
versus 89.6% who had smoked.  These three stratification factors were well balanced 
between treatment groups.  Demographics were also generally well balanced between 
treatment groups, with a median age of 68 years in both the tiragolumab plus 
atezolizumab and placebo plus atezolizumab arms.  There were more females 
(41.8% vs. 29.4%) and more White patients (62.7% vs. 58.8%) in the tiragolumab plus 
atezolizumab arm compared with the placebo plus atezolizumab arm. 
In the ITT population, the confirmed ORR was higher in the tiragolumab plus 
atezolizumab arm (31.3%) than in the placebo plus atezolizumab arm (16.2%).  In the 
subgroup of patients with TPS  50%, the confirmed ORR was higher in the tiragolumab 
plus atezolizumab arm (n  29; 55.2% [95% CI: 35.4% to 75.0%]) than the placebo plus 
atezolizumab arm (n  29; 17.2% [95% CI: 1.8% to 32.7%]).  Of note, responders in the 
tiragolumab plus atezolizumab arm included patients with both squamous and 
non-squamous histology.   

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
32/Protocol GO41767, Version 7 
In the ITT population, investigator-assessed PFS was improved in the tiragolumab plus 
atezolizumab group over the placebo plus atezolizumab group (stratified 
HR  0.57 [95% CI: 0.37 to 0.90]; median PFS 5.4 vs. 3.6 months, respectively).  In the 
subgroup of patients with TPS  50%, investigator-assessed PFS was improved in the 
tiragolumab plus atezolizumab group over the placebo plus atezolizumab group 
(unstratified HR  0.33 [95% CI: 0.15 to 0.72]; median PFS not estimable [NE] vs. 
3.9 months, respectively).  
1.4.2.4 
Clinical Pharmacokinetics and Immunogenicity of Tiragolumab 
and Atezolizumab  
Clinical Pharmacokinetics and Immunogenicity of Tiragolumab 
 
 
 
 
 
 
 
 
 
 
 
 
   
Refer to the Tiragolumab Investigator’s Brochure for further details and the most current 
information.   
Clinical Pharmacokinetics and Immunogenicity of Atezolizumab 
 
 
 
 
 
 
  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
33/Protocol GO41767, Version 7 
 
   
Please refer to the Atezolizumab Investigator’s Brochure for details on the clinical 
pharmacokinetics of atezolizumab. 
1.5 
BACKGROUND ON ATEZOLIZUMAB  
Atezolizumab is a humanized IgG1 MAb that targets PD-L1 and inhibits the interaction 
between PD-L1 and its receptors, PD-1 and B7-1 (also known as CD80), both of which 
function as inhibitory receptors expressed on T cells.  Therapeutic blockade of PD-L1 
binding by atezolizumab has been shown to enhance the magnitude and quality of 
tumor-specific T-cell responses, resulting in improved anti-tumor activity 
(Fehrenbacher et al. 2016; Rosenberg et al. 2016).  Atezolizumab has minimal binding 
to Fc receptors, thus eliminating detectable Fc-effector function and associated 
antibody-mediated clearance of activated effector T cells. 
Atezolizumab shows anti-tumor activity in both nonclinical models and cancer patients 
and is being investigated as a potential therapy in a wide variety of malignancies.  
Atezolizumab is being studied as a single agent in the advanced cancer and adjuvant 
therapy settings, as well as in combination with chemotherapy, targeted therapy, and 
CIT. 
Atezolizumab is approved for the treatment of urothelial carcinoma, NSCLC, SCLC, 
triple-negative breast cancer, hepatocellular carcinoma, melanoma, and alveolar soft 
part sarcoma.  
Refer to the Atezolizumab Investigator's Brochure for details on nonclinical and clinical 
studies. 
1.6 
STUDY RATIONALE AND BENEFITRISK ASSESSMENT 
1.6.1 
Rationale for Testing Tiragolumab in Combination with 
Atezolizumab and Carboplatin and Etoposide in First-Line 
Extensive-Stage Small Cell Lung Cancer 
The current standard first-line treatment for patients with ES-SCLC is atezolizumab plus 
CE.  Despite the survival benefit observed with this regimen, median survival remains at 
approximately 1 year, leaving considerable room for improvement in outcomes.  
Tumor-cell killing by cytotoxic chemotherapy can reasonably be expected to expose the 
immune system to high levels of tumor antigens.  Therefore, invigorating tumor-specific 
T-cell immunity by inhibiting PD-L1/PD-1 signaling and TIGIT/PVR may result in deeper 
and more durable responses compared with standard chemotherapy alone 
(Merritt et al. 2003; Apetoh et al. 2007; Yu et al. 2018a, 2018b; Xu et al. 2019).  
Evaluating the safety and efficacy of these treatment combinations in patients with SCLC 
will enable future tests of this hypothesis. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
34/Protocol GO41767, Version 7 
In light of these observations, this study (Study GO41767) is designed to evaluate 
whether the anti-tumor effect of the combination of atezolizumab plus CE (IMpower133 
regimen) can be enhanced by adding tiragolumab in treating patients with 
chemotherapy-naive ES-SCLC.  This study will allow for the evaluation of efficacy of 
tiragolumab plus atezolizumab plus chemotherapy in the full analysis set (FAS) 
 
  
Patients with SCLC frequently present with symptoms of widespread metastatic disease 
and may experience fast clinical deterioration; therefore, there is a need for rapid 
treatment initiation for these patients.  In addition, tissue sample collection for 
investigational 
 may be difficult in this patient population because the 
amount of tissue available in many cases is limited.  Because the benefit of 
atezolizumab plus chemotherapy was observed in all-comer patients in IMpower133, this 
study will enroll patients with ES-SCLC whose disease is unselected for PD-L1 
expression.  
 
 
  
This study will enroll patients with ES-SCLC who are chemotherapy-naive for their 
extensive-stage disease, and for whom the experimental arm can represent a valuable 
treatment option and a reasonable benefit–risk balance.   
In summary, treatment with tiragolumab plus atezolizumab in combination with CE offers 
the potential for clinical benefit in patients with ES-SCLC.   
1.6.2 
Study Rationale 
Encouraging clinical data emerging in the field of tumor immunotherapy have 
demonstrated that therapies focused on enhancing T-cell responses against cancer can 
result in a significant survival benefit in patients with metastatic cancer, including SCLC.  
Recent approvals by the U.S. Food and Drug Administration (FDA) of atezolizumab plus 
chemotherapy in metastatic SCLC in the first-line setting validate the inhibition of the 
PD-L1/PD-1 pathway for achieving clinical benefit in these patients.  Furthermore, the 
safety profile of atezolizumab plus chemotherapy appears to be as tolerable as 
chemotherapy doublet combinations in the front-line setting. 
Nevertheless, despite the robust activity observed with atezolizumab plus 
chemotherapy, durable clinical benefit appears limited to a minority of treated patients.  It 
is hypothesized that many of these patients with metastatic SCLC may have intrinsic or 
acquired resistance to checkpoint inhibition.  Thus, another strategy to increase the 
response to checkpoint inhibitors among patients has focused on treatment with novel 
immunotherapy combinations that may overcome such intrinsic or acquired resistance to 
PD-L1/PD-1 antibodies. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
35/Protocol GO41767, Version 7 
T-cell immunoreceptor with Ig and ITIM domains is an inhibitory immunoreceptor that 
can limit the effector function of tumor-associated lymphocytes.  
 
 
 
 
 
 
 
 
 
 
.  In preliminary 
data from the interim analysis of the Phase II Study GO40290, the ORR (confirmed and 
unconfirmed responses) was higher in the tiragolumab plus atezolizumab group than in 
the placebo plus atezolizumab group in both the ITT and TPS  50% populations.  
Consistent with the Phase Ib study, the combination of tiragolumab with atezolizumab 
was well tolerated in the Phase II study. 
Therefore, the current study is designed to evaluate whether the anti-tumor effects of 
atezolizumab plus chemotherapy, as measured by OS, PFS, ORR, and DOR, can be 
improved with the addition of the anti-TIGIT antibody tiragolumab to atezolizumab and 
chemotherapy in patients with ES-SCLC. 
1.6.3 
BenefitRisk Assessment 
This study will enroll patients with ES-SCLC with no prior systemic treatment, and all 
patients will receive standard atezolizumab plus chemotherapy, either in the 
experimental arm or in the placebo arm.  The standard of care of atezolizumab plus 
chemotherapy was well tolerated in the pivotal IMpower133 study, with a safety profile 
consistent with the known risks of individual treatment and comparable to the treatment 
of chemotherapy alone.  The combination of tiragolumab plus atezolizumab with 
chemotherapy in the experimental arm can represent a potential valuable treatment 
option and can offer a reasonable benefitrisk balance for patients in this study.  
The combination of tiragolumab plus atezolizumab was tolerated in both the Phase Ib 
(GO30103) and Phase II (GO40290) studies.  In Study GO40290, tiragolumab plus 
atezolizumab demonstrated an overall safety profile similar to that of placebo plus 
atezolizumab in terms of any grade adverse events, Grade 34 adverse events, serious 
adverse events, and adverse events leading to study treatment discontinuation 
(see Section 1.4.2.2).  While adverse events related to any study treatment and adverse 
events leading to dose interruption of any study treatment were higher in the tiragolumab 
plus atezolizumab arm, there was no increase in Grade 5 adverse events 
(see Section 1.4.2.2).  Adverse events with potentially immune-mediated causes were 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
36/Protocol GO41767, Version 7 
observed with a higher incidence in the tiragolumab plus atezolizumab arm in 
Study GO40290.  However, the imbalance was mostly attributed to Grade 12 rash and 
IRRs (see Section 1.4.2).  Grade 34 immune-mediated adverse events were similar 
between the treatment arms.  To date, immune-mediated adverse events have been 
manageable with standard medical practice supplemented with corticosteroids, 
immunosuppressive agents, and/or hormone replacement therapy.  There were no 
Grade 5 immune-mediated adverse events reported in the Phase Ib and Phase II 
studies. 
In summary, the combination of tiragolumab with atezolizumab plus chemotherapy in 
this study may benefit patients beyond treatment with atezolizumab plus chemotherapy.  
 
.  Immune-mediated adverse events, although 
reported at a higher frequency for the tiragolumab plus atezolizumab arm in the Phase II 
study (GO40290), are generally mild, transient, monitorable, and manageable in nature.  
The toxicities of the combination of tiragolumab and atezolizumab plus chemotherapy 
are also expected to be similar with the standard of care of atezolizumab plus 
chemotherapy.  Therefore, the overall benefitrisk ratio is considered to be appropriate 
for the study population. 
 
 
 
COVID-19 Benefit-Risk Assessment 
In the setting of the coronavirus disease 2019 (COVID-19) pandemic, patients with 
comorbidities, including those with cancer, are considered a more vulnerable population, 
with the potential for more severe clinical outcomes from severe acute respiratory 
syndrome coronavirus 2 (SARS-CoV-2) infection.  However, it is unclear whether or how 
systemic cancer therapies, such as chemotherapy, targeted therapy, or immunotherapy, 
impact the incidence or severity of SARS-CoV-2 infection. 
A possible consequence of immune checkpoint inhibition may be the modulation of the 
host immune response to acute infection, which may result in immunopathology or 
dysregulated immune system defenses.  In nonclinical models, PD-L1/PD-1 blockade 
appears to be associated with serious exacerbation of inflammation in the setting of 
acute (as opposed to chronic) viral infection with lymphocytic choriomeningitis virus 
(Clone 13) (Frebel et al. 2012; Wykes and Lewin 2018; Schorer et al. 2020).  However, 
there are insufficient and inconsistent clinical data to assess if outcome from 
SARS-CoV-2 infection is altered by CIT. 
Severe SARS-CoV-2 infection appears to be associated with a cytokine-release 
syndrome (CRS) involving the inflammatory cytokines interleukin (IL)-6, IL-10, IL-2, and 
IFN- (Merad and Martin 2020).  
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
37/Protocol GO41767, Version 7 
 
  At this time, 
there is insufficient evidence for causal association between atezolizumab or 
tiragolumab and an increased risk of severe outcomes from SARS-CoV-2 infection. 
There may be potential synergy or overlap in clinical and radiologic features for 
immune-mediated pulmonary toxicity with immune checkpoint inhibitors and clinical and 
radiologic features for SARS-CoV-2related interstitial pneumonia.  Thus, investigators 
should use their clinical judgment when evaluating and managing patients with 
pulmonary symptoms. 
There are limited data concerning the possible interactions between CIT treatment and 
COVID-19 vaccination, and it is recognized that human immune responses are highly 
regulated and that immune-modifying therapies may positively or negatively impact the 
efficacy and safety of COVID-19 vaccination (Society for Immunotherapy of Cancer 
[SITC] 2020). 
Per recommendations of the NCCN COVID-19 Vaccination Advisory Committee, 
COVID-19 vaccination is recommended for all patients with cancer receiving active 
therapy (including immune checkpoint inhibitors), with the understanding that there are 
limited safety and efficacy data in such patients (NCCN 2021).  Given the lack of clinical 
data, currently no recommendations can be made regarding the optimal sequence of 
COVID-19 vaccination in patients who are receiving CIT (SITC 2020).  For patients 
enrolling in this study and receiving atezolizumab and/or tiragolumab/placebo treatment, 
a decision to administer the vaccine to a patient should be made on an individual basis 
by the investigator in consultation with the patient. 
In alignment with clinical practice procedures, factors to consider when making the 
individualized decision for patients receiving atezolizumab and/or tiragolumab/placebo 
treatment to receive COVID-19 vaccination include the following:  the risk of 
SARS-CoV-2 infection and potential benefit from the vaccine, the general condition of 
the patient and potential complications associated with SARS-CoV-2 infection, 
underlying disease, and the severity of COVID-19 outbreak in a given area or region. 
Society for Immunotherapy of Cancer and NCCN recommendations along with 
institutional guidelines should be used by the investigator when deciding on 
administering COVID-19 vaccines.  When administered, COVID-19 vaccines must be 
given in accordance with the approved or authorized vaccine label.  Receipt of the 
COVID-19 vaccine is considered a concomitant medication and should be documented 
as such (see Section 4.4.1). 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
38/Protocol GO41767, Version 7 
2. 
OBJECTIVES AND ENDPOINTS 
2.1 
EFFICACY OBJECTIVES 
2.1.1 
Primary Efficacy Objective 
The primary efficacy objective for this study is to evaluate the efficacy of tiragolumab 
plus atezolizumab and CE compared with placebo plus atezolizumab and CE in patients 
with untreated ES-SCLC on the basis of the following co-primary endpoints: 
 
PFS after randomization, defined as the time from randomization to the first 
occurrence of disease progression as determined by the investigator according to 
RECIST v1.1 or death from any cause, whichever occurs first in patients who are 
randomly assigned without presence or history of brain metastases at baseline 
(primary analysis set [PAS])  
 
OS after randomization, defined as the time from randomization to death from any 
cause in the PAS 
 
2.1.2 
Secondary Efficacy Objective 
The secondary efficacy objective for this study is to evaluate the efficacy of tiragolumab 
plus atezolizumab and CE compared with placebo plus atezolizumab and CE on the 
basis of the following endpoints: 
 
PFS in the FAS 
 
OS in the FAS 
 
Confirmed ORR, defined as the proportion of patients with a confirmed objective 
response (i.e., CR or PR on two consecutive occasions  4 weeks apart), as 
determined by the investigator according to RECIST v1.1 in the PAS and the FAS 
who have measurable disease at baseline 
 
DOR for patients with confirmed objective response, defined as the time from the 
first occurrence of a documented, confirmed objective response to disease 
progression, as determined by the investigator according to RECIST v1.1, or death 
from any cause, whichever occurs first in the PAS and the FAS  
 
PFS rates at 6 months and at 12 months in the PAS and the FAS  
 
OS rates at 12 months and 24 months in the PAS and the FAS 
 
Time to confirmed deterioration (TTCD) in patient-reported physical functioning and 
global health status/quality of life (GHS/QoL), as measured by the European 
Organisation for the Research and Treatment of Cancer (EORTC) Quality of 
LifeCore 30 Questionnaire (QLQ-C30) in the PAS and the FAS 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
40/Protocol GO41767, Version 7 
2.4 
IMMUNOGENICITY OBJECTIVES 
The immunogenicity objective for this study is to evaluate the immune response to 
tiragolumab and atezolizumab on the basis of the following endpoints: 
 
Prevalence of ADAs to tiragolumab at baseline and incidence of ADAs to 
tiragolumab during the study 
 
Prevalence of ADAs to atezolizumab at baseline and incidence of ADAs to 
atezolizumab during the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.6 
HEALTH STATUS UTILITY OBJECTIVE 
The health status utility objective for this study is to evaluate the impact of health status 
utility scores of patients treated with tiragolumab plus atezolizumab and CE compared 
with placebo plus atezolizumab and CE on the basis of the following endpoint: 
 
Change in EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) index-based 
and Visual Analog Scale scores at specified timepoints during the study (including 
post-progression) 
 
3. 
STUDY DESIGN 
3.1 
DESCRIPTION OF THE STUDY 
3.1.1 
Overview of Study Design 
This is a randomized, Phase III, global, multicenter, double-blinded, placebo-controlled 
study designed to evaluate the safety and efficacy of tiragolumab in combination with 
atezolizumab and CE compared with treatment with placebo in combination with 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
42/Protocol GO41767, Version 7 
Figure 1 Study Schema (cont.) 
1L  first-line; CE  carboplatin and etoposide; ECOG PS  Eastern Cooperative Oncology Group 
Performance Status; ES-SCLC  extensive-stage small cell lung cancer; FAS  full analysis set; 
PAS  primary analysis set; RECIST  Response Evaluation Criteria in Solid Tumors; ULN  upper 
limit of normal. 
a For the first 24 patients (approximately 12 per arm) who are randomly assigned, safety and 
tolerability data will be assessed by an independent Data Monitoring Committee. 
  
After providing informed consent, patients will undergo screening procedures as outlined 
in the schedule of activities (Appendix 1).  Patients who do not initially meet all eligibility 
criteria for participation in this study may qualify for one re-screening opportunity (for a 
total of two screenings per patient) at the investigator’s discretion.  Patients are not 
required to re-sign the consent form if they are re-screened within 60 days after 
previously signing the consent form.  For patients who are re-screened, all eligibility 
criteria must be re-evaluated and screening assessments should be repeated as 
applicable to meet the eligibility criteria outlined in Section 4.1.  The investigator will 
record reasons for screening failure in the screening log (see Section 4.5.1). 
Eligible patients will be stratified by ECOG Performance Status (0 vs. 1), LDH ( upper 
limit of normal [ULN] vs.  ULN), and presence or history of brain metastasis (yes vs. no) 
and randomly assigned in a 1:1 ratio to receive one of the following treatment regimens 
as shown in Table 1. 
Table 1 
Study GO41767 Treatment Arms 
Treatment Arm 
Induction 
(Four 21-Day Cycles) 
Maintenance 
(21-Day Cycles) 
A 
Tiragolumab  Atezolizumab  CE 
Tiragolumab  Atezolizumab 
B 
Placebo  Atezolizumab  CE 
Placebo  Atezolizumab 
CE  carboplatin and etoposide. 
  
Induction treatment will be administered on a 21-day cycle for 4 cycles.  
Following the induction phase, patients will continue maintenance therapy with either 
atezolizumab plus tiragolumab (Arm A) or atezolizumab plus placebo (Arm B).  During 
the maintenance phase, prophylactic cranial irradiation (PCI) is permitted (although not 
mandated) per local standard of care, and will be reported on the PCI electronic Case 
Report Form (eCRF).  Consolidative thoracic radiation with curative intent or the intent to 
eliminate residual disease is not permitted.  Palliative radiation for symptomatic 
management is allowed (please refer to Section 4.4.1 for further details).   
Treatment will be continued until radiographic disease progression according to 
RECIST v1.1, or as long as patients are experiencing clinical benefit, as assessed by the 
investigator, in the absence of unacceptable toxicity or symptomatic deterioration 
attributed to disease progression after an integrated assessment of radiographic data, 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
43/Protocol GO41767, Version 7 
biopsy results (if available), and clinical status.  Patients who meet the criteria for 
disease progression per RECIST v1.1 will be permitted to continue study treatment 
(tiragolumab plus atezolizumab or placebo plus atezolizumab) if they meet all of the 
criteria specified in Section 3.1.2 and provide written consent. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patients will undergo tumor assessments at baseline and every 6 weeks ( 7 days) for 
48 weeks following Cycle 1, Day 1, regardless of treatment dose delays.  After 
completion of the Week 48 tumor assessment, tumor assessments will be required every 
9 weeks ( 7 days) thereafter, regardless of treatment dose delays.  Patients will 
undergo tumor assessments until radiographic disease progression per RECIST v1.1, 
withdrawal of consent, study termination by the Sponsor, or death, whichever occurs 
first.  Patients who are treated beyond disease progression per RECIST v1.1 (see 
Section 3.1.2) will undergo tumor assessments at the frequency described above until 
study treatment is discontinued.  Patients who discontinue treatment for reasons other 
than radiographic disease progression per RECIST v1.1 (e.g., toxicity, symptomatic 
deterioration) will continue scheduled tumor assessments at the same frequency as 
would have been followed if the patient had remained on study treatment (i.e., every 
6 weeks [ 7 days] for 48 weeks following Cycle 1, Day 1 and then every 9 weeks 
[ 7 days] thereafter, until radiographic disease progression per RECIST v1.1, withdrawal 
of consent, study termination by the Sponsor, or death, whichever occurs first), 
regardless of whether the patient starts a new anti-cancer therapy. 
 
 
 
  
The investigator’s assessment of overall tumor response at all timepoints should be 
based on RECIST v1.1.  Assessments should be performed by the same evaluator, if 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
44/Protocol GO41767, Version 7 
possible, to ensure internal consistency across visits.  All primary imaging data used for 
tumor assessments will be collected by the Sponsor; centralized, blinded, independent 
review of response endpoints by an independent review facility (IRF) may be conducted. 
In order not to confound the OS endpoint, crossover will not be allowed from the 
control arm (placebo plus atezolizumab plus CE) to the experimental arm (tiragolumab 
plus atezolizumab plus CE). 
During the study, patients will be asked to complete PRO questionnaires at the 
beginning of the study, at treatment discontinuation, and during survival follow-up (see 
Section 4.5.10 and Appendix 1 for details on the surveys and schedule). 
 
 
 
 
 
Safety assessments will include the incidence, nature, and severity of adverse events, 
and other protocol-specified tests, such as laboratory abnormalities, that are deemed 
critical to the safety evaluation of the study. 
3.1.2 
Treatment after Disease Progression 
During the study, patients who meet criteria for radiographic disease progression per 
RECIST v1.1 may continue treatment at the investigator’s discretion, provided that the 
patients meet all of the following criteria: 
 
Evidence of clinical benefit, as assessed by the investigator 
 
Absence of symptoms and signs (including worsening of laboratory values 
[e.g., new or worsening hypercalcemia]) indicating unequivocal progression of 
disease 
 
No decline in ECOG Performance Status that can be attributed to disease 
progression 
 
Absence of tumor progression at critical anatomical sites (e.g., leptomeningeal 
disease) that cannot be managed by protocol-allowed medical interventions 
 
Patients must provide written consent to acknowledge deferring other treatment 
options in favor of continuing study treatment at the time of initial radiographic 
progression per RECIST v1.1 
 
Investigator assessment of overall tumor response at all timepoints will be based on 
RECIST v1.1. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
45/Protocol GO41767, Version 7 
3.1.3 
Independent Data Monitoring Committee 
An iDMC will be used to evaluate safety during the study.  
 
