A Phase III, Open-Label, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Best Supportive Care Following Adjuvant Cisplatin-Based Chemotherapy in Patients With Completely Resected Stage IB-IIIA Non-Small Cell Lung Cancer
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Sponsor: Hoffmann-La Roche



CONFIDENTIAL 
This clinical study is being sponsored globally by F. Hoffmann-La Roche Ltd of Basel, 
Switzerland.  
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any unpublished data, is the property of F. Hoffmann-La Roche Ltd (or under its control) and therefore 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. 
Atezolizumab
F. Hoffmann-La Roche Ltd 
Protocol GO29527, Version 12 
PROTOCOL 
PROTOCOL TITLE: 
A PHASE III, OPEN-LABEL, RANDOMIZED STUDY 
TO INVESTIGATE THE EFFICACY AND SAFETY OF 
ATEZOLIZUMAB (ANTI PD-L1 ANTIBODY) 
COMPARED WITH BEST SUPPORTIVE CARE 
FOLLOWING ADJUVANT CISPLATIN-BASED 
CHEMOTHERAPY IN PATIENTS WITH 
COMPLETELY RESECTED STAGE IB IIIA 
NON SMALL CELL LUNG CANCER 
PROTOCOL NUMBER: GO29527 
STUDY NAME: 
IMpower010 
VERSION NUMBER: 
12 
TEST PRODUCT: 
Atezolizumab (MPDL3280A; RO5541267) 
REGULATORY 
AGENCY IDENTIFIER 
NUMBERS: 
IND Number:  117296  
EudraCT Number:  2014-003205-15 
EU CT Number: 2023-505981-26-00 
NCT Number:  NCT02486718 
PS ID:  RD002503 (SP142), RD005400 (SP263) 
CV ID:  CIV-23-04-042935 (SP142),  
CIV-23-04-042936 (SP263)
SPONSOR
AND LEGAL 
REGISTERED  
ADDRESS: 
F. Hoffmann La Roche Ltd
Grenzacherstrasse 124
4058 Basel, Switzerland
APPROVAL: 
See electronic signature and date stamp on the final page 
of this document. 

Atezolizumab
F. Hoffmann-La Roche Ltd 
2/Protocol GO29527, Version 12 
PROTOCOL HISTORY 
Protocol 
Associated Region-Specific Protocol 
Version
Date Final 
Region 
Version
Date Final 
12 
See electronic signature 
and date stamp on the 
final page of this 
document. 
 
 
 
11 
16 February 2023 
10 
3 February 2022 
9 
17 April 2021 
 
 
 
8 
11 February 2020 
 
 
 
7 
30 October 2018 
 
 
 
5 
29 June 2016 
VHP 
6 
2 March 2018 
4 
5 October 2015 
 
 
 
3 
5 September 2015 
 
 
 
2 
8 June 2015 
 
 
 
1 
1 April 2015 
 
 
 
 

Atezolizumab
F. Hoffmann-La Roche Ltd 
3/Protocol GO29527, Version 12 
PROTOCOL AMENDMENT, VERSION 12: 
RATIONALE 
Protocol GO29527 has been amended primarily to update the risks and management 
guidelines for atezolizumab to align with the latest Atezolizumab Investigator's Brochure 
Version 20 and to reduce the requirements of the study for ongoing patients after the final 
disease free survival (DFS) analysis is conducted.  Changes to the protocol, along with a 
rationale for each change, are summarized below: 
 
The requirement for tumor assessments/disease status assessments has been 
removed following the completion of the final DFS analysis to reduce burden on 
patients and investigators.  After this, any recurrence or new primary non-small cell 
lung cancer (NSCLC) or new primary non-NSCLC malignancy diagnosed as a result 
of local standard of care is to be recorded in the electronic data capture 
system(Sections 3.1, 4.5.5, and 4.6.4.1, and Appendix 2). 
 
The requirement for biomarker sample collection at recurrence has been removed 
following the final DFS analysis to reduce burden on patients and investigators 
(Sections 3.1 and 4.5.8.1 and Appendices 2 and 3). 
 
Text in Section 4.3.6 has been modified to indicate that the Sponsor does not 
currently have any plans to provide atezolizumab or any other study treatments to 
participants who have completed the study and that the Sponsor may evaluate 
whether to continue providing atezolizumab in accordance with the Roche Global 
Policy on Continued Access to Investigational Medicinal Products. 
 
The frequency for the collection of survival follow-up information has been updated 
from 3 months or more often to 6 months or more often to reduce the burden on 
patients and investigators during long term survival follow-up (Section 4.6.4.4 and 
Appendix 2). 
 
It has been made explicit that expedited safety reports are notified to EudraVigilance 
(Section 5.7). 
 
The medical term "Wegener granulomatosis" has been replaced by the term 
"granulomatosis with polyangiitis" to align with the updated preferred term in MedDRA 
(Appendix 6). 
 
The adverse event management guidelines have been streamlined by removing 
standard of care information and restructured, for consistency with regulatory 
guidelines and industry standards (Appendix 9). 
 
The adverse event management guidelines have been updated to align with the 
9). 
 
The list of investigational, non-investigational, and auxiliary medicinal products has 
been corrected to include cisplatin and additional details for the non-investigational 
and auxiliary medicinal products (Appendix 10). 
 
Additional minor changes have been made to improve clarity and consistency.  
Substantive new information appears in italics.  This amendment represents cumulative 
changes to the original protocol. 

Atezolizumab
F. Hoffmann-La Roche Ltd 
4/Protocol GO29527, Version 12 
 
TABLE OF CONTENTS 
PROTOCOL AMENDMENT ACCEPTANCE FORM .......................................... 14 
PROTOCOL SYNOPSIS .................................................................................... 15 
1. 
BACKGROUND ............................................................................ 21 
1.1 
Adjuvant Treatment Options for Patients with Surgically 
Resected Stage IB IIIA NSCLC .............................................. 21 
1.2 
Background on Atezolizumab (MPDL3280A) .......................... 23 
1.2.1 
Summary of Nonclinical Studies .............................................. 24 
1.3 
Clinical Experience with Atezolizumab .................................... 24 
1.3.1 
Ongoing Clinical Studies .......................................................... 24 
1.3.2 
Clinical Safety .......................................................................... 25 
1.3.2.1 
Single-Agent Clinical Safety in Patients with NSCLC in 
Study PCD4989g ..................................................................... 25 
1.3.2.2 
Single-Agent Clinical Safety in Patients with NSCLC in the 
Study GO28753 ....................................................................... 27 
1.3.2.3 
Single-Agent Clinical Safety in Patients with Non Small 
Cell Lung Cancer in Study GO28754 (BIRCH) ........................ 28 
1.3.2.4 
Immune-Mediated Adverse Events .......................................... 28 
1.3.3 
Clinical Activity ......................................................................... 29 
1.3.3.1 
Single-Agent Clinical Activity in Patients with NSCLC in 
Study PCD4989g ..................................................................... 29 
1.3.3.2 
Single-Agent Clinical Activity in Patients with NSCLC in 
Study GO28753 ....................................................................... 30 
1.3.3.3 
Single-Agent Clinical Activity in Patients with Non Small 
Cell Lung Cancer in Study GO28754 (BIRCH) ........................ 32 
1.3.4 
Clinical Pharmacokinetics and Immunogenicity ....................... 33 
1.3.5 
Additional Studies with Atezolizumab ...................................... 33 
1.4 
Study Rationale and Benefit Risk Assessment ....................... 33 
2. 
OBJECTIVES ................................................................................ 36 
2.1 
Efficacy Objectives .................................................................. 36 
2.1.1 
Primary Efficacy Objective ....................................................... 36 
2.1.2 
Secondary Efficacy Objectives ................................................ 36 
2.2 
Safety Objectives ..................................................................... 36 
2.3 
Pharmacokinetic Objective ...................................................... 37 

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2.4 
Exploratory Objectives ............................................................. 37 
3. 
STUDY DESIGN ........................................................................... 37 
3.1 
Description of the Study ........................................................... 37 
3.1.1 
Independent Review Facility .................................................... 40 
3.2 
End of Study and Duration of Participation .............................. 40 
3.3 
Rationale for Study Design ...................................................... 41 
3.3.1 
Rationale for Testing Atezolizumab in PD-L1 Unselected 
Patients with NSCLC ............................................................... 41 
3.3.2 
Rationale for Best Supportive Care Arm (Arm B) ..................... 41 
3.3.3 
Rationale for Atezolizumab Dosage and Treatment 
Duration ................................................................................... 41 
3.3.4 
Rationale for Collection of Resected Tumor Specimens .......... 42 
3.3.5 
Rationale for Blood Biomarker Assessments ........................... 43 
3.3.6 
Rationale for the Collection of Tumor Specimens at 
Disease Recurrence and/or Confirmation of a New Primary 
NSCLC .................................................................................... 43 
3.4 
Efficacy Outcome Measures .................................................... 44 
3.4.1 
Primary Efficacy Outcome Measure ........................................ 44 
3.4.2 
Secondary Efficacy Outcome Measures .................................. 44 
3.5 
Safety Outcome Measures ...................................................... 44 
3.6 
Pharmacokinetic Outcome Measures ...................................... 44 
3.7 
Exploratory Outcome Measures .............................................. 45 
4. 
MATERIALS AND METHODS ...................................................... 45 
4.1 
Patients .................................................................................... 45 
4.1.1 
Inclusion Criteria ...................................................................... 45 
4.1.1.1 
Inclusion Criteria for Enrollment Phase .................................... 45 
4.1.1.2 
Inclusion Criteria for Randomized Phase ................................. 47 
4.1.2 
Exclusion Criteria ..................................................................... 48 
4.1.2.1 
Exclusion Criteria for Enrollment Phase .................................. 48 
4.1.2.2 
Exclusion Criteria for Randomized Phase ............................... 50 
4.2 
Method of Treatment Assignment and Blinding ....................... 51 
4.3 
Study Treatment ...................................................................... 52 
4.3.1 
Cisplatin-Based Chemotherapy Regimens .............................. 52 

Atezolizumab
F. Hoffmann-La Roche Ltd 
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4.3.2 
Formulation, Packaging, and Handling of Cisplatin-Based 
Chemotherapy ......................................................................... 52 
4.3.2.1 
Cisplatin ................................................................................... 52 
4.3.2.2 
Vinorelbine ............................................................................... 53 
4.3.2.3 
Docetaxel ................................................................................. 53 
4.3.2.4 
Gemcitabine ............................................................................. 53 
4.3.2.5 
Pemetrexed ............................................................................. 54 
4.3.3 
Dosage, Administration, and Supportive Care 
Recommendations for Cisplatin-Based Chemotherapy ........... 54 
4.3.3.1 
Chemotherapy Regimen 1:  Cisplatin/Vinorelbine ................... 54 
4.3.3.2 
Chemotherapy Regimen 2:  Cisplatin/Docetaxel ..................... 55 
4.3.3.3 
Chemotherapy Regimen 3:  Cisplatin/Gemcitabine ................. 56 
4.3.3.4 
Chemotherapy Regimen 4:  Cisplatin/Pemetrexed 
(For Patients with Non-Squamous Histology) .......................... 56 
4.3.3.5 
Supportive Care Recommendations for Cisplatin-Based 
Chemotherapy ......................................................................... 57 
4.3.4 
Atezolizumab ........................................................................... 57 
4.3.4.1 
Atezolizumab Formulation, Packaging, and Handling .............. 57 
4.3.4.2 
Atezolizumab Dosage, Administration, and Compliance ......... 57 
4.3.5 
Investigational Medicinal Product Accountability ..................... 58 
4.3.6 
Post-Study Access to Atezolizumab ........................................ 59 
4.4 
Concomitant Therapy .............................................................. 59 
4.4.1 
Contraindications and Use of Concomitant Medications 
with Cisplatin-Based Chemotherapy Regimens ....................... 59 
4.4.1.1 
Cisplatin ................................................................................... 59 
4.4.1.2 
Docetaxel ................................................................................. 59 
4.4.1.3 
Vinorelbine ............................................................................... 60 
4.4.1.4 
Gemcitabine ............................................................................. 60 
4.4.1.5 
Pemetrexed ............................................................................. 61 
4.4.2 
Permitted Therapy with Atezolizumab ..................................... 61 
4.4.3 
Cautionary Therapy for Atezolizumab-Treated Patients .......... 62 
4.4.4 
Prohibited Therapy .................................................................. 62 
4.5 
Study Assessments ................................................................. 63 
4.5.1 
Informed Consent Forms and Screening Log .......................... 63 

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4.5.2 
Medical History and Demographic Data .................................. 64 
4.5.3 
Physical Examinations ............................................................. 64 
4.5.4 
Vital Signs ................................................................................ 64 
4.5.5 
Tumor and Response Evaluations ........................................... 64 
4.5.6 
Laboratory, Biomarker, and Other Biological Samples ............ 65 
4.5.7 
Resected Tumor Tissue Samples ............................................ 67 
4.5.8 
Resected Tumor Tissue Samples for Screening ...................... 67 
4.5.8.1 
Tumor Samples at the Time of Disease Recurrence ............... 68 
4.5.8.2 
Tumor Samples at Other Timepoints ....................................... 68 
4.5.8.3 
Use and Storage of Remaining Samples from Study-
Related Procedures ................................................................. 69 
4.5.9 
Anti-Therapeutic Antibody Testing (Atezolizumab-Treated 
Patients Only) .......................................................................... 69 
4.5.10 
Electrocardiogram .................................................................... 69 
4.5.11 
Optional Tumor and Blood Samples for Roche Clinical 
Repository (Optional Future Research) ................................... 70 
4.5.11.1 
Overview of the Roche Clinical Repository .............................. 70 
4.5.11.2 
Approval by the Institutional Review Board or 
Ethics Committee ..................................................................... 70 
4.5.11.3 
Optional Samples for Roche Clinical Repository ..................... 70 
4.5.11.4 
Confidentiality .......................................................................... 71 
4.5.11.5 
Consent to Participate in the Roche Clinical Repository .......... 72 
4.5.11.6 
Withdrawal from the Roche Clinical Repository ....................... 72 
4.5.11.7 
Monitoring and Oversight ......................................................... 72 
4.6 
Timing of Study Assessments .................................................. 73 
4.6.1 
Screening and Pre-Treatment Assessments ........................... 73 
4.6.2 
Assessments during Treatment/Best Supportive Care 
Period ...................................................................................... 73 
4.6.3 
Assessments at Treatment Discontinuation Visit ..................... 74 
4.6.4 
Follow-Up Assessments .......................................................... 75 
4.6.4.1 
Ongoing Tumor Assessments .................................................. 75 
4.6.4.2 
Adverse Events ........................................................................ 75 
4.6.4.3 
Anti-Therapeutic Antibody and Pharmacokinetic 
Assessments ........................................................................... 76 
4.6.4.4 
Survival and Subsequent Anti-Cancer Therapy ....................... 76 

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4.7 
Patient, Study, and Site Discontinuation .................................. 76 
4.7.1 
Patient Discontinuation ............................................................ 76 
4.7.2 
Discontinuation from Study Treatment ..................................... 77 
4.7.3 
Study and Site Discontinuation ................................................ 77 
5. 
ASSESSMENT OF SAFETY ......................................................... 78 
5.1 
Safety Plan .............................................................................. 78 
5.1.1 
Risks Associated with Atezolizumab ........................................ 78 
5.1.2 
Risk and Side Effects Associated with Administration of 
Cisplatin-Based Chemotherapy ............................................... 79 
5.1.2.1 
Cisplatin ................................................................................... 79 
5.1.2.2 
Vinorelbine ............................................................................... 79 
5.1.2.3 
Docetaxel ................................................................................. 79 
5.1.2.4 
Gemcitabine ............................................................................. 80 
5.1.2.5 
Pemetrexed ............................................................................. 80 
5.1.3 
General Plan to Manage Safety Concerns .............................. 81 
5.1.4 
Management of Chemotherapy-Specific Adverse Events ........ 81 
5.1.4.1 
Cisplatin Dose Modifications, Treatment Delays, or 
Treatment Discontinuation and Management of Specific 
Adverse Events ........................................................................ 81 
5.1.4.2 
Pemetrexed Dose Modifications, Treatment Delays or 
Treatment Discontinuation, and Management of Specific 
Adverse Events ........................................................................ 83 
5.1.4.3 
Gemcitabine Dose Modifications, Treatment Delays or 
Treatment Discontinuation, and Management of Specific 
Adverse Events ........................................................................ 85 
5.1.4.4 
Docetaxel Dose Modification and Management of Specific 
Adverse Events ........................................................................ 87 
5.1.4.5 
Vinorelbine Dose Modification and Management of 
Specific Adverse Events .......................................................... 89 
5.2 
Safety Parameters and Definitions .......................................... 92 
5.2.1 
Adverse Events ........................................................................ 92 
5.2.2 
Serious Adverse Events (Immediately Reportable to the 
Sponsor) .................................................................................. 92 
5.2.3 
Non-Serious Adverse Events of Special Interest 
(Immediately Reportable to the Sponsor) ................................ 93 

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5.3 
Methods and Timing for Capturing and Assessing 
Safety Parameters ................................................................... 94 
5.3.1 
Adverse Event Reporting Period .............................................. 94 
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............................ 95 
5.3.5 
Procedures for Recording Adverse Events .............................. 96 
5.3.5.1 
Diagnosis versus Signs and Symptoms ................................... 96 
5.3.5.2 
Infusion-Related Reactions ...................................................... 96 
5.3.5.3 
Adverse Events That Are Secondary to Other Events ............. 96 
5.3.5.4 
Persistent or Recurrent Adverse Events .................................. 97 
5.3.5.5 
Abnormal Laboratory Values ................................................... 97 
5.3.5.6 
Abnormal Vital Sign Values ..................................................... 98 
5.3.5.7 
Abnormal Liver Function Tests ................................................ 98 
5.3.5.8 
Deaths ..................................................................................... 99 
5.3.5.9 
Preexisting Medical Conditions ................................................ 99 
5.3.5.10 
Lack of Efficacy or NSCLC Recurrence ................................. 100 
5.3.5.11 
Hospitalization or Prolonged Hospitalization .......................... 100 
5.3.5.12 
Adverse Events Associated with an Overdose ...................... 101 
5.4 
Immediate Reporting Requirements from Investigator to 
Sponsor ................................................................................. 101 
5.4.1 
Emergency Medical Contacts ................................................ 101 
5.4.2 
Reporting Requirements for Serious Adverse Events and 
Non-Serious Adverse Events of Special Interest ................... 102 
5.4.2.1 
Events That Occur Prior to Study Treatment Initiation ........... 102 
5.4.2.2 
Events That Occur After Study Treatment Initiation ............... 102 
5.4.3 
Reporting Requirements for Pregnancies .............................. 102 
5.4.3.1 
Pregnancies in Female Patients ............................................ 102 
5.4.3.2 
Pregnancies in Female Partners of Male Patients ................. 103 
5.4.3.3 
Abortions................................................................................ 103 
5.4.3.4 
Congenital Anomalies/Birth Defects ...................................... 104 
5.5 
Follow-Up of Patients after Adverse Events........................... 104 
5.5.1 
Investigator Follow-Up ........................................................... 104 
5.5.2 
Sponsor Follow-Up ................................................................ 104 

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5.6 
Post-Study Adverse Events ................................................... 104 
5.7 
Expedited Reporting to Health Authorities, Investigators, 
Institutional Review Boards, and Ethics Committees ............. 105 
6. 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN ....... 105 
6.1 
Determination of Sample Size ............................................... 106 
6.2 
Summaries of Conduct of Study ............................................ 108 
6.3 
Summaries of Treatment Group Comparability ...................... 109 
6.4 
Efficacy Analyses ................................................................... 109 
6.4.1 
Primary Efficacy Endpoint ...................................................... 109 
6.4.2 
Secondary Efficacy Endpoints ............................................... 110 
6.4.2.1 
Overall Survival Analysis ....................................................... 110 
6.4.2.2 
Disease-Free Survival 3-Year and 5-Year Landmark 
Analysis ................................................................................. 110 
6.4.2.3 
Disease-Free Survival Analysis in Additional PD-L1 
Subpopulation Defined by the Anti PD-L1 (SP263) IHC 
Assay ..................................................................................... 110 
6.5 
Safety Analyses ..................................................................... 111 
6.6 
Pharmacokinetic Analyses ..................................................... 111 
6.7 
Exploratory Analyses ............................................................. 112 
6.7.1 
Exploratory Analyses of Disease-Free Survival and Overall 
Survival .................................................................................. 112 
6.7.2 
Exploratory Analyses of Biomarkers ...................................... 113 
6.8 
Interim Analyses .................................................................... 113 
6.8.1 
Planned Interim Analysis for Disease-Free Survival .............. 113 
6.8.2 
Planned Interim Analyses for Overall Survival ....................... 114 
7. 
DATA COLLECTION AND MANAGEMENT ............................... 115 
7.1 
Data Quality Assurance ......................................................... 115 
7.2 
Electronic Case Report Forms ............................................... 115 
7.3 
Source Data Documentation .................................................. 116 
7.4 
Use of Computerized Systems .............................................. 116 
7.5 
Retention of Records ............................................................. 117 
8. 
ETHICAL CONSIDERATIONS .................................................... 117 
8.1 
Compliance with Laws and Regulations ................................ 117 
8.2 
Informed Consent .................................................................. 117 

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8.3 
Institutional Review Board or Ethics Committee ..................... 119 
8.4 
Confidentiality ........................................................................... 119 
8.5 
Financial Disclosure ................................................................. 120 
9. 
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION ........................................................................ 120 
9.1 
Study Documentation ............................................................... 120 
9.2 
Protocol Deviations................................................................... 120 
9.3 
Site Inspections ........................................................................ 120 
9.4 
Administrative Structure ........................................................... 120 
9.5 
Publication of Data and Protection of Trade Secrets .............. 121 
9.6 
Protocol Amendments .............................................................. 122 
10. 
REFERENCES ............................................................................... 123 
 
LIST OF TABLES
Table 1 
Overview of Adjuvant Chemotherapy Studies .............................. 22 
Table 2 
Study PCD4989g:  Adverse Events with Frequency  10% of
Patients for All Grades ................................................................... 26
Table 3 
Adverse Events Reported in at Least 10% of Patients in
Study GO28753 ............................................................................. 27
Table 4 
Adverse Events Reported in Study GO28754 (BIRCH) ............... 28 
Table 5 
Patients with NSCLC in Study PCD4989g:
Investigator-Assessed Confirmed Objective Response Rate
by Tumor PD-L1 Expression, Duration of Response, and
6-Month Progression-Free Survival Rates (per RECIST
Version 1.1) .................................................................................... 30
Table 6 
Efficacy Results in Study GO28753:  Intent-to-Treat
Population ...................................................................................... 31
Table 7 
Study GO28753 Efficacy Results by Combination PD-L1 
Diagnostic 
Subgroups 
with 
Complementary 
Comparison 
Subgroupings:  Intent-to-Treat Population .................................... 32
Table 8 
Study GO28754 (BIRCH) Independent Review Facility-
Assessed Overall Response Rate:  Treated Population .............. 32
Table 9 
Cisplatin-Based Chemotherapy Regimens ................................... 52
Table 10 
Administration of First and Subsequent Infusions
of Atezolizumab ............................................................................. 58
Table 11 
Cisplatin Dose Modifications for Non-Hematologic Toxicities 
(Excluding Neurotoxicity and Nephrotoxicity) ............................... 82
Table 12 
Cisplatin Dose Modifications or Treatment Discontinuation
for Associated Neurotoxicity .......................................................... 83
Table 13 
Pemetrexed Dose Modifications for Hematologic Toxicities ........ 84

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Table 14 
Pemetrexed Dose Modifications for Non-Hematologic 
Toxicities ..................................................................................... 85 
Table 15 
Gemcitabine Dose Modifications or Treatment Delays for 
Hematologic Toxicities on Day 1 ................................................. 86 
Table 16 
Gemcitabine Dose Modifications or Treatment Delays for 
Hematologic Toxicities on Day 8 ................................................. 86 
Table 17 
Gemcitabine Dose Modifications, Treatment Delays, or 
Treatment Discontinuation and Patient Management for 
Grade 2, 3, or 4 Non-Hematologic Toxicities .............................. 87 
Table 18 
Guidelines for Management of Specific Docetaxel-Related 
Adverse Events ........................................................................... 88 
Table 19 
Guidelines for Management of Hepatotoxicity in Patients 
Treated with Docetaxel ............................................................... 88 
Table 20 
Guidelines for the Management of Edema in Patients 
Treated with Docetaxel ............................................................... 89 
Table 21 
Vinorelbine Dose Modifications or Treatment Delays for 
Hematologic Toxicities on Day 1 ................................................. 90 
Table 22 
Vinorelbine Dose Modifications or Treatment Delays for 
Hematologic Toxicities on Day 8 ................................................. 90 
Table 23 
Dose Reduction of Vinorelbine for Hepatic Toxicity .................... 91 
Table 24 
Vinorelbine Dose Reduction for Sensory or Motor 
Neuropathy ................................................................................. 91 
Table 25 
Adverse Event Severity Grading Scale ....................................... 95 
Table 26 
Analysis Timing and Stopping Boundaries for Disease-Free 
Survival ..................................................................................... 114 
Table 27 
Stopping Boundaries for Overall Survival:  Stage IB IIIA 
NSCLC ...................................................................................... 115 
 
 
LIST OF FIGURES 
Figure 1 
Study Schema ............................................................................. 38 
Figure 2 
Overview of the Alpha Control (One-Sided) .............................. 107 
 
 
LIST OF APPENDICES 
Appendix 1 
Schedule of Assessments for Enrollment Phase (Cisplatin-
Based Chemotherapy Administration) ...................................... 128 
Appendix 2 
 Schedule of Assessments for Randomized Phase 
(Atezolizumab or Best Supportive Care) ................................... 131 
Appendix 3 
Anti-Therapeutic Antibody, Biomarker, and Pharmacokinetic 
Sampling Schedule ................................................................... 136 
Appendix 4 
Anti PD-L1 (SP142) Immunohistochemistry ............................. 138 
Appendix 5 
Anti PD-L1 (SP263) Immunohistochemistry ............................. 139 
Appendix 6 
Preexisting Autoimmune Diseases ........................................... 140 

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Appendix 7 
Anaphylaxis Precautions ........................................................... 141 
Appendix 8 
Cockcroft and Gault Formula .................................................... 142 
Appendix 9 
Risks Associated with Atezolizumab and Guidelines for 
Management of Adverse Events Associated with 
Atezolizumab ............................................................................ 143 
Appendix 10 
Investigational, Non-Investigational, and Auxiliary Medicinal 
Product Designations (for Use in European Economic Area 
and United Kingdom) ................................................................ 158 

Atezolizumab
F. Hoffmann-La Roche Ltd 
14/Protocol GO29527, Version 12 
PROTOCOL AMENDMENT ACCEPTANCE FORM 
PROTOCOL TITLE: 
A PHASE III, OPEN-LABEL, RANDOMIZED STUDY 
TO INVESTIGATE THE EFFICACY AND SAFETY OF 
ATEZOLIZUMAB (ANTI PD-L1 ANTIBODY) 
COMPARED WITH BEST SUPPORTIVE CARE 
FOLLOWING ADJUVANT CISPLATIN-BASED 
CHEMOTHERAPY IN PATIENTS WITH 
COMPLETELY RESECTED STAGE IB IIIA 
NON SMALL CELL LUNG CANCER 
PROTOCOL NUMBER: GO29527 
VERSION NUMBER: 
12 
TEST PRODUCT: 
Atezolizumab (MPDL3280A; RO5541267) 
SPONSOR
AND LEGAL 
REGISTERED  
ADDRESS: 
F. Hoffmann La Roche Ltd 
Grenzacherstrasse 124 
4058 Basel, Switzerland 
 
I agree to conduct the study in accordance with the current protocol. 
 