 
 
 
 
 
 
The safety data will include disposition, demographic data, adverse events, serious 
adverse events, and relevant laboratory data. 
  
 
 
 
 
 
 
Members of the iDMC will be external to the Sponsor and will follow a separate iDMC 
Charter that outlines their roles and responsibilities, as well as a detailed monitoring 
plan. 
Any outcomes of these safety reviews that affect study conduct will be communicated in 
a timely manner to the investigators for notification of the sites’ Institutional Review 
Boards/Ethics Committees (IRBs/ECs). 
3.2 
END OF STUDY AND LENGTH OF STUDY 
 
 
  
 
. 
 
Additionally, the Sponsor may decide to terminate the study at any time.  If the Sponsor 
decides to terminate the study, patients who are still receiving study treatment or 
undergoing survival follow-up may be enrolled in a post-trial access program or an 
extension study. 
3.3 
DURATION OF PARTICIPATION 
The total duration of study participation for each individual is expected to be up to 
approximately
months. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
47/Protocol GO41767, Version 7 
of 1.07 compared to a HR of 0.68 for patients without brain metastases 
(Horn et al. 2018). 
KEYNOTE-604 is another Phase III trial that suggests that patients with ES-SCLC with 
brain metastasis at diagnosis may achieve less or no overall survival benefit to first-line 
immunotherapy plus chemotherapy in comparison to those without.  In fact, patients with 
brain metastases had an OS HR of 1.32 versus 0.75 for patients without brain 
metastases (Rudin et al. 2020).  The CASPIAN study initially reported an OS HR 
of 0.69 in patients with brain metastasis; however, in the updated analysis, the HR 
became 0.79.  The OS HR in those without brain metastasis in initial and updated 
reports was 0.74 and 0.76, respectively (Paz-Ares et al. 2018, 2020). 
It is critical to understand the benefit of the study regimen in both of the patient 
subgroups, thus, the testing statistical testing hierarchy was implemented to test the 
PAS first, and then subsequently the FAS (see Section 6.1.1, Figure 2). 
3.4.4 
Rationale for Progression-Free Survival and Overall Survival 
as Co-Primary Endpoints 
Investigator-assessed PFS and OS are the co-primary endpoints for this study. 
Progression-free survival as an endpoint can reflect tumor growth and can be assessed 
before the determination of a survival benefit; additionally, its determination is not 
generally confounded by subsequent therapies.  Whether an improvement in PFS 
represents a direct clinical benefit or a surrogate for clinical benefit depends upon the 
magnitude of the effect and the benefit-risk of the new treatment compared with 
available therapies (Guidance for Industry 2007; European Medicines Agency 2012). 
 
 
 
 
 
 
Overall survival is a co-primary endpoint in this study.  Improvement in OS is generally 
accepted as the best measure of clinical benefit for patients with advanced/unresectable 
or metastatic lung cancer.  In the randomized Phase III study in patients with advanced 
SCLC (IMpower133), an OS benefit in the atezolizumab plus chemotherapy arm was 
observed compared with the placebo plus chemotherapy arm (Horn et al. 2018).  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
48/Protocol GO41767, Version 7 
3.4.5 
Rationale for Tiragolumab and/or Atezolizumab Treatment 
Beyond Initial Radiographic Disease Progression 
Patients with ES-SCLC experience rapid tumor growth and fast clinical deterioration and 
have an overall poor prognosis.  First-line therapy with atezolizumab plus CE has 
demonstrated high response rates and significant clinical benefit.  However, after 
disease progression, treatment options are limited and such options have shown limited 
efficacy and significant toxicity (see Section 1.1.1).  Given that the greatest opportunity 
to achieve a clinically significant benefit from therapy is in the front-line setting and given 
the poor efficacy and high toxicity profile of second-line therapies, patients may be 
considered for treatment beyond radiographic disease progression per RECIST v1.1 at 
the discretion of the investigator and after appropriate discussion with the patient, only if 
they meet all of the criteria described in Section 3.1.2.  
In addition, conventional response criteria may not adequately assess the activity of 
immunotherapeutic agents because progressive disease (by initial radiographic 
evaluation) does not necessarily reflect therapeutic failure.  Because of the potential for 
pseudoprogression/tumor-immune infiltration, this study will allow patients to remain on 
treatment after apparent radiographic disease progression per RECIST v1.1, provided all 
criteria in Section 3.1.2 are met.  Treatment should be discontinued if clinical 
deterioration due to disease progression occurs at any time.  In addition, patients should 
be discontinued for unacceptable toxicity or for any other signs or symptoms of 
deterioration attributed to disease progression as determined by the investigator after an 
integrated assessment of radiographic data and clinical status (see Section 4.6.1).  
3.4.6 
Rationale for Patient-Reported Outcome Assessments 
In the treatment of lung cancer, it is important to both increase survival and palliate 
symptoms because disease symptoms have negative impacts on health-related quality 
of life (Hyde and Hyde 1974; Hopwood and Stephens 1995; Sarna et al. 2004).  This is 
especially true for studies that have PFS as a primary endpoint, to inform how delays in 
radiographic progression might be associated with delays in clinical progression of 
symptoms and their interference on functioning, including maintenance of low disease 
burden.  
In addition, many of the most frequent adverse events attributed to tiragolumab and 
atezolizumab (e.g., fatigue, rash, nausea) are symptoms directly reportable by patients; 
therefore, patients’ reporting of their experience with these symptoms will complement 
the evaluation of treatment tolerability (King-Kallimanis et al. 2019).  
This study includes use of validated patient-reported measures of symptom severity and 
symptom impact on functioning,
 
 
  Data generated from these instruments will inform 
patients’ experience with disease burden and treatment tolerability as part of the totality 
of evidence generated to inform the riskbenefit profile of tiragolumab and atezolizumab.   

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
49/Protocol GO41767, Version 7 
The EQ-5D-5L (see Appendix 8) is also included in this study to generate utility scores 
for use in economic models for reimbursement.   
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. 
MATERIALS AND METHODS 
4.1 
PATIENTS 
Patients may be eligible if they are chemotherapy-naive for their ES-SCLC. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
50/Protocol GO41767, Version 7 
4.1.1 
Inclusion Criteria 
Patients must meet the following criteria to be eligible for study entry: 
 
Signed Informed Consent Form 
 
Age  18 years at time of signing Informed Consent Form 
 
Ability to comply with the study protocol, in the investigator's judgment 
 
ECOG Performance Status of 0 or 1 (see Appendix 9) 
 
Histologically or cytologically confirmed ES-SCLC (per the modified Veterans 
Administration Lung Study Group [VALG] staging system) (Micke et al. 2002; see 
Appendix 3) 
 
No prior systemic treatment for ES-SCLC 
 
For patients who have received prior chemoradiotherapy for limited-stage SCLC:  
must have had treatment with curative intent and a treatment-free interval of at least 
6 months between the last dose/cycle of chemotherapy, thoracic radiotherapy, or 
chemoradiotherapy and the diagnosis of ES-SCLC 
 
Measurable disease, as defined by RECIST v1.1 
 
Submission of a pre-treatment tumor tissue sample (see Section 4.5.7 for 
information on tumor specimens) 
. 
 
 
 
Adequate hematologic and end-organ function, defined by the following laboratory 
test results, obtained within 14 days prior to initiation of study treatment (Day 1 of 
Cycle 1): 
– 
– 
– 
– 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
51/Protocol GO41767, Version 7 
– 
– 
– 
– 
 
For patients receiving therapeutic anticoagulation:  stable anticoagulant regimen 
 
 
 
 
 
 
 
For women of childbearing potential:  agreement to remain abstinent (refrain from 
heterosexual intercourse) or use contraception, and agreement to refrain from 
donating eggs, as defined below: 
Women must remain abstinent or use contraceptive methods with a failure rate 
of  1% per year during the treatment period and for 90 days after the final dose 
of tiragolumab or placebo, for 5 months after the final dose of atezolizumab, 
and for 6 months after the final dose of CE.  Women must refrain from donating 
eggs during this same period. 
A woman is considered to be of childbearing potential if she is postmenarchal, 
has not reached a postmenopausal state ( 12 continuous months of 
amenorrhea with no identified cause other than menopause), and is not 
permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, 
and/or uterus) or another cause as determined by the investigator 
(e.g., Müllerian agenesis).  The definition of childbearing potential may be 
adapted for alignment with local guidelines or regulations. 
Examples of contraceptive methods with a failure rate of  1% per year include 
bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit 
ovulation, hormone-releasing intrauterine devices, and copper intrauterine 
devices. 
The reliability of sexual abstinence should be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the patient.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
52/Protocol GO41767, Version 7 
methods) and withdrawal are not adequate methods of contraception.  
If required per local guidelines or regulations, locally recognized adequate 
methods of contraception and information about the reliability of abstinence will 
be described in the local Informed Consent Form. 
Women who would like to become pregnant after study treatment 
discontinuation should seek advice on oocyte cryopreservation prior to initiation 
of study treatment because of the possibility of irreversible infertility due to 
treatment with carboplatin and/or etoposide. 
 
For men:  agreement to remain abstinent (refrain from heterosexual intercourse) or 
use a condom, and agreement to refrain from donating sperm, as defined below: 
With a female partner of childbearing potential who is not pregnant, men who 
are not surgically sterile 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 90 days after the final dose of 
tiragolumab or placebo, and for 6 months after the final dose of carboplatin or 
etoposide.  Men must refrain from donating sperm during this same period. 
With a pregnant female partner, men must remain abstinent or use a condom 
during the treatment period, for 90 days after the final dose of tiragolumab, and 
for 6 months after the final dose of carboplatin or etoposide to avoid exposing 
the embryo. 
The reliability of sexual abstinence should be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the patient.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not adequate methods of preventing drug 
exposure.  If required per local guidelines or regulations, information about the 
reliability of abstinence will be described in the local Informed Consent Form. 
Men who would like to father a child after study treatment initiation should seek 
advice on conservation of sperm prior to initiation of study treatment because of 
the possibility of irreversible infertility due to treatment with carboplatin and/or 
etoposide. 
 
4.1.2 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from study entry: 
 
Symptomatic or actively progressing CNS metastases  
Note:  Asymptomatic patients with treated (i.e., local CNS-directed therapy) or 
untreated CNS lesions are eligible, provided that all of the following criteria are 
met: 
– 
Measurable disease, per RECIST v1.1, must be present outside the CNS. 
– 
The patient has no history of intracranial hemorrhage or spinal cord 
hemorrhage from CNS disease.  
– 
Metastases are limited to the cerebellum or the supratentorial region (i.e., no 
metastases to the midbrain, pons, medulla, or spinal cord). 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
53/Protocol GO41767, Version 7 
– 
The patient has no symptoms caused by CNS disease (i.e., no headache, 
nausea, vomiting, convulsion, paralysis, etc.). 
– 
The patient has no ongoing requirement for anticonvulsants for CNS disease. 
– 
The patient has no ongoing requirement for dexamethasone/corticosteroids for 
CNS disease (previously untreated patients must also not have any history of 
requiring or receiving dexamethasone/corticosteroids for CNS disease). 
– 
For patients with previously treated CNS metastases, there is no evidence of 
interim CNS progression between the completion of CNS-directed therapy and 
randomization.  
– 
For previously untreated patients, there is no evidence of brain edema related 
to CNS disease (e.g., vasogenic edema). 
– 
For previously untreated patients, a brain magnetic resonance imaging (MRI) 
scan with contrast is required at screening and is the preferred modality for all 
subsequent scheduled follow-up tumor assessments. 
Note:  Computed tomography (CT) scan with contrast may be 
acceptable for all subsequent scheduled follow-up tumor assessments 
if the following criteria are met. 
– 
Both brain MRI and CT scan with contrast must be performed at 
screening to assess untreated CNS disease.  
– 
The CT scan with contrast can be used to reliably evaluate lesions 
identified on the screening MRI with contrast. 
If CT scan with contrast cannot be used to reliably evaluate lesions 
identified on the screening MRI with contrast, then MRI scan with 
contrast must be used at all subsequent scheduled follow-up tumor 
assessments. 
The same modality must be used at every tumor assessment. 
 
Spinal cord compression not definitively treated with surgery and/or radiation, or 
previously diagnosed and treated spinal cord compression without evidence that 
disease has been clinically stable for  1 week prior to randomization 
 
Leptomeningeal disease 
 
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent 
drainage procedures (once monthly or more frequently) 
Patients with indwelling catheters (e.g., PleurX) are allowed regardless of 
drainage frequency. 
 
Uncontrolled or symptomatic hypercalcemia (ionized calcium  1.5 mmol/L, total 
serum calcium  12 mg/dL, or corrected calcium  ULN) 
 
Known clinically significant liver disease, including active viral, alcoholic, or other 
hepatitis, cirrhosis, and inherited liver disease, or current alcohol abuse 
 
Malignancies other than SCLC within 5 years prior to randomization, with the 
exception of those with a negligible risk of metastasis or death (e.g., expected 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
55/Protocol GO41767, Version 7 
 
Significant cardiovascular disease (such as New York Heart Association cardiac 
disease Class II or greater, myocardial infarction, or cerebrovascular accident) 
within 3 months prior to randomization, unstable arrhythmias, or unstable angina 
Patients with known coronary artery disease, congestive heart failure not 
meeting the above criteria, or left ventricular ejection fraction  50% must be on 
a stable medical regimen that is optimized in the opinion of the treating 
physician, in consultation with a cardiologist if appropriate. 
 
Major surgical procedure other than for diagnosis 
 prior to 
randomization or anticipation of need for a major surgical procedure during the 
course of the study 
 
Prior allogeneic bone marrow transplantation or solid organ transplant 
 
Any other diseases, metabolic dysfunction, physical examination finding, or clinical 
laboratory finding giving reasonable suspicion of a disease or condition that 
contraindicates the use of an investigational drug or that may affect the 
interpretation of the results or render the patient at high-risk for treatment 
complications 
 
Patients with illnesses or conditions that interfere with their capacity to understand, 
follow, and/or comply with study procedures 
 
Treatment with investigational agent within 28 days prior to initiation of study 
treatment 
 
 
Administration of a live, attenuated vaccine 
 before randomization or 
anticipation that such a live, attenuated vaccine will be required during the study 
Patients must not receive live, attenuated influenza vaccines (e.g., FluMist) 
within 4 weeks prior to randomization, during treatment, and for 5 months 
following the last dose of study treatment 
 
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, 
anti-cytotoxic T lymphocyteassociated protein 4, anti-TIGIT, antiPD-1, and 
antiPD-L1 therapeutic antibodies 
 
Treatment with systemic immunostimulatory agents (including, but not limited to, 
interferon and IL-2) within 4 weeks or 5 drug elimination half-lives (whichever is 
longer) prior to randomization 
 
Treatment with systemic immunosuppressive medications (including, but not limited 
to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and 
anti‑tumor necrosis factor [anti-TNF] agents) 
 prior to randomization or 
anticipation of need for systemic immunosuppressive medication during study 
treatment, with the following exceptions: 
Patients who received acute, low-dose systemic immunosuppressant 
medication or a one-time pulse dose of systemic immunosuppressant 
medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible 
for the study. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
56/Protocol GO41767, Version 7 
Patients who received mineralocorticoids (e.g., fludrocortisone), inhaled or 
low-dose systemic corticosteroids for chronic obstructive pulmonary disease 
(COPD) or asthma, or low-dose mineralocorticoids for orthostatic hypotension 
or low-dose mineralocorticoids and corticosteroids for adrenal insufficiency are 
eligible for the study. 
 
History of severe allergic anaphylactic reactions to chimeric or humanized 
antibodies or fusion proteins 
 
Known hypersensitivity to CHO cell products or to any component of the 
tiragolumab or atezolizumab formulations 
 
History of allergic reactions to carboplatin or etoposide 
 
Pregnancy or breastfeeding, or intention of becoming pregnant during study 
treatment or within 5 months after the final dose of atezolizumab or tiragolumab or 
for 6 months after the final dose of carboplatin or etoposide   
Women of childbearing potential must have a negative serum pregnancy test 
result within 14 days prior to initiation of study treatment.  
 
4.2 
METHOD OF TREATMENT ASSIGNMENT AND BLINDING 
4.2.1 
Treatment Assignment 
This is a randomized, double-blind, placebo-controlled study.  After written informed 
consent has been obtained, all screening procedures and assessments have been 
completed, and eligibility has been established, the study site will obtain the patient’s 
identification number and treatment assignment from the interactive voice or web-based 
response system (IxRS).  
Randomization will occur in a 1:1 ratio through use of a permuted-block randomization 
method.  Patients will be randomly assigned to one of two treatment arms:  
A) tiragolumab  atezolizumab  CE or B) placebo  atezolizumab  CE.  The 
randomization scheme is designed to ensure that an approximately equal number of 
patients will be enrolled in each treatment arm within the baseline characteristics of the 
following stratification factors: 
 
ECOG Performance Status (0 vs. 1) 
 
LDH ( ULN vs.  ULN) 
 
Presence or history of brain metastasis (yes vs. no) 
 
 
 
4.2.2 
Blinding 
Study site personnel and patients will be blinded to treatment assignment during the 
study until the time of the final OS analysis.  The Sponsor and its agents will also be 
blinded to treatment assignment, with the exception of individuals who require access to 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
57/Protocol GO41767, Version 7 
patient treatment assignments to fulfill their job roles during a clinical trial.  These roles 
include the unblinding group responsible, clinical supply chain managers, sample 
handling staff, operational assay group personnel, IxRS service provider, and iDMC 
members. 
While PK and immunogenicity samples must be collected from patients assigned to the 
comparator arm to maintain the blinding of treatment assignment, PK and ADA assay 
results for tiragolumab in these patients are generally not needed for the safe conduct or 
proper interpretation of the study data.  Laboratories responsible for performing 
tiragolumab PK and ADA assays will be unblinded to patient treatment assignments to 
identify appropriate samples for analysis.  Pharmacokinetic samples from patients 
assigned to the comparator arm will not be analyzed for tiragolumab PK concentration 
except by request (e.g., to evaluate a possible error in dosing).  Baseline (Cycle 1, Day 1 
pre-infusion) immunogenicity samples will be analyzed for all patients.  Postbaseline 
immunogenicity samples from patients assigned to the comparator arm will not be 
analyzed for ADAs to tiragolumab except by request. 
If unblinding is necessary for a medical emergency (e.g., in the case of a serious 
adverse event for which patient management might be affected by knowledge of 
treatment assignment), the investigator will be able to break the treatment code by 
contacting the IxRS.  The treatment code should not be broken except in emergency 
situations.  The investigator is not required to contact the Medical Monitor prior to 
breaking the treatment code.  However, the investigator should inform the 
Medical Monitor that the treatment code has been broken. 
If the investigator wishes to know the identity of the study drug for any reason other than 
a medical emergency, he or she should contact the Medical Monitor directly.  Unblinding 
may be permitted if an investigator is deciding whether a patient should withdraw from 
the study and initiate subsequent treatment with a proven therapy.  However, unblinding 
will not be permitted if an investigator is deciding whether a patient should initiate 
subsequent treatment with an unproven therapy.  The investigator should document and 
provide an explanation for any non-emergency unblinding.  If the Medical Monitor agrees 
to patient unblinding, the investigator will be able to break the treatment code by 
contacting the IxRS. 
As per health authority reporting requirements, the Sponsor's Drug Safety representative 
will break the treatment code for all serious, unexpected suspected adverse reactions 
(see Section 5.7) that are considered by the investigator or Sponsor to be related to 
tiragolumab/placebo.  The patient may continue to receive treatment, and the 
investigator, patient, and Sponsor personnel, with the exception of the Drug Safety 
representative and personnel who must have access to patient treatment assignments to 
fulfill their roles (as defined above), will remain blinded to treatment assignment. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
58/Protocol GO41767, Version 7 
4.3 
STUDY TREATMENT AND OTHER TREATMENTS RELEVANT 
TO THE STUDY DESIGN 
The investigational medicinal products (IMPs) for this study are tiragolumab, placebo, 
and atezolizumab.  Carboplatin and etoposide are considered non-IMPs.  Appendix 12 
identifies all IMPs, auxiliary medicinal products, and non-IMPs for this study. 
4.3.1 
Study Treatment Formulation, Packaging, and Handling 
4.3.1.1 
Tiragolumab and Placebo 
Tiragolumab and placebo will be supplied by the Sponsor as a sterile liquid in a 
single-use, 15-mL glass vial.  The vial contains approximately 10 mL (600 mg) of 
tiragolumab or placebo solution. 
For information on the formulation and handling of tiragolumab and placebo, see the 
pharmacy manual and the Tiragolumab Investigator’s Brochure. 
4.3.1.2 
Atezolizumab 
The atezolizumab drug product will be supplied by the Sponsor as a sterile liquid in a 
single-use, 20-mL glass vial.  The vial contains approximately 20 mL (1200 mg) of 
atezolizumab solution. 
For information on the formulation and handling of atezolizumab, refer to the 
Atezolizumab Pharmacy Manual and Investigator’s Brochure. 
4.3.1.3 
Carboplatin and Etoposide 
Carboplatin and etoposide will be used in the commercially available formulation.  
For information on the formulation, packaging, and handling of CE, refer to the 
prescribing information for each drug. 
4.3.2 
Study Treatment Dosage, Administration, and Compliance 
The treatment regimens are summarized in Section 3.1, Table 1. 
The induction phase of the study will consist of 4 cycles of atezolizumab plus 
tiragolumab/placebo plus chemotherapy, with each cycle being 21 days in duration.  On 
Day 1 of each cycle, all eligible patients will be administered study drug infusions in the 
following order: 
Arm A:  atezolizumab  tiragolumab  carboplatin  etoposide  
Arm B:  atezolizumab  placebo  carboplatin  etoposide 
 
For Cycle 1, premedication administered for atezolizumab or tiragolumab/placebo is not 
permitted.  Patients should receive anti-emetics and IV hydration for CE according to the 
local standard of care and manufacturer’s instruction.  However, because of the 
immunomodulatory effects of corticosteroids, premedication with corticosteroids should 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
59/Protocol GO41767, Version 7 
be minimized to the extent that is clinically feasible (see Section 4.4.2).  All medications 
must be recorded on the appropriate Concomitant Medications eCRF. 
During the induction phase, study treatment should be administered in the following 
manner on Day 1: 
1. 
Atezolizumab 1200 mg administered intravenously over 60 ( 15) minutes (for the 
first infusion and shortening to 30 [ 10] minutes for subsequent infusions) (see 
Table 2), followed by 
2. 
Tiragolumab/placebo 600 mg administered intravenously over
 minutes (for 
the first infusion and shortening to
minutes for subsequent infusions) (see 
Table 2), followed by 
3. 
Carboplatin administered intravenously over 3060 minutes to achieve an initial 
target area under the concentrationtime curve (AUC) of
mg/mL/min (Calvert 
formula dosing), followed by 
4. 
Etoposide (100 mg/m2) administered intravenously over 60 minutes  
 
During the induction phase, etoposide (100 mg/m2) will be also administered 
intravenously over 60 minutes on Days 2 and 3. 
Cycles in which no chemotherapy is given do not count toward the total number of 
induction chemotherapy cycles. 
After the induction phase, patients will begin maintenance therapy with atezolizumab 
plus tiragolumab/placebo.  
The suggested infusion times for CE may be adapted in accordance with local standard 
of care. 
Any dose modification should be noted on the Study Drug Administration eCRF.  Cases 
of accidental overdose or medication error, along with any associated adverse events, 
should be reported as described in Section 5.3.5.12. 
Administration of atezolizumab and tiragolumab/placebo will be performed in a 
monitored setting where there is immediate access to trained personnel and adequate 
equipment and medicine to manage potentially serious reactions.  For anaphylaxis 
precautions, see Appendix 10.   
Guidelines for dose modification and treatment interruption or discontinuation for CE are 
provided in Sections 5.1.6 and 5.1.6.3. 
4.3.2.1 
Atezolizumab 
All patients will receive 1200 mg atezolizumab administered by IV infusion on Day 1 of 
each 21-day cycle.  The atezolizumab dose is fixed and is not dependent on body weight.  
Atezolizumab infusions will be administered per the instructions outlined in Table 2. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
60/Protocol GO41767, Version 7 
No dose modification for atezolizumab is allowed.  Guidelines for treatment interruption 
or discontinuation are provided in Appendix 13 and Appendix 14.  Guidance on study 
drug administration in the context of management of specific adverse events is provided 
in Section 5.1.6.2. 
For further details on dose preparation, storage, and administration instructions for 
atezolizumab, please refer to the pharmacy manual and/or the Atezolizumab 
Investigator’s Brochure.  
4.3.2.2 
Tiragolumab/Placebo 
 (see Table 2), 
patients will receive 600 mg tiragolumab/placebo administered by IV infusion on Day 1 of 
each 21-day cycle (see Section 3.4.1).  The tiragolumab/placebo dose is fixed and is not 
dependent on body weight.  Tiragolumab/placebo infusions will be administered per the 
instructions outlined in Table 2. 
No dose modification for tiragolumab/placebo is allowed.  Guidelines for treatment 
interruption or discontinuation are provided in Appendix 13 and Appendix 14.  Guidance 
on study drug administration in the context of management of specific adverse events is 
provided in Section 5.1.6.2.  
For further details on dose preparation, storage, and administration instructions for 
tiragolumab/placebo, please refer to the pharmacy manual and/or the Tiragolumab 
Investigator’s Brochure.  
Table 2 
Administration of First and Subsequent Atezolizumab and 
Tiragolumab/Placebo Infusions 
 
First Infusion 
Subsequent Infusions 
Atezolizumab 
infusion 
 No premedication is permitted 
prior to the atezolizumab 
infusion. 
 Vital signs (pulse rate, 
respiratory rate, blood pressure, 
and temperature) should be 
measured within 60 minutes 
prior to the infusion. 
 Atezolizumab should be infused 
over 60 ( 15) minutes. 
 If clinically indicated, vital signs 
should be measured every 
15 ( 5) minutes during the 
infusion and at 
30 (  10) minutes after the 
infusion.  
 If the patient experienced an IRR during 
any previous infusion of atezolizumab, 
premedication with antihistamines. 
anti-pyretic medications, and/or 
analgesics may be administered for 
subsequent doses at the discretion of the 
investigator. 
 Vital signs should be measured within 
60 minutes prior to the infusion.  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
62/Protocol GO41767, Version 7 
Table 2 
Administration of First and Subsequent Atezolizumab and 
Tiragolumab/Placebo Infusions (cont.) 
 