 
 
(print) 
 
 
 
 
 
 
 
Date 
Please retain the signed original copy for your study files.  Please return a copy of the 
form to the Sponsor or their designee.  Contact details will be provided to the 
investigator prior to the start of the study. 
 

 
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PROTOCOL SYNOPSIS 
PROTOCOL TITLE: 
A PHASE III, OPEN-LABEL, RANDOMIZED STUDY TO 
INVESTIGATE THE EFFICACY AND SAFETY OF 
ATEZOLIZUMAB (ANTI PD-L1 ANTIBODY) COMPARED WITH 
BEST SUPPORTIVE CARE FOLLOWING ADJUVANT 
CISPLATIN-BASED CHEMOTHERAPY IN PATIENTS WITH 
COMPLETELY RESECTED STAGE IB IIIA NON SMALL CELL 
LUNG CANCER 
REGULATORY AGENCY 
IDENTIFIER NUMBERS: 
IND Number:  117296  
EudraCT Number:  2014-003205-15 
EU CT Number:  2023-505981-26-00 
NCT Number: NCT02486718 
PS ID:  RD002503 (SP142), RD005400 (SP263) 
CIV ID:  CIV-23-04-042935 (SP142), CIV-23-04-042936 (SP263) 
 
STUDY RATIONALE 
The purpose of this study is to assess the efficacy and safety of atezolizumab, (MPDL3280A 
[anti programmed death-ligand 1 [PD-L1] antibody]).  This trial will enroll patients with Stage 
IB Stage IIIA NSCLC following resection and adjuvant chemotherapy.  Given the relatively poor 
prognosis and limited treatment options for these patients, this population is considered 
appropriate for trials of novel therapeutic candidates. 
OUTCOME MEASURES 
EFFICACY OUTCOME MEASURES 
Primary Efficacy Outcome Measure 
The primary efficacy outcome measure for this study is as follows: 
 
DFS, defined as the time from randomization to the date of occurrence of any of the 
following, whichever occurs first: 
 
First recurrence of NSCLC, as determined by the investigator after an integrated 
assessment of radiographic data, biopsy sample results (if available), and clinical status 
 
Occurrence of new primary NSCLC, as assessed by the investigator 
 
Death from any cause 
This efficacy outcome measure will be assessed in the PD-L1 subpopulation (defined as 
 1% 
TC expression by the SP263 IHC assay) within the Stage II-IIIA population, in all randomized 
patients with Stage II-IIIA NSCLC, and in the ITT population. 
 
Secondary Efficacy Outcome Measures 
The secondary efficacy outcome measures for this study are as follows: 
 
OS, defined as the time from randomization to death from any cause, in the ITT population 
 
DFS rates at 3 years and 5 years in the PD-L1 subpopulation (defined as 
 1% TC 
expression by the SP263 IHC assay), in the Stage II IIIA population (i.e., all randomized 
patients with Stage II IIIA NSCLC) and in the ITT population 
 
DFS in the PD-L1 subpopulation, defined as TC 
 50% by the SP263 IHC assay within 
patients with Stage II IIIA NSCLC 
 

 
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STUDY TREATMENT 
Four cycles of cisplatin-based chemotherapy will be administered prior to randomization with 
each cycle being 3 weeks (21 days) in length.  The investigator will select the chemotherapy 
regimen (1, 2, 3, or 4) for the patient prior to enrollment. 
Cisplatin-Based Chemotherapy Regimens 
Regimen
Cisplatin 75 mg/m2 IV, Day 1, Plus
1
Vinorelbine 30 mg/m2 IV push, Days 1 and 8
2
Docetaxel 75 mg/m2 IV, Day 1
3
Gemcitabine 1250 mg/m2 IV, Days 1 and 8
4
Pemetrexed 500 mg/m2 IV, Day 1 (non-squamous cell NSCLC 
only) 
IV 
 intravenous; NSCLC 
 non small cell lung cancer.
 
After randomization, in Arm A, atezolizumab will be administered intravenously on Day 1 of 
each 21-day cycle for a total of 16 cycles.   
 
DURATION OF PARTICIPATION 
Treatment will continue until disease recurrence, unacceptable toxicity, medical condition that 
may jeopardize the patient's safety, or withdrawal of consent. The total duration of study 
participation for each individual from screening until completion may vary depending on arm, 
tumor type, patient demographics, and availability of standard of care for specific tumor 
types.  The total duration of study participation for each individual is expected to range from 
1 day to more than 12 years. 
COMMITTEES 
Independent Committees: Not applicable 
Other Committees: 
Not applicable 
 
 

 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
AJCC 
American Joint Committee on Cancer 
ASCO 
American Society of Clinical Oncology 
ATA 
anti therapeutic antibody 
BICR 
blinded independent central review 
BID 
twice a day 
BSA 
body surface area 
BSC 
best supportive care 
CALGB 
Cancer and Leukemia Group B 
Cmax 
maximum serum concentration observed 
Cmin 
minimum serum concentration under steady state conditions 
within a dosing interval 
COVID-19 
coronavirus disease 2019 
CRCL 
creatinine clearance 
CRS 
cytokine release syndrome 
CT 
computed tomography 
ctDNA 
circulating tumor DNA 
Ctrough 
steady state concentration at the end of a dosing interval (i.e., 
just prior to next drug administration) 
DFS 
disease free survival 
DLT 
dose-limiting toxicity  
DOR 
duration of response 
EC 
Ethics Committee 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic Case Report Form 
EDC 
electronic data capture 
EGFR 
epidermal growth factor receptor 
ESA 
erythropoietin stimulating agents 
FDA 
(U.S.) Food and Drug Administration 
FFPE 
formalin-fixed paraffin embedded 
GGT 
gamma glutamyl transferase 
HBc 
hepatitis B core antigen 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HLH 
hemophagocytic lymphohistiocytosis 

 
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Abbreviation 
Definition 
HR 
hazard ratio 
HUS 
hemolytic-uremic syndrome 
IC 
tumor infiltrating immune cell 
ICH 
International Conference on Harmonisation 
iDMC 
independent Data Monitoring Committee 
IFN 
interferon 
Ig 
immunoglobulin 
IHC 
immunohistochemistry 
IL 
interleukin 
imAE 
immune-mediated adverse event 
IMP 
investigational medicinal product 
IND 
Investigational New Drug (Application) 
IRB 
Institutional Review Board 
IRF 
Independent Review Facility 
IRR 
infusion-related reaction 
ITT 
intent to treat 
IV 
Intravenous 
IxRS 
interactive voice/Web response system 
LACE 
Lung Adjuvant Cisplatin Evaluation 
LFT 
liver function test 
MAS 
macrophage activation syndrome 
MLND 
mediastinal lymph node dissection 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NCCN 
National Comprehensive Cancer Network 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for 
Adverse Events 
NGS 
next-generation sequencing 
NSAIDS 
nonsteroidal anti-inflammatory agents 
NSCLC 
non small cell lung cancer 
ORR 
objective response rate 
OS 
overall survival 
PD-1 
programmed death 1 
PD-L1 
programmed death ligand 1 
PFS 
progression-free survival 
PK 
pharmacokinetic 
PO 
by mouth 

 
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Abbreviation 
Definition 
PVC 
polyvinylchloride 
RCR 
Roche Clinical Repository 
RECIST 
Response Evaluation Criteria in Solid Tumors 
Q3W 
every 3 weeks 
QID 
four times a day 
qRT-PCR 
quantitative reverse transcriptase polymerase chain reaction 
RCC 
renal cell carcinoma 
RCR 
Roche Clinical Repository 
SAP 
Statistical Analysis Plan 
SARS CoV-2 
severe acute respiratory syndrome coronavirus 2 
SITC 
Society for Immunotherapy of Cancer 
TC 
tumor cell 
TNF 
tumor necrosis factor 
TSH 
thyroid-stimulating hormone 
UICC 
Union Internationale Contre le Cancer 
ULN 
upper limit of normal 

 
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1. 
BACKGROUND 
Lung cancer is the leading cause of cancer deaths worldwide.  It was estimated 
that there would be 224,210 new cases of lung cancer (116,000 in men and 
108,210 in women) and 159,260 deaths in the United States in 2014 
(American Cancer Society 2014).  Similar data from Europe estimate that there were 
214,000 new cases of lung cancer and 268,000 deaths in 2012 (GLOBOCAN 2012). 
Non small cell lung cancer (NSCLC) is one of the two major types of lung cancer, 
accounting for approximately 85% of all lung cancer cases (Molina et al. 2008).  
The two predominant histologic types of NSCLC are adenocarcinoma, which accounts 
for more than half of cases, and squamous cell carcinoma, which accounts for 
approximately 25% of cases (Langer et al. 2010; Travis et al. 2011). 
The overall 5-year survival rate for advanced NSCLC is 2% 4%, depending on 
geographic location (Cetin et al. 2011).  Poor prognostic factors for survival in patients 
with NSCLC include advanced stage of disease at the time of initial diagnosis, poor 
Eastern Cooperative Oncology Group (ECOG) Performance Status, and a history of 
unintentional weight loss.  More than half of the patients with NSCLC present with 
distant metastatic disease at the time of initial diagnosis, which directly contributes to 
poor survival prospects. 
In its early stages, NSCLC is treated surgically with curative intent.  However, 
30% 70% of patients undergoing resection develop recurrence and die as a result of 
disease progression (Ponn et al. 2005).  Adjuvant radiotherapy is no longer 
recommended after surgery as an adjuvant treatment option for patients with early-stage 
disease, specifically in Stage I and II patients because it has been shown to have a 
deleterious effect on long-term survival (PORT Meta-Analysis Trialists Group 1998). 
1.1 
ADJUVANT TREATMENT OPTIONS FOR PATIENTS WITH 
SURGICALLY RESECTED STAGE IB IIIA NSCLC 
Adjuvant chemotherapy is the standard of care for fully resected (Stage IB IIIA) NSCLC.  
Additional studies are looking at the role of molecularly targeted adjuvant studies in 
relatively uncommon molecular subsets (epidermal growth factor receptor [EGFR], 
anaplastic lymphoma kinase) that account for 
 15% of NSCLC. 
The Lung Adjuvant Cisplatin Evaluation (LACE) reported on the results of a pooled 
analysis of data from several large studies of cisplatin-based adjuvant chemotherapy in 
patients with NSCLC.  The pooled analysis of these data was used to identify treatment 
options associated with a higher degree of benefit or groups of patients benefiting more 
from adjuvant treatment (Pignon et al. 2008).  With a median follow-up time of 5.2 years, 
the overall hazard ratio (HR) of death was 0.89 (95% CI: 0.82, 0.96; p 
 0.005), 
corresponding to a 5-year absolute benefit of 5.4% from chemotherapy.  Further analysis 
revealed no heterogeneity of chemotherapy effect among studies.  The benefit varied 

 
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The CALGB 9633 study was designed to evaluate the role of adjuvant 
paclitaxel/carboplatin in node-negative Stage I NSCLC.  In this study, 344 patients were 
randomly assigned to observation or paclitaxel and carboplatin.  Median follow-up was 
74 months.  Groups were well balanced with regard to demographics, histology, and 
extent of surgery.  Survival was not significantly different (HR 
 0.83; CI: 0.64, 1.08; 
p 
 0.12).  However, an exploratory analysis demonstrated a significant survival 
difference in favor of adjuvant chemotherapy for patients who had tumors 
 4 cm in 
diameter (HR 
 0.69; CI: 0.48, 0.99; p 
 0.043; Strauss et al. 2008).  This study has 
formed the basis for subsequent adjuvant studies including patients with Stage IB whose 
tumors were 
 4 cm. 
Study E1505 is a randomized study of chemotherapy, consisting of four cisplatin-based 
chemotherapy regimens (pemetrexed, gemcitabine, paclitaxel, or docetaxel) given for 
four cycles alone or with 1 year of bevacizumab beginning concurrently with 
chemotherapy (Wakelee et al. 2011; Wakelee et al. 2015).  In this study, 1501 patients 
were enrolled.  The interim analysis of the study, with a median follow-up of 41 months, 
was presented at the World Conference on Lung Cancer (WCLC) in 2015.  This study 
did not meet its primary endpoint of overall survival (OS).  The OS hazard ratio 
comparing the bevacizumab-containing arm (Arm B) to chemotherapy alone (Arm A) 
was 0.99 (95% CI: 0.81, 1.21, p 
 0.93).  The disease-free survival (DFS) HR was 
0.98 (95% CI: 0.84, 1.14, p 
 0.75).  Statistically significant Grade 3 5 toxicities of note 
(all attributions) included overall worst grade (67% vs. 84%), hypertension (8% vs. 30%), 
and neutropenia (33% vs. 38%) for Arm A and Arm B, respectively.  There was no 
significant difference in Grade 5 adverse events per arm, with 16 (2%) in Arm A and 
19 (3%) in Arm B. 
1.2 
BACKGROUND ON ATEZOLIZUMAB (MPDL3280A) 
Atezolizumab (MPDL3280A [anti programmed death-ligand 1 [PD-L1] antibody]) is a 
humanized Ig G1 monoclonal antibody consisting of two heavy chains (448 amino acids) 
and two light chains (214 amino acids) and is produced in Chinese hamster ovary cells.  
Atezolizumab was engineered to eliminate Fc-effector function via a single amino acid 
substitution (asparagine to alanine) at position 298 on the heavy chain, which results in a 
non-glycosylated antibody that has minimal binding to Fc receptors and prevents 
Fc-effector function at expected concentrations in humans.  Atezolizumab targets human 
PD-L1 and inhibits its interaction with its receptors, programmed death 1 (PD-1) and 
B7.1 (CD80, B7-1).  Both of these interactions are reported to provide inhibitory signals 
to T cells. 
Atezolizumab is being investigated as a potential therapy against solid tumors and 
hematologic malignancies in humans.  Atezolizumab is approved for the treatment of 
urothelial carcinoma, non small cell lung cancer, small-cell lung cancer, triple-negative 
breast cancer, hepatocellular carcinoma, and melanoma. 

 
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Refer to the Atezolizumab Investigator's Brochure for details on nonclinical and 
clinical studies. 
1.2.1 
Summary of Nonclinical Studies 
The nonclinical strategy of the atezolizumab program was to demonstrate in vitro and 
in vivo activity, to determine in vivo pharmacokinetic (PK) behavior, to demonstrate an 
acceptable safety profile, and to identify a Phase I starting dose.  Comprehensive 
pharmacology, PK, and toxicology evaluations were thus undertaken with atezolizumab. 
The safety, pharmacokinetics, and toxicokinetics of atezolizumab were investigated in 
mice and cynomolgus monkeys to support intravenous (IV) administration and to aid 
in projecting the appropriate starting dose in humans.  Given the similar binding of 
atezolizumab for cynomolgus monkey and human PD-L1, the cynomolgus monkey was 
selected as the primary and relevant nonclinical model for understanding the safety, 
pharmacokinetics, and toxicokinetics of atezolizumab. 
Overall, the nonclinical pharmacokinetics and toxicokinetics observed for atezolizumab 
supported entry into clinical studies, including providing adequate safety factors for the 
proposed Phase I starting doses.  The results of the toxicology program were consistent 
with the anticipated pharmacologic activity of downmodulating the PD-L1/PD-1 pathway 
and supported entry into clinical studies in patients. 
 
1.3 
CLINICAL EXPERIENCE WITH ATEZOLIZUMAB 
1.3.1 
Ongoing Clinical Studies 
Atezolizumab is currently being tested in multiple Phase I, II, and III studies, both as 
monotherapy and in combination with several anti-cancer therapies (see the 
descriptions). 
The single-agent safety and efficacy data summarized below are from the following 
three studies: 
 
Study PCD4989g:  A Phase Ia, multicenter, first-in-human, open-label, 
dose-escalation study evaluating the safety, tolerability, immunogenicity, 
pharmacokinetics, exploratory pharmacodynamics, and preliminary evidence of 
biologic activity of atezolizumab administered as a single agent by IV infusion 
every 3 weeks (Q3W) to patients with locally advanced or metastatic solid 
malignancies or hematologic malignancies. 
 
Study GO28753 (POPLAR):  A randomized, Phase II, open-label study assessing 
the clinical benefit of atezolizumab as a single agent versus docetaxel in 
PD-L1 unselected patients with locally advanced or metastatic NSCLC that has 
progressed during or following treatment with a platinum-containing regimen. 

 
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Study GO28754 (BIRCH):  A Phase II, open-label study assessing the clinical 
benefit of atezolizumab as a single agent in patients with PD-L1 selected, locally 
advanced or metastatic NSCLC representing all lines of therapy (previously 
untreated to heavily pretreated patients with exposure to multiple prior regimens) 
 
1.3.2 
Clinical Safety 
1.3.2.1 
Single-Agent Clinical Safety in Patients with NSCLC in 
Study PCD4989g 
Study PCD4989g is a Phase Ia dose-escalation and expansion study in which 
atezolizumab is being used as a single agent in patients with locally advanced or 
metastatic solid tumors or hematologic malignancies.  Study PCD4989g provides the 
majority of data (with 558 safety-evaluable patients as of the data extraction date of 
11 May 2015) for the safety profile of atezolizumab as monotherapy. 
Currently, no maximum tolerated dose (MTD), no dose-limiting toxicities (DLTs), and no 
clear dose-related trends in the incidence of adverse events have been determined. 
The safety profile of atezolizumab as a single agent is observed to be consistent across 
different indications.  The most common cancer types for these patients include NSCLC, 
urothelial bladder cancer, melanoma, and renal cell carcinoma.  Safety data for NSCLC 
are also derived from Study GO28753 (POPLAR). 
Adverse Events 
Of the 558 patients, 520 patients (93.2%) experienced at least one adverse event, 
including 376 patients (67.4%) who experienced one treatment-related adverse event.  
Commonly reported events (reported in 
 10% of all patients) included fatigue, 
decreased appetite, nausea, pyrexia, constipation, and cough (see Table 2). 

 
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Table 2 
Study PCD4989g:  Adverse Events with Frequency 
 10% of 
Patients for All Grades 
Preferred Term 
All Grades 
n (%) 
All Grades 
Related 
n (%) 
Grade 3 4 
n (%) 
Grade 3 4 
Related 
n (%) 
Any adverse event 
520 (93.2) 
376 (67.4) 
239 (42.8) 
66 (11.8) 
Fatigue 
192 (34.4) 
115 (20.6) 
13 (2.3) 
6 (1.1) 
Decreased Appetite
142 (25.4) 
62 (11.1) 
4 (0.7) 
0 (0.0) 
Nausea 
136 (24.4) 
65 (11.6) 
5 (0.9) 
2 (0.4) 
Pyrexia 
117 (21.0) 
63 (11.3) 
2 (0.4) 
0 (0.0) 
Constipation 
116 (20.8) 
8 (1.4) 
2 (0.4) 
0 (0.0) 
Cough 
113 (20.3) 
11 (2.0) 
1 (0.2) 
1 (0.2) 
Dyspnea 
112 (20.1) 
18 (3.2) 
18 (3.2) 
4 (0.7) 
Diarrhea 
110 (19.7) 
53 (9.5) 
2 (0.4) 
1 (0.2) 
Anemia 
104 (18.6) 
26 (4.7) 
23 (4.1) 
5 (0.9) 
Vomiting 
96 (17.2) 
28 (5.0) 
3 (0.5) 
2 (0.4) 
Asthenia 
88 (15.8) 
53 (9.5) 
8 (1.4) 
4 (0.7) 
Back Pain 
85 (15.2) 
9 (1.6) 
8 (1.4) 
1 (0.2) 
Headache 
83 (14.9) 
32 (5.7) 
2 (0.4) 
1 (0.2) 
Arthralgia 
79 (14.2) 
35 (6.3) 
2 (0.4) 
0 (0.0) 
Pruritus 
75 (13.4) 
55 (9.9) 
0 (0.0) 
0 (0.0) 
Rash 
73 (13.1) 
53 (9.5) 
0 (0.0) 
0 (0.0) 
Abdominal Pain 
63 (11.3) 
12 (2.2) 
8 (1.4) 
0 (0.0) 
Insomnia 
62 (11.1) 
7 (1.3) 
1 (0.2) 
0 (0.0) 
Peripheral edema 
59 (10.6) 
7 (1.3) 
 
 
Chills 
57 (10.2) 
31 (5.6) 
0 (0.0) 
0 (0.0) 
 
 
Common Terminology Criteria grade.
  
Grade 3 4 adverse events (based on National Cancer Institute Common Terminology 
Criteria for Adverse Events, Version 4.0 [NCI CTCAE v4.0]) were reported in 
239 patients (42.8%), of which 66 (11.8%) were considered related.  Grade 3 and 4 
adverse events considered related by the investigator included dyspnea, pneumonitis, 
increased ALT, increased AST, increased gamma-glutamyl transferase (GGT), 
lymphocyte count decreased, cardiac tamponade, asthenia, autoimmune hepatitis, 
pneumonia, influenza, and hypoxia. 

 
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1.3.3 
Clinical Activity 
1.3.3.1 
Single-Agent Clinical Activity in Patients with NSCLC in 
Study PCD4989g 
As of the 2 December 2014 cutoff date, the efficacy-evaluable population included 
88 patients with locally advanced or metastatic NSCLC.  The median age was 
60.5 years (range 24 84 years) and represented a heavily pre-treated patient 
population, with 97% of patients having received two or more prior systemic therapies, 
and 77.3% having received four or more prior systemic therapies. 
Overall, responses were observed in 20 of 88 (22.7%) patients with NSCLC and 
included responses in patients with squamous and non-squamous NSCLC 
(4 in 21 patients and 16 in 67 patients, respectively).  A total of 8 of the 20 responding 
patients have continued to respond at the time of the clinical data cutoff. 
Table 5 displays the confirmed objective response rate (ORR), duration of confirmed 
response (DoR), and 6-month PFS rates by PD-L1 expression for patients with NSCLC.  
These results are based on Response Evaluation Criteria in Solid Tumors, Version 1.1 
(RECIST v1.1) as assessed by the investigator.  Analyses of tumor-infiltrating immune 
cells (ICs) and tumor cells (TCs) for PD-L1 expression on baseline tumor tissue from 
NSCLC patients have been performed.  Higher ORRs were associated with higher 
PD-L1 expression. 
atients 
with NSCLC treated to date. 

 
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The study met its primary objective of demonstrating a statistically significant and 
clinically meaningful ORR assessed by IRF per RECIST v1.1 compared with historical 
controls in the seven pre-specified subpopulations.  At the clinical cutoff, more than 
58% of responders assessed by IRF per RECIST v1.1 had an ongoing response in each 
line of therapy and each PD-L1 expression level.  The estimated median DOR was 
8.4 months in the TC2/3 or IC2/3 patients although follow-up is limited.  OS data are not 
yet mature. 
1.3.4 
Clinical Pharmacokinetics and Immunogenicity 
On the basis of available preliminary PK data (0.03 20 mg/kg), atezolizumab appeared 
to show linear pharmacokinetics at doses 
 1 mg/kg.  For the 1 mg/kg and 20 mg/kg 
dose groups, the mean apparent total clearance of drug (CL) and the mean volume of 
distribution under steady-state conditions (Vss) had a range of 3.20 to 4.43 mL/day/kg 
and 48.1 to 64.1 mL/kg, respectively, which is consistent with the expected profile of an 
IgG1 antibody in humans. 
The development of anti-therapeutic antibodies (ATAs, also called anti-drug antibodies) 
has been observed in patients in all dose cohorts and was associated with changes in 
pharmacokinetics for some patients in the lower dose cohorts (0.3, 1, and 3 mg/kg).  
The development of detectable ATAs has not had a significant impact on 
pharmacokinetics for doses from 10 20 mg/kg.  Patients dosed at the 10, 15, and 
20 mg/kg dose levels have maintained the expected target trough levels of drug despite 
the detection of ATAs.  To date, no clear relationship between the detection of ATAs and 
adverse events or infusion reactions has been observed. 
1.3.5 
Additional Studies with Atezolizumab 
Several studies that include targeted agents such as bevacizumab, erlotinib, and 
vemurafenib are being explored in combination with both atezolizumab and standard 
chemotherapy. 
1.4 
STUDY RATIONALE AND BENEFIT RISK ASSESSMENT 
PD-L1 is an extracellular protein that downregulates immune responses primarily in 
peripheral tissues through binding to its two receptors, PD-1 and B7.1.  PD-1 is an 
inhibitory receptor expressed on Tcells following T-cell activation, which is sustained in 
states of chronic stimulation such as in chronic infection or cancer (Blank et al. 2005; 
Keir et al. 2008).  Ligation of PD-L1 with PD-1 inhibits T-cell proliferation, cytokine 
production, and cytolytic activity, leading to the functional inactivation or exhaustion of 
Tcells.  B7.1 is a molecule expressed on antigen-presenting cells and activated T cells.  
PD-L1 binding to B7.1 on Tcells and antigen-presenting cells can mediate 
downregulation of immune responses, including inhibition of T cell activation and 
cytokine production (Butte et al. 2007; Yang et al. 2011). 

 
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Overexpression of PD-L1 on TCs has been reported to impede anti-tumor immunity, 
resulting in immune evasion (Blank and Mackensen 2007).  Therefore, interruption of the 
PD-L1/PD-1 pathway represents an attractive strategy to reinvigorate tumor-specific 
T-cell immunity. 
PD-L1 expression is prevalent in many human tumors, and elevated PD-L1 expression 
is associated with a poor prognosis in patients with NSCLC (Mu et al. 2011).  In mouse 
tumor models, interruption of the interaction between PD-L1 and PD-1 resulted in 
anti-tumor effects (Iwai et al. 2002; Strome et al. 2003). 
Targeting the PD-L1 pathway with atezolizumab has demonstrated activity in patients 
with advanced malignancies and who have failed standard-of-care therapies.  
In Study PCD4989g, a Phase Ia dose-escalation and expansion study, objective 
responses with atezolizumab monotherapy were observed in a broad range of 
malignancies (see Section 1.3.3).  In addition, in the NSCLC cohort, patients who 
had a high level of PD-L1 expression in TCs or ICs were more likely to respond to 
atezolizumab than those with low or no PD-L1 expression in TCs or ICs 
(see Section 1.3.3). 
Data from the randomized Phase II Study GO28753 (POPLAR) have suggested an OS 
benefit in the atezolizumab arm in a PD-L1 unselected population, with a stratified HR of 
0.73 (95% CI: 0.53, 0.99).  PFS and ORR for the atezolizumab arm were similar to those 
for the docetaxel arm (see Section 1.3.3.2 and Table 6). 
Atezolizumab has been generally well tolerated (see Section 1.3.2).  Adverse events 
with potentially immune-mediated causes consistent with an immunotherapeutic agent, 
including rash, hypothyroidism, hepatitis/transaminitis, colitis, and myasthenia gravis, 
have been observed in Study PCD4989g.  To date, these events have been 
manageable with treatment. 
Given the evidence of the clinical activity of atezolizumab in previously treated NSCLC 
and the need to continue to improve upon the survival for patients with resected NSCLC 
treated with adjuvant cisplatin based chemotherapy, the Sponsor proposes 
Study GO29527.  Patients with completely resected Stage IB (tumors 
 4 cm) IIIA 
NSCLC will receive up to four cycles of cisplatin-based chemotherapy unless 
followed by randomization to either 16 cycles of atezolizumab treatment or best 
supportive care (BSC). 
This trial will enroll patients with Stage IB Stage IIIA NSCLC following resection and 
adjuvant chemotherapy.  Given the relatively poor prognosis and limited treatment 
options for these patients, this population is considered appropriate for trials of novel 
therapeutic candidates.  The benefit risk ratio for atezolizumab is expected to be 
acceptable in this setting. 

 
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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 inhibiting the PD-1/PD-L1 pathway 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-1/PD-L1 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).  However, there are insufficient and inconsistent clinical 
data to assess if outcome from SARS-CoV-2 infection is altered by cancer 
immunotherapy. 
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 
interferon (IFN)-  (Merartin 2020).  While it is not known, there may be a potential for an 
increased risk of an enhanced inflammatory response if a patient develops acute 
SARS-CoV-2 infection while receiving atezolizumab.  At this time, there is insufficient 
evidence for causal association between atezolizumab 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 atezolizumab 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 cancer 
immunotherapy 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 National Comprehensive Cancer Network (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). 

 
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In alignment with clinical practice procedures, factors to consider when making the 
individualized decision for patients receiving atezolizumab 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. 
SITC and NCCN recommendations along with institutional guidelines should be used by 
the investigator when deciding on administering COVID19 vaccines.  When 
administered, COVID19 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 4.4.2). 
2. 
OBJECTIVES 
The following objectives will be evaluated in patients with Stage IB IIIA NSCLC. 
2.1 
EFFICACY OBJECTIVES 
2.1.1 
Primary Efficacy Objective 
The primary efficacy objective of the study is as follows: 
 
To evaluate the efficacy of atezolizumab monotherapy treatment compared with 
BSC as measured by DFS as assessed by the investigator in the PD-L1 
subpopulation (defined as 
 1% TC expression by the SP263 IHC assay) within the 
Stage II IIIA population, in all randomized patients with Stage II IIIA NSCLC, and in 
the ITT population as detailed in Figure 2 
 
2.1.2 
Secondary Efficacy Objectives 
The secondary efficacy objectives of the study are to evaluate the efficacy of 
atezolizumab monotherapy treatment compared with BSC on the basis of the following 
outcome measures (see also Section 3.4.2): 
 
OS in the ITT population 
 
3-year and 5-year DFS rates in the PD-L1 subpopulation (defined as 
 1%TC 
expression by the SP263 IHC assay) within the Stage II IIIA population, in all 
randomized patients with Stage II IIIA NSCLC, and in the ITT population 
 
DFS in the PD-L1 subpopulation (defined as 
 50% TC expression by the SP263 
IHC assay) in patients with Stage II IIIA NSCLC 
 
2.2 
SAFETY OBJECTIVES 
The safety objectives of the study are as follows: 
 
To evaluate the safety and tolerability of atezolizumab treatment after up to 
four cycles of cisplatin-based chemotherapy in the adjuvant setting 

 
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To evaluate the incidence and titers of ATAs against atezolizumab in the adjuvant 
setting and to explore the potential relationship of the immunogenicity response with 
pharmacokinetics, safety, and efficacy 
 
2.3 
PHARMACOKINETIC OBJECTIVE 
The PK objective of the study is as follows: 
 
To characterize the pharmacokinetics of atezolizumab treatment in the adjuvant 
setting 
 
2.4 
EXPLORATORY OBJECTIVES 
The exploratory objectives for this study are as follows: 
 
To evaluate DFS in TC3 or IC3, TC2/3 or IC2/3, TC1/2/3 or IC1/2/3 subpopulations 
defined by PD-L1 SP142 IHC in both the Stage II IIIA and the ITT populations 
 
To evaluate DFS in the PD-L1 subpopulations defined by 22C3 TPS 1% and 
TPS 
 50% in both the Stage II IIIA and the ITT populations 
 
To evaluate DFS in the PD-L1 subpopulations defined by SP263 TC 1% and 
TC 
 50% in the ITT population 
 
To evaluate the relationship between tumor and blood-based biomarkers (including 
but not limited to PD-L1, PD-1, somatic mutations, and others), as defined by IHC or 
quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), 
nextgeneration sequencing (NGS), and/or other methods and measures of efficacy 
 
To assess predictive, prognostic, and pharmacodynamic exploratory biomarkers in 
archival and/or fresh tumor tissue and blood and their association with disease 
status, mechanisms of resistance, and/or response to atezolizumab in the adjuvant 
treatment setting 
 
To evaluate biomarkers at the time of apparent recurrence of primary disease 
(i.e., NSCLC primary disease recurrence, occurrence of new primary NSCLCs) and 
to distinguish any immunomodulatory activity of atezolizumab (i.e., tumor-immune 
infiltration) in patients with confirmed recurrence of disease in patients assigned to 
atezolizumab 
 
3. 
STUDY DESIGN 
3.1 
DESCRIPTION OF THE STUDY 
This study is a Phase III, global, multicenter, open-label, randomized, study 
(IMpower010) comparing the efficacy and safety of atezolizumab versus BSC in 
patients with Stage IB Stage IIIA NSCLC following resection and adjuvant 
chemotherapy, as assessed by DFS per the investigator and OS.  The study consists of 
two phases:  an enrollment phase and randomized phase. 
In the enrollment phase, patients who have recently undergone complete resection of 
their NSCLC will be screened, and eligible patients will be enrolled to receive one of 
four regimens of cisplatin-based chemotherapy (cisplatin plus vinorelbine, docetaxel, 

 
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laboratory with use of an IHC assay, but patients will be enrolled in the study regardless 
of the PD-L1 status.  Patients who fulfill the eligibility criteria (see Section 4.1.1) will 
receive adjuvant cisplatin-based chemotherapy in the enrollment phase of the study.  
Patients will receive up to four cycles of cisplatin-based chemotherapy unless 
 
Patients who experience disease recurrence of their primary disease at any time up to 
completion of chemotherapy will not be eligible for the randomized phase of the study.  
Additionally, patients must fulfill the eligibility criteria of the randomized phase 
(see Section 4.1.1.2) prior to randomization. 
Eligible patients will go on to be randomized in a 1:1 ratio to receive either atezolizumab 
(Arm A) or BSC (Arm B). 
In Arm A, atezolizumab will be administered intravenously on Day 1 of each 21-day 
cycle for a total of 16 cycles.  Patients randomized to Arm B will be continually followed 
starting on Day 1 of each 21-day cycle.  To ensure the same frequency of study 
assessments between the treatment arms, including assessments for disease 
recurrence and safety, patients in Arm B will be required to undergo medical contacts 
Q3W for assessments during the first year, which will consist of formal clinic visits 
alternating with clinical contacts (either via telephone call or formal outpatient clinic visit) 
for symptom and adverse event assessment.  No crossover will be allowed from Arm B 
to Arm A. 
All patients in the randomized phase will undergo scheduled tumor assessments at 
baseline and every 4 months starting at Cycle 1, Day 1 in the first year and every 
6 months in the second year by computed tomography (CT) following randomization.  
Patients who have not experienced recurrence of disease will undergo tumor 
assessments every 6 months by CT or X-ray during Years 3 5 post-randomization.  In 
the absence of disease recurrence, tumor assessments should continue regardless of 
whether patients start new anti-cancer therapy, until disease recurrence, withdrawal of 
consent, death, loss to follow-up, or study termination by the Sponsor, whichever occurs 
first.   
Before completion of the final analysis of DFS, patients from both treatment arms will 
undergo a mandatory tumor biopsy sample collection, unless not clinically feasible as 
assessed by investigators, at the first evidence of radiographic disease recurrence.  
These data will be used to explore whether the radiographic findings are consistent with 
the presence of tumor or, for patients treated with atezolizumab, if the appearance of 
recurrence was caused by tumor immune infiltration.  In addition, these data will be 
analyzed to evaluate the association between changes in tumor tissue and clinical 
outcome as well as to understand further the potential mechanisms of resistance and 
recurrence to atezolizumab compared with such mechanisms after treatment with 

 
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chemotherapy alone.  This exploratory biomarker evaluation will not be used for any 
treatment-related decisions.  Tumor assessments will be performed by the investigator. 
After Year 5 and the completion of the final analysis of DFS, there will no longer be a 
study requirement for tumor assessments to be completed and patients are to be 
followed according to the local standard as a part of their regular medical care.  If a 
recurrence of the primary NSCLC, or a new second primary NSCLC or new primary 
non-NSCLC malignancy is diagnosed as a part of regular medical care, this data is to 
be entered in the study's electronic data capture (EDC) system. 
Safety assessments will include the incidence, nature, and severity of adverse events; 
serious adverse events; adverse events of special interest; and laboratory abnormalities, 
graded per NCI CTCAE v4.0.  Laboratory safety assessments will include the regular 
monitoring of hematology and blood chemistry. 
Serum samples will be collected to monitor atezolizumab pharmacokinetics and to detect 
the presence of ATAs to atezolizumab.  Patient samples, including archival and fresh 
tumor tissues, as well as serum and plasma and whole blood, will be collected for future 
exploratory biomarker assessments. 
All patients in the randomized phase will undergo safety, tolerability, and exploratory 
assessments on Day 1 of each 21-day cycle until recurrence of disease during the 
first 48 weeks, and patients who have experienced recurrence of disease will undergo 
these assessments within 30 days after the last dose of atezolizumab is administered 
(see Appendix 2). 
Approximately 1280 patients are expected to be accrued in the enrollment phase to 
meet the goal of approximately 1005 patients total in the randomized phase, under the 
assumption that a dropout rate of approximately 21% is expected during adjuvant 
cisplatin-based chemotherapy treatment. 
3.1.1 
Independent Review Facility 
An Independent Review Facility (IRF) may perform a blinded, independent central 
review (BICR) of images and other clinical data as needed.  IRF membership and 
procedures will be detailed in a BICR charter. 
3.2 
END OF STUDY AND DURATION OF PARTICIPATION 
The end of the study is defined as when approximately 564 OS events (the required 
number of deaths for the final OS analysis) have occurred in the ITT population 
(see Section 6.8.2).  Additionally, the Sponsor may decide to terminate the study at any 
time (see Section 4.7.3). 
Treatment will continue until disease recurrence, unacceptable toxicity, medical 
condition that may jeopardize the patient's safety, or withdrawal of consent. The total 

 
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duration of study participation for each individual from screening until completion may 
vary depending on arm, tumor type, patient demographics, and availability of standard of 
care for specific tumor types.  The total duration of study participation for each individual 
is expected to range from 1 day to more than 12 years.  
3.3 
RATIONALE FOR STUDY DESIGN 
This Phase III study is designed to test the hypothesis that 16 cycles of atezolizumab 
treatment following cisplatin based adjuvant chemotherapy in patients with completely 
resected Stage IB IIIA NSCLC will prolong DFS and OS compared with patients 
receiving adjuvant cisplatin based chemotherapy alone.  This hypothesis will be studied 
in the Stage IB IIIA population as well as the Stage II IIIA and PD-L1 selected 
subpopulations. 
3.3.1 
Rationale for Testing Atezolizumab in PD-L1 Unselected 
Patients with NSCLC 
Inhibition of PD-L1/PD-1 signaling has been shown to produce durable responses in 
some patients, and expression of PD-L1 by TCs in several tumor types 
(including NSCLC) correlates with response to therapy (Topalian et al. 2012). 
Data from the Phase Ia study PCD4989g, evaluating single-agent atezolizumab in 
several tumor types including NSCLC, suggest that PD-L1 expression in TCs and ICs as 
determined by IHC correlates with response to atezolizumab.  An ORR of 31.6% (12 of 
38 patients, 95% CI: 17.5%, 48.6%) was observed in patients with high levels of PD-L1 
staining in TCs or ICs (TC3 or IC2/3 group) compared with an ORR of 14.3% (6 of 42 
patients, 95% CI: 6.4%, 27.7%) in patients with low or no PD-L1 staining in TCs and ICs 
(TC0/1/2 and IC0/1 group). 
Data from the randomized Phase II Study GO28753 (POPLAR) have suggested an OS 
benefit in the atezolizumab arm in a PD-L1-unselected population, with a stratified HR of 
0.73 (95% CI: 0.53, 0.99,) which suggest the benefit of atezolizumab might also occur in 
an unselected population. 
3.3.2 
Rationale for Best Supportive Care Arm (Arm B) 
The standard of care for resected patients with NSCLC is four cycles of cisplatin-based 
chemotherapy followed by periodic chest X-rays and/or CT scans (see Section 1.1). 
3.3.3 
Rationale for Atezolizumab Dosage and Treatment Duration 
The fixed dose of 1200 mg (equivalent to an average body weight based dose of 
15 mg/kg) was selected on the basis of both nonclinical studies and available clinical 
data from Study PCD4989g. 
The target exposure for atezolizumab was projected on the basis of nonclinical tissue 
distribution data in tumor-bearing mice, target receptor occupancy in the tumor, the 
observed atezolizumab interim pharmacokinetics in humans, and other factors.  

 
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The target trough concentration (steady-state concentration at the end of a dosing 
interval [i.e., just prior to next drug administration]; Ctrough) was projected to be 6 g/mL 
on the basis of several assumptions, including the following:  1) 95% tumor-receptor 
saturation is needed for efficacy and 2) the tumor-interstitial concentration to plasma 
ratio is 0.30 based on tissue distribution data in tumor-bearing mice. 
The selection of the atezolizumab dose is also informed by available clinical activity, 
safety, PK, and immunogenicity data (see Section 1.3.3.2).  Anti-tumor activity has been 
observed across doses from 1 mg/kg to 20 mg/kg.  The MTD of atezolizumab was not 
reached, and no DLTs have been observed at any dose in Study PCD4989g.  Currently 
available PK and ATA data suggest that the 15 mg/kg atezolizumab Q3W regimen (or 
fixed-dose equivalent) for Phase II and Phase III studies would be sufficient to both 
maintain Ctrough 
 6 g/mL and further safeguard against both inter-patient variability and 
the potential effect of ATAs that could lead to subtherapeutic levels of atezolizumab 
relative to the 10-mg/kg atezolizumab Q3W regimen (or fixed-dose equivalent).  
From inspection of available observed Ctrough data, moving further to the 20-mg/kg 
atezolizumab Q3W regimen does not appear to be warranted to maintain targeted Ctrough 
levels relative to the proposed 15-mg/kg atezolizumab Q3W level. 
Simulations (Bai et al. 2012) do not suggest any clinically meaningful differences in 
exposure following a fixed dose or a dose adjusted for weight.  Therefore, a fixed dose 
of 1200 mg has been selected (equivalent to an average body weight based dose of 
15 mg/kg).  Selection of an every-21-day dosing interval is supported by this preliminary 
pharmacokinetics evaluation. 
A 1-year period of adjuvant treatment has been selected because this is believed to 
balance the expected benefit in the adjuvant setting with the risks and tolerability of 
therapy on the basis of an assessment of benefit versus risk observed in the metastatic 
cancer setting. 
clinical pharmacology of atezolizumab. 
3.3.4 
Rationale for Collection of Resected Tumor Specimens 
Published results suggest that the expression of PD-L1 in tumors correlates with 
response to anti-PD-1 therapy (Topalian et al. 2012).  This correlation is also observed 
with atezolizumab in preliminary data from Study PCD4989g.  In this study, tumor 
specimens from patients will be prospectively tested for PD-L1 expression by a central 
laboratory during the screening period and patients will be stratified by PD-L1 expression 
defined by the SP142 IHC assay.  In addition, the PD-L1 status using the SP263 and 
22C3 IHC assays will also be centrally evaluated.  The study will allow for the evaluation 
of the efficacy of atezolizumab in both the ITT population, as well as in patients with 
PD-L1 selected tumors (defined by expression of PD-L1 in TCs).  In addition to the 
assessment of PD-L1 status using the SP142, SP263, and 22C3 IHC assays, other 

 
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exploratory markers, such as potential predictive and prognostic markers related to the 
clinical benefit of atezolizumab, tumor immunobiology, mechanisms of resistance, or 
tumor type may also be analyzed. 
3.3.5 
Rationale for Blood Biomarker Assessments 
An exploratory objective of this study is to evaluate surrogate biomarkers that may 
include circulating-tumor DNA (ctDNA), gene expression, and others in blood samples.  
Evaluation of blood biomarkers may provide evidence for biologic activity of 
atezolizumab in patients with NSCLC and may allow for the development of blood-based 
biomarkers to help predict which patients may benefit from atezolizumab. 
PD-L1 will be assessed centrally through the use of the VENTANA PD-L1 (SP263 [also 
known as RD0827375], and also SP142 [also known as RD0827376] in earlier protocol 
versions) assays (Appendix 5 and Appendix 4, respectively), which may be considered 
investigational per local regulations. 
In addition, potential correlations of these biomarkers with the dose, safety, and activity 
of atezolizumab will be explored. 
3.3.6 
Rationale for the Collection of Tumor Specimens at Disease 
Recurrence and/or Confirmation of a New Primary NSCLC 
This initial apparent recurrence may occur as a result of either delayed anti-tumor 
activity and/or robust tumor-immune infiltration with a concomitant increase in tumor 
size.  In addition, lesions that would otherwise be undetectable with conventional 
imaging (i.e., micrometastatic disease) may increase in size as a result of these 
processes and be recorded as new lesions (Hales et al. 2010). 
Patients from both treatment arms will undergo a mandatory tumor biopsy sample 
collection, unless not clinically feasible as assessed and documented by investigators, at 
the first evidence of radiographic disease recurrence.  These data will be used to explore 
whether the radiographic findings are consistent with the presence of tumor or, for 
patients treated with atezolizumab, if the appearance of recurrence was caused by 
tumor immune infiltration.  In addition, these biopsies are important for the evaluation of 
predictive mechanisms related to tumor recurrence or occurrence, resistance, 
prognostic, and pharmacodynamic relationships in tumor biomarkers (including but not 
limited to PD-L1, CD8, mutation status, and others) as well as to efficacy in the adjuvant 
treatment setting.  DNA and/or RNA extractions may be performed to enable the 
identification of somatic mutations by NGS to contribute to an improved understanding of 
the dynamics of PD-L1 expression, tumor immunobiology, and the relationship to 
disease recurrence and DFS in the adjuvant setting. 