First Infusion 
Subsequent Infusions 
Observation 
period after 
infusion of 
tiragolumab/ 
placebo 
 After the infusion of 
tiragolumab/placebo, the patient 
begins a
-minute observation 
period. 
 Record the patient’s vital signs 
at
minutes after the 
infusion.  
 Patients will be informed about 
the possibility of delayed 
post-infusion symptoms and will 
be instructed to contact their 
study physician if they develop 
such symptoms. 
 If the patient tolerated the previous infusion 
of tiragolumab/placebo well without an IRR, 
the observation period may be reduced to 
minutes for subsequent infusions. 
 If the patient experienced an IRR in the 
previous infusion, the observation period 
should be
 minutes. 
 If clinically indicated, record the patient’s 
vital signs at
minutes after the 
infusion of tiragolumab/placebo. 
IRR  infusion-related reaction. 
  
Guidelines for medical management of IRRs are provided in Appendix 14. 
4.3.2.3 
Atezolizumab and Tiragolumab/Placebo 
The following rules apply as long as neither atezolizumab nor tiragolumab/placebo has 
been permanently discontinued:  
 
Treatment cycles will normally begin with dosing of atezolizumab and 
tiragolumab/placebo on Day 1 of each 21-day cycle.  
 
 
 
 
 
  
 
 
 
Carboplatin and/or etoposide may be administered as planned in the event that 
atezolizumab and/or tiragolumab/placebo dose(s) are delayed.  If carboplatin and/or 
etoposide doses must be delayed, atezolizumab and/or tiragolumab may be 
administered as planned. 
Guidelines for treatment interruption or discontinuation are provided in Sections 4.6.1 
and 5.1.6. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
63/Protocol GO41767, Version 7 
4.3.2.4 
Carboplatin  Etoposide 
Carboplatin 
During the induction phase, carboplatin will be administered after completion of 
tiragolumab/placebo by IV infusion over 3060 minutes to achieve an initial target AUC 
of
mg/mL/min (Calvert formula dosing) with standard anti-emetics per local practice 
guidelines.  Because the effects of corticosteroids on T-cell proliferation have the 
potential to attenuate tiragolumab- and/or atezolizumab-mediated anti-tumor immune 
activity, premedication with corticosteroids should be minimized to the extent that is 
clinically feasible (see Section 4.4.2).  Carboplatin infusion times may be adapted in 
accordance with local standard of care. 
The carboplatin dose of AUC
will be calculated using the Calvert formula 
(Calvert et al. 1989): 
Calvert Formula 
Total dose (mg)  (target AUC)  (glomerular filtration rate [GFR]  25) 
NOTE:  The GFR used in the Calvert formula to calculate AUC-based dosing should 
not exceed 125 mL/min. 
 
For the purposes of this protocol, the GFR is considered to be equivalent to the 
creatinine clearance (CRCL).  The CRCL is calculated by institutional guidelines or by 
the method of Cockcroft and Gault (1976) using the following formula: 
CRCL   
(140  age)  (wt) 
( 0.85 if female) 
72  Scr 
 
Where: 
CRCL  creatinine clearance in mL/min 
  
age  patient's age in years  
  
wt  patient’s weight in kg 
  
Scr  serum creatinine in mg/dL 
 
NOTE:  For patients with an abnormally low serum creatinine level, estimate the GFR 
through use of a minimum creatinine level of 0.8 mg/dL or cap the estimated GFR at 
125 mL/min. 
If a patient’s GFR is estimated based on serum creatinine measurements by the isotope 
dilution mass spectroscopy method, the FDA recommends that physicians consider 
capping the dose of carboplatin for desired exposure (AUC) to avoid potential toxicity 
due to overdosing.  On the basis of the Calvert formula described in the carboplatin 
label, the maximum doses can be calculated as follows: 
Maximum carboplatin dose (mg)  target AUC (mg  min/mL)  (GFR  25 mL/min) 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
64/Protocol GO41767, Version 7 
The maximum dose is based on a GFR estimate that is capped at 125 mL/min for 
patients with normal renal function.  No higher estimated GFR values should be used. 
 
Guidelines for treatment interruption or discontinuation are provided in Sections 4.6.1 
and 5.1.6. 
Etoposide 
During the induction phase, on Day 1 of each cycle, etoposide (100 mg/m2) will be 
administered by IV infusion over 60 minutes following carboplatin administration.  On 
Days 2 and 3 of each cycle, etoposide (100 mg/m2) will be administered by IV infusion 
over 60 minutes.  Premedication should be administered according to local standard of 
care.  Because the effects of corticosteroids on T-cell proliferation have the potential to 
attenuate tiragolumab- and/or atezolizumab-mediated anti-tumor immune activity, 
premedication with corticosteroids should be minimized to the extent that is clinically 
feasible (see Section 4.4.2).  Etoposide infusion times may be adapted in accordance 
with local standard of care. 
Guidelines for treatment interruption or discontinuation are provided in Sections 4.6.1 
and 5.1.6. 
4.3.3 
Investigational Medicinal Product Accountability 
All IMPs required for completion of this study (tiragolumab and atezolizumab) will be 
provided by the Sponsor.  The study site (i.e., investigator or other authorized personnel 
[e.g., pharmacist]) is responsible for maintaining records of IMP delivery to the site, IMP 
inventory at the site, IMP use by each patient, and disposition or return of unused IMP, 
thus enabling reconciliation of all IMP received, and for ensuring that patients are 
provided with doses specified by the protocol. 
The study site should follow all instructions included with each shipment of IMP.  The 
study site will acknowledge receipt of IMPs supplied by the sponsor using IxRS to 
confirm the shipment condition and content.  Any damaged shipments will be replaced.  
The investigator or designee must confirm that appropriate temperature conditions have 
been maintained during transit, either by time monitoring (shipment arrival date and 
time) or temperature monitoring, for all IMPs received and that any discrepancies have 
been reported and resolved before use of the IMPs.  All IMPs must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions, with access limited to the investigator 
and authorized staff. 
Only patients enrolled in the study may receive IMPs, and only authorized staff may 
supply or administer IMPs. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
65/Protocol GO41767, Version 7 
Investigational medicinal products 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 destroying Sponsor-supplied 
IMPs must be agreed to by the Sponsor.  The site must obtain written authorization from 
the Sponsor before any Sponsor-supplied IMP is destroyed, and IMP destruction must 
be documented on the appropriate form. 
Accurate records of all IMPs received at, dispensed from, returned to, and disposed of 
by the study site should be recorded on the drug accountability log. 
Refer to the pharmacy manual for information on IMP handling, including preparation, 
storage, and accountability.  
4.3.4 
Continued Access to Tiragolumab and/or Atezolizumab  
Patients may be eligible to receive tiragolumab and/or atezolizumab as part of a 
post-trial access program, or an extension study, as described in Section 3.2.  The 
Roche Global Policy on Continued Access to Investigational Medicinal Product is 
available at the following website: 
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf 
4.4 
CONCOMITANT THERAPY 
Concomitant therapy consists of any medication (e.g., prescription drugs, 
over-the-counter drugs, vaccines, herbal or homeopathic remedies, nutritional 
supplements) used by a patient from 7 days prior to initiation of study treatment to the 
treatment discontinuation visit.  All such medications should be reported to the 
investigator and recorded on the Concomitant Medications eCRF. 
4.4.1 
Permitted Therapy 
Patients are permitted to use the following therapies during the study: 
 
 
 
 
 
 
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
66/Protocol GO41767, Version 7 
 
 
 
 
 
 
 
 
 
. 
In general, investigators should manage a patient's care (including preexisting 
conditions) with supportive therapies other than those defined as cautionary or 
prohibited therapies (see Sections 4.4.2 and 4.4.3) as clinically indicated, per local 
standard practice.  Patients who experience infusion-associated symptoms may be 
treated symptomatically with acetaminophen, ibuprofen, diphenhydramine, and/or 
H2-receptor antagonists (e.g., famotidine, cimetidine), or equivalent medications per local 
standard practice.  Serious infusion-associated events manifested by dyspnea, 
hypotension, wheezing, bronchospasm, tachycardia, reduced oxygen saturation, or 
respiratory distress should be managed with supportive therapies as clinically indicated 
(e.g., supplemental oxygen and 2-adrenergic agonists; see Appendix 10). 
4.4.2 
Cautionary Therapy for Tiragolumab- and/or 
Atezolizumab-Treated Patients 
4.4.2.1 
Corticosteroids, Immunosuppressive Medications, and Tumor 
Necrosis Factor- Inhibitors 
Systemic corticosteroids or immunosuppressive medications are recommended, at the 
discretion of the investigator, for the treatment of specific adverse events when 
associated with tiragolumab and/or atezolizumab therapy (refer to Appendix 14 for 
details). 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
67/Protocol GO41767, Version 7 
4.4.2.2 
Herbal Therapies 
Concomitant use of herbal therapies is not recommended because their 
pharmacokinetics, safety profiles, and potential drugdrug interactions are generally 
unknown.  However, herbal therapies not intended for the treatment of cancer (see 
Section 4.4.3) may be used during the study at the discretion of the investigator. 
4.4.3 
Prohibited Therapy 
Use of the following concomitant therapies is prohibited as described below: 
 
 
 
 
 
 
4.5 
STUDY ASSESSMENTS 
The schedule of activities to be performed during the study is provided in Appendix 1.  
All activities should be performed and documented for each patient.  
Patients will be closely monitored for safety and tolerability throughout the study.  
Patients should be assessed for toxicity prior to each dose; dosing will occur only if the 
clinical assessment and local laboratory test values are acceptable. 
Screening tests and evaluations will be performed within 28 days prior to Day 1 of 
Cycle 1.  Results of standard of care tests or examinations performed prior to obtaining 
informed consent and within 28 days prior to Day 1 of Cycle 1 may be used; such tests 
do not need to be repeated for screening. 
All treatment visits must occur  3 days from the scheduled date unless otherwise noted 
(see Appendix 1).  All assessments will be performed on the day of the specified visit 
unless a time window is specified.  Assessments scheduled on the day of study 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
68/Protocol GO41767, Version 7 
treatment administration (Day 1) of each cycle should be performed prior to study 
treatment infusion unless otherwise noted. 
If scheduled dosing and study assessments are precluded because of a holiday, 
weekend, or other event, then dosing may be postponed to the soonest following date, 
with subsequent dosing continuing on a 21-day schedule.  If treatment was postponed 
for fewer than 3 days, the patient can resume the original schedule. 
 
 
 
 
 
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 (including screening evaluations).  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 randomization.  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. 
Patients who show apparent radiographic disease progression per RECIST v1.1 at a 
tumor response evaluation, and are eligible and willing to continue study treatment 
beyond disease progression, must sign an informed consent at that time to acknowledge 
the deferment of other treatment options in favor of continuing study treatment.   
4.5.2 
Medical History, Baseline Conditions, Concomitant Medication, 
and Demographic Data 
Medical history, including clinically significant diseases, surgeries, cancer history 
(including prior cancer therapies and procedures), reproductive status, smoking 
history, and use of alcohol and drugs of abuse, will be recorded at baseline.  In addition, 
all concomitant medications (e.g., prescription drugs, over-the-counter drugs, vaccines, 
herbal or homeopathic remedies, nutritional supplements) used by the patient within 
7 days prior to initiation of study treatment will be recorded.  At the time of each 
follow-up physical examination, an interval medical history should be obtained and any 
changes in medications and allergies should be recorded. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
69/Protocol GO41767, Version 7 
Small cell lung cancer history will include the VALG staging system and staging by the 
American Joint Committee on Cancer, Eighth Edition. 
Demographic data will include age, sex, and self-reported race/ethnicity. 
4.5.3 
Physical Examinations 
A complete physical examination, performed at screening and other specified visits, 
should include an evaluation of the head, eyes, ears, nose, and throat and the 
cardiovascular, dermatologic, musculoskeletal, respiratory, gastrointestinal, 
genitourinary, and neurologic systems.  Any abnormality identified at baseline should be 
recorded on the General Medical History and Baseline Conditions eCRF. 
Limited, symptom-directed physical examinations should be performed at specified 
postbaseline visits and as clinically indicated.  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, systolic and 
diastolic blood pressure, and temperature.  Record abnormalities observed at baseline 
on the General Medical History and Baseline Conditions eCRF.  At subsequent visits, 
record new or worsened clinically significant abnormalities on the Adverse Event eCRF. 
See Table 2 for details on the measurements of vital signs during study treatment.  
4.5.5 
Performance Status 
Performance status will be measured using the ECOG Performance Status at baseline 
and will be assessed at regular intervals throughout the study (see Appendix 1). 
4.5.6 
Tumor and Response Evaluations 
Screening and subsequent tumor assessments must include CT scans (with IV contrast, 
unless contraindicated, and oral contrast as appropriate per institutional standards) of 
the chest and abdomen.  A CT scan, with contrast, of the pelvis is required at screening 
and as clinically indicated or as per local standard of care at subsequent response 
evaluations.  Magnetic resonance imaging scans with contrast of the chest, abdomen, 
and pelvis with a non-contrast CT scan of the chest may be used in patients for whom 
CT scans with IV contrast are contraindicated (i.e., patients with iodine-based contrast 
allergy or impaired renal clearance).  
A CT (with contrast) or MRI scan with contrast (if CT contrast is contraindicated) of the 
head must be done at screening to evaluate CNS metastasis in all patients.  If CT with 
contrast is performed and the presence of brain metastases is considered equivocal, an 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
70/Protocol GO41767, Version 7 
MRI scan of the brain is required to confirm or refute the diagnosis of CNS metastases 
at baseline.   
Patients with active or untreated symptomatic CNS metastases are not eligible for the 
study (see Section 4.1.2).  Patients with untreated asymptomatic CNS metastasis at 
screening may be eligible.  For untreated patients, brain MRI scan with contrast at 
screening is required, and need to meet all eligibility criteria as specified in Section 4.1.2. 
If a CT scan for tumor assessment is performed in a positron emission tomography/CT 
scanner, the CT acquisition must be consistent with the standards for a full contrast 
diagnostic CT scan. 
Further investigations, such as bone scans and CT scans of the neck, should also be 
performed if clinically indicated.  At the investigator’s discretion, other methods of 
assessment of measurable disease as per RECIST v1.1 may be used. 
Tumor assessments performed as standard of care prior to obtaining informed consent 
and within 28 days of Cycle 1, Day 1 may be used rather than repeating tests.  All known 
sites of disease, including measurable and/or non-measurable disease, must be 
documented at screening and re-assessed at each subsequent tumor evaluation.   
 
 
  The same 
radiographic procedure used to assess disease sites at screening should be used 
throughout the study (e.g., the same contrast protocol for CT scans). 
For patients with previously untreated CNS metastases, a brain MRI scan with contrast 
is required at screening and is the preferred modality for all subsequent scheduled 
follow-up tumor assessments.  
 
 
 
 
  The same modality must be used at every 
tumor assessment. 
 
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
71/Protocol GO41767, Version 7 
Patients will undergo tumor assessments at baseline and at every 6 weeks ( 7 days) for 
48 weeks following Day 1 of Cycle 1 regardless of treatment delays.  After the 
completion of the Week 48 tumor assessment, tumor assessment will be required every 
9 weeks ( 7 days) regardless of treatment delays, until radiographic disease 
progression per RECIST v1.1 (or loss of clinical benefit for patients who continue study 
treatment after disease progression per RECIST v1.1), withdrawal of consent, death, or 
study termination by the Sponsor, whichever occurs first (see Section 3.1.2).  At the 
investigator’s discretion, scans may be performed at any time if progressive disease or 
loss of clinical benefit is suspected. 
 
 
 
  
Response will be assessed by the investigator on the imaging modalities detailed above, 
using RECIST v1.1 (see Appendix 4).  The investigator’s assessment of overall tumor 
response at all timepoints should be based on RECIST v1.1.  Assessments should be 
performed by the same evaluator, if possible, to ensure internal consistency across 
visits.  Results must be reviewed by the investigator before dosing at the next cycle. 
Study treatment may be continued as long as patients are experiencing clinical benefit 
as assessed by the investigator in the absence of unacceptable toxicity or symptomatic 
deterioration attributed to disease progression after an integrated assessment of 
radiographic data, biopsy results (if available), and clinical status.  Patients who meet 
criteria for disease progression per RECIST v1.1 will be permitted to continue study 
treatment if they meet all of the criteria specified in Section 3.1.2 and provide written 
consent. 
Patients who discontinue treatment for reasons other than radiographic disease 
progression per RECIST v1.1 (e.g., toxicity, symptomatic deterioration) will continue 
scheduled tumor assessments at the frequency described above until radiographic 
disease progression per RECIST v1.1, withdrawal of consent, death, or study 
termination by Sponsor, whichever occurs first.  Patients who start a new anti-cancer 
therapy in the absence of radiographic disease progression per RECIST v1.1 will 
continue tumor assessments at the frequency described above until radiographic 
disease progression per RECIST v1.1, withdrawal of consent, death, or study 
termination by the Sponsor, whichever occurs first. 
To facilitate evaluation of post-progression tumor changes while treatment is ongoing, 
tumor assessments must be continued after disease progression per RECIST v1.1 for 
patients who receive study treatment beyond progression.  This includes continued 
measurement of target lesions, evaluation of non-target lesions (including monitoring for 
further worsening of any non-target lesions that have shown unequivocal progression), 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
72/Protocol GO41767, Version 7 
and evaluation of any newly identified lesions (including measurements, if lesions are 
measurable; see Appendix 4) at all subsequent assessments.  
4.5.7 
Laboratory, Biomarker, and Other Biological Samples 
Samples for the following laboratory tests will be sent to the study site's local laboratory 
for analysis: 
 
Hematology: 
 
 
 
Chemistry panel (serum or plasma): 
 
 
 
 
Coagulation:  
 
 
Thyroid function testing: 
 
 
 
EBV serology, 
 
– 
  
– 
  
– 
 
 
HIV serology 
 
 
 
  
 
 
 
 
 
Pregnancy test 
All women of childbearing potential will have a serum pregnancy test at 
screening.  During the study, urine pregnancy tests will be performed on Day 1 
of every cycle and after study treatment is discontinued (see Appendix 1).  
If a urine pregnancy test is positive, it must be confirmed by a serum pregnancy 
test. 
A woman is considered to be of childbearing potential if she is postmenarchal, 
has not reached a postmenopausal state ( 12 continuous months of 
amenorrhea with no identified cause other than menopause), and is not 
permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, 
and/or uterus) or another cause as determined by the investigator 
(e.g., Müllerian agenesis). 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
73/Protocol GO41767, Version 7 
 
Urinalysis 
 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
74/Protocol GO41767, Version 7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
When a patient withdraws from the study, samples collected prior to the date of 
withdrawal may still be analyzed, unless the patient specifically requests that the 
samples be destroyed or local laws require destruction of the samples.  However, if 
samples have been tested prior to withdrawal, results from those tests will remain as 
part of the overall research data. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
75/Protocol GO41767, Version 7 
Data arising from sample analysis will be subject to the confidentiality standards 
described in Section 8.4. 
Given the complexity and exploratory nature of exploratory biomarker analyses, data 
derived from these analyses will generally not be provided to study investigators or 
patients unless required by law.  The aggregate results of any conducted research will 
be available in accordance with the effective Sponsor policy on study data publication. 
4.5.8 
Optional Tumor Biopsies  
 
 
 
 
 
 
 
 
 
 
  
 
 
  
4.5.9 
Electrocardiograms 
Electrocardiogram is required at screening and as clinically indicated during the study.  
Electrocardiograms should be obtained on the same machine whenever possible.  Lead 
placement should be as consistent as possible.  Electrocardiogram recordings should be 
performed after the patient has been resting in a supine position for at least 10 minutes. 
 