 
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3.4 
EFFICACY OUTCOME MEASURES 
3.4.1 
Primary Efficacy Outcome Measure 
The primary efficacy outcome measure for this study is as follows: 
 
DFS, defined as the time from randomization to the date of occurrence of any of the 
following, whichever occurs first: 
First recurrence of NSCLC, as determined by the investigator after an 
integrated assessment of radiographic data, biopsy sample results (if available), 
and clinical status 
Occurrence of new primary NSCLC, as assessed by the investigator 
Death from any cause 
 
This efficacy outcome measure will be assessed in the PD-L1 subpopulation (defined as 
 1% TC expression by the SP263 IHC assay) within the Stage II-IIIA population, in all 
randomized patients with Stage II-IIIA NSCLC, and in the ITT population. 
Of note, SP263 TC 1% is determined on the basis of PD-L1 expression in tumor cell 
membrane detected by Ventana PD-L1 (SP263) Assay (see Appendix 5). 
3.4.2 
Secondary Efficacy Outcome Measures 
The secondary efficacy outcome measures for this study are as follows: 
 
OS, defined as the time from randomization to death from any cause, in the ITT 
population 
 
DFS rates at 3 years and 5 years in the PD-L1 subpopulation (defined as 
 1% TC 
expression by the SP263 IHC assay), in the Stage II IIIA population (i.e., all 
randomized patients with Stage II IIIA NSCLC) and in the ITT population 
 
DFS in the PDL1 subpopulation, defined as TC 
 50% by the SP263 IHC assay 
within patients with Stage II IIIA NSCLC 
 
3.5 
SAFETY OUTCOME MEASURES 
The safety outcome measures for this study are as follows: 
 
Incidence, nature, and severity of adverse events, serious adverse events, and 
adverse events of special interest graded according to the NCI CTCAE v4.0 
 
Changes from baseline in vital signs, physical findings, and targeted clinical 
laboratory results 
 
Incidence of ATA response to atezolizumab and potential correlation with PK, 
safety, and efficacy parameters 
 
3.6 
PHARMACOKINETIC OUTCOME MEASURES 
The PK outcome measures for this study are as follows: 
 
Atezolizumab maximum serum concentration (Cmax) observed after infusion on 
Day 1 of Cycle 1 

 
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Atezolizumab minimum serum concentration (Cmin) under steady state conditions 
within a dosing interval prior to the infusion on Day 1 of Cycles 2, 3, 4, 8, and 16 and 
at study termination 
 
3.7 
EXPLORATORY OUTCOME MEASURES 
The exploratory outcome measures for this study are as follows: 
 
DFS in TC3 or IC3, TC2/3 or IC2/3, TC1/2/3 or IC1/2/3 subpopulations defined by 
PD-L1 SP142 IHC in both the Stage II-IIIA and the ITT populations 
 
DFS in the PD-L1 subpopulations defined by 22C3 TPS 
 1% and TPS 
 50% in both 
the Stage II-IIIA and the ITT populations 
 
DFS in the PD-L1 subpopulations defined by SP263 TC 1% and TC 
 50% in the 
ITT population 
 
Status of PD-L1 , immune-, and NSCLC related and other exploratory biomarkers 
in tumor tissues, and blood collected before, during, or after treatment with 
atezolizumab or at first evidence of radiographic disease recurrence or confirmation 
of new primary NSCLC 
 
Exploratory biomarkers in biopsy specimens and blood collected at the first 
evidence of radiographic disease recurrence or confirmation of new primary NSCLC 
  
4. 
MATERIALS AND METHODS 
4.1 
PATIENTS 
Patients will be screened and enrolled if they have had a complete surgical resection of 
Stage IB (tumors 
 4 cm) IIIA (per the Union Internationale Contre le Cancer 
[UICC]/American Joint Committee on Cancer [AJCC] staging system, Version 7) NSCLC 
and are eligible for the enrollment phase where they will receive up to four cycles of 
cisplatin-
decision to discontinue occur.  Patients who are enrolled will receive one of 
four chemotherapy regimens at the choice of the investigator.  Provided that they still 
meet eligibility criteria, patients who complete chemotherapy will be randomized to 
receive either atezolizumab (Arm A) or BSC (Arm B). 
4.1.1 
Inclusion Criteria 
4.1.1.1 
Inclusion Criteria for Enrollment Phase 
Patients must meet all of the following criteria to be eligible to enter the enrollment phase 
and receive cisplatin-based chemotherapy regimen in this study: 
 
A representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in 
paraffin block (preferred) or 15 (or more) unstained, freshly cut, serial sections 
(on slides) from an FFPE resected tumor specimen is required for participation in 
this study.  This specimen must be accompanied by the associated pathology 
report. 
 
Signed Informed Consent Form 
 
Age 
 18 years 

 
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ECOG Performance Status of 0 or 1 
 
Histological or cytological diagnosis of Stage IB (tumors 
 4 cm) IIIA (T2 3 N0, 
T1 3 N1, T1-3 N2, T4 N0-1) NSCLC (per the UICC/AJCC staging system, 
7th edition; Detterbeck et al. 2009) 
 
Patients must have had complete resection of NSCLC 4 12 weeks (
 28 days and 
 84 days) prior to enrollment and must be adequately recovered from surgery 
Accepted types of resection include any of the following:  lobectomy, sleeve 
lobectomy, bilobectomy, or pneumonectomy. 
Resection by segmentectomy or wedge resection is not allowed. 
 
If mediastinoscopy was not performed preoperatively, it is expected that, at a 
minimum, mediastinal lymph node systematic sampling will have occurred, though 
complete mediastinal lymph node dissection (MLND) is preferred.  Systematic 
sampling is defined as removal of at least one representative lymph node at 
specified levels.  MLND entails resection of all lymph nodes at those same levels.  
For a right thoracotomy, sampling or MLND is required at levels 4 and 7 and for a 
left thoracotomy, levels 5 and/or 6 and 7.  Exceptions will be granted for the 
following situations: 
If there is clear documentation in the operative report or in a separately 
submitted addendum by the surgeon of exploration of the required lymph node 
areas, the patient will be considered eligible if no lymph nodes are found in 
those areas. 
If patients have documented N2 disease in one level (per the UICC/AJCC 
staging system, 7th edition; Detterbeck et al. 2009), not all levels need to be 
sampled. 
If the preoperative staging imaging results (contrast CT and PET scans) do not 
suggest evidence of disease in the mediastinum, the patient will be considered 
 
 
Eligible to receive a cisplatin-based chemotherapy regimen 
 
Adequate hematologic and end-organ function, defined by the following laboratory 
results obtained within 14 days prior to enrollment: 
ANC 
 1500 cells/ L 
Platelet count 
 100,000 cells/ L 
Prothrombin time/INR 
 1.5, or, if patient is receiving therapeutic 
anticoagulation, prothrombin time/INR 
 3.0 
aPTT 
 institutional upper limit of normal (ULN) OR, if patient is receiving 
therapeutic anticoagulation, aPTT must be 
 1.5 
 ULN 
Total bilirubin 
 1.25 
 ULN 
Patients with known Gilbert disease who have serum bilirubin 
 3 
 ULN 
may be enrolled. 
SGOT (AST) 
 2.5
 ULN 

 
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SGPT (ALT) 
 2.5 
 ULN 
Calculated creatinine clearance (CRCL) 
 60 mL/min, with use of institutional 
guidelines or the standard Cockcroft and Gault formula (1976) (see Appendix 8) 
 
For women of childbearing potential and men with partners of childbearing potential, 
agreement (by patient and/or partner) to use a highly effective form(s) of 
contraception during study treatment that results in a low failure rate of 
 1% per 
year when used consistently and correctly.  Women and men should continue 
contraceptive use for 6 months after the last dose of cisplatin-based chemotherapy 
(cisplatin plus vinorelbine, docetaxel, gemcitabine, or pemetrexed).  Women treated 
with atezolizumab should continue contraception use for 5 months after the last 
dose.  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 has not 
undergone surgical sterilization (removal of ovaries and/or uterus). 
Examples of contraceptive methods with a failure rate of 
  1% per year include 
bilateral tubal ligation, male sterilization, established, proper use of hormonal 
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, 
and copper intrauterine devices. 
The reliability of sexual abstinence should be evaluated in relation to the 
duration of the clinical study and the preferred and usual lifestyle of the patient.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not acceptable methods of contraception. 
Women who are not postmenopausal (
 12 months of non therapy-induced 
amenorrhea) or surgically sterile must have a negative serum pregnancy test 
result within 14 days prior to initiation of cisplatin-based chemotherapy. 
  
4.1.1.2 
Inclusion Criteria for Randomized Phase 
Patients must meet all of the following criteria to be eligible to be randomized to 
receive either atezolizumab or BSC after completion of the enrollment phase and 
up to four cycles of cisplatin-based chemotherapy: 
 
Adequate hematologic and end-organ function defined by the following 
laboratory results obtained within 14 days prior to randomization: 
ANC 
 1500 cells/ L (without granulocyte colony-stimulating factor support) 
Lymphocyte count 
 500 cells/ L 
Platelet count 
 100,000 cells/ L 
Hemoglobin 
 9.0 g/dL 
Patients may be transfused to meet this criterion. 
INR or aPTT 
 1.5 
 ULN 

 
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This applies only to patients who are not receiving therapeutic 
anticoagulation; patients receiving therapeutic anticoagulation should be 
on a stable dose.  
AST, ALT, and alkaline phosphatase  2.5  ULN 
Serum bilirubin  1.25  ULN 
Patients with known Gilbert disease who have serum bilirubin level 
 3 
 ULN may be enrolled. 
Calculated CRCL  30 mL/min 
The CRCL is calculated by institutional guidelines or by the method of 
Cockcroft and Gault formula (1976) (see Appendix 8) 
 
Women who are not postmenopausal (
 12 months of non therapy-induced 
amenorrhea) or surgically sterile must have a negative serum pregnancy test result 
within 14 days prior to initiation of atezolizumab or BSC 
  
4.1.2 
Exclusion Criteria 
4.1.2.1 
Exclusion Criteria for Enrollment Phase 
Patients who meet any of the following criteria will be excluded from study enrollment: 
 
and/or comply with study procedures 
 
Pregnant and lactating women 
 
Treatment with prior systemic chemotherapy, with the following exceptions: 
Chemotherapy for early stage of malignancy with curative intent, provided that 
the last dose received was more than 5 years prior to enrollment, is allowed. 
Low-dose chemotherapy for non-malignant conditions is allowed. 
 
Hormonal cancer therapy or radiation therapy as prior cancer treatment within 
5 years before enrollment 
Prior surgery, biologic therapy, hormonal therapy, or radiation therapy for a 
malignancy over 5 years prior to enrollment that is now considered cured is 
acceptable. 
 
Treatment with any other investigational agent with therapeutic intent within 28 days 
prior to enrollment 
 
A hearing loss (measured by audiometry) of 25 dB at two contiguous frequencies 
(audiometry will only be required for patients who have suspected or definitive 
hearing loss) 
 
Known sensitivity to any component of the chemotherapy regimen the patient will be 
assigned to, or to mannitol 
 
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, 
anti PD-1, and anti PD-L1 therapeutic antibodies 

 
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Patients who have had prior anti CTLA-4 treatment may be enrolled, provided 
the following requirements are met: 
Last dose of anti CTLA-4 at least 6 weeks prior to randomization 
No history of severe immune-mediated adverse effects from anti CTLA-4 
(NCI CTCAE Grades 3 and 4) 
 
Malignancies other than NSCLC within 5 years prior to enrollment, with the 
exception of those with a negligible risk of metastasis or death (e.g., expected 
5-year OS 
 90%) treated with expected curative outcome (such as adequately 
treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized 
prostate cancer treated surgically with curative intent, ductal carcinoma in situ 
treated surgically with curative intent) 
 
History of severe allergic, anaphylactic, or other hypersensitivity reactions 
to chimeric or humanized antibodies or fusion proteins 
 
Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary 
cells or any component of the atezolizumab formulation 
 
History of autoimmune disease, including but not limited to myasthenia gravis, 
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, 
inflammatory bowel disease, vascular thrombosis associated with antiphospholipid 
syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, 
multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix 6 for a more 
comprehensive list of autoimmune diseases) 
Patients with a history of autoimmune-mediated hypothyroidism on a stable 
dose of thyroid replacement hormone are eligible for this study. 
Patients with controlled Type I diabetes mellitus on a stable dose of insulin 
regimen are eligible for this study. 
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with 
dermatologic manifestations only (e.g., no psoriatic arthritis) are permitted 
provided that they meet the following conditions: 
Rash must cover less than 10% of body surface area (BSA). 
Disease is well controlled at baseline and only requiring low-potency topical 
steroids. 
No acute exacerbations of underlying condition within the last 12 months 
requiring treatment with either PUVA [psoralen plus ultraviolet A radiation], 
methotrexate, retinoids, biologic agents, oral calcineurin inhibitors or high 
potency or oral steroids. 
 
Positive test for HIV 
All patients will be tested for HIV prior to the inclusion into the study, and 
patients who are HIV-positive will be excluded from the clinical study. 

 
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Patients with active hepatitis B (chronic or acute; defined as having a positive 
hepatitis B surface antigen [HbsAg] test at screening) or hepatitis C 
Patients with past hepatitis B virus (HBV) infection or resolved HBV infection 
(defined as the presence of hepatitis B core (HBc) antibody and absence of 
HbsAg) are eligible only if they are negative for HBV DNA.  HBV DNA must be 
obtained in these patients prior to enrollment. 
Patients positive for hepatitis C virus (HCV) antibody are eligible only if 
polymerase chain reaction is negative for HCV RNA. 
 
Active tuberculosis 
 
Significant cardiovascular disease, such as New York Heart Association cardiac 
disease (Class II or greater), myocardial infarction, or cerebrovascular accident 
within the previous 3 months, 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. 
 
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis 
obliterans), drug-IKLinduced pneumonitis, idiopathic pneumonitis, or evidence of 
active pneumonitis on screening chest CT scan 
History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 
 
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 renders the patient at high risk from treatment 
complications 
 
Known tumor PD-L1 expression status as determined by an IHC assay from other 
clinical studies (e.g., patients whose PD-L1 expression status was determined 
during screening for entry into a study with anti PD-1 or anti PD-L1 antibodies but 
were not eligible are excluded) 
 
Specific Exclusions for Pemetrexed Treatment 
 
Patients with squamous cell histology 
  
4.1.2.2 
Exclusion Criteria for Randomized Phase 
Patients who meet any of the following criteria will be excluded from study 
randomization: 
 
Signs or symptoms of infection within 14 days prior to randomization (severe 
infection within 28 days prior to randomization), including but not limited to 
hospitalization for complications of infection, bacteremia, or severe pneumonia 

 
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Received therapeutic oral or IV antibiotics within 14 days prior to randomization 
Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract 
infection or to prevent chronic obstructive pulmonary disease exacerbation) 
are eligible. 
 
Major surgical procedure within 28 days prior to randomization or anticipation of 
need for a major surgical procedure during the course of the study 
 
Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study 
treatment or anticipation that such a live attenuated vaccine will be required during 
the study 
 
Treatment with systemic immunostimulatory agents (including, but not limited to, 
IFNs or IL-2) within 4 weeks or 5 drug-elimination half-lives of the drug, whichever is 
longer, prior to randomization 
Prior treatment with cancer vaccines is allowed. 
 
Treatment with systemic corticosteroids or other immunosuppressive medications 
(including but not limited to prednisone, dexamethasone, cyclophosphamide, 
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] 
agents) within 14 days prior to randomization 
Patients who have received acute, low-dose (
 10 mg oral prednisone or 
equivalent), systemic immunosuppressant medications may be randomized in 
the study. 
The use of corticosteroids (
 10 mg oral prednisone or equivalent) for chronic 
obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for 
patients with orthostatic hypotension, or low dose supplemental corticosteroids 
for adrenocortical insufficiency are allowed. 
  
4.2 
METHOD OF TREATMENT ASSIGNMENT AND BLINDING 
This is an open-label study.  After written informed consent has been obtained and 
eligibility for both enrollment and randomization has been established (which includes 
completion of up to four cycles of cisplatin-based chemotherapy), the study site will enter 
demographic and baseline characteristics in the interactive voice/Web response system 
(IxRS).  For those patients who are eligible for study randomization, the study site will 
Randomization to the treatment and control arms will occur in a 1:1 ratio with use of a 
permuted-block randomization method.  Randomization will be stratified by the 
following factors: 
 
Sex (female vs. male) 
 
Tumor histology (squamous vs. non-squamous) 
 
Extent of disease (Stage IB vs. Stage II vs. Stage IIIA) 
 
PD-L1 tumor expression status (TC2/3 and any IC vs. TC0/1 and IC2/3 vs. TC0/1 
and IC0/1 using the SP142 IHC assay) 
 

 
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Patients should undergo randomization within 3 8 weeks after receiving their last dose 
of induction treatment. 
Patients should receive their first dose of study treatment (chemotherapy or 
atezolizumab) on the day of enrollment or randomization, respectively, if possible.  
If this is not possible, the first dose should occur within 5 days after enrollment or 
randomization. 
4.3 
STUDY TREATMENT 
The term "study treatment" refers to all protocol-mandated treatments and includes 
atezolizumab and cisplatin plus vinorelbine, docetaxel, gemcitabine, or pemetrexed.  
The investigational medicinal product (IMP) for this study is atezolizumab.  Appendix 10 
identifies all investigational, non-investigational, and auxiliary medicinal products for this 
study. 
4.3.1 
Cisplatin-Based Chemotherapy Regimens 
Once patients are pre-screened to receive cisplatin-based chemotherapy and have been 
determined to be eligible, surgically resected patients will be enrolled to receive one of 
four cisplatin-based chemotherapy options (see Table 9).  Patients will receive up to 
four cycles of cisplatin-based chemotherapy unless unacceptable toxicity, disease 
(21 days) in length.  The investigator will select the chemotherapy regimen (1, 2, 3, or 4) 
for the patient prior to enrollment. 
Table 9 
Cisplatin-Based Chemotherapy Regimens 
Regimen 
Cisplatin 75 mg/m2 IV, Day 1, Plus 
1 
Vinorelbine 30 mg/m2 IV push, Days 1 and 8 
2 
Docetaxel 75 mg/m2 IV, Day 1 
3 
Gemcitabine 1250 mg/m2 IV, Days 1 and 8 
4 
Pemetrexed 500 mg/m2 IV, Day 1 (non-squamous cell NSCLC only) 
IV 
 intravenous; NSCLC 
 non small cell lung cancer. 
  
4.3.2 
Formulation, Packaging, and Handling of Cisplatin-Based 
Chemotherapy 
4.3.2.1 
Cisplatin 
Cisplatin is commercially available as a 1 mg/mL solution in 50- and 100-mg vials.  Intact 
vials of cisplatin are stored at room temperature.  Solutions diluted with sodium chloride 
or dextrose are stable for up to 72 hours at room temperature.  Because of the risk of 
precipitation, cisplatin solutions should not be refrigerated.  In preparation, the desired 
dose of cisplatin is diluted with 250 1000 mL of saline and/or dextrose solution.  
Varying concentrations of 0.225% 5% sodium chloride and 5% dextrose may be used.  

 
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To maintain stability of cisplatin, a final sodium chloride concentration of at least 0.2% is 
recommended. 
4.3.2.2 
Vinorelbine 
Vinorelbine is commercially available in 10 mg/mL ampules and 50-mg/5 mL vials.  
Intact vials are stored under refrigeration (2 C 8 C) and must be protected from light.  
Unopened vials are stable at temperatures up to 25 C for up to 72 hours.  Vials should 
not be frozen.  The drug must be diluted prior to administration.  Diluted vinorelbine is 
stable for 24 hours under normal room light when stored in polypropylene syringes or 
polyvinyl chloride (PVC) bags at 5 C 30 C). 
For administration via syringe, the dose of the drug should be diluted to a concentration 
between 1.5 and 3.0 mg/mL with dextrose 5% or normal saline.  For administration via 
IV bag, the dose of vinorelbine should be diluted between 0.5 and 2 mg/mL.  
The following solutions may be used for dilution:  0.9% sodium chloride, 0.45% sodium 
chloride, 5% 
 
4.3.2.3 
Docetaxel 
Docetaxel is commercially available in single-dose vials containing 20 mg (0.5 mL) or 
80 mg (2.0 mL) docetaxel (anhydrous).  Docetaxel is stored at 4 C protected from light.  
The solvent vials may be stored at room temperature or at 4 C.  The premix solution is 
stable for 8 hours at room temperature (15 C 25 C) or refrigerated (at 2 C 8 C).  The 
final dilution is also stable for 8 hours.  Note that the company (Aventis Pharmaceuticals) 
is no longer recommending that the final product be placed in PVC bags. 
Just prior to use, allow the docetaxel vial to reach room temperature for 5 minutes.  
Add the entire contents of the ethanol diluent vial and mix by gently rotating the vial for 
15 seconds.  Allow to stand for 5 minutes at room temperature and check that the 
solution is homogeneous and clear (persistent foam is normal).  The resulting solution 
contains 10 mg/mL of docetaxel.  Note that the solution contains 15% overfill.  Dosing 
amounts should be based in the concentration per extractable volume, not the total 
volume of the vial.  The desired dose is diluted in 5% dextrose in water or normal saline 
(NS).  The volume of the infusion should be adjusted in order to have a final docetaxel 
concentration of between 0.3 mg/mL and 0.9 mg/mL.  Non PVC-containing IV infusion 
bags and administration sets should be used to avoid patient exposure to the 
plasticizer DEHP. 
4.3.2.4 
Gemcitabine 
Gemcitabine is commercially available in 200-mg and 1-g vials.  Un-reconstituted drug 
vials are stored at controlled room temperature.  Reconstituted solution should be stored 
at controlled room temperature and used within 24 hours.  Solutions of gemcitabine 
should not be refrigerated because this could cause crystallization to occur.  The unused 
portion should be discarded.  In preparation, reconstitute the 200-mg vial with 5 mL and 

 
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the 1-g vial with 25 mL preservative-free normal saline to make a solution containing 
38 mg/mL.  Shake to dissolve. 
4.3.2.5 
Pemetrexed 
Pemetrexed is supplied as a sterile lyophilized powder for IV infusion available in 
single-dose vials (100-mg and 500-mg vials).  The product is a white to either light 
yellow or green-yellow lyophilized solid.  Each 500-mg vial of pemetrexed contains 
pemetrexed disodium equivalent to 500 mg pemetrexed and 500 mg mannitol.  Each 
100-mg vial of pemetrexed disodium contains equivalent to 100 mg pemetrexed and 
106 mg mannitol.  Hydrochloric acid and/or sodium hydroxide may have been added to 
adjust pH.  Pemetrexed for injection should be stored at 25 C (77 F); excursions 
permitted to 15 C 30°C (59 F 86 F; see USP Controlled Room Temperature).  
Chemical and physical stability of reconstituted and infusion solutions of pemetrexed 
were demonstrated for up to 24 hours following initial reconstitution, when stored 
refrigerated, 2 C 8 C (36 F 46 F), or at 25 C (77 F), excursions permitted to 
15 C 30 C (59 F 86 F; see USP Controlled Room Temperature).  When prepared as 
directed, reconstituted and infusion solutions of pemetrexed contain no antimicrobial 
preservatives.  Discard unused portion.  Pemetrexed is not light sensitive. 
4.3.3 
Dosage, Administration, and Supportive Care 
Recommendations for Cisplatin-Based Chemotherapy 
used for calculating BSA.  B
by 
 10%. 
Institutions should follow their standard administration regimens (e.g., administration 
sequence or time) for the chemotherapy treatment.  The premedication doses 
administered should be in compliance with prescribing information. 
4.3.3.1 
Chemotherapy Regimen 1:  Cisplatin/Vinorelbine 
Administer 30 mg/m2 IV vinorelbine push over 6 10 minutes on Days 1 and 8.  
Administer 75 mg/m2 IV cisplatin over 60 minutes on Day 1 immediately following 
vinorelbine.  Institutional standards that require a prolonged cisplatin infusion are 
acceptable if the infusion does not exceed 4 hours. 
Vinorelbine.  Vinorelbine must be administered intravenously.  The diluted vinorelbine is 
administered over 6 10 minutes into a running infusion via a side-arm port closest to the 
IV bag.  The IV line should be flushed well with at least 75 125 mL of one of the 
solutions.  NOTE:  It is extremely important that the IV needle or catheter be properly 
positioned before any vinorelbine is injected.  Leakage into surrounding tissue during 
IV administration of vinorelbine may cause considerable irritation, local tissue necrosis, 
and/or thrombophlebitis.  If extravasation occurs, the injection should be discontinued 
immediately, and any remaining portion of the dose should then be introduced into 

 
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another vein.  Because there are no established guidelines for the treatment of 
extravasation injuries with vinorelbine, institutional guidelines may be used. 
Cisplatin.  Cisplatin is usually administered as an IV infusion over 60 minutes. 
See Section 4.3.3.5 for supportive care recommendations with cisplatin-based 
chemotherapy. 
4.3.3.2 
Chemotherapy Regimen 2:  Cisplatin/Docetaxel 
Administer 75 mg/m2 IV docetaxel over 60 minutes on Day 1.  Administer 75 mg/m2 
IV cisplatin over 60 minutes, Day 1, immediately following docetaxel. 
Docetaxel.  Docetaxel will be given by IV infusion at a dose of 75 mg/m2 over 
60 minutes on Day 1 (each cycle to be repeated every 3 weeks), immediately prior to 
cisplatin administration.  It is recommended that docetaxel be administered with use of a 
peristaltic infusion pump. 
Cisplatin.  Cisplatin is usually administered as an IV infusion over 60 minutes. 
Premedications 
Patients should receive steroid premedication for docetaxel according to local standard 
 
It is recommended to give a dexamethasone (or equivalent steroid) regimen of 8 mg 
by mouth (PO) every 12 hours for 5 doses starting 24 hours prior to docetaxel 
infusion, continuing the day of docetaxel infusion, and finishing the day after the 
docetaxel infusion. 
Supportive Care 
See Section 4.3.3.5 for supportive care recommendations with cisplatin-based 
chemotherapy. 
Other Prophylaxis Treatments 
Granulocyte colony-stimulating factor treatment is permitted for patients treated with 
the cisplatin/docetaxel regimen.  The primary prophylaxis should be administered 
per the American Society of Clinical Oncology (ASCO), European Organisation for 
Research and Treatment of Cancer, and European Society of Medical Oncology 
guidelines in patients who are 
 60 years of age and/or with comorbidities 
(Smith et al. 2006; Crawford et al. 2009; Aapro et al. 2011).  Anti-emetics, anti-allergic 
measures, and other treatments for concomitant docetaxel toxicities may be used at the 
discretion of the investigator, taking into account precautions from the Summary of 
Product Characteristics. 
Refer to the Summary of Product Characteristics (Package Insert) for docetaxel for all 
boxed warnings and contraindications. 

 
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4.3.3.3 
Chemotherapy Regimen 3:  Cisplatin/Gemcitabine 
Administer gemcitabine 1250 mg/m2 IV over 30 minutes on Days 1 and 8.  Administer 
cisplatin 75 mg/m2 IV over 60 minutes on Day 1 immediately following gemcitabine. 
Gemcitabine.  Gemcitabine is administered over 30 minutes as prepared or further 
diluted with normal saline to a minimum concentration of 0.1 mg/mL.  Gemcitabine is 
commonly diluted in 100 mL or 250 mL of saline.  Reconstitution at greater than 
40 mg/mL may result in incomplete dissolution of drug. 
Cisplatin.  Cisplatin is usually administered as an IV infusion over 60 minutes. 
Supportive Care 
See Section 4.3.3.5 for supportive care recommendations with cisplatin-based 
chemotherapy. 
4.3.3.4 
Chemotherapy Regimen 4:  Cisplatin/Pemetrexed 
(For Patients with Non-Squamous Histology) 
Administer pemetrexed 500 mg/m2 IV over 10 minutes on Day 1.  Administer cisplatin 
75 mg/m2 IV over 60 minutes on Day 1 immediately following pemetrexed. 
Pemetrexed.  Pemetrexed is administered as an IV infusion over 10 minutes. 
Cisplatin.  Cisplatin is usually administered as an IV infusion over 60 minutes. 
Supportive Care 
See Section 4.3.3.5 for supportive care recommendations with cisplatin-based 
chemotherapy. 
Other Prophylaxis Treatments 
Patients should receive corticosteroid, folic acid, and vitamin B-12 premedication for 
pemetrexed.  The choice of steroid and timing of premedication can be administered 
All patients on 
pemetrexed must receive 1000 g of vitamin B-12 intramuscularly given within 2 weeks 
of the first dose of chemotherapy and repeated at least every 9 weeks until 3 weeks after 
the last dose of pemetrexed.  All patients in the pemetrexed group must take 
350 1000 g of folate (folic acid) orally daily starting at least 5 7 days prior to initiation 
of pemetrexed and continuing for at least 3 weeks after completion of the last dose of 
pemetrexed.  It is also recommended that patients receive dexamethasone 4 mg orally 
twice daily (or an equivalent corticosteroid) on the day before, day of, and day after each 
dose of pemetrexed to prevent the occurrence of rash.  All patients receiving 
pemetrexed therapy should avoid taking NSAIDs with long elimination half-lives for at 
least 5 days prior to, on the day of, and at least 2 days following administration of 
pemetrexed. 

 
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4.3.3.5 
Supportive Care Recommendations for Cisplatin-Based 
Chemotherapy 
Anti-Emetics 
It is strongly recommended that all patients receive adequate anti-emetics with 
cisplatin-based chemotherapy.  The specifics of the regimen are at the discretion of the 
treating physician, provided adequate control is achieved.  One potential regimen 
consists of 20 mg of oral dexamethasone and a high dose of oral or IV 5HT3 antagonist 
(such as 2 mg oral or 10 mcg/kg IV granisetron, or 32 mg oral or IV ondansetron) on the 
day of cisplatin administration, followed by additional anti-emetics consisting of 4 days of 
oral dexamethasone (8 mg PO twice a day [BID] for 2 days [Days 2 and 3] then 4 mg PO 
BID for 2 days [Days 4 and 5]) and scheduled metoclopramide or 5HT3 antagonist for 
Days 2 5 for delayed emesis.  NOTE:  Dexamethasone dose should be reduced by 50% 
when administered with aprepitant. 
Hydration Requirements 
Hydration guidelines may be modified at the discretion of the treating physician 
provided adequate pre- and post-cisplatin hydration is achieved and that renal 
function remains adequate.  One suggested regimen consists of administering 
cisplatin in 500 cc to 1000 cc of IV fluids following adequate hydration and the 
establishment of adequate urinary output.  It is suggested the pre-cisplatin 
hydration consist of NS at 500 cc/hr 
 1 liter and post-cisplatin hydration consist of 
0.5L NS 
 10 mEq KCl/L 
 1 gram magnesium sulfate/L 
 25 grams mannitol/L at 
500 cc/hr for at least 1 hour, followed by additional hydration at the discretion of 
the investigator. 
4.3.4 
Atezolizumab 
4.3.4.1 
Atezolizumab Formulation, Packaging, and Handling 
The atezolizumab (MPDL3280A) drug product is provided as a sterile liquid in 20 mL 
glass vials.  The vial is designed to deliver 20 mL (1200 mg) of atezolizumab solution but 
may contain more than the stated volume to enable delivery of the entire 20 mL volume. 
For further details on the storage and preparation of atezolizumab, see the Atezolizumab 
re. 
4.3.4.2 
Atezolizumab Dosage, Administration, and Compliance 
Patients who are randomized to be treated with atezolizumab will receive 
1200 mg atezolizumab administered by IV infusion every 21 days in a monitored setting 
where there is immediate access to trained personnel and adequate 
equipment/medicine to manage potentially serious reactions (see Appendix 7). 
Atezolizumab infusions will be administered per the instructions outlined in Table 10. 

 
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standard operating procedure or returned to the Sponsor with the appropriate 
of IMP destruction must be agreed upon by the 
Sponsor.  The site must obtain written authorization from the Sponsor before any IMP is 
destroyed, and IMP destruction must be documented on the appropriate form. 
Accurate records of all IMP received at, dispensed from, returned to, and disposed of by 
the study site should be recorded on the Drug Inventory Log. 
4.3.6 
Post-Study Access to Atezolizumab 
Currently, the Sponsor does not have any plans to provide Roche IMP (atezolizumab) 
or any other study treatments to participants who have completed the study.  The 
Sponsor may evaluate whether to continue providing atezolizumab in accordance with 
the Roche Global Policy on Continued Access to Investigational Medicinal Product, 
available at the following website: 
https://assets.cwp.roche.com/f/176343/x/92d6b13ee6/policy_continued_access_to_invest
igational_medicines.pdf 
4.4 
CONCOMITANT THERAPY 
Concomitant therapy includes any prescription medications or over-the-counter 
preparations used by a patient between the 7 days preceding the screening evaluation 
and the treatment discontinuation visit. 
4.4.1 
Contraindications and Use of Concomitant Medications with 
Cisplatin-Based Chemotherapy Regimens 
4.4.1.1 
Cisplatin 
Cisplatin is highly contraindicated in patients with preexisting renal impairment and 
should not be administered in patients who have a history of myelosuppression or 
patients with hearing impairment (see Section 4.3.3 for further instructions for reducing 
cisplatin related side effects). 
Cisplatin is contraindicated in patients with a history of allergic reactions to cisplatin or 
other platinum-containing compounds.  Incompatibilities with cisplatin include the 
following drugs:  amsacrine, cefepime, gallium nitrate, mesna, piperacillin, sodium 
bicarbonate, and thiotepa.  Cisplatin may react with aluminum, which is found in some 
syringe needles or IV sets, forming a black precipitate.  Plasma levels of anticonvulsant 
agents may become subtherapeutic during cisplatin therapy.  In a randomized study in 
advanced ovarian cancer, response duration was adversely affected when pyridoxine 
was used in combination with altretamine (hexamethylmelamine) and cisplatin 
(see the Cisplatin Package Insert). 
4.4.1.2 
Docetaxel 
Docetaxel is contraindicated in patients who have a history of severe hypersensitivity 
reactions to docetaxel or to other drugs formulated with polysorbate 80.  Severe 

 
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reactions, including anaphylaxis, have occurred [see the Docetaxel Package Insert for 
additional information].  Patients with bilirubin greater than ULN, or patients with AST 
and/or ALT 
 1.5 
 ULN and alkaline phosphatase 
 2.5 
 ULN should not be treated with 
docetaxel because patients with these liver enzyme abnormalities are at risk for the 
development of Grade 4 neutropenia, febrile neutropenia, infections, severe 
thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death.  Additionally, 
patients with neutrophil counts of 
 1500 cells/mm³ should not be dosed with docetaxel 
and frequent blood cell counts should be performed on all patients receiving this 
regimen. 
Docetaxel is a CYP3A4 substrate.  Patients who receive docetaxel must avoid using 
concomitant strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, 
atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and 
voriconazole).  There are no clinical data with a dose adjustment in patients receiving 
strong CYP3A4 inhibitors.  In addition, concomitant treatment with CYP3A4 inducers 
may decrease plasma concentrations of docetaxel.  Concomitant medications that are 
CYP3A4 inducers should therefore be used with caution.  
4.4.1.3 
Vinorelbine 
Acute pulmonary reactions have been reported and can occur with vinorelbine and other 
anti-cancer vinca alkaloids used in conjunction with mitocycin.  Vinorelbine 
pharmacokinetics are not affected with concurrent administration of cisplatin although 
granulocytopenia has been reported to occur when both are administered together as 
opposed to vinorelbine administered alone.  Patient monitoring is suggested when 
vinorelbine is given with drugs that inhibit metabolism of the P450 isoenzyme (CYP3A) 
or in patients who have hepatic impairment because concurrent administration of 
vinorelbine with these drugs often causes additional and more severe side effects (see 
the Vinorelbine Package Insert). 
4.4.1.4 
Gemcitabine 
No formal drug interaction studies have been conducted with gemcitabine or in 
post-marketing experience, but with concurrent administrations of gemcitabine 
(1250 mg/m2 on Days 1 and 8) and cisplatin (75 mg/m2 on Day 1) in patients with 
NSCLC, the clearance of gemcitabine on Day 1 was 128 L/hr/m2 and on Day 8 was 
107 L/hr/m2 (see the Gemcitabine Package Insert).  The incidence of febrile neutropenia 
(9/262 vs. 2/260), sepsis (4% vs. 1%), Grade 3 cardiac dysrhythmias (3% vs. 
 1%) were 
all higher in the patients who received concurrent combinations of gemcitabine with 
cisplatin compared with patients who received cisplatin alone.  The two-drug 
combination was more myelosuppressive with 4 possibly treatment-related deaths 
(1.5%), including 3 resulting from myelosuppression with infection and one case of renal 
failure associated with pancytopenia and infection. 

 
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4.4.1.5 
Pemetrexed 
Cisplatin does not affect the pharmacokinetics of pemetrexed and the pharmacokinetics 
of total platinum is unaltered by pemetrexed.  Co-administration of oral folic acid or 
intramuscular vitamin B-12 does not affect the pharmacokinetics of pemetrexed.  Results 
from in vitro studies with human liver microsomes demonstrated that pemetrexed would 
not cause clinically significant inhibition of metabolic clearance of drugs metabolized by 
CYP3A, CYP2D6, CYP2C9, and CYP1A2.  No studies were conducted to determine the 
cytochrome P450 isozyme induction potential of pemetrexed, because pemetrexed used 
as recommended (once every 21 days) would not be expected to cause any significant 
enzyme induction.  Aspirin, administered in low to moderate doses (325 mg every 
6 hours), does not affect the pharmacokinetics of pemetrexed.  The effect of greater 
doses of aspirin on pemetrexed pharmacokinetics is unknown. 
All patients receiving pemetrexed therapy should avoid taking NSAIDs with long 
elimination half-lives for at least 5 days prior to, on the day of, and at least 2 days 
following administration of pemetrexed.  If concomitant administration of an NSAID is 
necessary, patients should be monitored closely for toxicity, especially 
myelosuppression, renal, and gastrointestinal toxicity. 
4.4.2 
Permitted Therapy with Atezolizumab 
Concomitant therapy includes any medication (e.g., prescription drugs, over-the-counter 
drugs, herbal or homeopathic remedies, nutritional supplements) used by a patient from 
7 days prior to screening for enrollment and randomization until the treatment 
discontinuation visit.  All such medications should be reported to the investigator. 
Premedication with antihistamines may be administered for any atezolizumab infusions 
after Cycle 1. 
The following therapies should continue while patients are in the study: 
 
Oral contraceptives 
 
Hormone-replacement therapy 
 
Prophylactic or therapeutic anticoagulation therapy (such as low-molecular weight 
heparin or warfarin at a stable dose level) 
 
Vaccinations (such as influenza, COVID19) 
Live, attenuated vaccines are not permitted (see Section 4.4.4). 
 
Megestrol administered as an appetite stimulant 
 
Corticosteroids (
 10 mg oral prednisone or equivalent) for chronic obstructive 
pulmonary disease 
 
Mineralocorticoids (e.g., fludrocortisone) 
 
Low-dose corticosteroids for patients with orthostatic hypotension or adrenocortical 
insufficiency 
 

 
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In general, investigators should 
clinically indicated, as per local standards.  Patients who experience infusion-associated 
symptoms may be treated symptomatically with acetaminophen, ibuprofen, 
diphenhydramine, and/or famotidine or another H2-receptor antagonist as per standard 
practice (for sites outside the United States, equivalent medications may be substituted 
per local 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 7). 
All medications must be recorded on the Concomitant Medications electronic Case 
Report Form (eCRF). 
4.4.3 
Cautionary Therapy for Atezolizumab-Treated Patients 
Systemic corticosteroids, immunosuppressive medications, and TNF-  inhibitors may 
attenuate potential beneficial immunologic effects of treatment with atezolizumab.  
Therefore, in situations where systemic corticosteroids, immunosuppressive 
medications, or TNF-  inhibitors would be routinely administered, alternatives (including 
antihistamines) should be considered first by the treating physician.  If the alternatives 
are not feasible, systemic corticosteroids, immunosuppressive medications, and TNF-  
inhibitors may be administered at the discretion of the treating physician except in the 
case of patients for whom CT scans with contrast are contraindicated (i.e., patients with 
contrast allergy or impaired renal clearance; see Section 4.4.4). 
Systemic corticosteroids or immunosuppressive medications are recommended, with 
caution, at the discretion of the treating physician, for the treatment of specific adverse 
events when associated with atezolizumab therapy.  Guidelines for management of 
immune-mediated adverse events are described in Appendix 9. 
4.4.4 
Prohibited Therapy 
Any concomitant therapy intended for the treatment of cancer, whether 
health authority-approved or experimental, is prohibited for various time periods prior 
to starting study treatment (depending on the anti-cancer agent; see Section 4.1.2) 
and during study treatment until disease recurrence is documented and patient has 
discontinued study treatment.  This includes but is not limited to chemotherapy, 
hormonal therapy, immunotherapy, radiotherapy, investigational agents, or 
herbal therapy. 
The following medications are prohibited while in the study, unless otherwise noted: 
 
Any live, attenuated vaccine (e.g., FluMist®) within 4 weeks prior to initiation of study 
treatment, during atezolizumab treatment, and for 5 months after the final dose of 
atezolizumab (for patients randomized to atezolizumab) 

 
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Use of steroids to premedicate patients for whom CT scans with contrast are 
contraindicated (i.e., patients with contrast allergy or impaired renal clearance).  In 
such patients, non-contrast CT of the chest and non-contrast CT/MRI of other 
locations (if needed) should be performed. 
 
The concomitant use of herbal therapies is not recommended because their 
pharmacokinetics, safety profiles, and potential drug-drug interactions are generally 
unknown.  However, their use for patients in the study is allowed at the discretion of the 
investigator.  As noted above, herbal therapies that are intended for the treatment of 
cancer are prohibited. 
4.5 
STUDY ASSESSMENTS 
Flowcharts of scheduled study assessments are provided in Appendix 1, Appendix 2, 
and Appendix 3. 
Patients will be closely monitored for safety and tolerability throughout the study.  
All assessments must be performed and documented for each patient. 
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. 
If the timing of a protocol-mandated study visit coincides with a holiday and/or weekend 
that precludes the visit, the visit should be scheduled on the nearest following feasible 
date, with subsequent visits rescheduled accordingly. 
4.5.1 
Informed Consent Forms and Screening Log 
Written informed consent for participation in the study must be obtained before 
performing any study-specific screening tests or evaluations and may be obtained more 
than 28 days before initiation of study treatment. 
Prior to signing the main consent form for the study, patients may specifically allow for 
the collection and testing of archival or fresh tumor tissue by signing the pre-screening 
consent form. 
Informed Consent Forms for enrolled patients and for patients who are not subsequently 
enrolled will be maintained at the study site. 
All screening evaluations must be completed and reviewed to confirm that patients meet 
all eligibility criteria before enrollment and 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. 

 
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4.5.2 
Medical History and Demographic Data 
Medical history includes clinically significant diseases, surgeries, cancer history 
(including prior cancer therapies and procedures), reproductive status, smoking history, 
use of alcohol and drugs of abuse, and all medications (e.g., prescription drugs, 
over-the-counter drugs, herbal or homeopathic remedies, nutritional supplements) used 
by the patient within 7 days prior to the screening visit.  Demographic data will include 
age, sex, and self-reported race/ethnicity.  Cancer history will include an assessment of 
tumor mutational status, if the result is available (e.g., sensitizing EGFR mutation, ALK 
fusion status). 
4.5.3 
Physical Examinations 
A complete physical examination should include a weight measurement and an 
evaluation of the head, eyes, ears, nose, and throat, and the cardiovascular, 
dermatological, musculoskeletal, respiratory, gastrointestinal, genitourinary, and 
neurological systems at screening.  Any abnormality identified at baseline should be 
recorded on the General Medical History and Baseline Conditions eCRF. 
At subsequent visits (or as clinically indicated), limited, symptom-directed physical 
examinations should be performed.  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 the measurements of respiratory rate, heart rate, systolic and 
diastolic blood pressures while the patient is in a seated position, and temperature. 
For patients assigned to Arm A (atezolizumab treatment arm), at the first infusion, vital 
signs (heart rate, respiratory rate, blood pressures, and temperature) should be 
determined within 60 minutes before the infusion and 30 (
 10) minutes after the 
infusion, if clinically indicated.  Vital signs will also be collected during the first infusion 
(every 15 [
 5] minutes), if clinically indicated.  For subsequent infusions, vital signs will 
be collected within 60 minutes prior to the infusion and should be collected during or 
after the infusion if clinically indicated or if symptoms occurred in the prior infusion.  
See Table 10 for more details. 
For patients in Arm B, vital signs will be collected as per standard of care. 
4.5.5 
Tumor and Response Evaluations 
Patients must be disease free at screening and reassessed at each subsequent tumor 
evaluation once randomized into study.  Tumor assessments are to be performed at 
the timepoints specified in Appendix 2, with a window of 
 7 days in the first year, 
 14 days for Year 2 and Year 3, and 
 1 month after Year 3, regardless of drug delays 
or interruptions. 

 
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Screening assessments in the enrollment phase will include an X-ray of the chest, 
CT scans (with oral/IV contrast unless contraindicated) of the chest and abdomen and a 
CT/MRI of the brain to rule out CNS metastasis, especially if patient has Stage IIIA 
disease.  A spiral CT scan of the chest may be obtained but is not a requirement.  
MRI of the chest and abdomen with a non-contrast CT scan of the chest may be used in 
patients for whom CT scans with contrast are contraindicated (i.e., patients with contrast 
allergy or impaired renal clearance). 
Screening assessments in the randomization phase will include CT scan (with oral/IV 
contrast unless contraindicated) of the chest (including liver and adrenal). 
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. 
Bone scans and CT scans of the neck should also be performed if clinically indicated. 
Subsequent tumor assessments will include CT scans (with oral/IV contrast unless 
contraindicated) of the chest (including liver and adrenal) every 4 months in the first year 
and every 6 months in the second year after randomization.  During Years 3 5, tumor 
assessment will be conducted every 6 months, by chest X-ray or chest CT (including 
liver and adrenal), until disease recurrence, death, loss to follow-up, consent withdrawal, 
or study termination by the Sponsor, whichever occurs first.  After Year 5 and the 
completion of the final analysis of DFS, there will no longer be a study requirement for 
tumor assessments to be completed and patients are to be followed according to the local 
standard as a part of their regular medical care.  If a recurrence of the primary NSCLC, 
or a new second primary NSCLC or new primary non-NSCLC malignancy is diagnosed 
as a part of regular medical care, this data is to be entered in the study's electronic data 
capture (EDC) system. 
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).  Assessments 
should be performed by the same evaluator if possible to ensure internal consistency 
across visits. 
4.5.6 
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 (CBC, including RBC count, hemoglobin, hematocrit, WBC count with 
differential [neutrophils, eosinophils, lymphocytes, monocytes, basophils, and other 
cells], and platelet count) 
 
Serum chemistries (glucose, BUN or urea, creatinine, sodium, potassium, 
magnesium, chloride, bicarbonate or total carbon dioxide (if considered standard of 

 
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care for the site), calcium, phosphorus, total bilirubin, ALT, AST, alkaline 
phosphatase, LDH, total protein, and albumin) 
 
Coagulation (aPTT and INR for the enrollment phase; aPTT or INR for the 
randomization phase) 
 
Serum pregnancy test for women of childbearing potential, including women who 
have had a tubal ligation; urine pregnancy tests will be performed at each cycle 
during treatment.  A serum pregnancy test must be performed if the urine pregnancy 
test is positive. 
Childbearing potential is defined as not having undergone surgical sterilization, 
hysterectomy, and/or bilateral oophorectomy or not being postmenopausal 
(
 12 months of amenorrhea). 
 
Urinalysis (specific gravity, pH, glucose, protein, ketones, and blood); dipstick 
permitted 
 
Thyroid function testing (thyroid-stimulating hormone [TSH], free T3, free T4) 
Total T3 (instead of free T3) should be tested only at sites where free T3 testing 
cannot be performed. 
 
HIV 
All patients will be tested for HIV prior to the inclusion into the study and 
patients who are HIV-positive will be excluded from the clinical study. 
 
HBV serology (HBsAg, antibody to HBsAg [anti-HBs], anti-HBc) 
HBV DNA is required on or before enrollment (only patients negative for HBV 
DNA are eligible) if patient has negative serology for HBsAg and positive 
serology for anti-HBc. 
 
HCV serology:  hepatitis C virus antibody (anti-HCV) 
HCV RNA should be obtained prior to enrollment if the patient tests positive for 
anti-HCV. 
 
A central laboratory will coordinate the sample collection of tissue and blood samples for 
research-related testing at central laboratories or at the Sponsor.  Instruction manuals 
and supply kits will be provided for all central laboratory assessments.  Samples for the 
following laboratory tests will be sent to one or several laboratories for analysis: 
 
ATA assays (patients assigned to atezolizumab only) 
Serum samples will be assayed for the presence of ATAs to atezolizumab with 
use of validated immunoassays. 
 
PK assay (patients assigned to atezolizumab only) 
Serum samples will be assayed for atezolizumab concentration with use of a 
validated immunoassay. 

 
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Biomarker assays in blood samples 
Blood samples will be obtained for biomarker evaluation (including but not 
limited to biomarkers that are related to NSCLC or tumor immune biology) from 
all eligible patients according to the schedule in Appendix 3.  Samples will be 
processed to obtain EDTA plasma and serum for the determination of changes 
in blood-based biomarkers (e.g., cytokines, ctDNA).  Whole blood samples may 
be processed to obtain their derivatives (e.g., RNA and DNA) and may be 
evaluated for immune-mediated, tumor type-related, and other exploratory 
biomarkers (e.g., alterations in gene expression or single nucleotide 
polymorphisms). 
Residual PK and ATA samples will be retained for further method development, 
assay validation, and characterization.  Samples will be stored for up to 5 years 
after the final clinical study report has been completed. 
 
For patients who consent to the optional collection of samples for the Roche Clinical 
Repository (RCR) any remaining material from the above sample collection will be 
stored and used for exploratory analyses as indicated in Section 4.5.11.  
For patients who consent to RCR optional future research on their whole blood 
samples collected at screening but are determined to be ineligible for study 
participation, these samples and their derivatives (e.g., DNA, RNA, protein) may be 
used for future development of biomarker and/or diagnostic tests as indicated in 
Section 4.5.11. 
 
See the Laboratory Manual for additional details on laboratory assessments and 
sample handling. 
4.5.7 
Resected Tumor Tissue Samples 
A central laboratory will coordinate the sample collection of resected tumor tissue 
samples for research-related testing at central laboratories or at the Sponsor.  Instruction 
manuals and supply kits will be provided for all central laboratory assessments. 
See the Laboratory Manual for additional details on tissue sample handling. 
4.5.8 
Resected Tumor Tissue Samples for Screening 
Representative tumor specimens in paraffin blocks (preferred) or 15 or more freshly cut, 
serial unstained sections (on slides) with an associated pathology report must be 
submitted for determination of PD-L1 status prior to study enrollment.  Analysis of PD-L1 
will be performed using the VENTANA PD-L1 (SP263, and also SP142 in earlier protocol 
versions) assays (Appendix 5 and Appendix 4, respectively), which may be considered 
investigational per local regulations. 
In addition, exploratory biomarkers (including, but not limited to markers related to 
immune or NSCLC biology, such as T-cell markers or non-inherited biomarkers identified 
through NGS on extracted DNA and/or RNA) may be evaluated. 