 
4.5.10 
Clinical Outcome Assessments 
Patient-reported outcome data will be collected to document the treatment benefit and 
more fully characterize the clinical profile of tiragolumab  atezolizumab.  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
76/Protocol GO41767, Version 7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
77/Protocol GO41767, Version 7 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
78/Protocol GO41767, Version 7 
4.5.11 
Blood Samples for Whole Genome Sequencing or Whole 
Exome Sequencing (Patients at Participating Sites)  
At participating sites, blood samples will be collected for DNA extraction to enable WGS 
or WES to identify variants that are predictive of response to study drug, are associated 
with progression to a more severe disease state, are associated with acquired 
resistance to study drug, are associated with susceptibility to developing adverse events, 
can lead to improved adverse event monitoring or investigation, or can increase the 
knowledge and understanding of disease biology and drug safety.  DNA extracted from 
blood may be used to identify germline mutations and may be compared with DNA 
extracted from tissue to identify somatic variants.  The samples may be sent to one or 
more laboratories for analysis. 
Collection and submission of blood samples for WGS or WES is contingent upon the 
review and approval of the exploratory research by each site's IRB or EC and, if 
applicable, an appropriate regulatory body.  If a site has not been granted approval for 
WGS or WES, this section of the protocol (Section 4.5.11) will not be applicable at that 
site. 
Genomics is increasingly informing researcher's understanding of disease pathobiology.  
Whole genome sequencing and WES provide a comprehensive characterization of the 
genome and exome, respectively, and, along with clinical data collected in this study, 
may increase the opportunity for developing new therapeutic approaches or new 
methods for monitoring efficacy and safety or predicting which patients are more likely to 
respond to a drug or develop adverse events.  Data will be analyzed in the context of 
this study but may also be explored in aggregate with data from other studies.  The 
availability of a larger dataset will assist in identification and characterization of important 
biomarkers and pathways to support future drug development. 
For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual.   

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
79/Protocol GO41767, Version 7 
Blood samples collected for WGS or WES are to be stored until they are no longer 
needed or until they are exhausted.  However, the storage period will be in accordance 
with the IRB/EC approved Informed Consent Form and applicable laws (e.g., health 
authority requirements). 
Refer to Section 4.5.7 for details on use of samples after patient withdrawal, 
confidentiality standards for data, and availability of data from biomarker analyses. 
4.5.12 
Optional Samples for Research Biosample Repository  
4.5.12.1 
Overview of the Research Biosample Repository 
The Research Biosample Repository (RBR) is a centrally administered group of facilities 
used for the long-term storage of human biological specimens, including body fluids, 
solid tissues, and derivatives thereof (e.g., DNA, RNA, proteins, peptides).  The 
collection, storage, and analysis of RBR samples will facilitate the rational design of new 
pharmaceutical agents and the development of diagnostic tests, which may allow for 
individualized drug therapy for patients in the future. 
Samples for the RBR will be collected from patients who give specific consent to 
participate in this optional research.  Research Biosample Repository samples will be 
analyzed to achieve one or more of the following objectives: 
 
To study the association of biomarkers with efficacy or disease progression 
 
To identify safety biomarkers that are associated with susceptibility to developing 
adverse events or can lead to improved adverse event monitoring or investigation 
 
To increase knowledge and understanding of disease biology and drug safety 
 
To study drug response, including drug effects and the processes of drug absorption 
and disposition 
 
To develop biomarker or diagnostic assays and establish the performance 
characteristics of these assays 
 
4.5.12.2 
Approval by the Institutional Review Board or Ethics 
Committee 
Collection, storage, and analysis of RBR samples is contingent upon the review and 
approval of the exploratory research and the RBR portion of the Informed Consent Form 
by each site's IRB or EC and, if applicable, an appropriate regulatory body.  If a site has 
not been granted approval for RBR sampling, this section of the protocol 
(Section 4.5.12) will not be applicable at that site. 
4.5.12.3 
Sample Collection 
The following samples will be stored in the RBR and used for research purposes, 
including, but not limited to, research on biomarkers related to tiragolumab, 
atezolizumab, SCLC, or drug safety: 
 
Leftover blood, serum, plasma, and tumor tissue samples (with the exception of 
remaining archival tissue blocks, which will be returned to sites) and any derivatives 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
80/Protocol GO41767, Version 7 
thereof (e.g., DNA, RNA, proteins, peptides), including leftover tissue samples from 
medically indicated procedures (e.g., bronchoscopy, esophagogastroduodenoscopy, 
colonoscopy) performed at the investigator's discretion during the course of the 
study 
 
Optional whole blood sample for DNA extraction collected at any time during study 
 
The above samples may be sent to one or more laboratories for analysis of germline or 
somatic variants via WGS, WES, or other genomic analysis methods.  Genomics is 
increasingly informing researcher's understanding of disease pathobiology.  Whole 
genome sequencing and WES provide a comprehensive characterization of the genome 
and exome, respectively, and, along with clinical data collected in this study, may 
increase the opportunity for developing new therapeutic approaches or new methods for 
monitoring efficacy and safety or predicting which patients are more likely to respond to 
a drug or develop adverse events. 
Data generated from RBR samples will be analyzed in the context of this study but may 
also be explored in aggregate with data from other studies.  The availability of a larger 
dataset will assist in identification and characterization of important biomarkers and 
pathways to support future drug development. 
For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual.   
Research Biosample Repository samples are to be stored until they are no longer 
needed or until they are exhausted.  However, the RBR storage period will be in 
accordance with the IRB/EC-approved Informed Consent Form and applicable laws 
(e.g., health authority requirements). 
4.5.12.4 
Confidentiality 
Research Biosample Repository samples and associated data will be labeled with a 
unique patient identification number. 
Patient medical information associated with RBR samples is confidential and may be 
disclosed to third parties only as permitted by the Informed Consent Form (or separate 
authorization for use and disclosure of personal health information) signed by the 
patient, unless permitted or required by law. 
Given the complexity and exploratory nature of the analyses of RBR samples, data 
derived from these analyses will generally not be provided to study investigators or 
patients unless required by law.  The aggregate results of any conducted research will 
be available in accordance with the effective Sponsor policy on study data publication. 
Data generated from RBR samples must be available for inspection upon request by 
representatives of national and local health authorities, and Sponsor monitors, 
representatives, and collaborators, as appropriate. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
81/Protocol GO41767, Version 7 
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of the RBR data will become and remain the exclusive and unburdened property 
of the Sponsor, except where agreed otherwise. 
4.5.12.5 
Consent to Participate in the Research Biosample Repository 
The Informed Consent Form will contain a separate section that addresses participation 
in the RBR.  The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential hazards of participation in the RBR.  Patients will be 
told that they are free to refuse to participate and may withdraw their consent at any time 
and for any reason during the storage period.  A separate, specific signature will be 
required to document a patient's agreement to provide optional RBR samples.  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 and (if applicable) the date(s) of consent, by completing the RBR Research 
Sample Informed Consent eCRF. 
In the event of an RBR participant's death or loss of competence, the participant's 
samples and data will continue to be used as part of the RBR research. 
4.5.12.6 
Withdrawal from the Research Biosample Repository 
Patients who give consent to provide RBR samples have the right to withdraw their 
consent at any time for any reason.  After withdrawal of consent, any remaining samples 
will be destroyed or will no longer be linked to the patient.  However, if RBR samples 
have been tested prior to withdrawal of consent, results from those tests will remain as 
part of the overall research data.  If a patient wishes to withdraw consent to the testing of 
his or her RBR samples during the study, the investigator must inform the 
Medical Monitor in writing of the patient's wishes through use of the appropriate RBR 
Subject Withdrawal Form and must enter the date of withdrawal on the RBR Research 
Sample Withdrawal of Informed Consent eCRF.  If a patient wishes to withdraw consent 
to the testing of his or her RBR samples after closure of the site, the investigator must 
inform the Sponsor by emailing the study number and patient number to the following 
email address: 
global.rcr-withdrawal@roche.com 
A patient's withdrawal from this study does not, by itself, constitute withdrawal of consent 
for testing of RBR samples.  Likewise, a patient's withdrawal of consent for testing of 
RBR samples does not constitute withdrawal from this study. 
4.5.12.7 
Monitoring and Oversight 
Research Biosample Repository samples will be tracked in a manner consistent with 
Good Clinical Practice by a quality-controlled, auditable, and appropriately validated 
laboratory information management system, to ensure compliance with data 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
82/Protocol GO41767, Version 7 
confidentiality as well as adherence to authorized use of samples as specified in this 
protocol and in the Informed Consent Form.  Sponsor monitors and auditors will have 
direct access to appropriate parts of records relating to patient participation in the RBR 
for the purposes of verifying the data provided to the Sponsor.  The site will permit 
monitoring, audits, IRB/EC review, and health authority inspections by providing direct 
access to source data and documents related to the RBR samples. 
4.6 
PATIENT, TREATMENT, STUDY, AND SITE DISCONTINUATION 
4.6.1 
Study Treatment Discontinuation 
Patients must discontinue study treatment if they experience any of the following: 
 
Symptomatic deterioration attributed to disease progression as determined by the 
investigator after integrated assessment of radiographic data, biopsy results if 
available, and the patient’s clinical status 
 
Intolerable toxicity related to study treatment, including development of an 
immune-mediated adverse event determined by the investigator to be unacceptable 
given the individual patient’s potential response to therapy and severity of the event 
 
Any medical condition that may jeopardize the patient’s safety if he or she continues 
on study treatment 
 
Use of another nonprotocol-specified anti-cancer therapy (see Section 4.4.3) 
 
Pregnancy 
 
Radiographic disease progression per RECIST v1.1 (unless treating beyond 
radiographic progression; see below) 
 
However, to better accommodate standard clinical practice, which is guided by the fact 
that patients with ES-SCLC whose disease progresses after first-line treatment have 
limited treatment options and such options also have limited efficacy and significant 
toxicity, patients may be considered for treatment beyond radiographic progression per 
RECIST v1.1 at the discretion of the investigator and after appropriate discussion with 
the patient, only if all of the following criteria are met: 
 
Evidence of clinical benefit as assessed by the investigator 
 
Absence of symptoms and signs (including worsening of laboratory values 
[e.g., new or worsening hypercalcemia]) indicating unequivocal progression of 
disease 
 
No decline in ECOG Performance Status that can be attributed to disease 
progression 
 
Absence of tumor progression at critical anatomical sites (e.g., leptomeningeal 
disease) that cannot be managed by protocol-allowed medical interventions 
 
Patients must provide written consent to acknowledge deferring other treatment 
options in favor of continuing study treatment at the time of initial radiographic 
progression per RECIST v1.1 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
83/Protocol GO41767, Version 7 
Treatment should be discontinued if clinical deterioration due to disease progression 
occurs at any time.  In addition, patients should be discontinued for unacceptable toxicity 
or for any other signs or symptoms of deterioration attributed to disease progression as 
determined by the investigator after an integrated assessment of radiographic data and 
clinical status. 
The primary reason for study treatment discontinuation should be documented on the 
appropriate eCRF.  Patients who discontinue study treatment prematurely will not be 
replaced. 
Patients will return to the clinic for a treatment discontinuation visit  30 days after the 
final dose of study treatment (see Appendix 1). 
 
 
4.6.2 
Patient Discontinuation from the Study 
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 patient discontinuation from the study may include, but are not limited to, 
the following: 
 
Patient withdrawal of consent 
 
Study termination or site closure 
 
Loss to follow-up 
 
Patient non-compliance, defined as failure to comply with protocol requirements as 
determined by the investigator or Sponsor 
 
Every effort should be made to obtain a reason for patient discontinuation from the 
study.  The primary reason for discontinuation from the study should be documented on 
the appropriate eCRF.  If a patient requests to be withdrawn from the study, this request 
must be documented in the source documents and signed by the investigator.  Patients 
who withdraw from the study will not be replaced. 
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
84/Protocol GO41767, Version 7 
4.6.3 
Study 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. 
4.6.4 
Site Discontinuation 
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 
 
Non-compliance with the International Council for Harmonisation (ICH) guideline for 
Good Clinical Practice 
 
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 anticipated mechanism of action, 
results from nonclinical studies, published data on similar molecules, clinical experience 
with tiragolumab alone and in combination with atezolizumab in Phase I and II studies, 
and the clinical safety profile of atezolizumab as a single agent.  The anticipated 
important safety risks for tiragolumab and atezolizumab are outlined below 
(see Sections 5.1.1, 5.1.2, and 5.1.3).  Refer to the Tiragolumab Investigator’s Brochure 
and the Atezolizumab Investigator’s Brochure for a complete summary of safety 
information for each respective study drug. 
Measures will be taken to ensure the safety of patients participating in this study, 
including the use of stringent inclusion and exclusion criteria and close monitoring of 
patients during the study.  An iDMC has also been incorporated into the study design to 
periodically review safety data (see the iDMC Charter for a detailed monitoring plan). 
Administration of study treatment will be performed in a monitored setting in which there 
is immediate access to trained personnel and adequate equipment and medicine to 
manage potentially serious reactions.  Guidelines for managing patients who experience 
anticipated adverse events, including criteria for treatment interruption or 
discontinuation, are provided in Appendix 13 and Appendix 14.  Refer to 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
85/Protocol GO41767, Version 7 
Sections 5.25.6 for details on safety reporting (e.g., adverse events, pregnancies) for 
this study. 
Patients with active infection are excluded from study participation.  In the setting of a 
pandemic or epidemic, screening for active infections (including SARS-CoV-2) prior to 
and during study participation should be considered according to local or institutional 
guidelines or guidelines of applicable professional societies (e.g., American Society of 
Clinical Oncology or European Society for Medical Oncology). 
5.1.1 
Risks Associated with Tiragolumab 
Refer to Appendix 14 of the protocol and Section 6 of the Tiragolumab Investigator's 
Brochure for a detailed description of anticipated safety risks for tiragolumab. 
5.1.1.1 
Infusion-Related Reactions 
Because tiragolumab is a therapeutic monoclonal antibody and targets tumor-infiltrating 
immune cells, IRRs associated with hypersensitivity reactions and/or target-mediated 
cytokine release may occur.  Clinical signs and symptoms of such reactions may include 
rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. 
 
 
 
 
 
  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
86/Protocol GO41767, Version 7 
Please see Sections 4.3.2.1 and 4.3.2.2 for detailed guidance on administration of 
atezolizumab and tiragolumab/placebo in this study.  Please see Appendix 10 for 
guidance on anaphylaxis precautions, and see Appendix 14 for guidance on 
management of IRRs and risks associated with tiragolumab. 
 
 
 
 
. 
5.1.1.3 
Immune-Mediated Adverse Events 
Nonclinical models have suggested a role of TIGIT signaling interruption in 
autoimmunity.  In a knockout model (TIGIT/), loss of TIGIT signaling resulted in 
hyperproliferative T-cell responses and exacerbation of experimental autoimmune 
encephalitis (EAE).  TIGIT/ and wild-type B6 mice were immunized with myelin 
oligodendrocyte glycoprotein peptide in an EAE using suboptimal doses.  In contrast to 
the wild-type B6 mice, the majority of the TIGIT/ mice developed severe EAE 
(Joller et al. 2011). 
Clinical experience with therapeutics intended to enhance anti-tumor T-cell responses 
has demonstrated that development of autoimmune inflammatory conditions is a general 
risk and may therefore be considered a potential risk of tiragolumab.  
 
 
 
  Refer to the Tiragolumab Investigator’s Brochure for more 
details on these adverse events. 
Patients with a history of autoimmune disease will be excluded from this study (see 
Section 4.1.2).   
Management guidelines for individual suspected immune-mediated adverse events are 
provided in Appendix 14. 
5.1.1.4 
Lymphopenia 
 
 
   
Transient lymphocyte count decreases without clinical sequelae have been observed in 
patients treated with tiragolumab with or without atezolizumab. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
87/Protocol GO41767, Version 7 
5.1.1.5 
Embryofetal Toxicity 
Refer to Section 6 of the Tiragolumab Investigator’s Brochure for a detailed description 
of embryofetal toxicity. 
5.1.2 
Risks Associated with Atezolizumab 
Atezolizumab has been associated with risks such as the following:  IRRs and 
immune-mediated hepatitis, pneumonitis, colitis, pancreatitis, diabetes mellitus, 
hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, Guillain-Barré 
syndrome, myasthenic syndrome or myasthenia gravis, facial paresis, myelitis, 
meningoencephalitis, myocarditis, pericardial disorders, nephritis, myositis, and severe 
cutaneous adverse reactions.  In addition, immune-mediated reactions may involve any 
organ system and lead to hemophagocytic lymphohistiocytosis (HLH).  Refer to 
Appendix 14 of the protocol and Section 6 of the Atezolizumab Investigator's Brochure 
for a detailed description of anticipated safety risks for atezolizumab.   
5.1.3 
Risks Associated with Combination Use of Tiragolumab and 
Atezolizumab 
Based on results from clinical data with tiragolumab and atezolizumab, there are known 
and potential for overlapping toxicities in patients treated with tiragolumab plus 
atezolizumab.  Because the expected pharmacologic activity of these two molecules is 
to increase adaptive T-cell immune responses, there is the possibility of heightened 
immune responses.   
Refer to Section 6 of the Tiragolumab Investigator's Brochure for a list of identified risks 
associated with tiragolumab in combination with atezolizumab.  
 
 
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
88/Protocol GO41767, Version 7 
Based on clinical experience to date, it is anticipated that immune-mediated adverse 
events following treatment with tiragolumab and atezolizumab will be amenable to 
monitoring and manageable in the setting of this combination study.  The extensive 
experience with immune checkpoint inhibitors to date has been incorporated into the 
design and safety management plan (see Section 5.1) in order to reduce the potential 
risks to participating patients.  Patients with a history of autoimmune disease will be 
excluded from this study
 
, see Section 4.1.2).  Patients previously treated 
with approved or experimental CIT will also be excluded from participation in this study.  
 
 
 
5.1.4 
Risks Associated with Etoposide 
The risk of overlapping toxicities between tiragolumab/atezolizumab and CE is thought 
to be minimal (see Section 5.1.7).  Etoposide is known to cause bone marrow 
suppression including myelosuppression, anemia, thrombocytopenia, gastrointestinal 
symptoms (e.g., nausea, vomiting, diarrhea), hepatotoxicity, and alopecia.  
Etoposide-based chemotherapy is considered to be moderately emetogenic.  Etoposide 
carries a risk of secondary hematologic malignancy.  Patients will be monitored for 
etoposide-related adverse events. 
For more details regarding the safety profile of etoposide, refer to the etoposide 
prescribing information. 
5.1.5 
Risks Associated with Carboplatin 
The risk of overlapping toxicities between tiragolumab/atezolizumab and CE is thought 
to be minimal (see Section 5.1.7).  Carboplatin is known to cause bone marrow 
suppression including myelosuppression, anemia, and thrombocytopenia.  
Carboplatin-based chemotherapy is considered to be moderately emetogenic.  Patients 
will be monitored for carboplatin-related adverse events. 
For more details regarding the safety profile of carboplatin, refer to the carboplatin 
prescribing information. 
5.1.6 
Management of Adverse Events 
5.1.6.1 
Dose Modification 
General Notes Regarding Dose Modification 
Reasons for dose modifications including dose delays, the supportive measures taken, 
and the outcomes will be documented in the patient's chart and recorded on the eCRF.  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
89/Protocol GO41767, Version 7 
The severity of adverse events will be graded according to the NCI CTCAE v5.0 grading 
system. 
 
When several toxicities with different grades of severity occur at the same time, 
the dose modifications should be according to the highest grade observed. 
 
When treatment is temporarily interrupted because of toxicity caused by 
tiragolumab/placebo, atezolizumab, carboplatin, or etoposide, the treatment cycles 
should be restarted such that the atezolizumab and tiragolumab/placebo infusions 
remain synchronized and aligned with the chemotherapy schedule. 
 
If, in the opinion of the investigator, a toxicity is considered to be due solely to 
one chemotherapy drug, the dose of the other chemotherapy drug does not 
require modification. 
 
The investigator may use discretion in modifying or accelerating the dose modification 
guidelines described below depending on the severity of toxicity and an assessment of 
the risk versus benefit for the patient, with the goal of maximizing patient compliance and 
access to supportive care. 
5.1.6.2 
Tiragolumab and/or Atezolizumab Dose Modification, 
Treatment Interruption, or Treatment Discontinuation 
Dose Modifications 
There will be no dose modifications, including dose reductions, for tiragolumab/placebo 
or atezolizumab in this study. 
Treatment Interruption 
Study treatment may be temporarily suspended as appropriate for management of 
toxicity.  On the basis of the available characterization of mechanism of action, 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
91/Protocol GO41767, Version 7 
5.1.6.3 
Chemotherapy Dose Modifications, Treatment Delays, or 
Treatment Discontinuation and Management of Specific 
Adverse Events 
Refer to Appendix 13 for details on chemotherapy dose modifications, treatment delays, 
or treatment discontinuation and management of specific adverse events. 
5.1.7 
Potential Overlapping Toxicities 
Based on nonclinical and/or clinical studies with tiragolumab or atezolizumab as a single 
agent, clinical data from studies with tiragolumab and atezolizumab as a combination 
therapy, and data from molecules with similar mechanisms of action, there is a potential 
for overlapping toxicity in patients treated with tiragolumab plus atezolizumab. 
 
 
 
 
 
Based on the clinical experience to date, it is anticipated that immune-mediated adverse 
events following treatment with tiragolumab and atezolizumab will be amenable to 
monitoring and manageable in the setting of this combination study.  The extensive 
experience with immune checkpoint inhibitors to date has been incorporated into the 
design and safety management plan (see Section 5.1) in order to reduce the potential 
risks to participating patients.  Patients with a history of autoimmune disease will be 
excluded from this study (see Section 4.1.2).  Patients previously treated with approved 
or experimental CIT will also be excluded from participation in this study.  
 
 
 
The risk of overlapping toxicities between tiragolumab/atezolizumab and 
carboplatin/etoposide is thought to be minimal.  Nevertheless, the attribution and 
management of certain adverse events that have been associated with each agent 
separately (e.g., hepatotoxicity, skin and gastrointestinal toxicity) may be ambiguous 
when the agents are administered together.  It is theoretically possible that allergic or 
inflammatory adverse events associated with CE (e.g., dermatitis, infusion-associated 
symptoms) could be exacerbated by the immunostimulatory activity of tiragolumab 
and/or atezolizumab.  
Toxicities should initially be managed according to the recommendations in 
Sections 5.1.5 and 5.1.6 and Appendix 13, with dose holds and modifications (if 
applicable) applied to the component of the study drug judged to be the primary cause.  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
92/Protocol GO41767, Version 7 
For severe (Grade 3) or persistent Grade 12 diarrhea, an endoscopic evaluation should 
be considered.  Additional tests, such as autoimmune serology or biopsies, may be used 
to determine a possible immunogenic etiology for adverse events listed above.  If, in the 
opinion of the investigator, tiragolumab and/or atezolizumab is a potential inciting factor, 
the dose of tiragolumab and/or atezolizumab may be held for a 
 
 after event onset (see Appendix 13).  The acceptable length of treatment 
interruption must be based on an assessment of benefit–risk by the investigator and in 
alignment with the protocol requirements for the duration of treatment and documented 
by the investigator.  The Medical Monitor is available to advise as needed.  Prompt 
symptomatic management is appropriate for mild immune-mediated adverse events.  
In severe cases, immune-mediated toxicities may be acutely managed with systemic 
corticosteroids or TNF- inhibitors.  These cases should be discussed with the 
Medical Monitor. 
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. 
5.2.1 
Adverse Events 
According to the ICH guideline for Good Clinical Practice, 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) (see Sections 5.3.5.9 
and 5.3.5.10 for more information) 
 
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 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
93/Protocol GO41767, Version 7 
 
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; 
see Section 5.3.3); the event itself may be of relatively minor medical significance (such 
as severe headache without any further findings). 
Severity and seriousness need to be independently assessed for each adverse event 
recorded on the 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).  
 
 
 
 
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
94/Protocol GO41767, Version 7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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). 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
95/Protocol GO41767, Version 7 
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 
 days after 
the final dose of study treatment 
 
 and serious adverse events will continue to be reported until 
days after the final dose of study treatment 
 
.  In addition, adverse events of special 
interest will continue to be reported until 
 days after the final dose of study treatment, 
.   
Instructions for reporting adverse events that occur after the adverse event reporting 
period are provided in 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 v5.0 will be used for 
assessing adverse event severity.  Table 3 will be used for assessing severity for 
adverse events that are not specifically listed in the NCI CTCAE. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
98/Protocol GO41767, Version 7 
Table 5 
Causal Attribution Guidance 
Is the adverse event suspected to be caused by study treatment on the basis of facts, 
evidence, science-based rationales, and clinical judgment? 
YES 
There is a plausible temporal relationship between the onset of the adverse event and 
administration of study treatment, and the adverse event cannot be readily explained by 
the patient's clinical state, intercurrent illness, or concomitant therapies; and/or the 
adverse event follows a known pattern of response to study treatment; and/or the 
adverse event abates or resolves upon discontinuation of study treatment or dose 
reduction and, if applicable, reappears upon re-challenge. 
NO 
An adverse event will be considered related, unless it fulfills the criteria specified below.   
Evidence exists that the adverse event has an etiology other than study treatment 
(e.g., preexisting medical condition, underlying disease, intercurrent illness, 
or concomitant medication); and/or the adverse event has no plausible temporal 
relationship to administration of study treatment (e.g., cancer diagnosed 2 days after 
first dose of study treatment). 
  
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. 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
99/Protocol GO41767, Version 7 
 
 
 
 
 
 
 
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. 
 
If a severe gastrointestinal hemorrhage leads to renal failure, both events should be 
reported separately on the eCRF. 
 
If dizziness leads to a fall and consequent fracture, all 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. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
100/Protocol GO41767, Version 7 
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.  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. 
If a clinically significant laboratory abnormality is a sign of a disease or syndrome 
(e.g., alkaline phosphatase 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 whether the test result is above or below the normal range 
(e.g., "elevated potassium," as opposed to "abnormal potassium").  If the laboratory 
abnormality can be characterized by a precise clinical term per standard definitions, the 
clinical term should be recorded as the adverse event.  For example, an elevated serum 
potassium level of 7.0 mEq/L should be recorded as "hyperkalemia." 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
101/Protocol GO41767, Version 7 
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). 
5.3.5.7 
Abnormal Liver Function Tests 
The finding of an elevated ALT or AST ( 3  ULN) in combination with either an elevated 
total bilirubin ( 2  ULN) or clinical jaundice in the absence of cholestasis or other 
causes of hyperbilirubinemia is considered to be an indicator of severe liver injury (as 
defined by Hy’s Law).  Therefore, investigators must report as an adverse event the 
occurrence of either of the following: 
 
 
 
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). 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
102/Protocol GO41767, Version 7 
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 SCLC should be recorded on the Death 
Attributed to Progressive Disease eCRF.  All other deaths that occur during the adverse 
event reporting period, regardless of relationship to study treatment, must be recorded 
on the Adverse Event eCRF and immediately reported to the Sponsor (see 
Section 5.4.2).  An iDMC 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"). 
Deaths that occur after the adverse event reporting period should be reported as 
described in Section 5.6. 
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. 
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 Small Cell Lung Cancer 
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 RECIST v1.1.  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. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
103/Protocol GO41767, Version 7 
5.3.5.11 
Hospitalization or Prolonged Hospitalization 
Any adverse event that results in hospitalization (i.e., inpatient 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 performance of an efficacy measurement for the study) 
 
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 
 
5.3.5.12 
Cases of Accidental Overdose or Medication Error 
Accidental overdose and medication error (hereafter collectively referred to as "special 
situations"), are defined as follows: 
 
Accidental overdose:  accidental administration of a drug in a quantity that is higher 
than the assigned dose 
 
Medication error:  accidental deviation in the administration of a drug  
In some cases, a medication error may be intercepted prior to administration of 
the drug. 
 
Special situations are not in themselves adverse events, but may result in adverse 
events.  Each adverse event associated with a special situation should be recorded 
separately on the Adverse Event eCRF.  If the associated adverse event fulfills 
seriousness criteria or qualifies as an adverse event of special interest, the event should 
be reported to the Sponsor immediately (i.e., no more than 24 hours after learning of the 
event; see Section 5.4.2).  For tiragolumab (or matching placebo) and atezolizumab, 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
104/Protocol GO41767, Version 7 
adverse events associated with special situations should be recorded as described 
below for each situation: 
 
Accidental overdose:  Enter the adverse event term.  Check the "Accidental 
overdose" and "Medication error" boxes. 
 
Medication error that does not qualify as an overdose:  Enter the adverse event 
term.  Check the "Medication error" box. 
 
Medication error that qualifies as an overdose:  Enter the adverse event term.  
Check the "Accidental overdose" and "Medication error" boxes. 
 
In addition, all special situations associated with tiragolumab (or matching placebo) and 
atezolizumab, regardless of whether they result in an adverse event, should be recorded 
on the Adverse Event eCRF as described below: 
 
Accidental overdose:  Enter the drug name and "accidental overdose" as the event 
term.  Check the "Accidental overdose" and "Medication error" boxes. 
 
Medication error that does not qualify as an overdose:  Enter the name of the drug 
administered and a description of the error (e.g., wrong dose administered, wrong 
dosing schedule, incorrect route of administration, wrong drug, expired drug 
administered) as the event term.  Check the "Medication error" box. 
 
Medication error that qualifies as an overdose:  Enter the drug name and "accidental 
overdose" as the event term.  Check the "Accidental overdose" and "Medication 
error" boxes.  Enter a description of the error in the additional case details. 
 
Intercepted medication error:  Enter the drug name and "intercepted medication 
error" as the event term.  Check the "Medication error" box.  Enter a description of 
the error in the additional case details. 
 
As an example, an accidental overdose that resulted in a headache would require two 
entries on the Adverse Event eCRF, one entry to report the accidental overdose and one 
entry to report the headache.  The "Accidental overdose" and "Medication error" boxes 
would need to be checked for both entries. 
5.3.5.13 
Patient-Reported Outcome Data 
Adverse event reports will not be derived from 
 PRO data by the 
Sponsor.  In addition, the Sponsor will make no attempt to reconcile patient reports of 
treatment-related symptoms (via 
) with investigator reports of adverse 
events.  Sites are not expected to review the 
 PRO data for 
adverse events.  
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 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
105/Protocol GO41767, Version 7 
of events that the investigator must report to the Sponsor within 24 hours after learning 
of the event, regardless of relationship to study treatment: 
 
Serious adverse events (defined in Section 5.2.2; see Section 5.4.2 for details on 
reporting requirements) 
 
Adverse events of special interest (defined in Section 5.2.3; see Section 5.4.2 for 
details on reporting requirements) 
 
Pregnancies (see Section 5.4.3 for details on reporting requirements) 
 
For serious adverse events and adverse events of special interest, the investigator must 
report new significant follow-up information to the Sponsor immediately (i.e., no more 
than 24 hours after 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 
 
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 
To ensure the safety of study participants, access to the Medical Monitors is available 
24 hours per day, 7 days per week.  
An Emergency Medical Call Center will also be available 24 hours per day, 7 days per 
week.  The Emergency Medical Call Center will connect the investigator with an 
Emergency Medical Contact, provide medical translation service if necessary, and track 
all calls.  Contact information, including toll-free numbers for the Emergency Medical 
Call Center, will be distributed to investigators.  
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 paper Clinical Trial Adverse Event/Special Situations Form provided to investigators 
should be completed and submitted to the Sponsor or its designee immediately (i.e., no 
more than 24 hours after learning of the event), either by faxing or by scanning and 
emailing the form using the fax number or email address provided to investigators. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
106/Protocol GO41767, Version 7 
5.4.2.2 
Events that Occur After Study Treatment Initiation 
After initiation of study treatment, serious adverse events will be reported until 90 days 
after the final dose of study treatment or until initiation of new systemic anti-cancer 
therapy, whichever occurs first.  In addition, adverse events of special interest will be 
reported until 90 days after the final dose of study treatment, regardless of initiation of 
subsequent anti-cancer therapy.  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 paper Clinical Trial Adverse 
Event/Special Situations Form provided to investigators should be completed and 
submitted to the Sponsor or its designee immediately (i.e., no more than 24 hours after 
learning of the event), either by faxing or by scanning and 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 serious adverse events that occur after the reporting period are 
provided in Section 5.6. 
5.4.3 
Reporting Requirements for Pregnancies 
5.4.3.1 
Pregnancies in Female Patients 
Female patients of childbearing potential will be instructed through the Informed Consent 
Form to immediately inform the investigator if they become pregnant during the study, 
within 90 days after the final dose of tiragolumab/placebo, or within 5 months after the 
final dose of atezolizumab, or within 6 months after the final dose of carboplatin or 
etoposide, whichever is later.  A paper Clinical Trial Pregnancy Reporting Form should 
be completed and submitted to the Sponsor or its designee immediately (i.e., no more 
than 24 hours after 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 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, within 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
107/Protocol GO41767, Version 7 
6 months after the final dose of chemotherapy study treatment (i.e., CE), or within 
90 days after the final dose of tiragolumab/placebo), whichever is later.  The investigator 
should report the pregnancy on the paper Clinical Trial Pregnancy Reporting Form and 
submit the form to the Sponsor or its designee immediately (i.e., no more than 24 hours 
after learning of the pregnancy), either by faxing or by scanning and 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.  When permitted by the site, the 
pregnant partner would need to sign an Authorization for Use and Disclosure of 
Pregnancy Health Information to allow for follow-up on her pregnancy.  If the 
authorization has been signed, the investigator should submit a Clinical Trial Pregnancy 
Reporting Form with additional information on the pregnant partner and the course and 
outcome of the pregnancy as it becomes available.  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. 
5.4.3.3 
Abortions 
A spontaneous abortion should be classified as a serious adverse event (as the Sponsor 
considers abortions to be medically significant), recorded on the Adverse Event eCRF, 
and reported to the Sponsor immediately (i.e., no more than 24 hours after learning of 
the event; see Section 5.4.2). 
If a therapeutic or elective abortion was performed because of an underlying maternal or 
embryofetal toxicity, the toxicity should be classified as a serious adverse event, 
recorded on the Adverse Event eCRF, and reported to the Sponsor immediately (i.e., no 
more than 24 hours after learning of the event; see Section 5.4.2).  A therapeutic or 
elective abortion performed for reasons other than an underlying maternal or 
embryofetal toxicity is not considered an adverse event. 
All abortions should be reported as pregnancy outcomes on the paper Clinical Trial 
Pregnancy Reporting Form. 
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 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
108/Protocol GO41767, Version 7 
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, email, 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 reporting period for serious adverse events (defined as 
days after 
the final dose of study treatment 
 
), and adverse events of special interest (defined as 
 days after 
the final 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.  However, if the EDC system is not available, the 
investigator should report these events directly to the Sponsor or its designee, either by 
faxing or by scanning and emailing the paper Clinical Trial Adverse Event/Special 
Situations 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. 
The Sponsor has a legal responsibility to notify regulatory authorities about the safety 
of a study treatment under clinical investigation.  The Sponsor will comply with 
regulatory requirements for expedited safety reporting to regulatory authority (which 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
109/Protocol GO41767, Version 7 
includes the use of applicable systems, such as EudraVigilance), IRBs, ECs, and 
investigators. 
To determine reporting requirements for single adverse event cases, the Sponsor will 
assess the expectedness of these events through use of the reference safety 
information in the documents listed below: 
Drug 
Document 
Tiragolumab 
Tiragolumab Investigator's Brochure 
Atezolizumab 
Atezolizumab Investigator’s Brochure 
 
The Sponsor will compare the severity of each event and the cumulative event 
frequency reported for the study with the severity and frequency reported in the 
applicable reference document. 
Reporting requirements will also be based on the investigator's assessment of causality 
and seriousness, with allowance for upgrading by the Sponsor as needed. 
An iDMC will monitor safety data during the study.  An aggregate report of any clinically 
relevant imbalances that do not favor the test product will be submitted to health 
authorities. 
6. 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN 
This is a randomized, Phase III, global, double-blind, placebo-controlled study designed 
to evaluate the safety and efficacy of tiragolumab plus atezolizumab in combination with 
CE compared with treatment with placebo plus atezolizumab and CE in patients who 
have ES-SCLC and are chemotherapy-naive for their extensive-stage disease. 
The analyses of PFS and OS will be performed in the PAS and the FAS.  Patients will be 
grouped according to the treatment assigned at randomization, regardless of whether 
they receive any assigned study drug.  Confirmed ORR will be analyzed in patients 
within the PAS and the FAS who have measurable disease at baseline.  Duration of 
response will be assessed in patients who have a confirmed objective response in the 
PAS and the FAS.  Time to confirmed deterioration analyses and change from baseline 
analysis on PROs will be performed in the PAS and the FAS. 
Safety analyses will be conducted in all patients who are randomly assigned who 
received at least one dose of study treatment.  Safety analyses will be performed by 
treatment arm and will be based on actual treatment received.  Specifically, a patient will 
be included in the tiragolumab plus atezolizumab arm in the safety analyses if the patient 
receives any amount of tiragolumab, regardless of the initial treatment assignment at 
randomization. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
110/Protocol GO41767, Version 7 
Hypothesis tests will be two-sided unless otherwise indicated.  Details of the analyses 
will be provided in the Statistical Analysis Plan (SAP). 
6.1 
DETERMINATION OF SAMPLE SIZE 
The primary objective of this study is to test the hypothesis that tiragolumab in 
combination with atezolizumab in combination with CE prolongs the duration of PFS 
and/or OS relative to the control arm in the PAS.  The PAS will include approximately 
400 patients, assuming a 15% prevalence of presence or history of brain metastases at 
baseline.  Approximately 470 patients in total will be randomly assigned in this study. 
 
6.1.2 
Co-Primary Endpoint:  Progression-Free Survival in the 
Primary Analysis Set 
 
 
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
111/Protocol GO41767, Version 7 
 
 
 
 
 
 
 
 
6.1.3 
Co-Primary Endpoint:  Overall Survival in the Primary Analysis 
Set 
The final analysis of the co-primary endpoint of OS will occur when approximately 
288 deaths (72% of 400; see Section 6.10.2) have been observed in the PAS.  This 
provides 
 power to detect a target HR of 
 for OS at a 
 
, based on the following assumptions: 
 
 
 
 
 
It is projected that an observed HR of 
 or better for OS in the PAS will result in a 
statistically significant difference between the treatment arms.  That is, an HR of 
 will be the minimally detectable difference for the analysis; this corresponds to an 
improvement of 
 in median OS from 
 in the 
placebo  atezolizumab  CE arm to 
 in the tiragolumab  atezolizumab  CE 
arm. 
The timing of the interim analyses and the final analysis for OS in the PAS are 
summarized in Table 6 below, with the additional assumption on accrual. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
112/Protocol GO41767, Version 7 
 
The OS interim analysis is planned to be conducted by the Sponsor when approximately 
202 deaths in the PAS have been observed.  The stopping boundaries for the OS interim 
and final analyses are to be computed using the
 
. 
6.2 
SUMMARIES OF CONDUCT OF STUDY 
Study enrollment, study drug administration, reasons for discontinuation from the study 
drug, and reasons for study termination will be summarized by treatment arm.  Major 
protocol deviations, including major deviations of inclusion/exclusion criteria, will be 
reported and summarized by treatment arm. 
6.3 
SUMMARIES OF TREATMENT GROUP COMPARABILITY 
Demographic characteristics, such as age, sex, race/ethnicity, and baseline disease 
characteristics (e.g., ECOG Performance Status) will be summarized by treatment arm.  
Descriptive statistics (mean, median, SD, and range) will be presented for continuous 
data, and frequencies and percentages will be presented for categorical data. 
Baseline measurements are the last available data obtained prior to the patient receiving 
the first dose of any component of protocol treatment. 
6.4 
EFFICACY ANALYSES 
6.4.1 
Co-Primary Efficacy Endpoints 
The co-primary efficacy endpoints are PFS (as assessed by the investigator according to 
RECIST v1.1) and OS in the PAS. 
Progression-free survival is defined as the time between the date of randomization and 
the date of first documented disease progression (as assessed by investigators 
according to RECIST v1.1) or death, whichever occurs first.  Patients who have not 
experienced disease progression and have not died by the data cutoff date will be 
censored at the time of the last tumor assessment.  Patients with no postbaseline tumor 
assessment will be censored at the date of randomization. 
Overall survival is defined as the time between the date of randomization and death from 
any cause. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
113/Protocol GO41767, Version 7 
Data for patients who are not reported as having died by the data cutoff date will be 
censored at the date when they were last known to be alive.  Data for patients who do not 
have postbaseline information will be censored at the date of randomization.  
Progression-free survival and OS will be compared between treatment arms with use of 
the stratified log-rank test.  The HR for PFS and OS will be estimated using a stratified 
Cox proportional hazards model.  The 95% CI for the HR will be provided.  The 
stratification factors will be those used for randomization from the IxRS (i.e., ECOG 
Performance Status and LDH).  Stratification factor(s) may be removed from the 
stratified analyses if there is risk of overstratification.  Analyses based on stratification 
factors recorded on the eCRF will also be provided if considerable discrepancy is 
observed between IxRS and eCRF records.  Results from an unstratified analysis will 
also be provided.  
Kaplan-Meier methodology will be used to estimate the median PFS and median OS for 
each treatment arm, and Kaplan-Meier curves will be constructed to provide a visual 
description of the difference between treatment arms.  The Brookmeyer-Crowley 
methodology will be used to construct the 95% CIs for the median PFS and median OS 
for each treatment arm (Brookmeyer and Crowley 1982). 
The timing of the final PFS analysis is described in Section 6.1.2, and the analysis timing 
for OS is described in Section 6.1.3.  To control the overall type I error rate at 0.05, the 
hypothesis test for PFS will be conducted at a two-sided  of 0.001.  If PFS is not 
statistically significant, OS will be tested at a two-sided  of 0.049; if PFS is statistically 
significant, OS will be tested at a two-sided  level of 0.05 (see Section 6.1.1). 
6.4.2 
Secondary Efficacy Endpoints 
6.4.2.1 
Progression-Free Survival and Overall Survival in the Full 
Analysis Set 
If the difference in OS in the PAS is statistically significant, PFS and OS will be tested in 
the FAS, following the same -allocation ratio (1:49) and -recycle strategy for the 
analysis of the co-primary efficacy endpoints as described in Section 6.4.1.  
Progression-free survival and OS in the FAS will be analyzed at the same time with the 
PAS, using the same methods as described in Section 6.4.1, except that all three 
stratification factors used for randomization from the IxRS (i.e., ECOG Performance 
Status, LDH, and presence or history of brain metastasis) will be included in the stratified 
analyses for the FAS.  Stratification factor(s) may be removed from the stratified 
analyses if there is risk of overstratification. 
6.4.2.2 
Confirmed Objective Response Rate 
A confirmed objective response is defined as either a CR or a PR on 2 consecutive 
occasions  4 weeks apart, as determined by the investigator using RECIST v1.1.  
Patients not meeting these criteria, including patients without any postbaseline tumor 
assessment, will be considered non-responders. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
114/Protocol GO41767, Version 7 
Confirmed ORR is defined as the proportion of patients who had a confirmed objective 
response.  The analysis population for confirmed ORR will be the PAS and the FAS with 
measurable disease at baseline.  An estimate of confirmed ORR and its 95% CI will be 
calculated using the Wilson score method for each treatment arm.  Confidence intervals 
for the difference in confirmed ORRs between the two treatment arms will be determined 
using the Newcombe method. 
6.4.2.3 
Duration of Response 
Duration of response will be assessed in patients who had a confirmed objective 
response as determined by the investigator using RECIST v1.1 in the PAS and the FAS.  
Duration of response is defined as the time interval from the date of the first occurrence 
of a confirmed objective response until the first date that progressive disease as 
determined by the investigator according to RECIST v1.1 or death is documented, 
whichever occurs first.  Patients who have not progressed and who have not died at the 
time of analysis will be censored at the time of last tumor assessment date.  Duration of 
response is based on a non-randomized subset of patients (specifically, patients who 
achieved a confirmed objective response); therefore, formal hypothesis testing will not 
be performed for this endpoint.  Comparisons between treatment arms will be made for 
descriptive purposes.  The methodologies detailed for the PFS analysis will be used for 
the DOR analysis. 
6.4.2.4 
Landmark Analysis on Progression-Free Survival and Overall 
Survival 
The PFS rates at 6 months and at 1 year after randomization will be estimated using 
Kaplan-Meier methodology for each treatment arm, along with 95% CIs calculated using 
the standard error derived from Greenwood’s formula.  The 95% CI for the difference in 
PFS rates between the two treatment arms will be estimated using the normal 
approximation method. 
Similar analyses will be performed for the OS rates at 1 and 2 years after randomization. 
6.4.2.5 
Patient-Reported Outcomes 
Time to confirmed deterioration in the PAS and the FAS for physical functioning and 
GHS/QoL using the EORTC QLQ-C30 is defined as the time from the date of 
randomization until the first confirmed clinically meaningful deterioration. 
Confirmed clinically meaningful deterioration for physical functioning and GHS/QoL is 
defined as a clinically meaningful decrease from baseline in physical functioning or 
GHS score that must be held for at least two consecutive assessments or an initial 
clinically meaningful decrease above baseline followed by death.   
A score change of  10-point change in GHS/QoL and functional subscale score is 
perceived by patients as clinically meaningful (Osoba et al. 1998). 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
115/Protocol GO41767, Version 7 
For TTCD, data for patients will be censored at the last time when they completed an 
assessment if they have not experienced a confirmed clinically meaningful deterioration 
at the clinical cutoff date.  If no baseline or postbaseline assessment is performed, 
patients will be censored at the randomization date.  Time to confirmed deterioration 
using the EORTC scale will be analyzed using the same methods as for PFS.  Further 
details regarding the TTCD analysis for the EORTC measures will be described in the 
SAP. 
Summary statistics (mean, SD, median, 25th and 75th percentiles, and range) and the 
mean change from baseline of linear-transformed scores will be reported for all of the 
items and subscales of the EORTC QLQ-C30 and EORTC IL46, an item for trouble with 
side effects questionnaires according to the EORTC scoring manual guidelines.   
 
 
 
 
 
 
 
 
 
 
 
  
 
 
Completion and compliance rates will be summarized at each timepoint by treatment 
arm. 
6.5 
SAFETY ANALYSES 
Safety analyses will be conducted in all patients who are randomly assigned who 
received at least one dose of study treatment. 
Safety analyses will be performed by treatment arm and will be based on actual 
treatment received.  Specifically, a patient will be included in the tiragolumab-containing 
arm in the safety analyses if the patient receives any amount of tiragolumab, regardless 
of the initial treatment assignment at randomization. 
Drug exposure will be summarized, including duration, dosage, and dose intensity. 
Verbatim description of adverse events will be mapped to the MedDRA thesaurus terms.  
Severity for all adverse events will be graded by the investigator according to the 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
116/Protocol GO41767, Version 7 
NCI CTCAE v5.0, 
 
  All adverse events will be summarized by 
treatment arm and NCI CTCAE grade. 
 