 
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Tumor tissue should be of good quality based on total and viable tumor content 
(sites will be informed if the quality of the submitted specimen is inadequate to determine 
tumor PD-L1 status). 
The remaining tumor tissue block for all patients enrolled will be returned to the site upon 
request or 18 months after final closure of the study database, whichever is sooner.  
Tissue samples from patients who are not eligible to enroll in the study will be returned 
no later than 6 weeks after eligibility determination. 
4.5.8.1 
Tumor Samples at the Time of Disease Recurrence 
For patients in both arms, a tumor sample should be obtained at the time of first 
radiographic confirmation of disease recurrence or confirmation of a new primary 
NSCLC for patients randomized in both arms unless not clinically feasible (within 
40 days of disease recurrence or prior to start of the next anti-cancer therapy, whichever 
is sooner). 
Acceptable samples include: 
 
Core needle biopsies for deep tumor tissue; at least three cores, embedded into a 
single paraffin block, should be submitted for evaluation. 
 
Excisional, incisional, punch, or forceps biopsy specimens for cutaneous, 
subcutaneous, or mucosal lesions 
 
Tumor tissue resection 
 
The status of immune-mediated and tumor type related and other exploratory 
biomarkers (including but not limited to T-cell markers and non-inherited biomarkers 
identified through NGS on extracted DNA and/or RNA) in tumor tissue samples may be 
evaluated. 
NGS may be performed by Foundation Medicine.  If performed by Foundation Medicine, 
the investigator can obtain results from the samples collected at the time of disease 
recurrence or occurrence in the form of an NGS report, which is available upon request 
directly from Foundation Medicine.  The investigator may share and discuss the results 
with the patient, unless the patient chooses otherwise.  The Foundation Medicine NGS 
assay has not been cleared or approved by the U.S. Food and Drug Administration 
(FDA); results from these investigational tests should not be used to guide future 
treatment decisions. 
After the DFS final analysis is complete, tumor tissue samples will no longer be 
collected. 
4.5.8.2 
Tumor Samples at Other Timepoints 
If a patient undergoes a medically indicated procedure (e.g., bronchoscopy, 
esophagogastroduodenoscopy, or colonoscopy) any time during the course of the study 
that has the likelihood of yielding tumor tissue, any remaining samples or a portion of the 

 
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sample not necessary for medical diagnosis (leftover tumor tissue) may be obtained for 
exploratory analysis. 
Patients with additional tissue samples from procedures performed at different times 
during the course of their study participation (during treatment and during survival 
follow-up) who have signed the Roche Clinical Repository (RCR) optional consent will be 
requested (but not required) to also submit these optional fresh biopsy samples for 
central testing.  Tumor tissue samples collected at the time of clinical response are 
preferred.  Tissue samples obtained at multiple times for individual patients will greatly 
contribute to an improved understanding of the dynamics of PD-L1 expression and 
relationship with intervening anti-cancer therapy. 
4.5.8.3 
Use and Storage of Remaining Samples from Study-Related 
Procedures 
The remainder of samples obtained for study-related procedures (including blood 
samples and tumor tissues) will be destroyed no later than 5 years after the end of the 
study or earlier depending on local regulations.  If the patient provides optional consent 
for storing samples into the RCR for future research (see Section 4.5.11), the samples 
will be destroyed no later than 15 years after the date of final closure of the clinical 
database. 
4.5.9 
Anti-Therapeutic Antibody Testing (Atezolizumab-Treated 
Patients Only) 
Atezolizumab may elicit an immune response.  Patients with signs of any potential 
immune response to atezolizumab will be closely monitored.  Validated screening and 
confirmatory assays will be employed to detect ATAs at multiple timepoints 
before, during, and after treatment with atezolizumab (see Appendix 3).  
The immunogenicity evaluation will utilize a risk-based immunogenicity strategy 
(Rosenberg and Worobec 2004; Koren et al. 2008) to characterize ATA responses to 
atezolizumab in support of the clinical development program.  This tiered strategy will 
include an assessment of whether ATA responses correlate with relevant clinical 
endpoints.  Implementation of ATA characterization assays will depend on the safety 
profile and clinical immunogenicity data. 
4.5.10 
Electrocardiogram 
A twelve-lead ECG is required at screening and as clinically indicated.  ECGs for each 
patient should be obtained on the same machine whenever possible.  Lead placement 
should be as consistent as possible.  ECG recordings must be performed after the 
patient has been resting in a supine position. 
For safety monitoring purposes, the investigator must review, sign, and date all ECG 
tracings.  Paper copies of ECG tracings will be kept as part of the patient's permanent 
study file at the site.  Any morphologic waveform changes or other ECG abnormalities 
must be documented on the eCRF. 

 
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4.5.11 
Optional Tumor and Blood Samples for Roche Clinical 
Repository (Optional Future Research) 
4.5.11.1 
Overview of the Roche Clinical Repository 
The Roche Clinical Repository (RCR) is a centrally administered group of facilities for 
the long-term storage of human biologic specimens, including body fluids, solid tissues, 
and derivatives thereof (e.g., DNA, RNA, proteins, peptides).  The collection and 
analysis of RCR specimens will facilitate the rational design of new pharmaceutical 
agents and the development of diagnostic tests, which may allow for individualized drug 
therapy for patients in the future. 
Specimens for the RCR will be collected from patients who give specific consent to 
participate in this optional research.  RCR specimens will be used to achieve the 
following objectives: 
 
To study the association of biomarkers with efficacy, adverse events, or disease 
recurrence 
 
To increase knowledge and understanding of disease biology 
 
To study drug response, including drug effects and the processes of drug absorption 
and disposition 
 
To develop biomarker or diagnostic assays and establish the performance 
characteristics of these assays 
 
4.5.11.2 
Approval by the Institutional Review Board or 
Ethics Committee 
Collection and submission of biological samples to the RCR is contingent upon the 
review and approval of the exploratory research and the RCR portion of the Informed 
and, if applicable, an appropriate regulatory body.  If a site has not been granted 
approval for RCR sampling, this section of the protocol (Section 4.5.11) will not be 
applicable at that site. 
4.5.11.3 
Optional Samples for Roche Clinical Repository 
The following samples will be collected for patients who have signed the RCR 
optional consent: 
 
Whole blood samples collected at screening (for screen fail patients only) 
 
Optional fresh biopsy samples 
 
Remaining fluids (serum, plasma, blood cell derivatives) after study-related tests 
have been performed 
 
Remaining FFPE tissue (with the exception of archival FFPE blocks, which will be 
returned to sites) after study-related tests have been performed 
 
The following sample will be used for identification of genetic (inherited) biomarkers: 
 
Whole blood sample for DNA extraction (6 mL; see Appendix 2 and Appendix 3) 

 
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For all samples, dates of consent and specimen collection should be recorded on the 
associated RCR page of the eCRF.  For sampling procedures, storage conditions, and 
shipment instructions, see the Laboratory Manual. 
RCR specimens will be destroyed no later than 15 years after the date of final closure of 
the associated clinical database.  The RCR storage period will be in accordance with the 
IRB/EC-approved Informed Consent Form and applicable laws (e.g., health authority 
requirements).  The dynamic biomarker specimens will be subject to the confidentiality 
standards described in Section 8.4.  The genetic biomarker specimens will undergo 
additional processes to ensure confidentiality, as described in Section 4.5.11.4. 
4.5.11.4 
Confidentiality 
Given the sensitive nature of genetic data, Roche has implemented additional processes 
to ensure patient confidentiality for RCR specimens and associated data.  Upon receipt 
by the RCR, each specimen is "double-coded" by replacing the patient identification 
number with a new independent number.  Data generated from the use of these 
specimens and all clinical data transferred from the clinical database and considered 
relevant are also labeled with this same independent number.  A "linking key" between 
the patient identification number and this new independent number is stored in a secure 
database system.  Access to the linking key is restricted to authorized individuals and is 
monitored by audit trail.  Legitimate operational reasons for accessing the linking key are 
documented in a standard operating procedure.  Access to the linking key for any other 
reason requires written approval from the Pharma Repository Governance Committee 
and Roche's Legal Department, as applicable. 
Data generated from RCR specimens must be available for inspection upon request by 
representatives of national and local health authorities and Roche monitors, 
representatives, and collaborators, as appropriate. 
Patient medical information associated with RCR specimens is confidential and may be 
disclosed only to third parties as permitted by the Informed Consent Form (or separate 
authorization for use and disclosure of personal health information) signed by the 
patient, unless permitted or required by law. 
Data derived from RCR specimen analysis on individual patients will generally not be 
provided to study investigators unless a request for research use is granted.  The 
aggregate results of any research conducted using RCR specimens will be available in 
accordance with the effective Roche policy regarding study data publication. 
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of the RCR data will become and remain the exclusive and unburdened property 
of Roche, except where agreed otherwise. 

 
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4.5.11.5 
Consent to Participate in the Roche Clinical Repository 
The Informed Consent Form will contain a separate section that addresses participation 
in the RCR.  The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential hazards of participation in the RCR.  Patients will be 
told that they are free to refuse to participate and may withdraw their specimens at any 
time and for any reason during the storage period.  A separate, specific signature will be 
required to document a patient's agreement to provide optional RCR specimens.  
Patients who decline to participate will not provide a separate signature. 
The investigator should document whether or not the patient has given consent to 
participate by completing the Research Sample Informed Consent eCRF. 
specimens and data will continue to be used as part of the RCR research. 
4.5.11.6 
Withdrawal from the Roche Clinical Repository 
Patients who give consent to provide RCR specimens have the right to withdraw their 
specimens from the RCR at any time for any reason.  However, if RCR specimens 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 specimens during the study, the investigator must inform the Medical Monitor in 
the date of withdrawal on the appropriate Research Sample Withdrawal of Informed 
Consent eCRF.  If a patient wishes to withdraw consent to the testing of his or her 
specimens 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 
tudy GO29527 does not, by itself, constitute withdrawal of 
constitute withdrawal from Study GO29527. 
4.5.11.7 
Monitoring and Oversight 
RCR specimens will be tracked in a manner consistent with Good Clinical Practice by a 
quality-controlled, auditable, and appropriately validated laboratory information 
management system to ensure compliance with data confidentiality, as well as 
adherence to authorized use of specimens as specified in this protocol and in the 
Informed Consent Form.  Roche monitors and auditors will have direct access to 
appropriate parts of records relating to patient participation in the RCR for the purposes 
of verifying the data provided to Roche.  The site will permit monitoring, audits, IRB/EC 
review, and health authority inspections by providing direct access to source data and 
documents related to the RCR samples. 

 
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4.6 
TIMING OF STUDY ASSESSMENTS 
Flowcharts of scheduled study assessments are provided in Appendix 1 and Appendix 2.  
Patients will be closely monitored for safety and tolerability throughout the study.  
All assessments must be performed and documented for each patient.  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.  If the timing of a 
protocol-mandated study visit coincides with a holiday and/or weekend that precludes 
the visit, the visit should be scheduled on the nearest following feasible date. 
4.6.1 
Screening and Pre-Treatment Assessments 
Written informed consent for participation in the study (enrollment/randomized phases) 
must be obtained before performing any study-specific screening tests or evaluations.  
Informed Consent Forms for enrolled patients and for patients who are not subsequently 
enrolled will be maintained at the study site. 
Screening tests and evaluations will be performed within 28 days prior to enrollment into 
study (screening/enrollment phase).  Patients who are eligible to receive adjuvant 
cisplatin-based chemotherapy will be treated for up to four cycles (approximately 
12 weeks).  Within 3 weeks to 8 weeks after completion of the last dose of 
chemotherapy treatment, eligible patients will then be randomized into study.  Results of 
standard-of-care tests or examinations performed prior to obtaining informed consent 
and within 28 days (or as otherwise specified) prior to enrollment period may be used; 
such tests do not need to be repeated for screening.  All screening evaluations must be 
completed and reviewed to confirm that patients meet all eligibility criteria before 
receiving both adjuvant chemotherapy and prior to randomization into study.  
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. 
See Appendix 1 and Appendix 2 for the schedules of screening and pre-treatment 
assessments for the enrollment phase and randomization phase, respectively. 
4.6.2 
Assessments during Treatment/Best Supportive Care Period 
All visits must occur within 
 3 days from the scheduled date unless otherwise noted.  
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 treatment administration 
(Day 1) of each cycle should be performed prior to study treatment infusion unless 
otherwise noted. 
For patients in Arm A, if scheduled dosing is precluded because of a holiday, 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.  If scheduled study assessments cannot be 
obtained because of a holiday, these assessments should then be obtained at 

 
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the soonest following date, provided that the soonest following date is not within 3 days 
of other regularly scheduled study assessments. 
After five cycles of atezolizumab treatment, one of three cycles may be delayed by 
1 week (28 days instead of 21 days for one cycle) to allow for vacations and/or holidays.  
Following the delay, the next cycle must be delivered 21 days from the previous dose 
administration.  Two consecutive 28-day cycles are not permitted. 
For both the enrollment and randomization phases, screening assessments performed 
 96 hours before Cycle 1, Day 1 are not required to be repeated for Cycle 1, Day 1.  
The following assessments may be performed 
 96 hours before Day 1 of each cycle: 
 
ECOG Performance Status 
 
Limited physical examination 
 
Local laboratory tests 
 
See Appendix 1 and Appendix 2 for the schedule of screening and pre-treatment 
assessments for the enrollment phase and randomization phase. 
For patients in Arm B, if medical visits are completed during the randomization phase 
instead of a telephone contact, additional assessments including limited physical exam 
and laboratory tests may be completed as clinically indicated, according to local 
standard of care.  See Appendix 2 for the schedule of required assessments for the 
randomization phase. 
Blood samples for pharmacodynamic biomarker analysis and pharmacokinetics will be 
obtained according to the schedules in Appendix 3. 
4.6.3 
Assessments at Treatment Discontinuation Visit 
For the enrollment phase, patients who discontinue early from chemotherapy or who 
complete up to four cycles of chemotherapy will be asked to return to the clinic not more 
than 30 days after the last treatment for a treatment discontinuation visit.  The visit at 
which the decision is made to discontinue treatment (e.g., after completion of up to 
four cycles, or when disease recurrence is determined or confirmed) may be considered 
as the treatment discontinuation visit. 
For randomized phase, atezolizumab-treated patients who discontinue early from 
treatment or who complete the study treatment in full (16 cycles) will be asked to 
return to the clinic not more than 30 days after the last treatment for a treatment 
discontinuation visit.  The visit at which the decision is made to discontinue treatment 
(e.g., disease recurrence is determined or confirmed) may be used as the treatment 
discontinuation visit. 
Patients randomized to BSC (Arm B) and who discontinue early from the BSC period 
or who complete BSC in full (1 year) will also be asked to return to the clinic not 

 
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more than 30 days after the last BSC visit for a discontinuation visit.  The visit at which 
the decision is made to discontinue patient from the BSC visit (e.g., disease recurrence 
is determined or confirmed) may be used as the BSC discontinuation visit. 
See Appendix 2 for the schedule of assessments performed at the treatment and study 
discontinuation as well as the treatment or BSC discontinuation visit. 
4.6.4 
Follow-Up Assessments 
4.6.4.1 
Ongoing Tumor Assessments 
All patients in the randomized phase will undergo scheduled tumor assessments at 
baseline and every 4 months in the first year and every 6 months in the second year by 
CT following randomization.  Patients who have not experienced recurrence of disease 
will undergo tumor assessments every 6 months by CT or X-ray during Years 3 5 
post-randomization.  In the absence of disease recurrence, tumor assessments should 
continue regardless of whether patients start new anti-cancer therapy until disease 
recurrence, withdrawal of consent, death, loss to follow-up, or study termination by the 
Sponsor, whichever occurs first. 
Patients who discontinue treatment before completing the 16 cycles of atezolizumab for 
reasons other than disease recurrence (e.g., toxicity) should continue to undergo 
scheduled tumor assessments at the same frequency as would have been followed if the 
patient had remained on study treatment until the patient has disease recurrence, dies, 
withdraws consent, is lost to follow-up, or until the study closes, whichever occurs first. 
Additionally, patients in either arm who start a new anti-cancer therapy in the absence of 
disease recurrence should be followed according to the protocol schedule unless they 
withdraw consent, die, experience disease recurrence, are lost to follow-up, or until the 
study closes, whichever occurs first. 
After Year 5 and the completion of the final analysis of DFS, there will no longer be a 
study requirement for tumor assessments to be completed and patients are to be 
followed according to the local standard as a part of their regular medical care.   
4.6.4.2 
Adverse Events 
During both the enrollment phase (cisplatin-based chemotherapy) and randomization 
phase (atezolizumab or BSC), all serious adverse events and adverse events of special 
interest will be recorded during the study and for 90 days after the last dose of study 
treatment (last study assessment for patients in Arm B) or initiation of new anti-cancer 
therapy, whichever occurs first.  All other adverse events will be recorded during the 
study and for 30 days after the last dose of study treatment (last study assessment for 
patients randomized to Arm B) or until the initiation of another anti-cancer therapy, 
whichever occurs first.  Investigators are instructed to report all serious adverse events 
and events of special interest considered related to study treatment regardless of time 
after study. 

 
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After the treatment discontinuation visit, adverse events should be followed as outlined 
in Section 5.5.1. 
4.6.4.3 
Anti-Therapeutic Antibody and Pharmacokinetic Assessments 
For patients assigned to atezolizumab only:  a post-treatment ATA and PK sample 
should be collected 120 days (
 30 days) after the last dose of atezolizumab received 
during the treatment period unless the patient withdraws consent, dies, or the study 
closes, whichever occurs first. 
See the schedule of assessments provided in Appendix 3 for specified follow-up 
assessments. 
4.6.4.4 
Survival and Subsequent Anti-Cancer Therapy 
Survival follow-up information will be collected via telephone calls, patient medical 
records, and/or clinic visits approximately every 6 months or more often until death, loss 
to follow-up, consent withdrawal, or study termination by Roche, whichever occurs first.  
All patients will be followed 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), is lost to follow-up, dies, or the 
study is terminated by the Sponsor, whichever occurs first.  If the patient withdraws from 
the study, the study staff may use a public information source (e.g., county records) to 
obtain information about survival status only. 
4.7 
PATIENT, STUDY, AND SITE DISCONTINUATION 
4.7.1 
Patient Discontinuation 
The investigator has the right to discontinue a patient from study treatment or withdraw a 
patient from the study at any time.  In addition, patients have the right to voluntarily 
discontinue study treatment or withdraw from the study at any time for any reason.  
Reasons for withdrawal from the study may include but are not limited to the following: 
 
Patient withdrawal of consent at any time 
 
Any medical condition that the investigator or Sponsor determines may jeopardize 
 
 
Investigator or Sponsor determines it is in the best interest of the patient 
 
Patient noncompliance 
 
Every effort should be made to obtain information on patients who withdraw from the 
study.  The primary reason for withdrawal from the study should be documented on the 
appropriate eCRF.  However, patients will not be followed for any reason after consent 
has been withdrawn.  Patients who withdraw from the study will not be replaced. 

 
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4.7.2 
Discontinuation from Study Treatment 
Patients in Arm A must discontinue study treatment if they experience any of 
the following: 
 
to receive study treatment 
 
Use of another non-protocol anti-cancer therapy (see Section 4.4.4) 
 
Pregnancy 
 
Disease recurrence as determined by the investigator after an integrated 
assessment of radiographic data, biopsy sample results (if available), and 
clinical status 
 
Occurrence of new primary NSCLC, as assessed by the investigator 
 
Intolerable toxicity related to atezolizumab, including development of an immune-
mediated adverse event determined by the investigator to be unacceptable given 
 severity of the event (for 
patients randomized to Arm A) 
 
The primary reason for study treatment discontinuation should be documented on the 
appropriate eCRF. 
4.7.3 
Study and Site Discontinuation 
The Sponsor has the right to terminate this study at any time.  Reasons for terminating 
the study may include but are not limited to the following: 
 
The incidence or severity of adverse events in this or other studies indicates a 
potential health hazard to patients. 
 
Patient enrollment is unsatisfactory. 
 
The Sponsor will notify the investigator if the study is placed on hold or if the Sponsor 
decides to discontinue the study or development program. 
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 
 
Noncompliance with the International Conference on Harmonisation (ICH) guideline 
for Good Clinical Practice 
 
No study activity (i.e., all patients have completed and all obligations have been 
fulfilled) 
 

 
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5. 
ASSESSMENT OF SAFETY 
5.1 
SAFETY PLAN 
Measures will be taken to ensure the safety of patients participating in this study, 
including the use of stringent inclusion and exclusion criteria (see Sections 4.1.1 
and 4.1.2) and close monitoring (as indicated in Section 5.1.3). 
An independent Data Monitoring Committee (iDMC) that has been involved in the review 
of aggregate safety data (refer to the iDMC charter for a detailed monitoring plan) from 
prior and current atezolizumab studies will be employed for this study.  This committee 
will conduct periodic reviews of safety data according to procedures outlined in an 
iDMC charter. 
For patients randomized to the atezolizumab arm, administration of atezolizumab will 
be performed in a monitored setting where there is immediate access to trained 
personal and adequate equipment/medicine to manage potentially serious reactions.  
The potential safety issues anticipated in this study, as well as measures intended to 
avoid or minimize such toxicities, are outlined in the following sections. 
In the setting of a pandemic or epidemic, screening for active infections (including 
SARS-CoV-2) during study participation should be considered according to local or 
institutional guidelines or guidelines of applicable professional societies (e.g., ASCO or 
European Society for Medical Oncology). 
Severe SARS-CoV-2 infection appears to be associated with a CRS involving the 
inflammatory cytokines IL-6, IL-10, IL-2, and IFN-  (Merad and Martin 2020).  If a patient 
develops suspected CRS during the study, a differential diagnosis should include 
SARS-CoV-2 infection, which should be confirmed or refuted through assessment of 
exposure history, appropriate laboratory testing, and clinical or radiologic evaluations per 
investigator judgment.  If a diagnosis of SARS-CoV-2 infection is confirmed, the disease 
should be managed as per local or institutional guidelines. 
5.1.1 
Risks Associated with Atezolizumab 
Atezolizumab has been associated with risks such as the following:  infusion-related 
reactions (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 9 of the protocol and Section 6 of the Atezolizumab Investigator's Brochure 
for a detailed description of anticipated safety risks for atezolizumab. 

 
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Guidelines for managing patients who experience anticipated adverse events are 
provided in Appendix 9. 
5.1.2 
Risk and Side Effects Associated with Administration of 
Cisplatin-Based Chemotherapy 
5.1.2.1 
Cisplatin 
Cisplatin is known to cause myelosuppression, ototoxicity, and nephrotoxicity.  
Cisplatin-based chemotherapy is considered to be moderately emetogenic.  Patients will 
be monitored for cisplatin-related adverse events. 
For more details regarding the safety profile of cisplatin, see the Cisplatin Package 
Insert. 
5.1.2.2 
Vinorelbine 
Common hematologic toxicities associated with vinorelbine therapy include leukopenia 
and neutropenia (dose limiting), and anemia.  Thrombocytopenia has also occurred, but 
is considered rare.  Neurological toxicities include peripheral neuropathy (decreased 
reflexes, paresthesia, hypoesthesia), infrequently tumor pain and jaw pain.  The most 
commonly reported gastrointestinal toxicities include constipation, mild or moderate 
nausea/vomiting, anorexia, and stomatitis. 
Dermatological toxicities often associated with vinorelbine therapy include alopecia, 
phlebitis, local reaction at the site of injection (erythema, pain, vein discoloration), and 
moderate vesicant.  Liver enzyme toxicities are rare, but mild transient increases in liver 
enzymes have been reported.  Hypersensitivity reactions that are reported include 
reversible bronchospasm.  Cardiovascular toxicities such as chest pain have also been 
reported, but are often associated with patients with preexisting cardiovascular disease 
or tumors within the chest.  Pulmonary toxicities that have been documented include 
shortness of breath and some interstitial pulmonary changes.  Fatigue is also commonly 
reported with vinorelbine treatment. 
5.1.2.3 
Docetaxel 
Cardiac toxicities reported with docetaxel use include arrhythmias, pericardial effusions, 
and palpitations.  Hematological toxicities reported can be severe or life threatening and 
include dose related neutropenia, leukopenia, thrombocytopenia, anemia, 
hypoglycemia, and hypernatremia.  The most commonly reported gastrointestinal 
toxicities include nausea and vomiting, diarrhea, oral mucositis, pancreatitis, and 
esophagitis. 
Neurological toxicities reported include reversible dysthesias or paresthesias, peripheral 
neuropathy, mild or moderate lethargy or somnolence, headache, and seizures. 
Hypersensitivity reactions can be severe with docetaxel use.  Reported cases include 
local or general skin rash, flushing, pruritus, drug fever, chills and rigors, low back pain, 

 
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and severe anaphylactoid reactions such as flushing with hypo- or hypertension, with or 
without dyspnea. 
Dermatological toxicities include alopecia, desquamation following localized pruriginous 
maculopapular eruption, skin erythema with edema, extravasation reaction (erythema, 
swelling, tenderness, pustules), reversible peripheral phlebitis, and nail changes.  
Common hepatotoxicities reported include increased transaminase, alkaline 
phosphatase, and bilirubin.  Less commonly reported hepatic events include hepatic 
failure and/or hepatic drug reactions.  Pulmonary events reported include dyspnea with 
restrictive pulmonary syndrome and pleural effusions.  Other associated toxicities 
include asthenia, dysgeusia, anorexia, conjunctivitis, arthralgia, muscle aches, 
myopathy, peripheral edema fluid retention syndrome, ascites, flu-like symptoms, 
and fever. 
5.1.2.4 
Gemcitabine 
Infusion times of gemcitabine longer than 60 minutes and more frequent than weekly 
dosing have been shown to increase toxicity. 
Pulmonary toxicity has been reported with the use of gemcitabine.  In cases of severe 
lung toxicity, gemcitabine therapy should be discontinued immediately and appropriate 
supportive care measures instituted. 
Myelosuppression manifested by neutropenia, thrombocytopenia, and anemia has been 
reported with gemcitabine as a single agent or in combination with other cytotoxic drugs.  
Monitor for myelosuppression should occur prior to each cycle. 
Hemolytic-uremic syndrome (HUS) and/or renal failure have been reported following one 
or more doses of gemcitabine.  Renal failure leading to death or requiring dialysis, 
despite discontinuation of therapy, has been rarely reported.  The majority of the cases 
of renal failure leading to death were a result of HUS. 
Serious hepatotoxicity, including liver failure and death, has been reported very rarely 
in patients receiving gemcitabine alone or in combination with other potentially 
hepatotoxic drugs. 
Use caution in patients with preexisting renal impairment or hepatic insufficiency. 
For more details regarding the safety profile of gemcitabine, see the Gemcitabine 
Package Insert. 
5.1.2.5 
Pemetrexed 
The most common side effects of pemetrexed include gastrointestinal symptoms 
(nausea, vomiting, diarrhea, or constipation), myelosuppression, infection, fatigue, 
stomatitis, loss of appetite, and rash. 