.  In addition, serious 
adverse events and adverse events leading to study treatment discontinuation or 
interruption will be summarized accordingly.  Multiple occurrence of the same event will 
be counted once at the maximum severity.  Laboratory data with values outside of the 
normal ranges will be identified.  Additionally, selected laboratory data, including ADA 
results, will be summarized by treatment arm and grade.  Vital signs will also be 
summarized by treatment arm and visit.  Deaths and causes of deaths will be 
summarized. 
6.6 
PHARMACOKINETIC ANALYSES 
Pharmacokinetic samples of tiragolumab and atezolizumab will be collected in this study 
as outlined in Appendix 2.  Tiragolumab and atezolizumab serum concentration data 
(minimum serum concentration and maximum serum concentration) will be tabulated 
and summarized.  Descriptive statistics will include arithmetic and geometric means, 
medians, ranges, and standard deviations, as appropriate. 
Plasma concentrations of CE will be collected in a subset of patients in this study as 
outlined in Appendix 2.  The concentrations of CE will be summarized using descriptive 
statistics as described above. 
Additional PK analyses will be conducted, as appropriate, based on the availability of 
data. 
6.7 
IMMUNOGENICITY ANALYSES 
The immunogenicity analyses will include patients with any ADA assessments, with 
patients grouped according to treatment received. 
The numbers and proportions of treatment-emergent ADA-positive patients and 
ADA-negative patients during both the treatment and follow-up periods for both 
tiragolumab and atezolizumab will be summarized by treatment arm. 
The relationship between ADA status and safety, efficacy, and PK endpoints may be 
analyzed and reported via descriptive statistics. 
  
  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
117/Protocol GO41767, Version 7 
 
 
 
 
 
 
 
 
 
 
 
6.10.2 
Overall Survival 
 
 
.  The final OS 
analysis will be conducted when approximately 
 OS events in the PAS have been 
observed.  This is expected to occur approximately 
 after the first patient is 
randomly assigned.  The exact timing of these analyses will depend on the actual 
number of OS events.  
 
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
118/Protocol GO41767, Version 7 
Table 7 
Analysis Timing and Stopping Boundary of Overall Survival in 
the Primary Analysis Set 
  
A total of two analyses are planned for the co-primary endpoint of OS in the FAS, to be 
conducted at the same time as for the PAS.  The same information fraction in the PAS, 
based on the actual number of events observed, will be applied to calculate the 
statistical boundary for the OS analyses in the FAS. 
6.10.3 
Safety Monitoring 
An external iDMC will be set up to evaluate safety data on an ongoing basis.  All 
summaries/analyses by treatment arm for the iDMC’s review will be prepared by an 
iDCC.  Members of the iDMC will be external to the Sponsor and will follow a charter that 
outlines their roles and responsibilities.  Any outcomes of these safety reviews that affect 
study conduct will be communicated in a timely manner to the investigators for 
notification of the IRBs/ECs.  A detailed plan will be included in the iDMC Charter.  
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 will be sent 
directly to the Sponsor, using the Sponsor’s standard procedures to handle and process 
the electronic transfer of these data. 
Electronic Case Report Forms 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. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
119/Protocol GO41767, Version 7 
Patient-reported outcome data will be collected on paper questionnaires.  The data from 
the questionnaires will be entered into the EDC system by site staff.  
7.2 
ELECTRONIC CASE REPORT FORMS 
Electronic Case Report Forms 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.  Electronic Case Report Forms will be submitted electronically to the 
Sponsor and should be handled in accordance with instructions from the Sponsor. 
All eCRFs should be completed by designated, trained site staff.  Electronic Case Report 
Forms 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 that must be kept with the study records.  Acknowledgement of receipt 
of the data are required. 
7.3 
SOURCE DATA DOCUMENTATION 
Study monitors will perform ongoing source data verification and review 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 and review, 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. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
120/Protocol GO41767, Version 7 
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. 
7.5 
RETENTION OF RECORDS 
Records and documents pertaining to the conduct of this study and the distribution of 
IMP, including eCRFs, paper PRO data, Informed Consent Forms, laboratory test 
results, and medication inventory records, must be retained by the Principal Investigator 
for 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. 
Roche will retain study data for 25 years after the final study results have been reported 
or for the length of time required by relevant national or local health authorities, 
whichever is longer. 
8. 
ETHICAL CONSIDERATIONS 
8.1 
COMPLIANCE WITH LAWS AND REGULATIONS 
This study will be conducted in full conformance with the ICH E6 guideline for Good 
Clinical Practice and the principles of the Declaration of Helsinki, or the applicable 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. FDA 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 Trials Directive (2001/20/EC) 
or Clinical Trials Regulation (536/2014) and applicable local, regional, and national laws. 
8.2 
INFORMED CONSENT 
The Sponsor's sample Informed Consent Form (and ancillary sample Informed Consent 
Forms, such as an Assent Form or Mobile Nursing Informed Consent Form, 
if applicable) will be provided to each site.  If applicable, it will be provided in a certified 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
121/Protocol GO41767, Version 7 
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. 
The Informed Consent Form will also contain a separate signature page for patients who 
meet all of the criteria specified in Section 3.1.2, and decide to continue study treatment 
beyond radiographic disease progression per RECIST v1.1.  This separate consent is to 
be signed after initial radiographic disease progression has occurred and patients have 
discussed other available treatment options and the potential risks of continuing study 
treatment. 
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. 
If the Consent Forms are revised (through an amendment or an addendum) while a 
patient is participating in the study, the patient or a legally authorized representative 
must re-consent by signing the most current version of the Consent Forms or the 
addendum, in accordance with applicable laws and IRB/EC policy.  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. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
122/Protocol GO41767, Version 7 
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 (HIPAA) of 1996.  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 9.7). 
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 
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 
Information technology systems used to collect, process, and store study-related data 
are secured by technical and organizational security measures designed to protect such 
data against accidental or unlawful loss, alteration, or unauthorized disclosure or access.  
In the event of a data security breach, appropriate mitigation measures will be 
implemented. 
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. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
123/Protocol GO41767, Version 7 
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. 
Given the complexity and exploratory nature of exploratory biomarker analyses, data 
derived from these analyses will generally not be provided to study investigators or 
patients unless required by law.  The aggregate results of any conducted research will 
be available in accordance with the effective Sponsor policy on study data publication 
(see Section 9.6). 
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. 
Study data, which may include data on genomic variants, may be submitted to 
government or other health research databases or shared with researchers, government 
agencies, companies, or other groups that are not participating in this study.  These data 
may be combined with or linked to other data and used for research purposes, to 
advance science and public health, or for analysis, development, and commercialization 
of products to treat and diagnose disease.  In addition, redacted Clinical Study Reports 
and other summary reports will be provided upon request (see Section 9.6). 
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 (see definition of end of 
study in Section 3.2). 
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. 
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 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
124/Protocol GO41767, Version 7 
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 
MANAGEMENT OF STUDY QUALITY 
The Sponsor will implement a system to manage the quality of the study, focusing on 
processes and data that are essential to ensuring patient safety and data integrity.  Prior 
to study initiation, the Sponsor will identify potential risks associated with critical trial 
processes and data and will implement plans for evaluating and controlling these risks.  
Risk evaluation and control will include the selection of risk-based parameters 
(e.g., adverse event rate, protocol deviation rate) and the establishment of quality 
tolerance limits for these parameters prior to study initiation.  Detection of deviations 
from quality tolerance limits will trigger an evaluation to determine if action is needed.  
Details on the establishment and monitoring of quality tolerance limits will be provided in 
a Quality Tolerance Limit Management Plan. 
9.4 
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. 
9.5 
ADMINISTRATIVE STRUCTURE 
This study will be sponsored and managed by F. Hoffmann-La Roche Ltd.  
Approximately 150 sites globally will participate in the study and approximately 
470 patients will be randomly assigned during the study.  Randomization will occur 
through an IxRS.   
Central facilities will be used for certain study assessments throughout the study 
(e.g., specified laboratory tests, biomarker analyses, and PK analyses), as specified in 
Section 4.5.7.  Accredited local laboratories will be used for routine monitoring; local 
laboratory ranges will be collected. 
An iDMC will monitor and evaluate patient safety throughout the study, as detailed in 
Section 3.1.3.  Tumor response and progression will be evaluated by the investigator.  
All primary imaging data used for tumor assessments will be collected by the Sponsor 
and a centralized, blinded, independent review by an IRF may be conducted. 
9.6 
DISSEMINATION 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, at scientific 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
125/Protocol GO41767, Version 7 
congresses, in clinical trial registries, and in peer-reviewed journals.  The Sponsor will 
comply with all requirements for publication of study results.  Study data may be shared 
with others who are not participating in this study (see Section 8.4 for details), and 
redacted Clinical Study Reports and/or other summaries of clinical study results may be 
available in health authority databases for public access, as required by local regulation, 
and will be made available upon request.  For more information, refer to the Roche 
Global Policy on Sharing of Clinical Study Information at the following website:   
https://www.roche.com/innovation/process/clinical-trials/data-sharing/  
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 
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. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
126/Protocol GO41767, Version 7 
9.7 
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). 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
127/Protocol GO41767, Version 7 
10. 
REFERENCES 
Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research 
and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in 
international clinical trials in oncology. J Natl Cancer Inst 1993;85:36576. 
Apetoh L, Ghiringhelli F, Tesniere A, et al. Toll-like receptor 4-dependent contribution of 
the immune system to anticancer chemotherapy and radiotherapy. Nat Med 
2007;13:10509. 
Basch E, Reeve BB, Mitchell SA, et al. Development of the National Cancer Institute’s 
patient-reported outcomes version of the common terminology criteria for adverse 
events (PRO-CTCAE). J Natl Cancer Inst 2014;106:111.  
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics 
1982;38:2941. 
Burman CF, Sonesson C, Guilbaud O, et al. A recycling framework for the construction 
of Bonferroni-based multiple tests. Stat Med 2009;28:73961. 
Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage: prospective evaluation 
of a simple formula based on renal function. J Clin Oncol 1989;7:174856. 
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. 
Nephron 1976;16:3141. 
Demedts IK, Vermaelen KY, van Meerbeeck JP. Treatment of extensive-stage small cell 
lung carcinoma: current status and future prospects. Eur Respir J 2010;35:20215. 
DeMets D, Lan KKG. Interim analysis: the alpha spending function approach. Stat Med 
1994;13:134152. 
Dueck AC, Mendoza TR, Mitchell SA, et al. Validity and reliability of the US National 
Cancer Institute’s Patient-Reported Outcomes Version of the Common 
Terminology Criteria for Adverse Events (PRO-CTCAE). JAMA Oncol 
2015;1:10519.  
European Medicines Agency Guideline on the Evaluation of Anticancer Medicinal 
Products in Man EMA/CHPM/205/95/Rev.4 [resource on the Internet]. 2012. 
Available from: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/201
3/01/WC500137128.pdf. 
Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence 
and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer 
2019;144:194153. 
Fehrenbacher L, Spira A, Ballinger M, et al. Atezolizumab versus docetaxel for patients 
with previously treated non-small-cell lung cancer (POPLAR): a multicentre, 
open-label, phase 2 randomised controlled trial. Lancet 2016;387:183746. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
128/Protocol GO41767, Version 7 
Fitzsimmons D, Johnson CD, George S, et al. Development of a disease specific quality 
of life (QoL) questionnaire module to supplement the EORTC core cancer QoL 
questionnaire, the QLQ-C30 in patients with pancreatic cancer. EORTC Study 
Group on Quality of Life. Eur J Cancer 1999;35:93941. 
Foster NR, Mandrekar SJ, Schild SE, et al. Prognostic factors differ by tumor stage for 
small cell lung cancer: a pooled analysis of north central cancer treatment group 
trials. Cancer 2009;115:272131. 
Frebel H, Nindl V, Schuepbach RA, et al. Programmed death 1 protects from fatal 
circulatory failure during systemic virus infection of mice. J Exp Med 
2012;209:248599. 
Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in 
metastatic non–small-cell lung cancer. New Engl J Med 2018;378:207892. 
Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small cell lung 
cancer in the United States over the last 30 years: analysis of the surveillance, 
epidemiologic, and end results database. J Clin Oncol 2006;24:453944. 
Guidance for Industry: Clinical Trial Endpoints for the Approval of Cancer Drugs and 
Biologics [resource on the Internet]. 2007. [updated: December 2018]. Available 
from: http://www.fda.gov/downloads/Drugs/Guidances/ucm071590.pdf. 
Hopwood P, Stephens RJ. Symptoms at presentation for treatment in patients with lung 
cancer: implications for the evaluation of palliative treatment. The Medical 
Research Council (MRC) Lung Cancer Working Party. Br J Cancer 
1995;71:6336. 
Horn L, Mansfield AS, Szczęsna A, et al. First-Line Atezolizumab plus Chemotherapy in 
Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018;379:22209. 
Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 19752012, 
National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2012/, 
based on November 2014 SEER data submission, posted to the SEER website, 
April 2015. 
Hyde L, Hyde CI. Clinical manifestations of lung cancer. Chest 1974;65:299306. 
Johnson BE, Janne PA. Basic treatment considerations using chemotherapy for patients 
with small cell lung cancer. Hematol Oncol Clin 2004;18:30922. 
Johnston RJ, Comps-Agrar L, Hackney J, et al. The immunoreceptor TIGIT regulates 
antitumor and antiviral CD8(  ) T cell effector function. Cancer Cell 
2014;26:92337. 
Joller N, Hafler JP, Brynedal B, et al. Cutting edge: TIGIT has T cell-intrinsic inhibitory 
functions. J Immunol 2011;186:133842. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
129/Protocol GO41767, Version 7 
King-Kallimanis BL, Howie LJ, Roydhouse JK, et al. Patient reported outcomes in 
anti-PD-1/PD-L1 inhibitor immunotherapy registration trials: FDA analysis of data 
submitted and future directions. Clin Trials 2019;16:3226. 
Manieri NA, Chiang EY, Grogan JL. TIGIT: a key inhibitor of the cancer immunity cycle. 
Trends Immunol 2017;38:208. 
Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for 
monocytes and macrophages. Nat Rev Immunol 2020;20:35562. 
Merritt RE, Mahtabifard A, Yamada RE, et al. Cisplatin augments cytotoxic 
T-lymphocyte-mediated antitumor immunity in poorly immunogenic murine lung 
cancer. J Thorac Cardiovasc Surg 2003;126:160917. 
Micke P, Faldum A, Metz T, et al. Staging small cell lung cancer: Veterans 
Administration Lung Study Group versus International Association for the Study of 
Lung Cancer—what limits limited disease? Lung Cancer 2002;37:2716. 
Molina JR, Yang P, Cassivi SD, et al. Nonsmall cell lung cancer: epidemiology, risk 
factors, treatment, and survivorship. Mayo Clin Proc 2008;83:58494. 
[NCCN] National Comprehensive Cancer Network. NCCN guidelines for small cell lung 
cancer [resource on the Internet]. 2019. Available from: 
http://www.nccn.org/professionals/physician_gls/PDF/sclc.pdf. 
[NCCN] National Comprehensive Cancer Network. Recommendations of the NCCN 
COVID-19 Vaccination Advisory Committee [resource on the Internet]. 2021 
[cited: 28 May 2021]. Available from: 
https://www.nccn.org/docs/default-source/covid-
19/2021_covid-19_vaccination_guidance_v2-0.pdf?sfvrsn=b483da2b_2. 
Osoba D, Rodrigues G, Myles J, et al. Interpreting the significance of changes in 
health-related quality-of-life scores. J Clin Oncol 1998;16:13944. 
Pacheco J, Bunn PA. Advancements in small-cell lung cancer: The changing landscape 
following IMpower-133. Clin Lung Cancer 2019;20:14860. 
Paz-Ares L, Luft A, Vicente D, et al. Pembrolizumab plus chemotherapy for squamous 
non–small-cell lung cancer. N Engl J Med 2018;379:204051. 
Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus or minus tremelimumab plus 
platinum-etoposide in first-line extensive-stage small-cell lung cancer: updated 
results from the phase 3 CASPIAN study [abstract]. Am Soc Clin Oncol 
2020:abstract 9002. 
Pesch B, Kendzia B, Gustavsson P, et al. Cigarette smoking and lung cancerrelative 
risk estimates for the major histological types from a pooled analysis of 
case-control studies. Int J Cancer 2012;131:12109.  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
130/Protocol GO41767, Version 7 
Powell RM, Lissauer D, Tamblyn J, et al. Decidual T cells exhibit a highly differentiated 
phenotype and demonstrate potential fetal specificity and a strong transcriptional 
response to IFN. J Immunol 2017;199:340617. 
Rosenberg JE, Hoffman-Censits J, Powles, et al. Atezolizumab in patients with locally 
advanced and metastatic urothelial carcinoma who have progressed following 
treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 
trial. Lancet 2016;387:190920. 
Rudin CM, Awad MM, Navarro A, et al. Pembrolizumab or placebo plus etoposide and 
platinum as first-line therapy for extensive-stage small-cell lung cancer: 
Randomized double-blind, Phase III KEYNOTE-604 study. J Clin Oncology 
2020;38:236979. 
Sarna L, Evangelista L, Tashkin D, et al. Impact of respiratory symptoms and pulmonary 
function on quality of life of long-term survivors of non-small cell lung cancer. 
Chest 2004;125:43945. 
Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced 
triple-negative breast cancer. N Engl J Med 2018;379:210821. 
Schorer M, Rakebrandt N, Lambert K, et al. TIGIT limits immune pathology during viral 
infections. Nat Commun 2020;11:1288. 
Seute T, Leffers P, ten Velde, GPM, et al. Neurologic disorders in 432 consecutive 
patients with small cell lung carcinoma. Cancer 2004;100:8016. 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:734. 
Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth 
factors: American Society of Clinical Oncology clinical practice guideline update. 
J Clin Oncol 2015;33:3199212. 
[SITC] Society for Immunotherapy of Cancer. Society for Immunotherapy of Cancer 
statement on SARS-CoV-2 vaccination and cancer immunotherapy [resource on 
the Internet]. Press release: 23 December 2020 [cited: 28 May 2021]. Available 
from: 
https://www.sitcancer.org/aboutsitc/press-releases/2020/sitc-statement-sars-cov-2-
vaccination-cancer-immunotherapy. 
Socinski MA, Smit EF, Lorigan P, et al. Phase III study of pemetrexed plus carboplatin 
compared with etoposide plus carboplatin in chemotherapy-naive patients with 
extensive-stage small cell lung cancer. J Clin Oncol 2009;27:478792. 
Stanietsky N, Simic H, Arapovic J, et al. The interaction of TIGIT with PVR and PVRL2 
inhibits human NK cell cytotoxicity. Proc Natl Acad Sci USA 2009;106:1785863. 
Stinchcombe TE, Gore EM. Limited-stage small cell lung cancer: current 
chemoradiotherapy treatment paradigms. Oncologist 2010;15:18795. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
131/Protocol GO41767, Version 7 
van der Zwan A, Bi K, Norwitz ER, et al. Mixed signature of activation and dysfunction 
allows human decidual CD8+ T cells to provide both tolerance and immunity. Proc 
Natl Acad Sci USA 2018;115:38590. 
Vento-Tormo R, Efremova M, Botting RA, et al. Single-cell reconstruction of the early 
maternal-fetal interface in humans. Nature 2018;563:34753. 
Wang F, Hou H, Wu S, et al. TIGIT expression levels on human NK cells correlate with 
functional heterogeneity among healthy individuals. Eur J Immunol 
2015;45:288697. 
Wykes MN, Lewin SR. Immune checkpoint blockade in infectious diseases. Nat Rev 
Immunol 2018;18:91104. 
Xu Y, Cui G, Jiang Z, et al. Survival analysis with regard to PD‑L1 and CD155 
expression in human small cell lung cancer and a comparison with associated 
receptors. Oncology Lett 2019;17:29608. 
Yip D, Harper PG. Predictive and prognostic factors in small cell lung cancer: current 
status. Lung Cancer 2000;28:17385. 
Yu X, Harden K, Gonzalez LC, et al. The surface protein TIGIT suppresses T cell 
activation by promoting the generation of mature immunoregulatory dendritic cells. 
Nat Immunol 2009;10:4857. 
Yu H, Koczara C, Badzio A, et al. Expression of an immune checkpoint—poliovirus 
receptor (PVR) in small cell lung cancer [abstract]. Cancer Res 
2018a;78(13 Suppl):Abstract 3637. 
Yu H, Koczara C, Lohinai Z, et al. Expression of the immune checkpoint axis-PVR/TIGIT 
in small cell lung cancer. J Thorac Oncol 2018b;13(Suppl):S9745. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
132/Protocol GO41767, Version 7 
Appendix 1  
Schedule of Activities 
Procedure 
Screening 
All Treatment Cycles a 
Treatment 
Discontinuation Visit 
Survival Follow-Up 
Days  28 
to  1 
Induction Phase 
(Cycles 14) 
Maintenance 
Phase (Starting 
from Cycle 5) 
 30 Days After Last 
Dose of Study Treatment 
Approx. Every 6 Months 
After Disease 
Progression or Loss of 
Clinical Benefit 
Every 21 Days 
( 3 Days) b 
Every 21 Days 
( 3 Days)  
Informed consent 
x 
 
 
 
 
Screening tumor tissue specimen for 
 
  
x c 
x c 
 
 
 
Demographic data 
x 
 
 
 
 
Medical history and baseline conditions 
x 
 
 
 
 
SCLC cancer history 
x 
 
 
 
 
Vital signs d 
x 
x 
x 
x 
 
Weight 
x 
x 
x 
x 
 
Height 
x 
 
 
 
 
Complete physical examination 
x 
 
 
 
 
Limited physical examination e 
 
x f 
x f 
x 
 
ECOG Performance Status 
x 
x f 
x f 
x 
 
ECG 
x 
Perform when clinically indicated 
 
Hematology g 
x h 
x f 
x f 
x 
 
Serum chemistry i  
x h 
x f 
x f 
x 
 
Coagulation test 
 
x h 
 
 
x 
 

Appendix 1: 
Schedule of Activities 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
133/Protocol GO41767, Version 7 
 
Procedure 
Screening 
All Treatment Cycles a 
Treatment 
Discontinuation Visit 
Survival Follow-Up 
Days  28 
to  1 
Induction Phase 
(Cycles 14) 
Maintenance 
Phase (Starting 
from Cycle 5) 
 30 Days After Last 
Dose of Study Treatment 
Approx. Every 6 Months 
After Disease 
Progression or Loss of 
Clinical Benefit 
Every 21 Days 
( 3 Days) b 
Every 21 Days 
( 3 Days) 
Pregnancy test (women of 
childbearing-potential only) 
x j 
x k 
x k 
x k 
x k 
TSH, free T3, free T4 l 
x 
x l,f 
x l,f 
x 
 
x 
 
 
 
 
Urinalysis n 
x n 
Perform when clinically indicated 
 
Induction treatment administration  
Arm A:  atezolizumab  tiragolumab  CE 
Arm B:  atezolizumab  placebo + CE  
 
x o 
 
 
 
Maintenance treatment administration 
Arm A:  atezolizumab  tiragolumab  
Arm B:  atezolizumab  placebo 
 
 
x p 
 
 
PCI 
 
 
x p 
 
 
Tumor response assessment  
x q 
x r 
x r 
 
x s 
Informed consent to continue study treatment 
beyond radiographic disease progression per 
RECIST v1.1 
 
At time of initial radiographic progression 
 
Serum sample for tiragolumab ADA assessment 
 
Refer to Appendix 2, Table A2-1 
Serum sample for atezolizumab ADA assessment 
 
Refer to Appendix 2, Table A2-1 

Appendix 1: 
Schedule of Activities 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
134/Protocol GO41767, Version 7 
 
Procedure 
Screening 
All Treatment Cycles a 
Treatment 
Discontinuation Visit 
Survival Follow-Up 
Days  28 
to  1 
Induction Phase 
(Cycles 14) 
Maintenance 
Phase (Starting 
from Cycle 5) 
 30 Days After Last 
Dose of Study Treatment 
Approx. Every 6 Months 
After Disease 
Progression or Loss of 
Clinical Benefit 
Every 21 Days 
( 3 Days) b 
Every 21 Days 
( 3 Days) 
Serum sample for tiragolumab PK sampling 
 
Refer to Appendix 2, Table A2-1 
Serum sample for atezolizumab PK sampling 
 
Refer to Appendix 2, Table A2-1 
Plasma sample for carboplatin and etoposide PK 
sampling 
 
Refer to Appendix 2, Table A2-2 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse events 
x  
x 
x 
x v 
x v 
Cancer-related procedures (medical, surgical, and 
radiation) 
 
x 
x 
x 
x 
Concomitant medications  
x w 
x w 
x w 
x w 
 
 
 
 
 

Appendix 1: 
Schedule of Activities 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
136/Protocol GO41767, Version 7 
 
g Hematology 
 
h At screening, the patient must have adequate hematologic and end-organ function defined by laboratory test results obtained within 14 days prior to Cycle 1, 
Day1.  See Section 4.1.1 for details. 
i Chemistry panel 
 
  
j 
Serum pregnancy test within 14 days prior to initiation of study treatment. 
k During the study, urine pregnancy tests will be performed on Day 1 of every cycle.  After study treatment discontinuation, a urine pregnancy test will be 
performed at either 6 months after the final dose of carboplatin or etoposide, at 90 days after the final dose of tiragolumab/placebo, or at 5 months after the 
final dose of atezolizumab, whichever is later.  If a urine pregnancy test result is positive, it must be confirmed by a serum pregnancy test. 
l Thyroid-stimulating hormone, free T3 (or total T3 for sites where free T3 is not performed), and free T4 will be assessed on Day 1 of Cycles 1, 5, 9, and 13, 
and every fourth cycle thereafter.  The Cycle 1 thyroid function testing does not need to performed if the previous test was performed within the screening 
window. 
m 
. 
 
 
 
 
 
  
 
 
n Includes pH, specific gravity, glucose, protein, ketones, and blood; dipstick permitted.  Urinalysis is required at screening and will be obtained when clinically 
indicated. 
o 
 
  For CE, study drug will be administered as described 
in Section 4.3.2.  
  

Appendix 1: 
Schedule of Activities 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
137/Protocol GO41767, Version 7 
 
p 
  Additionally, during this phase, PCI is 
permitted as per local standard of care and will be reported on the Prophylactic Cranial Irradiation eCRF.  
q Computed tomography scans (with IV contrast unless contraindicated and oral contrast as appropriate per institutional standards) of the chest and abdomen.  
A CT with contrast of the pelvis is required at screening and as clinically indicated or as per local standard of care at subsequent response evaluations.  A CT 
(with contrast) or MRI scan of the head must be done at screening to evaluate CNS metastasis in all patients.  See Section 4.5.6 for details. 
r Perform every 6 weeks ( 7 days) for 48 weeks following Cycle 1, Day 1 and then every 9 weeks ( 7 days) thereafter, after completion of the Week 48 tumor 
assessment, regardless of treatment delays, until radiographic disease progression per RECIST v1.1 (or loss of clinical benefit for patients who continue study 
treatment after disease progression per RECIST v1.1), withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. 
 
 
 
s If the patient discontinues study treatment for any reason other than radiographic disease progression per RECIST v1.1 (e.g., toxicity, symptomatic 
deterioration), tumor assessments will continue at the same frequency as would have been followed if the patient had remained on study treatment (i.e., every 
6 weeks [ 7 days] for 48 weeks following Cycle 1, Day 1 and then every 9 weeks [ 7 days] thereafter) until radiographic disease progression per 
RECIST v1.1, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first, even if the patient starts a new anti-cancer therapy 
after study treatment discontinuation.  See Section 4.5.6 for details.  
 
 
t 
 
 
. 
u 
 
v  All serious adverse events regardless of relationship to study drug, will be reported until
days after the last dose of study drug 
 
.  In addition, adverse events of special interest will continue to be reported until 
days after the final dose of study treatment, 
.  All other adverse events, regardless of relationship 
to study drug, will be reported until 
 days after the last dose of study drug 
 
  After this period, all deaths should continue to be reported.  In addition, the Sponsor should be notified if the investigator becomes 
aware of any serious adverse event or adverse event of special interest that is believed to be related to prior exposure to study treatment (see Section 5.6).  
These events should be reported using the Adverse Event eCRF. 

Appendix 1: 
Schedule of Activities 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
138/Protocol GO41767, Version 7 
 
w From 7 days prior to initiation of study treatment until the treatment discontinuation visit.  All such medications should be reported to the investigator and 
recorded on the Concomitant Medications eCRF. 
x 
y After radiographic disease progression per RECIST v1.1 (or loss of clinical benefit for patients who continue study treatment after disease progression per 
RECIST v1.1) and study treatment has been discontinued, survival follow-up information will be collected by telephone, patient medical records, and/or clinic 
visits every 6 months or more frequently ( 30 days) until death, loss to follow-up, or study termination by the Sponsor, whichever occurs first.  All patients will 
be periodically contacted for survival and new anti-cancer therapy information unless the patient requests to be withdrawn from follow-up (this request must be 
documented in the source documents and signed by the investigator).  If the patient withdraws from the study, study staff may use a public information source 
(e.g., county records), when permissible, to obtain information about survival status only. 
  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
139/Protocol GO41767, Version 7 

Appendix 2: 
Schedule of Pharmacokinetic, Immunogenicity, and Biomarker Samples 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
140/Protocol GO41767, Version 7 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
141/Protocol GO41767, Version 7 
Table A2-2 Schedule of Pharmacokinetic Samples for Chemotherapy in a 
Subset of Patients 
Study Visit 
Time 
Sample type(s) 
Cycle 1 and 3, 
Day 1  
Predose (same day as treatment 
administration) 
 Carboplatin PK (plasma) 
 Etoposide PK (plasma) 
 
510 minutes before end of 
carboplatin infusion 
 Carboplatin PK (plasma) 
 
510 minutes before end of 
etoposide infusion 
 Etoposide PK (plasma) 
 
1 hour ( 15 minutes) after end of 
carboplatin infusion 
 Carboplatin PK (plasma) 
 
1 hour ( 15 minutes) after end of 
etoposide infusion 
 Etoposide PK (plasma) 
PK  pharmacokinetics. 
Note:  At select sites, a subset of approximately 40 patients (approximately 20 per arm) will 
undergo the above additional PK assessments for carboplatin and etoposide.  The additional 
PK assessments should be taken only if the patient is receiving both carboplatin and 
etoposide at the cycle. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
142/Protocol GO41767, Version 7 
Appendix 3  
Veterans Administration Lung Study Group (VALG) Staging 
System for SCLC 
Stage 
Characteristics 
Limited SCLC 
 Disease confined to one hemithorax, although local extensions 
may be present;  
 No extrathoracic metastases except for possible ipsilateral, 
supraclavicular nodes if they can be included in the same 
portal as the primary tumor; and  
 Primary tumor and regional nodes that can be adequately 
treated and totally encompassed in every portal  
Extensive SCLC 
 Inoperable patients who cannot be classified as having limited 
disease 
SCLC  small cell lung cancer. 
Source:  Micke et al. 2002. 
  
REFERENCE 
Micke P, Faldum A, Metz T, et al. Staging small cell lung cancer: Veterans 
Administration Lung Study Group versus International Association for the Study of 
Lung Cancer—what limits limited disease? Lung Cancer 2002;37:2716. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
143/Protocol GO41767, Version 7 
Appendix 4  
Response Evaluation Criteria in Solid Tumors, Version 1.1 
(RECIST v1.1) 
Selected sections from the Response Evaluation Criteria in Solid Tumors, Version 1.1 
(RECIST v1.1), (Eisenhauer et al. 2009) are presented below, with slight modifications 
from the original publication and the addition of explanatory text as needed for clarity.1 
TUMOR MEASURABILITY 
At baseline, tumor lesions/lymph nodes will be categorized as measurable or 
non-measurable as described below.  All measurable and non-measurable lesions 
should be assessed at screening and at subsequent protocol-specified tumor 
assessment timepoints.  Additional assessments may be performed as clinically 
indicated for suspicion of progression. 
DEFINITION OF MEASURABLE LESIONS 
Tumor Lesions 
Tumor lesions must be accurately measured in at least one dimension (longest diameter 
in the plane of measurement is to be recorded) with a minimum size as follows:  
 
10 mm by computed tomography (CT) or magnetic resonance imaging (MRI) scan 
(CT/MRI scan slice thickness/interval  5 mm) 
 
10-mm caliper measurement by clinical examination (lesions that cannot be 
accurately measured with calipers should be recorded as non-measurable) 
 
20 mm by chest X-ray 
 
Malignant Lymph Nodes 
To be considered pathologically enlarged and measurable, a lymph node must be 
 15 mm in the short axis when assessed by CT scan (CT scan slice thickness 
recommended to be  5 mm).  At baseline and follow-up, only the short axis will be 
measured and followed.  Additional information on lymph node measurement is provided 
below (see "Identification of Target and Non-Target Lesions" and "Calculation of Sum of 
Diameters"). 
 
 
1 For clarity and for consistency within this document, the section numbers and cross-references 
to other sections within the article have been deleted and minor changes have been made. 

Appendix 4: 
Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
144/Protocol GO41767, Version 7 
DEFINITION OF NON-MEASURABLE LESIONS 
Non-measurable tumor lesions encompass small lesions (longest diameter  10 mm or 
pathological lymph nodes with short axis  10 mm but  15 mm) as well as truly 
non-measurable lesions.  Lesions considered truly non-measurable include 
leptomeningeal disease, ascites, pleural or pericardial effusion, inflammatory breast 
disease, lymphangitic involvement of skin or lung, peritoneal spread, and abdominal 
mass/abdominal organomegaly identified by physical examination that is not measurable 
by reproducible imaging techniques. 
SPECIAL CONSIDERATIONS REGARDING LESION MEASURABILITY 
Bone lesions, cystic lesions, and lesions previously treated with local therapy require 
particular comment, as outlined below. 
Bone Lesions: 
 
Technetium-99m bone scans, sodium fluoride positron emission tomography scans, 
and plain films are not considered adequate imaging techniques for measuring bone 
lesions.  However, these techniques can be used to confirm the presence or 
disappearance of bone lesions. 
 
Lytic bone lesions or mixed lytic-blastic lesions with identifiable soft tissue 
components that can be evaluated by cross-sectional imaging techniques, such as 
CT or MRI, can be considered measurable lesions if the soft tissue component 
meets the definition of measurability described above. 
 
Blastic bone lesions are non-measurable. 
 
Cystic Lesions: 
 
Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered malignant lesions (neither measurable nor non-measurable) since they 
are, by definition, simple cysts. 
 
Cystic lesions thought to represent cystic metastases can be considered 
measurable lesions if they meet the definition of measurability described above.  
However, if non-cystic lesions are present in the same patient, these are preferred 
for selection as target lesions. 
 
Lesions with Prior Local Treatment: 
 
Tumor lesions situated in a previously irradiated area or in an area subjected to 
other loco-regional therapy are usually not considered measurable unless there has 
been demonstrated progression in the lesion.   
 

Appendix 4: 
Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
145/Protocol GO41767, Version 7 
METHODS FOR ASSESSING LESIONS 
All measurements should be recorded in metric notation, using calipers if clinically 
assessed.  All baseline evaluations should be performed as close as possible to the 
treatment start and never more than 4 weeks before the beginning of the treatment. 
The same method of assessment and the same technique should be used to 
characterize each identified and reported lesion at baseline and during the study.  
Imaging-based evaluation should always be the preferred option. 
CLINICAL LESIONS 
Clinical lesions will only be considered measurable when they are superficial and 
 10 mm in diameter as assessed using calipers (e.g., skin nodules).  For the case of 
skin lesions, documentation by color photography, including a ruler to estimate the size 
of the lesion, is suggested. 
CHEST X-RAY 
Chest CT is preferred over chest X-ray, particularly when progression is an important 
endpoint, since CT is more sensitive than X-ray, particularly in identifying new lesions.  
However, lesions on chest X-ray may be considered measurable if they are clearly 
defined and surrounded by aerated lung. 
COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING 
SCANS 
Computed tomography is the best currently available and reproducible method to 
measure lesions selected for response assessment.  In this guideline, the definition of 
measurability of lesions on CT scan is based on the assumption that CT slice thickness 
is  5 mm.  When CT scans have slice thickness of  5 mm, the minimum size for a 
measurable lesion should be twice the slice thickness.  Magnetic resonance imaging is 
also acceptable.  
If prior to enrollment it is known that a patient is unable to undergo CT scans with IV 
contrast because of allergy or renal insufficiency, the decision as to whether a 
non-contrast CT or MRI (without IV contrast) will be used to evaluate the patient at 
baseline and during the study should be guided by the tumor type under investigation 
and the anatomic location of the disease.  For patients who develop contraindications to 
contrast after baseline contrast CT is done, the decision as to whether non-contrast CT 
or MRI (enhanced or non-enhanced) will be performed should also be based on the 
tumor type and the anatomic location of the disease, and should be optimized to allow 
for comparison with the prior studies if possible.  Each case should be discussed with 
the radiologist to determine if substitution of these other approaches is possible and, if 
not, the patient should be considered not evaluable from that point forward.  Care must 

Appendix 4: 
Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
146/Protocol GO41767, Version 7 
be taken in measurement of target lesions and interpretation of non-target disease or 
new lesions on a different modality, since the same lesion may appear to have a 
different size using a new modality. 
ENDOSCOPY, LAPAROSCOPY, ULTRASOUND, TUMOR MARKERS, 
CYTOLOGY, HISTOLOGY 
Endoscopy, laparoscopy, ultrasound, tumor markers, cytology, and histology cannot be 
used for objective tumor evaluation. 
ASSESSMENT OF TUMOR BURDEN 
To assess objective response or future progression, it is necessary to estimate the 
overall tumor burden at baseline and use this as a comparator for subsequent 
measurements. 
IDENTIFICATION OF TARGET AND NON-TARGET LESIONS 
When more than one measurable lesion is present at baseline, all lesions up to a 
maximum of five lesions total (and a maximum of two lesions per organ) representative 
of all involved organs should be identified as target lesions and will be recorded and 
measured at baseline.  This means that, for instances in which patients have only one or 
two organ sites involved, a maximum of two lesions (one site) and four lesions (two 
sites), respectively, will be recorded.  Other lesions (albeit measurable) in those organs 
will be considered non-target lesions.   
Target lesions should be selected on the basis of their size (lesions with the longest 
diameter) and should be representative of all involved organs, but in addition should lend 
themselves to reproducible repeated measurements.  It may be the case that, on 
occasion, the largest lesion does not lend itself to reproducible measurement, in which 
circumstance the next largest lesion that can be measured reproducibly should be 
selected. 
Lymph nodes merit special mention since they are normal anatomical structures that 
may be visible by imaging even if not involved by tumor.  As noted above, pathological 
nodes that are defined as measurable and may be identified as target lesions must meet 
the criterion of a short axis of  15 mm by CT scan.  Only the short axis of these nodes 
will contribute to the baseline sum.  The short axis of the node is the diameter normally 
used by radiologists to judge if a node is involved by solid tumor.  Lymph node size is 
normally reported as two dimensions in the plane in which the image is obtained (for CT, 
this is almost always the axial plane; for MRI, the plane of acquisition may be axial, 
sagittal, or coronal).  The smaller of these measures is the short axis.  For example, an 
abdominal node that is reported as being 20 mm  30 mm has a short axis of 20 mm and 
qualifies as a malignant, measurable node.  In this example, 20 mm should be recorded 

Appendix 4: 
Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
147/Protocol GO41767, Version 7 
as the node measurement.  All other pathological nodes (those with short axis  10 mm 
but  15 mm) should be considered non-target lesions.  Nodes that have a short axis of 
 10 mm are considered non-pathological and should not be recorded or followed. 
All lesions (or sites of disease) not selected as target lesions (measurable or 
non-measurable), including pathological lymph nodes, should be identified as non-target 
lesions and should also be recorded at baseline.  Measurements are not required.  It is 
possible to record multiple non-target lesions involving the same organ as a single item 
on the Case Report Form (CRF) (e.g., "multiple enlarged pelvic lymph nodes" or 
"multiple liver metastases"). 
CALCULATION OF SUM OF DIAMETERS 
A sum of the diameters (longest diameter for nonlymph node lesions, short axis for 
lymph node lesions) will be calculated for all target lesions at baseline and at each 
subsequent tumor assessment as a measure of tumor burden. 
Measuring Lymph Nodes 
Lymph nodes identified as target lesions should always have the actual short axis 
measurement recorded (measured in the same anatomical plane as the baseline 
examination), even if the node regresses to  10 mm during the study.  Thus, when 
lymph nodes are included as target lesions, the sum of diameters may not be zero even 
if CR criteria are met, since a normal lymph node is defined as having a short axis of 
 10 mm. 
Measuring Lesions That Become Too Small to Measure 
During the study, all target lesions (lymph node and nonlymph node) recorded at 
baseline should have their actual measurements recorded at each subsequent 
evaluation, even when very small (e.g., 2 mm).  However, sometimes lesions or lymph 
nodes that are recorded as target lesions at baseline become so faint on CT scan that 
the radiologist may not feel comfortable assigning an exact measurement and may 
report them as being too small to measure.  When this occurs, it is important that a value 
be recorded on the CRF, as follows: 
 
If it is the opinion of the radiologist that the lesion has likely disappeared, the 
measurement should be recorded as 0 mm. 
 
If the lesion is believed to be present and is faintly seen but too small to measure, a 
default value of 5 mm should be assigned and "too small to measure" should be 
ticked.  (Note:  It is less likely that this rule will be used for lymph nodes since they 
usually have a definable size when normal and are frequently surrounded by fat, 
such as in the retroperitoneum; however, if a lymph node is believed to be present 
and is faintly seen but too small to measure, a default value of 5 mm should be 

Appendix 4: 
Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
148/Protocol GO41767, Version 7 
assigned in this circumstance as well and "too small to measure" should also be 
ticked). 
 
To reiterate, however, if the radiologist is able to provide an actual measurement, that 
should be recorded, even if it is  5 mm, and in that case "too small to measure" should 
not be ticked. 
Measuring Lesions That Split or Coalesce on Treatment 
When nonlymph node lesions fragment, the longest diameters of the fragmented 
portions should be added together to calculate the sum of diameters.  Similarly, as 
lesions coalesce, a plane between them may be maintained that would aid in obtaining 
maximal diameter measurements of each individual lesion.  If the lesions have truly 
coalesced such that they are no longer separable, the vector of the longest diameter in 
this instance should be the maximum longest diameter for the coalesced lesion. 
EVALUATION OF NON-TARGET LESIONS 
Measurements are not required for non-target lesions, except that malignant lymph node 
non-target lesions should be monitored for reduction to  10 mm in short axis.  
Non-target lesions should be noted at baseline and should be identified as "present" or 
"absent" and (in rare cases) may be noted as "indicative of progression" at subsequent 
evaluations.  In addition, if a lymph node lesion shrinks to a non-malignant size (short 
axis  10 mm), this should be captured on the CRF as part of the assessment of 
non-target lesions. 
RESPONSE CRITERIA 
CRITERIA FOR TARGET LESIONS 
Definitions of the criteria used to determine objective tumor response for target lesions 
are provided below: 
 
CR:  Disappearance of all target lesions 
Any pathological lymph nodes must have reduction in short axis to  10 mm. 
 
PR:  At least a 30% decrease in the sum of diameters of all target lesions, taking as 
reference the baseline sum of diameters, in the absence of CR 
 
Progressive disease (PD):  At least a 20% increase in the sum of diameters of target 
lesions, taking as reference the smallest sum of diameters at prior timepoints 
(including baseline)  
In addition to the relative increase of 20%, the sum of diameters must also 
demonstrate an absolute increase of  5 mm. 
 
Stable disease (SD):  Neither sufficient shrinkage to qualify for CR or PR nor 
sufficient increase to qualify for PD 
 

Appendix 4: 
Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
149/Protocol GO41767, Version 7 
CRITERIA FOR NON-TARGET LESIONS 
Definitions of the criteria used to determine the tumor response for the group of 
non-target lesions are provided below.  While some non-target lesions may actually be 
measurable, they need not be measured and instead should be assessed only 
qualitatively at the timepoints specified in the schedule of activities. 
 
CR:  Disappearance of all non-target lesions and (if applicable) normalization of 
tumor marker level 
All lymph nodes must be non-pathological in size ( 10 mm short axis). 
 
Non-CR/Non-PD:  Persistence of one or more non-target lesions and/or 
(if applicable) maintenance of tumor marker level above the normal limits 
 
PD:  Unequivocal progression of existing non-target lesions 
 
SPECIAL NOTES ON ASSESSMENT OF PROGRESSION OF NON-TARGET 
LESIONS 
Patients with Measurable and Non-Measurable Disease 
For patients with both measurable and non-measurable disease to achieve unequivocal 
progression on the basis of the non-target lesions, there must be an overall level of 
substantial worsening in non-target lesions in a magnitude that, even in the presence of 
SD or PR in target lesions, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy.  A modest increase in the size of one or more non-target 
lesions is usually not sufficient to qualify for unequivocal progression status.  The 
designation of overall progression solely on the basis of change in non-target lesions in 
the face of SD or PR in target lesions will therefore be extremely rare. 
The appearance of new malignant lesions denotes disease progression; therefore, some 
comments on detection of new lesions are important.  There are no specific criteria for 
the identification of new radiographic lesions; however, the finding of a new lesion 
should be unequivocal, that is, not attributable to differences in scanning technique, 
change in imaging modality, or findings thought to represent something other than tumor 
(for example, some "new" bone lesions may be simply healing or flare of preexisting 
lesions).  This is particularly important when the patient's baseline lesions show PR or 
CR.  For example, necrosis of a liver lesion may be reported on a CT scan report as a 
"new" cystic lesion, which it is not. 
A lesion identified during the study in an anatomical location that was not scanned at 
baseline is considered a new lesion and will indicate disease progression. 
If a new lesion is equivocal, for example because of its small size, continued therapy and 
follow-up evaluation will clarify if it represents truly new disease.  If repeat scans confirm 

Appendix 4: 
Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
150/Protocol GO41767, Version 7 
there is definitely a new lesion, progression should be declared using the date of the 
initial scan. 
CRITERIA FOR OVERALL RESPONSE AT A SINGLE TIMEPOINT 
Table A4-1 provides a summary of the overall response status calculation at each 
response assessment timepoint for patients who have measurable disease at baseline. 
Table A4-1 Criteria for Overall Response at a Single Timepoint:  Patients 
with Target Lesions (with or without Non-Target Lesions) 
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
Not all evaluated 
No 
PR 
PR 
Non-PD or not all 
evaluated 
No 
PR 
SD 
Non-PD or not all 
evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or no 
PD 
Any 
PD 
Yes or no 
PD 
Any 
Any 
Yes 
PD 
CR  complete response; NE  not evaluable; PD  progressive disease; PR  partial 
response; SD  stable disease. 
  