 
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For more details regarding the safety profile of pemetrexed, see the Pemetrexed 
Package Insert. 
5.1.3 
General Plan to Manage Safety Concerns 
Safety will be evaluated in this study through the monitoring of all serious and 
non-serious adverse events defined and graded according to NCI CTCAE v4.0.  Patients 
will be assessed for safety (including laboratory values according Appendix 1 and 
Appendix 2).  Laboratory values must be reviewed prior to each infusion. 
General safety assessments will include serial interval histories, physical examinations, 
and specific laboratory studies, including serum chemistries and blood counts.  
See Appendix 1 and Appendix 2 for the list and timing of study assessments.  During the 
study, patients will be closely monitored for the development of any adverse events, 
including signs or symptoms of autoimmune conditions and infection.  All serious 
adverse events and protocol-defined events of special interest (see Section 5.2) will be 
reported in an expedited fashion (see Section 5.4.2).  In addition, the iDMC and 
Medical Monitor will review and evaluate observed adverse events on a regular basis. 
Patients who have an ongoing study treatment-related adverse event upon study 
treatment completion or at discontinuation from the study will be followed until the event 
has resolved to baseline grade, the event is assessed by the investigator as stable, new 
anti-cancer treatment is initiated, the patient is lost to follow-up, the patient withdraws 
consent, or it has been determined that study treatment or participation is not the cause 
of the adverse event. 
5.1.4 
Management of Chemotherapy-Specific Adverse Events 
For all toxicities, if one drug in a chemotherapy regimen is held, the other chemotherapy 
agent must be held as well.  In general, treatment could be held for up to 63 days after 
Day 1 of last cycle of last cycle to allow sufficient time for recovery from the toxicities 
listed in the following sections.  If one drug in a chemotherapy regimen is discontinued, 
the other chemotherapy can be continued as a single agent. 
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. 
5.1.4.1 
Cisplatin Dose Modifications, Treatment Delays, or Treatment 
Discontinuation and Management of Specific Adverse Events 
The dose modification guidelines for cisplatin are provided below. 
Treatment with cisplatin 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 21 days because of toxicities. 

 
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Hematologic Toxicities 
At the start of each cycle, the ANC must be 
 1500/ L, and the platelet count must 
be 
 100,000/ L.  Treatment should be delayed for up to 63 days after Day 1 of the last 
cycle to allow sufficient time for recovery.  Growth factors may be used in accordance 
with American Society of Clinical Oncology (ASCO) and NCCN guidelines 
(Smith et al. 2006; NCCN 2012).  No dose adjustment for cisplatin is allowed for 
hematologic toxicities. 
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 must be 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 
 
Non-Hematologic Toxicities 
If a patient develops a non-hematologic toxicity (see Table 11), cisplatin should be 
withheld for up to 63 days after Day1 of the last cycle until resolution to less than or 
1 if patient did not have that toxicity at 
baseline).  Treatment should be resumed according to the guidelines in Table 11. 
Diarrhea should be controlled with adequate anti-diarrhea medication.  Nausea and/or 
vomiting should be controlled with adequate anti-emetics. 
Table 11 Cisplatin Dose Modifications for Non-Hematologic Toxicities 
(Excluding Neurotoxicity and Nephrotoxicity) 
Toxicity 
Cisplatin Dose  
Any diarrhea requiring hospitalization (irrespective of 
grade) or Grade 3 or 4 diarrhea that occurs on adequate 
anti-diarrhea medication 
75% of previous dose 
Grade 3 or 4 nausea/vomiting a 
75% of previous dose 
Any other Grade 3 or 4 toxicity 
75% of previous dose 
a Despite the use of anti-emetics. 
 
  
Nephrotoxicity 
CRCL must be 
 60 mL/min prior to the start of any cycle of cisplatin.  If there is a 
decrease in CRCL between cycles, but the CRCL is still 
 60 mL/min at the time of the 
next cycle, the investigator should use clinical judgment regarding the continuation of 
cisplatin, dos

 
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returned to 
 60 mL/min within 63 days after Day1 of the last cycle, the patient should be 
discontinued from cisplatin. 
Neurotoxicity 
In the event of neurotoxicity, the recommended dose adjustment for cisplatin is 
documented in Table 12.  For a Grade 3 or 4 neurotoxicity, cisplatin should be resumed 
at 50% of the previous dose upon improvement, or discontinued immediately (based on 
 
Table 12 Cisplatin Dose Modifications or Treatment Discontinuation for 
Associated Neurotoxicity 
Toxicity 
Cisplatin Dose  
Grade 0 1 neurotoxicity 
100% of previous dose 
Grade 2 neurotoxicity 
75% of previous dose 
Grade 3 or 4 neurotoxicity 
50% of previous dose or 
permanent discontinuation 
  
If the patient develops ototoxicity, subsequent doses of cisplatin should not be given until 
an audiometric analysis indicates that auditory acuity is within normal limits 
(http://www.drugs.com/pro/platinol.html).  See Table 12 for dose modifications. 
5.1.4.2 
Pemetrexed Dose Modifications, Treatment Delays or 
Treatment Discontinuation, and Management of Specific 
Adverse Events 
The dose modification guidelines are applicable for pemetrexed used as a single agent 
or in combination with cisplatin. 
Treatment with pemetrexed should be discontinued if a patient experiences any 
hematologic or non-hematologic Grade 3 or 4 toxicity after two dose reductions, 
or if treatment is delayed for more than 63 days after Day 1 of the last cycle because 
of toxicities. 
Hematologic Toxicity 
At the start of each cycle, the ANC must be 
 1500/ L and the platelet count must 
be 
 100,000/ L.  Treatment should be delayed for up to 63 days after Day 1 of the last 
cycle to allow sufficient time for recovery.  Growth factors may be used in accordance 
with ASCO and NCCN guidelines (Smith et al. 2006; NCCN 2012).  Upon recovery, dose 
adjustments at the start of a subsequent cycle will be made on the basis of the lowest 
(nadir) platelet and neutrophil values from the previous cycle (see Table 13). 
In the event that dose adjustments are needed for both ANC and platelets, patients are 
to receive the lower dose. 

 
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Table 14 Pemetrexed Dose Modifications for Non-Hematologic Toxicities  
Toxicity 
Pemetrexed Dose  
Any diarrhea requiring hospitalization 
(irrespective of grade) or Grade 3 or 4 diarrhea 
that occurs on adequate anti-diarrhea 
medication. 
75% of previous dose 
Neurotoxicity  
 
Grade 2  
75% of previous dose 
Grade 3 or 4 
50% of previous dose or 
permanent discontinuation 
Any other Grade 3 or 4 toxicities 
75% of previous dose 
  
Treatment Delays Caused by Insufficient Folic Acid or Vitamin B-12 
Supplementation 
Cycle 1 should not be started until both of the following requirements are met: 
 
The patient has taken folic acid for 5 to 7 days preceding the first dose of 
pemetrexed or as per local standard of care, but not later than Cycle 1, Day 1. 
 
The patient has received a vitamin B-12 injection (which can be given on 
Cycle 1, Day 1). 
 
Delay subsequent cycles until the patient has taken folic acid for at least 14 of the 
21 days before Day 1 of the subsequent cycle. 
For more details regarding pemetrexed dose modification, see the pemetrexed 
prescribing information. 
5.1.4.3 
Gemcitabine Dose Modifications, Treatment Delays or 
Treatment Discontinuation, and Management of Specific 
Adverse Events 
The dose modification guidelines are applicable for gemcitabine used as a single agent 
or in combination with cisplatin. 
The dose modification guidelines for gemcitabine are provided below. 
Treatment with gemcitabine should be discontinued if a patient experiences any 
hematologic or non-hematologic Grade 3 or 4 toxicity after two dose reductions, or if 
treatment is delayed for more than 21 days due to toxicities. 
Hematologic Toxicities 
At the start of each cycle, the ANC must be 
 1500 cells/ L and the platelet count must 
be 
 100,000 cells/ L.  Gemcitabine dose modifications for hematologic toxicity should 
be on the basis of the granulocyte and platelet counts taken on Days 1 and 8 of therapy 
(see Table 15 and Table 16).  Patients receiving gemcitabine should be monitored prior 
to each dose with a full blood count, including differential and platelet counts.  Treatment 

 
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Non-Hematologic Toxicities 
In general, for Grade 3 or 4 non-hematologic toxicities, gemcitabine should be withheld 
or the dose reduced by 50%, according to physician judgment. 
Permanent discontinuation should be considered for any of the following events: 
 
Unexplained dyspnea or other evidence of severe pulmonary toxicity 
 
Severe hepatic toxicity 
 
Hemolytic-uremic syndrome 
 
Capillary-leak syndrome 
 
Posterior reversible encephalopathy syndrome 
 
Table 17 provides dose modification guidelines for non-hematologic toxicities. 
Table 17 Gemcitabine Dose Modifications, Treatment Delays, or Treatment 
Discontinuation and Patient Management for Grade 2, 3, or 4 
Non-Hematologic Toxicities 
 
Grade 2 
Grade 3 
Grade 4 
First appearance  
Interrupt treatment until 
resolved to Grade 0 1, 
then continue at same 
dose with prophylaxis 
where possible.  
Interrupt treatment until 
resolved to Grade 0 1, 
then continue at 75% of 
original dose with 
prophylaxis where 
possible. 
Discontinue treatment 
unless investigator 
considers it to be in the 
best interest of the patient 
to continue at 50% of 
original dose, once 
toxicity has resolved to 
Grade 0 1. 
Second 
appearance of 
same toxicity  
Interrupt treatment until 
resolved to Grade 0 1, 
then continue at 75% of 
original dose. 
Interrupt treatment until 
resolved to Grade 0 1, 
then continue at 50% of 
original dose. 
 
Third appearance 
of same toxicity  
Interrupt treatment until 
resolved to Grade 0 1, 
then continue at 50% of 
original dose. 
Discontinue treatment 
permanently. 
 
Fourth 
appearance of 
same toxicity 
Discontinue treatment 
permanently. 
 
 
  
5.1.4.4 
Docetaxel Dose Modification and Management of Specific 
Adverse Events 
Treatment with docetaxel should be discontinued if a patient experiences any 
hematologic or non-hematologic Grade 3 or 4 toxicity after two dose reductions or 
if treatment is delayed for more than 63 days after Day1 of the last cycle because 
of toxicities. 

 
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Other Specific Toxicities Not Requiring Dose Adjustment 
Hypersensitivity Reactions 
Patients should be observed closely for hypersensitivity reactions, especially during the 
first and second infusions.  Severe hypersensitivity reactions characterized by 
generalized rash/erythema, hypotension and/or bronchospasm, or very rarely, fatal 
anaphylaxis, have been reported in patients premedicated with 3 days of corticosteroids.  
Severe hypersensitivity reactions require immediate discontinuation of the docetaxel 
infusion and aggressive therapy.  Patients with a history of severe hypersensitivity 
reactions should not be re-challenged with docetaxel. 
Hypersensitivity reactions may occur within a few minutes following initiation of 
docetaxel infusion.  If minor reactions such as flushing or localized skin reactions occur, 
interruption of therapy is not required. 
Fluid Retention 
Severe fluid retention has been reported following docetaxel therapy.  Patients should be 
premedicated with oral corticosteroids prior to each docetaxel infusion to reduce the 
incidence and severity of fluid retention.  Patients with preexisting effusions should be 
closely monitored from the first dose for the possible exacerbation of the effusions.  
See Table 20 for the management of edema. 
Table 20 Guidelines for the Management of Edema in Patients Treated 
with Docetaxel 
Edema 
Severity 
Effusion 
Asymptomatic 
Mild, Grade 1 
Asymptomatic, no intervention 
needed 
Symptomatic 
Moderate, Grade 2 
Symptomatic, may require 
intervention 
Symptomatic, resulting in 
interruption of treatment 
Severe, Grade 2 
Symptomatic, urgent 
intervention required 
  
5.1.4.5 
Vinorelbine Dose Modification and Management of Specific 
Adverse Events 
The dose modification guidelines are applicable for vinorelbine used as a single agent or 
in combination with cisplatin. 
Treatment with vinorelbine should be discontinued if a patient experiences any 
hematologic or non-hematologic Grade 3 or 4 toxicity after two dose reductions, or if 
treatment is delayed for more than 63 days after Day1 of the last cycle because of 
toxicities. 
Hematologic Toxicity 
Day 1 dosing may only start for platelet count 
 100,000 cells/ L and ANC 
 1500 cells/ L.  Vinorelbine dose modifications for hematologic toxicity should be based 

 
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5.2 
SAFETY PARAMETERS AND DEFINITIONS 
Safety assessments will consist of the monitoring and recording of adverse events, 
including serious adverse events and non-serious adverse events of special interest, the 
measurement of protocol-specified safety laboratory assessments, the measurement of 
protocol-specified vital signs, and 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), except as described in 
Section 5.3.5.10. 
 
Recurrence of an intermittent medical condition (e.g., headache) not present 
at baseline. 
 
Any deterioration in a laboratory value or other clinical test (e.g., ECG, Xray) that is 
associated with symptoms or leads to a change in study treatment or concomitant 
treatment or discontinuation from study drug 
 
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) 

 
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Results in persistent or significant disability/incapacity (i.e., the adverse event 
functions) 
 
Is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to 
study drug 
 
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) 
 
not synonymous.  Severity refers to the intensity of 
an adverse event (rated as mild, moderate, or severe, or according to NCI CTCAE 
criteria; see Section 5.3.3); the event itself may be of relatively minor medical 
significance (such as severe headache without any further findings). 
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 
Non-Serious Adverse Events of Special Interest (Immediately 
Reportable to the Sponsor) 
Non-serious adverse events of special interest are required to be reported immediately 
by the investigator to the Sponsor (i.e., no more than 24 hours after learning of the 
event; see Section 5.4.2 for reporting instructions).  Adverse events of special interest 
for this study include the following: 
 
Cases of potential drug--induced liver injury that include an elevated ALT or AST in 
combination with either an elevated bilirubin or clinical jaundice, as defined by 
 law (see Section 5.3.5.7) 
 
Suspected transmission of an infectious agent by the study drug, is defined 
as follows: 
Any organism, virus, or infectious particle (e.g., prion protein transmitting 
transmissible spongiform encephalopathy), pathogenic or non-pathogenic, is 
considered an infectious agent.  A transmission of an infectious agent may be 
suspected from clinical symptoms or laboratory findings that indicate an 
infection in a patient exposed to a medicinal product.  This term applies only 
when a contamination of the study drug is suspected. 
 
The following confirmed treatment-emergent autoimmune conditions: 
Pneumonitis 
Hypoxia or dyspnea Grade 
 3 
Colitis 

 
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Endocrinopathies:  diabetes mellitus, pancreatitis, or adrenal insufficiency 
Vasculitis 
Hepatitis 
Transaminitis:  Grade 
 2 (AST or ALT 
 3 
 ULN and bilirubin 
 2 
 ULN) OR 
AST/ALT 
 10 
 ULN 
Systemic lupus erythematosus 
Guillain-Barré syndrome 
Skin reactions:  vitiligo, pemphigoid 
 
Events suggestive of hypersensitivity, IRRs, CRS, influenza like illness, HLH, 
and MAS 
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 5.3.1, 5.3.5, 5.4, 
and 5.4.2. 
For each adverse event, 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) on the Adverse Event eCRF. 
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 the study personnel, will 
 
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., serious 
adverse events related to invasive procedures such as biopsies) should be reported 
(see Section 5.4.2 for instructions for reporting serious adverse events). 
After initiation of study drug, during both the enrollment phase (cisplatin-based 
chemotherapy) and randomization phase (atezolizumab or BSC), all serious adverse 
events and adverse events of special interest will be recorded during the study and for 
90 days after the last dose of study treatment (last study assessment for patients in 
Arm B) or initiation of new anti-cancer therapy, whichever occurs first.  All other adverse 
events will be recorded during the study and for 30 days after the last dose of study 
treatment (last study assessment for patients randomized to Arm B) or until the initiation 
of another anti-cancer therapy, whichever occurs first.  Investigators are instructed to 
report all serious adverse events and events of special interest considered related to 
study treatment regardless of time after study (see Section 5.6). 

 
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5.3.2 
Eliciting Adverse Event Information 
A consistent methodology of nondirective questioning should be adopted for eliciting 
adverse event information at all patient evaluation timepoints.  Examples of non-directive 
questions include the following: 
 
 
 
 
5.3.3 
Assessment of Severity of Adverse Events 
The adverse event severity grading scale for the NCI CTCAE v4.0 will be used for 
assessing adverse event severity.  Table 25 will be used for assessing the severity for 
adverse events that are not specifically listed in the NCI CTCAE. 
Table 25 Adverse Event Severity Grading Scale 
Grade 
Severity 
1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or 
intervention not indicated 
2 
Moderate; minimal, local, or non-invasive intervention indicated; or limiting 
age-appropriate instrumental activities of daily living a 
3 
Severe or medically significant, but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; or limiting self-care activities of 
daily living b, c 
4 
Life-threatening consequences or urgent intervention indicated d 
5 
Death related to adverse event d 
NCI CTCAE 
 National Cancer Institute Common Terminology Criteria for Adverse Events. 
Note:  Based on the NCI CTCAE (v4.0), which can be found at:  
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.0_2010-06-14_QuickReference_8.5x11.pdf. 
a Instrumental activities of daily living refer to preparing meals, shopping for groceries or 
clothes, using the telephone, managing money, etc. 
b Examples of self-care activities of daily living include bathing, dressing and undressing, 
feeding one's self, using the toilet, and taking medications, as performed by patients who are 
not bedridden. 
c If an event is assessed as a "significant medical event," it must be reported as a serious 
adverse event (see Section 5.4.2 for reporting instructions), per the definition of serious 
adverse event in Section 5.2.2. 
d Grade 4 and 5 events must be reported as serious adverse events (see Section 5.4.2 for 
reporting instructions), per the definition of serious adverse event in Section 5.2.2.   
  
5.3.4 
Assessment of Causality of Adverse Events 
Investigators should use their knowledge of the patient, the circumstances surrounding 
the event, and an evaluation of any potential alternative causes to determine whether or 
not an adverse event is considered to be related to the study treatment, indicating "yes" 
or "no" accordingly.  The following guidance should be taken into consideration: 
 
Temporal relationship of event onset to the initiation of study treatment 

 
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Course of the event, considering especially the effects of dose reduction, 
discontinuation of study treatment, or reintroduction of study treatment 
(where applicable) 
 
Known association of the event with study treatment or with similar treatments 
 
Known association of the event with the disease under study 
 
Presence of risk factors in the patient or use of concomitant medications known to 
increase the occurrence of the event 
 
Presence of non treatment-related factors that are known to be associated with the 
occurrence of the event 
 
5.3.5 
Procedures for Recording Adverse Events 
Investigators should use correct medical terminology/concepts when recording adverse 
events on the Adverse Event eCRF; colloquialisms and abbreviations should be 
avoided. 
Only one adverse event term should be recorded in the event field on the Adverse 
Event eCRF. 
5.3.5.1 
Diagnosis versus Signs and Symptoms 
For all adverse events, a diagnosis (if known) rather than individual signs and symptoms 
should be recorded on the Adverse Event eCRF (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. 
5.3.5.2 
Infusion-Related Reactions 
An exception to the above is symptoms that occur during or within 24 hours after an 
atezolizumab infusion.  These may be part of an acute infusion reaction and should not 
-
-serious 
symptoms should be recorded as separate adverse events on the Adverse Event eCRF. 
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. 

 
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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 subsequent 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 or not the events are associated. 
5.3.5.4 
Persistent or Recurrent Adverse Events 
A persistent adverse event is one that extends continuously, without resolution, between 
patient evaluation timepoints.  Such events should be recorded only once on the 
Adverse Event eCRF.  The initial severity (intensity) of the event should be recorded, 
and the severity should be updated to reflect the most extreme severity any time the 
event worsens.  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 is a change from baseline and 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 
 
I
 
 
scientific judgment should be exercised in deciding if an isolated laboratory abnormality 
should be classified as an adverse event. 

 
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If a clinically significant laboratory abnormality is a sign of a disease or syndrome 
(e.g., alkaline phosphatase and bilirubin 5 
 ULN associated with cholecystitis), only the 
diagnosis (i.e., cholecystitis) 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 
 
Observations of the same clinically significant laboratory abnormality from visit to visit 
should not be repeatedly recorded on the Adverse Event eCRF, unless the etiology 
changes (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 is a change from baseline and 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 
 
 
 
y to review all vital sign findings.  Medical and scientific 
judgment should be exercised in deciding if 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 not be repeatedly recorded on the Adverse Event eCRF, unless the etiology 
changes.  The initial severity of the event should be recorded, and the severity or 
seriousness should be updated any time the event worsens. 
5.3.5.7 
Abnormal Liver Function Tests 
The finding of an elevated ALT or AST (
 3 
 baseline value) in combination with either 
an elevated total bilirubin (
 2 
 ULN) or clinical jaundice in the absence of cholestasis or 
other causes of hyperbilirubinemia is considered to be an indicator of severe liver injury 

 
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(as 
occurrence of either of the following: 
 
Treatment-emergent ALT or AST 
 3 
 baseline value in combination with total 
bilirubin 
 2 
 ULN (of which 
 35% is direct bilirubin) 
 
Treatment-emergent ALT or AST 
 3 
 baseline value in combination with clinical 
jaundice 
 
The most appropriate diagnosis or (if a diagnosis cannot be established) the abnormal 
laboratory values should be recorded on the Adverse Event eCRF (see Section 5.3.5.1) 
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 a non-serious adverse event of special 
interest (see Section 5.4.2). 
5.3.5.8 
Deaths 
For this protocol, mortality is an efficacy endpoint.  Deaths that occur during the protocol 
specified adverse event reporting period (see Section 5.3.1) that are attributed by the 
investigator solely to disease recurrence or from confirmation of a new primary NSCLC 
should be recorded only on the Study Completion/Early Discontinuation eCRF.  All other 
on study deaths, regardless of relationship to study treatment, must be recorded on the 
Adverse Event eCRF and immediately reported to the Sponsor (see Section 5.4.2). 
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, 
 should be recorded on the Adverse Event eCRF.  If the 
 
be replaced by the established cause of death.  The term "sudden death" should not be 
used unless combined with the presumed cause of death (e.g., "sudden cardiac death"). 
During post-study treatment survival follow-up, deaths attributed to disease recurrence 
of NSCLC or from confirmation of a new primary NSCLC should be recorded only on the 
Study Completion/Early Discontinuation eCRF. 
5.3.5.9 
Preexisting Medical Conditions 
A preexisting medical condition is one that is present at the screening visit for this study.  
Such conditions should be recorded on the General Medical History and Baseline 
Conditions eCRF. 
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., 
 

 
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5.3.5.10 
Lack of Efficacy or NSCLC Recurrence 
Events that are clearly consistent with the expected pattern of disease recurrence 
should not be recorded as adverse events.  These data will be captured as efficacy 
assessment data only.  The expected pattern of disease recurrence will be based on 
determination by the investigator after an integrated assessment of radiographic data, 
biopsy sample results (if available), and clinical status.  Every effort should be made to 
document disease recurrence with use of objective criteria.  If there is any uncertainty 
as to whether an event is due to disease recurrence, it should be reported as an 
adverse event. 
Recurrence of disease should not be recorded as an adverse event or serious adverse 
event, since recurrence of disease will be captured as an efficacy endpoint.  However in 
situations in which there is no confirmation, the underlying symptoms should be captured 
as adverse events and assessed accordingly for seriousness, severity, and causality 
until a diagnosis or cause for such events is established or until confirmation of NSCLC 
recurrence.  If the symptoms are later confirmed to be due to recurrence of disease, then 
symptoms reported as adverse events should be retracted.  Data for disease recurrence 
will be captured as efficacy assessment data only. 
5.3.5.11 
Hospitalization or Prolonged Hospitalization 
Any adverse event that results in hospitalization (i.e., in-patient admission to a hospital) 
or prolonged hospitalization should be documented and reported as a serious adverse 
event (per the definition of serious adverse event in Section 5.2.2), except as 
outlined below. 
An event that leads to hospitalization under the following circumstances should not be 
reported as an adverse event or a serious adverse event: 
 
Hospitalization for respite care 
 
Planned hospitalization required by the protocol (e.g., for study treatment 
administration or to perform an efficacy measurement for the study) 
 
Hospitalization for a preexisting condition, provided that 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 suffered an adverse event. 
 