MISSING ASSESSMENTS AND NOT EVALUABLE DESIGNATION 
When no imaging/measurement is done at all at a particular timepoint, the patient is not 
evaluable at that timepoint.  If measurements are made on only a subset of target 
lesions at a timepoint, usually the case is also considered not evaluable at that 
timepoint, unless a convincing argument can be made that the contribution of the 
individual missing lesions would not change the assigned timepoint response.  This 
would be most likely to happen in the case of PD.  For example, if a patient had a 
baseline sum of 50 mm with three measured lesions and during the study only two 
lesions were assessed, but those gave a sum of 80 mm, the patient will have achieved 
PD status, regardless of the contribution of the missing lesion.  
SPECIAL NOTES ON RESPONSE ASSESSMENT 
Patients with a global deterioration in health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be reported as 
"symptomatic deterioration."  Every effort should be made to document objective 
progression even after discontinuation of treatment.  Symptomatic deterioration is not a 
descriptor of an objective response; it is a reason for stopping study therapy.  The 

Appendix 4: 
Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
151/Protocol GO41767, Version 7 
objective response status of such patients is to be determined by evaluation of target 
and non-target lesions as shown in Table A4-1. 
For equivocal findings of progression (e.g., very small and uncertain new lesions; cystic 
changes or necrosis in existing lesions), treatment may continue until the next scheduled 
assessment.  If at the next scheduled assessment, progression is confirmed, the date of 
progression should be the earlier date when progression was suspected. 
REFERENCE 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumors: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:22847. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
152/Protocol GO41767, Version 7 
Appendix 5  
EORTC QLQ-C30 
Do not reproduce or distribute.  The Sponsor will provide 
sites with all instruments to be completed in this study. 
 

Appendix 5: 
EORTC QLQ-C30 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
153/Protocol GO41767, Version 7 
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
156/Protocol GO41767, Version 7 
Appendix 8  
EuroQol EQ-5D-5L 
Do not reproduce or distribute.  The Sponsor will provide 
sites with all instruments to be completed in this study. 
 

Appendix 8: 
EuroQol EQ-5D-5L 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
157/Protocol GO41767, Version 7 

Appendix 8: 
EuroQol EQ-5D-5L 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
158/Protocol GO41767, Version 7 
 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
159/Protocol GO41767, Version 7 
Appendix 9  
Eastern Cooperative Oncology Group Performance Status Scale 
Grade 
Description 
0 
Fully active, able to carry on all predisease 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 
  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
160/Protocol GO41767, Version 7 
Appendix 10  
Anaphylaxis Precautions 
These guidelines are intended as a reference and should not supersede pertinent local 
or institutional standard operating procedures. 
REQUIRED EQUIPMENT AND MEDICATION 
The following equipment and medication are needed in the event of a suspected 
anaphylactic reaction during study treatment infusion: 
 
Monitoring devices:  ECG monitor, blood pressure monitor, oxygen saturation 
monitor, and thermometer 
 
Oxygen 
 
Epinephrine for subcutaneous, intramuscular, IV, and/or endotracheal administration 
in accordance with institutional guidelines 
 
Antihistamines 
 
Corticosteroids 
 
Intravenous 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: 
1 Stop the study treatment infusion. 
2 Call for additional medical assistance. 
3 Maintain an adequate airway. 
4 Ensure that appropriate monitoring is in place, with continuous ECG and pulse 
oximetry monitoring if possible. 
5 Administer antihistamines, epinephrine, or other medications and IV fluids as 
required by patient status and as directed by the physician in charge. 
6 Continue to observe the patient and document observations. 
 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
161/Protocol GO41767, Version 7 
Appendix 11  
Preexisting Autoimmune Diseases and Immune Deficiencies 
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 are 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, transient autoimmune manifestations of an 
acute infectious disease that resolved upon treatment of the infectious agent are not 
excluded (e.g., acute Lyme arthritis).  Caution should be used when considering 
atezolizumab and tiragolumab for patients who have previously experienced a severe or 
life-threatening skin adverse reaction or pericardial disorder while receiving another 
immunostimulatory anti-cancer agent.  The Medical Monitor is available to advise on any 
uncertainty over autoimmune exclusions. 
Autoimmune Diseases and Immune Deficiencies 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
162/Protocol GO41767, Version 7 
Appendix 12  
Investigational Medicinal Product and Non-Investigational 
Medicinal Product Designations (for Use in European Economic 
Area and United Kingdom) 
Table 12-1 Investigational, Authorized Auxiliary, and Unauthorized 
Auxiliary Medicinal Product Designations for European 
Economic Area 
Product Name 
IMP/AxMP Designation 
Marketing Authorization 
Status in EEA 
Used within Marketing 
Authorization 
Tiragolumab 
(RO7092284) 
IMP (test product) 
Unauthorized 
Not applicable 
Atezolizumab 
(RO5541267) 
IMP (test product) 
Authorized 
No a 
Tiragolumab 
placebo 
IMP (placebo) 
Unauthorized 
Not applicable 
Carboplatin 
Non-Roche AxMP  
(background treatment) 
Authorized 
No a 
Etoposide 
Non-Roche AxMP  
(background treatment) 
Authorized 
No a 
AxMP  auxiliary medicinal product; EEA  European Economic Area; IMP  investigational medicinal 
product. 
a Atezolizumab, carboplatin, and etoposide are approved for the treatment of small cell lung 
cancer, but not in combination with RO7092284. 
  
 
 

Appendix 12:  Investigational Medicinal Product and Non-Investigational Medicinal 
Product Designations (for Use in European Economic Area and United 
Kingdom) 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
163/Protocol GO41767, Version 7 
Table 12-2 Investigational, Authorized Auxiliary, and Unauthorized 
Auxiliary Medicinal Product Designations for European 
Economic Area 
Product Name 
IMP/NIMP Designation 
Marketing Authorization 
Status in EEA and UK  
Used within Marketing 
Authorization 
Tiragolumab 
(RO7092284) 
IMP (test product) 
Unauthorized 
Not applicable 
Atezolizumab 
(RO5541267) 
IMP (test product) 
Authorized 
No a 
Tiragolumab 
placebo 
IMP (placebo) 
Unauthorized 
Not applicable 
Carboplatin 
Non-Roche NIMPb 
(background treatment) 
Authorized 
No a 
Etoposide 
Non-Roche NIMPb 
(background treatment) 
Authorized 
No a 
IMP  investigational medicinal product; NIMP  non-investigational medicinal product; 
EEA  European Economic Area. 
a Atezolizumab, carboplatin, and etoposide are approved for the treatment of small cell lung 
cancer, but not in combination with RO7092284. 
b Carboplatin and etoposide are considered PeIMP in Italy. 

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
164/Protocol GO41767, Version 7 
Appendix 13  
Overall Guidelines for Management of Patients Who Experience 
Adverse Events 
DOSE MODIFICATIONS FOR TIRAGOLUMAB/PLACEBO AND/OR 
ATEZOLIZUMAB 
 
. 
TREATMENT INTERRUPTION FOR TIRAGOLUMAB/PLACEBO AND/OR 
ATEZOLIZUMAB 
See Appendix 14 for risks associated with tiragolumab or atezolizumab and guidelines 
for management of associated adverse events. 
Atezolizumab and tiragolumab/placebo treatment may be temporarily suspended in 
patients experiencing toxicity considered to be related to study treatment. 
 
 
DOSE MODIFICATIONS FOR CHEMOTHERAPY 
Dose modifications for carboplatin and etoposide are permitted for toxicity according to 
the prescribing information and local standard of care. 
Dose modification guidelines are provided below.  Once reduced, the dose cannot be 
increased back to 100%. 
Treatment with carboplatin or etoposide should be discontinued if a patient experiences 
any hematologic or non-hematologic Grade 3 or Grade 4 toxicity after two dose 
reductions or treatment is delayed for more than 
days due to toxicities.  

Appendix 13: Overall Guidelines for Management of Patients Who Experience 
Adverse Events 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
165/Protocol GO41767, Version 7 
HEMATOLOGIC TOXICITY 
At the start of each cycle, the ANC should be  1500/L and the platelet count should be 
 100,000/L.  Treatment could be delayed for up to 
days to allow sufficient time for 
recovery.  Growth factors may be used in accordance with American Society of Clinical 
Oncology and National Comprehensive Cancer Network (NCCN) guidelines (Smith et al. 
2015; NCCN 2019).  Upon recovery, dose adjustments at the start of a subsequent cycle 
will be made on the basis of the lowest platelet and neutrophil values from the previous 
cycle (see Table A13-1). 
In the event that dose adjustments are needed for both ANC and platelets, patients are 
to receive the lower dose. 
Table A13-1 
Chemotherapy Dose Modification for Hematologic Toxicities 
Toxicity a 
Dose 
ANC  500/L and platelets  50,000/L 
75% of previous dose 
Platelets  25,000/L, regardless of ANC 
75% of previous dose 
Platelets  50,000/L with Grade  2 bleeding, regardless of ANC 
50% of previous dose 
ANC  1000/L plus fever of  38.5°C 
75% of previous dose 
a Nadir of prior cycle. 
  
Investigators should be vigilant and alert to early and overt signs of myelosuppression, 
infection, or febrile neutropenia so that these complications can be promptly and 
appropriately managed.  Patients should be made aware of these signs and encouraged 
to seek medical attention at the earliest opportunity. 
If chemotherapy is withheld because of hematologic toxicity, full blood counts (including 
differential WBC) should be obtained weekly until the counts reach the lower limits for 
treatment as outlined.  The treatment can then be resumed. 
No dose reductions are recommended for anemia.  Patients should be supported per the 
investigator’s institution’s guidelines. 
NON-HEMATOLOGIC TOXICITY 
For a non-hematologic toxicity (see Table A13-2), treatment should be delayed for up to 
days until resolution to less than or equal to the patient’s baseline value (or Grade  1 
if the patient did not have that toxicity at baseline).  Dose reductions at the start of the 
subsequent cycle should be made on the basis of non-hematologic toxicities from the 
dose administered in the preceding cycle.  Table A13-2 provides recommended dose 
modifications for non-hematologic toxicities. 

Appendix 13: Overall Guidelines for Management of Patients Who Experience 
Adverse Events 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
166/Protocol GO41767, Version 7 
Table A13-2 
Dose Modifications or Treatment Discontinuation for 
Non-Hematologic Toxicities  
Toxicity 
Adjusted Dose as % 
of Previous Dose a 
Diarrhea 
Grade 3 or 4 b 
75% 
Nausea/vomiting 
Grade 3 or 4 c 
75% 
Neurotoxicity 
Grade 2  
75% 
 
Grade 3 or 4 
50% or permanent 
discontinuation 
Transaminase elevation 
Grade 3 
75% 
 
Grade 4 
Discontinue 
Other  
Grade 3 or 4 
75% 
AUC  area under the concentrationtime curve. 
a If deemed appropriate by the investigator, adjust carboplatin dose to the 
specified percentage of the previous AUC. 
b Grade 3 or 4 diarrhea that occurs on adequate anti-diarrhea medication or 
any grade of diarrhea requiring hospitalization. 
c Despite the use of anti-emetics. 
  
Diarrhea should be controlled with adequate anti-diarrhea medication.  Nausea and/or 
vomiting may be controlled with adequate anti-emetics.  For Grade 3 or 4 neurotoxicity 
chemotherapy should be resumed at 50% of the previous dose upon improvement or 
discontinued immediately (based on investigator’s clinical judgment). 
Suggested recommendations for dose modification of etoposide for renal impairment are 
provided in Table A13-3.  
Table A13-3 
Etoposide Dose Modification for Renal Impairment 
Creatinine clearance 
(mL/min) 
Etoposide Dose 
 50 
100% 
1550 
75% of dose 
  

 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
167/Protocol GO41767, Version 7 
Appendix 14  
Risks Associated with Tiragolumab or Atezolizumab and 
Guidelines for Management of Adverse Events Associated with 
Tiragolumab or Atezolizumab 
Toxicities associated or possibly associated with tiragolumab and/or 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, when clinically indicated. 
Although most immune-mediated adverse events observed with immunomodulatory 
agents have been mild and self-limiting, such events should be recognized early and 
treated promptly to avoid potential major complications.  Discontinuation of 
tiragolumab/placebo and/or atezolizumab may not have an immediate therapeutic effect, 
and in severe cases, immune-mediated toxicities may require acute management with 
topical corticosteroids, systemic corticosteroids, or other immunosuppressive agents.  
Patients and family caregivers should receive timely and up-to-date information about 
immunotherapies, their mechanism of action, and the clinical profile of possible 
immune-related adverse events prior to initiating therapy and throughout treatment 
and survival follow-up.  There should be a high level of suspicion that new symptoms 
are treatment related. 
The following are general recommendations for management of any other adverse 
events that may occur and are not specifically listed in the following subsections.  
 
 
 
 
 

Appendix 14: Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
168/Protocol GO41767, Version 7 
 
The investigator should consider the benefitrisk balance for a given patient 
to further administration of tiragolumab/placebo and/or atezolizumab. 
 
 
 
MANAGEMENT GUIDELINES 
PULMONARY EVENTS 
Pulmonary events may present as new or worsening cough, chest pain, fever, dyspnea, 
fatigue, hypoxia, pneumonitis, and pulmonary infiltrates. 
Patients will be assessed for pulmonary signs and symptoms throughout the study and 
will have computed tomography (CT) scans of the chest performed at every tumor 
assessment.   
All pulmonary events should be thoroughly evaluated for other commonly reported 
etiologies, such as pneumonia or other infection, lymphangitic carcinomatosis, 
pulmonary embolism, heart failure, chronic obstructive pulmonary disease, or pulmonary 
hypertension.  COVID-19 evaluation should be performed per institutional guidelines 
where relevant.  Management guidelines for pulmonary events are provided in 
Table A14-1.

Appendix 14: Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
169/Protocol GO41767, Version 7 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
170/Protocol GO41767, Version 7 
 
HEPATIC EVENTS 
Patients eligible for study treatment must have adequate liver function, as manifested by 
measurements of total bilirubin and hepatic transaminases; liver function will be 
monitored throughout study treatment.  Management guidelines for hepatic events are 
provided in Table A14-2. 
Patients with right upper-quadrant abdominal pain and/or unexplained nausea or 
vomiting should have liver function tests (LFTs) performed immediately and reviewed 
before administration of the next dose of study drug(s). 
For patients with elevated LFTs, concurrent medication, viral hepatitis, and toxic or 
neoplastic etiologies should be considered and addressed, as appropriate. 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
171/Protocol GO41767, Version 7 
 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
172/Protocol GO41767, Version 7 
GASTROINTESTINAL EVENTS 
Management guidelines for diarrhea or colitis are provided in Table A14-3. 
All events of diarrhea or colitis should be thoroughly evaluated for other more common 
etiologies.  For events of significant duration or magnitude or associated with signs of 
systemic inflammation or acute-phase reactants (e.g., increased C-reactive protein, 
platelet count, or bandemia):  Perform sigmoidoscopy (or colonoscopy, if appropriate) 
with colonic biopsy, with three to five specimens for standard paraffin block to check for 
inflammation and lymphocytic infiltrates to confirm colitis diagnosis.  

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
173/Protocol GO41767, Version 7 

Appendix 14: Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
174/Protocol GO41767, Version 7 
ENDOCRINE EVENTS 
Management guidelines for endocrine events are provided in Table A14-4. 
Patients with unexplained symptoms, such as headache, fatigue, myalgias, impotence, 
constipation, or mental status changes, should be investigated for the presence of 
thyroid, pituitary, or adrenal endocrinopathies.  The patient should be referred to an 
endocrinologist if an endocrinopathy is suspected.  Thyroid-stimulating hormone and 
free triiodothyronine and thyroxine levels should be measured to determine whether 
thyroid abnormalities are present.  Pituitary hormone levels and function tests 
(e.g., TSH, growth hormone, luteinizing hormone, follicle-stimulating hormone, 
testosterone, prolactin, adrenocorticotropic hormone [ACTH] levels, and ACTH 
stimulation test) and magnetic resonance imaging (MRI) of the brain (with detailed 
pituitary sections) may help to differentiate primary pituitary insufficiency from primary 
adrenal insufficiency. 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
175/Protocol GO41767, Version 7 
 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
176/Protocol GO41767, Version 7 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
177/Protocol GO41767, Version 7 
  

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
178/Protocol GO41767, Version 7 
OCULAR EVENTS 
An ophthalmologist should evaluate visual complaints (e.g., uveitis, retinal events).  
Management guidelines for ocular events are provided in Table A14-5. 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
179/Protocol GO41767, Version 7 
IMMUNE-MEDIATED CARDIAC EVENTS 
.  Management guidelines for 
cardiac events are provided in Table A14-6. 
IMMUNE-MEDIATED MYOCARDITIS 
Immune-mediated myocarditis should be suspected in any patient presenting with signs 
or symptoms suggestive of myocarditis, including, but not limited to, laboratory 
(e.g., troponin, B-type natriuretic peptide) or cardiac imaging abnormalities, dyspnea, 
chest pain, palpitations, fatigue, decreased exercise tolerance, or syncope.  Myocarditis 
may also be a clinical manifestation of myositis or associated with pericarditis (see 
section on immune-mediated pericardial disorders below) and should be managed 
accordingly.  Immune-mediated myocarditis needs to be distinguished from myocarditis 
resulting from infection (commonly viral, e.g., in a patient who reports a recent history of 
gastrointestinal illness), ischemic events, underlying arrhythmias, exacerbation of 
preexisting cardiac conditions, or progression of malignancy.   
 
Patients with signs and symptoms of myocarditis, in the absence of an identified 
alternate etiology, should be treated according to the guidelines in Table A14-6. 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
180/Protocol GO41767, Version 7 
IMMUNE-MEDIATED PERICARDIAL DISORDERS 
Immune-mediated pericarditis should be suspected in any patient presenting with chest 
pain and may be associated with immune-mediated myocarditis (see section on 
immune-mediated myocarditis above). 
 
 
 
 
 
. 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
181/Protocol GO41767, Version 7 
 
INFUSION-RELATED REACTIONS 
 
 
 
 
 
 
Infusion-related reactions are known to occur with the administration of monoclonal 
antibodies and have been reported with tiragolumab and atezolizumab.  These 
reactions, which are thought to be due to release of cytokines and/or other chemical 
mediators, occur within 24 hours of tiragolumab or atezolizumab administration and are 
generally mild to moderate in severity. 
Guidelines for medical management of IRRs during Cycle 1 are provided in Table A14-
7 .  For subsequent cycles, IRRs should be managed according to institutional 
guidelines. 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
182/Protocol GO41767, Version 7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
183/Protocol GO41767, Version 7 
 
 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
184/Protocol GO41767, Version 7 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
185/Protocol GO41767, Version 7 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
186/Protocol GO41767, Version 7 
  
PANCREATIC EVENTS 
The differential diagnosis of acute abdominal pain should include pancreatitis.  
Appropriate workup should include an evaluation for ductal obstruction, as well as serum 
amylase and lipase tests.  Management guidelines for pancreatic events, including 
pancreatitis, are provided in Table A14-9. 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
187/Protocol GO41767, Version 7 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
188/Protocol GO41767, Version 7 
 
DERMATOLOGIC EVENTS 
 
 
 
 
 
 Management guidelines for dermatologic events are 
provided in Table A14-10. 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
189/Protocol GO41767, Version 7 
.

Appendix 14: Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
190/Protocol GO41767, Version 7 
NEUROLOGIC DISORDERS 
Patients may present with signs and symptoms of sensory and/or motor neuropathy.  
Diagnostic workup is essential for an accurate characterization to differentiate between 
alternative etiologies.

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
191/Protocol GO41767, Version 7 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
192/Protocol GO41767, Version 7 
IMMUNE-MEDIATED MENINGOENCEPHALITIS 
Immune-mediated meningoencephalitis should be suspected in any patient presenting 
with signs or symptoms suggestive of meningitis or encephalitis, including, but not 
limited to, headache, neck pain, confusion, seizure, motor or sensory dysfunction, and 
altered or depressed level of consciousness.  Encephalopathy from metabolic or 
electrolyte imbalances needs to be distinguished from potential meningoencephalitis 
resulting from infection (bacterial, viral, or fungal) or progression of malignancy, or 
secondary to a paraneoplastic process.   
All patients being considered for meningoencephalitis should be urgently evaluated with 
a CT scan and/or MRI scan of the brain to evaluate for metastasis, inflammation, or 
edema.  If deemed safe by the treating physician, a lumbar puncture should be 
performed, and a neurologist should be consulted. 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
193/Protocol GO41767, Version 7 
Patients with signs and symptoms of meningoencephalitis, in the absence of an 
identified alternate etiology, should be treated according to the guidelines in 
Table A14--13. 
RENAL EVENTS 
Eligible patients must have adequate renal function.  Renal function, including serum 
creatinine, should be monitored throughout study treatment.  Patients with abnormal 
renal function should be evaluated and treated for other more common etiologies 
(including prerenal and postrenal causes, and concomitant medications, such as non-
steroidal anti-inflammatory drugs).  Refer the patient to a renal specialist if clinically 
indicated.  A renal biopsy may be required to enable a definitive diagnosis and 
appropriate treatment. 
Patients with signs and symptoms of nephritis, in the absence of an identified alternate 
etiology, should be treated according to the guidelines in Table A14--14. 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
194/Protocol GO41767, Version 7 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
196/Protocol GO41767, Version 7 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
197/Protocol GO41767, Version 7 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
198/Protocol GO41767, Version 7 

Appendix 14: Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or Atezolizumab 
 
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
199/Protocol GO41767, Version 7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
200/Protocol GO41767, Version 7 
 
 
 
REFERENCES 
Adashek ML, Feldman M. Cytokine release syndrome resulting from antiprogrammed 
death-1 antibody: raising awareness among community oncologist. J Oncol 
Practice 2019;15:5024. 
La Rosée P. Treatment of hemophagocytic lymphohistiocytosis in adults. Hematology 
Am Soc Hematol Educ Protram 2015;1:1906. 
La Rosée P, Horne A, Hines M, et al. Recommendations for the management of 
hemophagocytic lymphohistiocytosis in adults. Blood 2019;133:246577. 
McClain KL, Eckstein O. Clinical features and diagnosis of hemophagocytic 
lymphohistiocytosis. Up to Date [resouce on the Internet]. 2014 [updated 
29 October 2018; cited: 17 May 2019]. Available from: 
https://www.uptodate.com/contents/clinical-features-and-
diagnosis-of-hemophagocytic-lymphohistiocytosis. 
Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for 
monocytes and macrophages. Nat Rev Immunol 2020;20:35562. 
Riegler LL, Jones GP, Lee DW. Current approaches in the grading and management of 
cytokine release syndrome after chimeric antigen receptor T-cell therapy. Ther Clin 
Risk Manag 2019;15:32335. 

Appendix 14:  Risks Associated with Tiragolumab or Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Tiragolumab or 
Atezolizumab 
  
Tiragolumab and Atezolizumab—F. Hoffmann-La Roche Ltd 
201/Protocol GO41767, Version 7 
Rotz SJ, Leino D, Szabo S, et al. Severe cytokine release syndrome in a patient 
receiving PD-1-directed therapy. Pediatr Blood Cancer 2017;64:e26642. 
Schram AM, Berliner N. How I treat hemophagocytic lymphohistiocytosis in the adult 
patient. Blood 2015;125:290814. 

Signature Page for Protocol - GO41767 - TIRAGOLUMAB - v7 - Global/Core - Publish
System identifier: RIM-CLIN-515070
Approval Task
Company Signatory
11-Dec-2023 14:21:56 GMT+0000