Hospitalization due solely to disease recurrence 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 for an adverse event that would ordinarily have been treated in an 
outpatient setting had an outpatient clinic been available 
 

 
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5.3.5.12 
Adverse Events Associated with an Overdose 
Study treatment overdose is the accidental or intentional use of the drug in an amount 
higher than the dose being studied.  An overdose or incorrect administration of study 
treatment is not an adverse event unless it results in untoward medical effects. 
Any study treatment overdose or incorrect administration of study treatment should be 
noted on the Study Drug Administration eCRF. 
All adverse events associated with an overdose or incorrect administration of study 
treatment should be recorded on the Adverse Event eCRF.  If the associated adverse 
event fulfills serious criteria, the event should be reported to the Sponsor immediately 
(i.e., no more than 24 hours after learning of the event; see Section 5.4.2). 
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 study.  The investigator must report 
such events to the Sponsor immediately; under no circumstances should reporting take 
place more than 24 hours after the investigator learns of the event.  The following is a list 
of events that the investigator must report to the Sponsor within 24 hours after learning 
of the event, regardless of relationship to study treatment: 
 
Serious adverse events (see Section 5.4.2 for further details) 
 
Non-serious adverse events of special interest (see Section 5.4.2 for further details) 
 
Pregnancies (see Section 5.4.2 for further details) 
 
The investigator must report new significant follow-up information for these events to the 
Sponsor immediately (i.e., no more than 24 hours after becoming aware of the 
information).  New significant information includes the following: 
 
New signs or symptoms or a change in the diagnosis 
 
Significant new diagnostic test results 
 
Change in causality based on new information 
 
 
 
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 patients, an Emergency Medical Call Center Help Desk will 
access the Roche Medical Emergency List, escalate emergency medical calls, provide 
medical translation service (if necessary), connect the investigator with a Roche Medical 
Responsible (listed above and/or on the Roche Medical Emergency List), and track all 

 
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calls.  The Emergency Medical Call Center Help Desk will be available 24 hours per day, 
7 days per week.  Toll-free numbers for the Help Desk, as well as Medical Monitor 
Responsible contact information will be distributed to all investigators. 
5.4.2 
Reporting Requirements for Serious Adverse Events and 
Non-Serious 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 caused by a protocol-mandated intervention should be reported.  
The Clinical Trial Adverse Event/Special Situations Form provided to investigators 
should be completed and submitted to Roche 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 with use of the fax number or email address provided to investigators. 
5.4.2.2 
Events That Occur After Study Treatment Initiation 
After initiation of study treatment, during both the enrollment phase (cisplatin-based 
chemotherapy) and randomization phase (atezolizumab or BSC), all serious adverse 
events and adverse events of special interest will be recorded during the study and for 
90 days after the last dose of study treatment (last study assessment for patients in 
Arm B) or initiation of new anti-cancer therapy, whichever occurs first.  All other adverse 
events will be recorded during the study and for 30 days after the last dose of study 
treatment (last study assessment for patients randomized to Arm B) or until the initiation 
of another anti-cancer therapy, whichever occurs first.  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 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 Clinical Trial Adverse Event/Special 
Situations Form provided to investigators should be completed and submitted to Roche 
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 with use of the fax number or 
email address provided to investigators.  Once the EDC system is available, all 
information will need to be entered and submitted via the EDC system. 
Instructions for reporting post-study adverse events are provided in Section 5.6. 
5.4.3 
Reporting Requirements for Pregnancies 
5.4.3.1 
Pregnancies in Female Patients 
Female patients of childbearing potential will be instructed to immediately inform the 
investigator if they become pregnant during the study or within 5 months after the last 
dose of atezolizumab or 6 months after the last dose of cisplatin-based chemotherapy 
(cisplatin plus vinorelbine, docetaxel, gemcitabine, or pemetrexed).  A Clinical Trial 
Pregnancy Reporting Form should be completed and submitted by the investigator 
immediately (i.e., no more than 24 hours after learning of the pregnancy), either by 

 
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faxing or by scanning and emailing the form with use of 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 the conclusion of the pregnancy.  Any serious 
adverse events associated with the pregnancy (e.g., an event in the fetus, an event in 
the mother during or after the pregnancy, or a congenital anomaly/birth defect in the 
child) should be reported on the Adverse Event eCRF.  In addition, the investigator will 
submit a Clinical Trial Pregnancy Reporting Form when updated information on the 
course and outcome of the pregnancy becomes available. 
5.4.3.2 
Pregnancies in Female Partners of Male Patients 
Male patients will be instructed through the Informed Consent Form to immediately 
inform the investigator if their partner becomes pregnant during the study or within 
6 months after the last dose of cisplatin-based chemotherapy (cisplatin plus vinorelbine, 
docetaxel, gemcitabine, or pemetrexed).  A Clinical Trial Pregnancy Reporting Form 
should be completed and submitted to the Sponsor or its designee immediately (i.e., no 
more than 24 hours after learning of the pregnancy), either by faxing or by scanning and 
emailing the form using the fax number or email address provided to investigators.  
Attempts should be made to collect and report details of the course and outcome of any 
pregnancy in the partner of a male patient exposed to cisplatin-based chemotherapy.  
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 when updated information on the course and 
outcome of the pregnancy becomes available.  An investigator who is contacted by the 
male patient or his pregnant partner may provide information on the risks of the 
pregnancy and the possible effects on the fetus, to support an informed decision in 
cooperation with the treating physician and/or obstetrician. 
5.4.3.3 
Abortions 
A spontaneous abortion should be classified as a serious adverse event (because the 
Sponsor considers abortions to be medically significant events), 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. 

 
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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 or female partner 
of a male patient exposed to study treatment should be classified as a serious adverse 
event, recorded on the Adverse Event eCRF and reported to the Sponsor immediately 
(i.e., no more than 24 hours after learning of the event; see Section 5.4.2). 
5.5 
FOLLOW-UP OF PATIENTS AFTER ADVERSE EVENTS 
5.5.1 
Investigator Follow-Up 
The investigator should follow each adverse event until the event has resolved to 
baseline grade or better, the event is assessed as stable by the investigator, the patient 
is lost to follow-up, or the patient withdraws consent.  Every effort should be made to 
follow all serious adverse events considered related to study treatment or study-related 
procedures until a final outcome can be reported. 
During the study period, resolution of adverse events (with dates) should be documented 
edical record to facilitate source data 
verification.  If, after follow-up, return to baseline status or stabilization cannot be 
established, an explanation should be recorded on the Adverse Event eCRF. 
All pregnancies reported during the study should be followed until pregnancy outcome. 
5.5.2 
Sponsor Follow-Up 
For serious adverse events, non-serious adverse events of special interest, and 
pregnancies, the Sponsor or a designee may follow up by telephone, fax, electronic mail, 
and/or a monitoring visit to obtain additional case details and outcome information 
(e.g., from hospital discharge summaries, consultant reports, autopsy reports) in order to 
perform an independent medical assessment of the reported case. 
5.6 
POST-STUDY ADVERSE EVENTS 
At the treatment discontinuation visit, the investigator should instruct each patient to 
physician believes could be related to prior study treatment or study procedures. 
The Sponsor should be notified if the investigator becomes aware of any adverse event 
that occurs after the end of the adverse event reporting period (defined as 90 days for 
serious adverse events and adverse events of special or 30 days for all other adverse 
events).  Investigators are instructed to report all serious adverse events and adverse 
events of special interest considered to be related to study treatment regardless of the 
time after study.  The Sponsor should also be notified if the investigator becomes aware 
of the development of cancer or a congenital anomaly/birth defect in a subsequently 
conceived offspring of a patient that participated in this study.  These events should be 

 
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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 Clinical Trial Adverse 
Event/Special Situations Form with use of the fax number or email address provided to 
investigators. 
During survival follow-up, deaths attributed to disease recurrence of NSCLC or 
confirmation of new primary NSCLC should be recorded only on the Study 
Completion/Early Discontinuation eCRF. 
5.7 
EXPEDITED REPORTING TO HEALTH AUTHORITIES, 
INVESTIGATORS, INSTITUTIONAL REVIEW BOARDS, AND 
ETHICS COMMITTEES 
The Sponsor will promptly evaluate all serious adverse events and non-serious 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 authorities (which 
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 with use of the Atezolizumab Investigator's 
Brochure as a reference. 
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 external iDMC will monitor the incidence of these expected events 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 
Efficacy analyses will be performed on randomized patients within one or more 
populations, including PD-L1 subpopulations of patients with Stage II-IIIA NSCLC, all 
randomized patients with Stage II-IIIA NSCLC, and the ITT population, with patients 

 
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grouped according to the treatment assigned at randomization, regardless of whether 
they received any assigned study treatment. 
Safety analyses will be performed on all randomized patients who received any amount 
of study treatment, with patients allocated by whether any amount of atezolizumab 
treatment was received. 
6.1 
DETERMINATION OF SAMPLE SIZE 
Approximately 1280 patients are expected to be accrued during the enrollment phase.  
With an approximate 21% dropout rate during adjuvant cisplatin-based chemotherapy, 
approximately 1005 patients will enter the randomization phase, including approximately 
882 patients in the Stage II-IIIA population, and within Stage II-IIIA NSCLC patients, 
approximately 474 patients in the PD-L1 subpopulation ( 1% TC expression) defined by 
the SP263 IHC assay. 
Emerging data from atezolizumab first-line NSCLC Phase III Study GO29431 
(IMpower110; Herbst et al. 2019; Spigel et al. 2019) have observed clinical benefit with 
atezolizumab monotherapy in PD-L1 TC-defined subgroups.  The TC-based assay 
SP263 appeared to capture a broader patient population with similar efficacy as 
compared to SP142.  These findings are consistent with results observed in other 
PD-L1/PD-1 studies.  With these data external to Study GO29431 and evolving 
biomarker landscape, the primary analysis of DFS in the PD-L1 subgroups (TC2/3 or 
IC2/3, TC1/2/3 or IC1/2/3) defined by SP142 will be replaced with DFS in the PD-L1 
subgroup (
 1% TC expression) defined by SP263 (see Figure 2). 
The overall type I error rate will be controlled for the one-sided test at 0.025.  
The overview of the alpha control is shown in Figure 2. 
 

 
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One DFS interim analysis to be performed when approximately 80% of the total 
DFS events in the primary efficacy analysis populations required for the primary 
analysis have occurred.  The stopping boundaries for DFS interim and final 
analyses will be determined based on the Hwang-Shih-DeCani alpha spending 
function with the gamma parameter of 0.9 (Hwang et al. 1990; refer to 
Section 6.8.1 for details of the planned DFS interim analysis). 
 
Dropout rate of 5% per 24 months 
 
The estimates of the number of events required to demonstrate efficacy with regard to 
OS are based on the following assumptions: 
 
1:1 randomization ratio 
 
One-sided significance level of 0.025 in the ITT population (i.e., Stage IB-IIIA) 
 
77% power to detect an HR of 0.78, corresponding to an improvement in median 
OS from 66 months to 84.6 months in the ITT population 
 
Four interim OS analyses to be performed, one at the time of the DFS interim 
analysis, the second one at the time of DFS final analysis, and the other two when 
approximately 73% and 88% of the total OS events required for the final analysis 
have occurred, respectively.  The stopping boundaries for OS interim and final 
analyses will be determined based on the alpha spending function with the 
cumulative one-sided alpha of 0.001, 0.012, 0.022, 0.024, and 0.025 in the order of 
analyses (DeMets and Lan 1994; refer to Section 6.8.2 for details of the planned OS 
interim analyses). 
 
Dropout rate of 5% per 36 months 
 
With these assumptions, the DFS final analysis will be conducted when approximately 
237 DFS events in the PD-L1 subpopulation (defined by SP263 TC 1%) within the 
Stage II IIIA population have been observed.  This is expected to occur approximately 
68 months after the first patient is randomized.  This number of events corresponds to a 
minimum detectable difference in HR of approximately 0.758 in the PD-L1 subpopulation 
within the Stage II IIIA population. 
Given the sample size of 1005, the final OS analysis will be conducted when 
approximately 564 OS events in the all randomized Stage IB IIIA population have 
occurred, which is expected at approximately 121 months after the first patient is 
randomized. 
6.2 
SUMMARIES OF CONDUCT OF STUDY 
Study enrollment, study treatment administration, reasons for discontinuation from study 
treatment, and reasons for study termination will be summarized for patients who are 
enrolled but not randomized and for randomized patients in the PD-L1 subpopulation 
(defined by SP263 TC 1%) within the Stage II IIIA population, the Stage II IIIA 
population, and the ITT population by treatment arm (depending on the results of the 
primary endpoint analyses).  Major protocol deviations, including major deviations of 

 
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inclusion/exclusion criteria, will be reported and summarized by treatment arm for the 
ITT population. 
6.3 
SUMMARIES OF TREATMENT GROUP COMPARABILITY 
Demographic characteristics, such as age, sex, race/ethnicity, baseline disease 
characteristics (e.g., ECOG Performance Status), and cisplatin-based regimen, will be 
summarized by treatment arm.  Descriptive statistics (mean, median, standard deviation, 
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 atezolizumab or BSC in the randomized phase, unless otherwise noted. 
6.4 
EFFICACY ANALYSES 
To manage the small strata size with the consideration of prognostic significance, 
stratified analyses for DFS in the PD-L1 subpopulation defined by SP263 TC 
 1%, in all 
randomized patients with Stage II IIIA NSCLC, and stratified analyses for DFS in all 
randomized patients with Stage II IIIA NSCLC will use the following stratification factors 
at randomization:  Stage (II vs. IIIA), sex (female vs. male), and histology (squamous vs. 
non-squamous); stratified analyses for DFS in the ITT population will use the following 
stratification factors at randomization:  Stage ([IB and II combined] vs. IIIA), sex (female 
vs. male), histology (squamous vs. non-squamous), and SP142 PD-L1 tumor expression 
status by SP142 IHC assay ([TC2/3 and any IC, TC0/1 and IC2/3 combined] vs. [TC0/1 
and IC0/1]).  Stratified analyses of DFS in other PD-L1 subpopulations (e.g., SP263 
TC 50% in all randomized patients with Stage II IIIA NSCLC) will use the same set of 
stratification factors used for the stratified analyses of DFS in the PD-L1 subpopulation 
defined by SP263 TC 
 1% in all randomized patients with Stage II IIIA NSCLC.  The set 
of stratification factors used in the stratified analyses of DFS for a specific analysis 
population (e.g., the ITT population) will be applied to all other efficacy endpoints where 
stratified analyses are planned for the same analysis population. 
An IRF may conduct a BICR of response endpoints. 
6.4.1 
Primary Efficacy Endpoint 
The primary efficacy endpoint is duration of DFS as assessed by the investigator.  
DFS is defined as the time from the date of randomization to the date of occurrence of 
any of the following:  first documented recurrence of disease, new primary NSCLC or 
death due to any cause, whichever occurs first.  Data for patients who are not reported 
as experiencing disease recurrence, a new primary NSCLC, or death will be censored at 
the date of the last tumor assessment.  If no post-baseline data are available, DFS will 
be censored at the date of randomization. 
To control the overall level of significance at a one-sided error of 0.025, comparisons 
with respect to DFS between the treatment and control arm for the PD-L1 subpopulation 

 
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defined by SP263 TC 1% within the Stage II IIIA population, all-randomized 
Stage II IIIA population, and the ITT population, will be conducted hierarchically as 
described in Figure 2. 
The null and alternative hypotheses regarding DFS in each population can be phrased in 
terms of the DFS survival functions SA(t) in the atezolizumab arm (Arm A) and SB(t) in 
the control arm (Arm B), respectively: 
H0:  SA(t) 
 SB(t) versus H1:  SA(t) 
 SB(t) 
The HR will be estimated with use of a stratified Cox regression model, including 
two-sided 95% CIs.  The stratification factors used for the analysis are described in 
Section 6.4.  The unstratified HR will also be presented.  Kaplan-Meier methodology will 
be used to estimate the median DFS for each treatment arm and the Kaplan-Meier curve 
will be constructed to provide a visual description of the difference between the 
treatment and control arms.  Brookmeyer-Crowley methodology will be used to construct 
the two-sided 95% CI for the median DFS for each treatment arm (Brookmeyer and 
Crowley 1982). 
Analyses at landmark timepoints (Section 6.7.1) and subgroup analyses (Section 6.7.1) 
will be performed for the DFS endpoint described above. 
6.4.2 
Secondary Efficacy Endpoints 
6.4.2.1 
Overall Survival Analysis 
OS is defined as the time from the date of randomization to death due to any cause.  
Data for patients who are not reported as having died at the date of analysis will be 
censored at the date when they were last known to be alive.  If no post-baseline data are 
available, OS will be censored at the date of randomization. 
The methodology (as described in Section 6.4.1) used for DFS will be applied for OS.  
An overview of the OS testing schema is shown in Figure 2. 
6.4.2.2 
Disease-Free Survival 3-Year and 5-Year Landmark Analysis 
The DFS rate at 3 years and at 5 years will be analyzed for the PD-L1 subpopulation 
(defined by SP263 TC 1% in all randomized patients with Stage II IIIA NSCLC, the 
all-randomized Stage II IIIA population, and the ITT population.  These DFS rates will be 
estimated by the Kaplan-Meier methodology for each treatment arm, with two-sided 95% 
CIs calculated using 
 
6.4.2.3 
Disease-Free Survival Analysis in Additional PD-L1 
Subpopulation Defined by the Anti PD-L1 (SP263) IHC Assay 
DFS in the PD-L1 subpopulation, defined by SP263 TC 
 50% in all randomized patients 
with Stage II IIIA NSCLC, will be analyzed by using the same methodology in 
Section 6.4.1. 

 
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6.5 
SAFETY ANALYSES 
Safety analyses will be performed on the safety evaluable population, defined as all 
randomized patients who received any amount of the study drug, with patients allocated 
according to whether or not any amount of atezolizumab was received. 
Study drug exposure will be summarized to include treatment duration, number of doses, 
and dose intensity for each treatment arm using descriptive statistics. 
Verbatim description of adverse events will be mapped to thesaurus terms and graded 
according to NCI CTCAE v4.0.  All adverse events that occur during or after the first 
study drug dose will be summarized by treatment arm and NCI CTCAE grade.  
In addition, serious adverse events, severe adverse events (Grades 3, 4, or 5), adverse 
events of special interest, and adverse events leading to study drug discontinuation or 
interruption will be summarized accordingly.  Multiple occurrences of the same event will 
be counted once at the maximum severity. 
Summaries of treatment-related serious adverse events, adverse events of special 
interest, and all listings of adverse events will include all events that occur during or after 
the first study drug treatment.  Safety summaries of all other adverse events will include 
treatment-emergent adverse events until patients receive another anti-cancer therapy. 
Laboratory data with values outside the normal ranges will be identified.  In addition, 
selected laboratory data will be summarized by treatment arm and grade.  Changes in 
vital signs will be summarized by treatment arm. 
Serum levels and incidences of ATA against atezolizumab will be summarized to explore 
the potential relationship of the immunogenicity response with pharmacokinetics, safety, 
and efficacy.  ATA results will be summarized and listed by patient and cycle. 
Deaths reported during the study treatment period and those reported during the 
follow-up period after treatment completion/discontinuation will be summarized by 
treatment arm. 
6.6 
PHARMACOKINETIC ANALYSES 
PK and pharmacodynamic samples will be collected in this study as outlined in 
Appendix 2. 
Atezolizumab serum concentration data (Cmin and Cmax) will be tabulated and 
summarized.  Descriptive statistics will include means, medians, ranges, and standard 
deviations as appropriate. 
Additional PK and pharmacodynamic analysis will be conducted based on the availability 
of data. 

 
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6.7 
EXPLORATORY ANALYSES 
6.7.1 
Exploratory Analyses of Disease-Free Survival and Overall 
Survival 
Unless otherwise indicated, the exploratory efficacy endpoints will be analyzed in the 
PD-L1 subpopulation defined by SP263 TC 1% within the Stage II IIIA patients, all 
randomized Stage II IIIA patients, and/or the ITT population (depending on the results of 
the primary endpoint analyses). 
DFS and OS Rate at Landmark Timepoints.  In addition to DFS 3-year and 5-year 
survival rates as secondary endpoints, the DFS and OS rate at various other timepoints 
(every 1 year from randomization) will be estimated with use of Kaplan-Meier 
methodology for each treatment arm, along with two-sided 95% CIs calculated with use 
 
Subgroup Analysis.  The effects of demographics (e.g., age, sex, and race/ethnicity) 
and baseline prognostic characteristics (e.g., tumor stage, PD-L1 expression level, 
chemotherapy regimen before randomization, histology, smoking history, and ECOG 
Performance Status) on duration of DFS and OS will be examined.  Summaries of DFS 
and OS, including un-stratified HRs estimated from Cox proportional hazards models 
and Kaplan-Meier estimates of median survival time will be produced separately for each 
level of the categorical variables. 
Sensitivity Analyses.  The impact of loss to follow-up on DFS will be assessed 
depending on the number of patients who are lost to follow-up.  If more than 5% of 
patients are lost to follow-up for DFS in either treatment arm, a sensitivity analysis 
-
be performed in which patients who are lost to follow-up will 
be considered to have recurrent disease at the date of the last tumor assessment. 
To evaluate the impact of missed visits, sensitivity analyses with a different censoring 
rule will be performed for the primary endpoint of DFS.  Data for patients with a DFS 
event who missed two or more scheduled assessments immediately prior to the DFS 
event will be censored at the last date with adequate radiologic assessment prior to the 
missed visits. 
DFS Analyses in Other PD-L1 Subpopulations.  DFS in other PD-L1 subpopulations will 
be analyzed by using the same methodology in Section 6.4.1.  These PD-L1 
subpopulations include TC3 or IC3, TC2/3 or IC2/3, TC1/2/3 or IC1/2/3 subpopulations 
defined by PD-L1 SP142 IHC in both the Stage II IIIA and the ITT populations; the 
PD-L1 subpopulations defined by 22C3 TPS 1% and TPS 50% in both the Stage II IIIA 
and the ITT populations; and the PD-L1 subpopulations defined by SP263 TC  1% and 
TC   50% in the ITT population. 

 
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6.7.2 
Exploratory Analyses of Biomarkers 
Exploratory biomarker analyses will be performed in an effort to understand the 
association of these markers with disease status and/or study drug response, including 
efficacy and/or adverse events.  The biomarkers include but are not limited to ctDNA and 
PD-L1 and CD8, as defined by IHC, qRT-PCR, or other methods. 
6.8 
INTERIM ANALYSES 
6.8.1 
Planned Interim Analysis for Disease-Free Survival 
An external iDMC will evaluate safety data on an ongoing basis and will also review the 
interim analysis of DFS data.  All summaries and analyses by treatment arm for the 
(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. 
There will be one planned interim analysis for DFS in the study.  To ensure the study 
continues to meet the highest standards of integrity, the interim analysis of DFS will be 
conducted by an iDCC and reviewed by the iDMC.  Interactions between the iDMC and 
Sponsor will be carried out as specified in the iDMC charter. 
This DFS interim analysis will be conducted when approximately 80% of the information 
has been observed in the PD-L1 subpopulation defined by SP263 TC 
 1% within the 
Stage II IIIA population (i.e., at the date when approximately 190 DFS events occur in 
the PD-L1 subpopulation within the Stage II IIIA population).  This is expected to occur 
approximately 56 months after the first patient is randomized; however, the exact timing 
of this analysis will depend on the actual number and the timing of DFS events. 
The final DFS analysis will be conducted at the date when approximately 237 DFS 
events occur in the PD-L1 subpopulation within the Stage II IIIA population.  This is 
expected to occur approximately 68 months after the first patient is randomized; 
however, the exact timing of this analysis will depend on the actual number and timing of 
DFS events. 
To control type I error for DFS at one-sided alpha of 0.025, the stopping boundaries for 
DFS interim and final analysis are to be computed with use of the Hwang-Shih-DeCani 
alpha spending function with the gamma parameter of 0.9 as shown in Table 26. 

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

 
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7.5 
RETENTION OF RECORDS 
Records and documents pertaining to the conduct of this study and the distribution of 
IMP, including eCRFs, 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. 
All primary imaging data used for tumor assessments will be collected by the Sponsor.  
An IRF may conduct a BICR of response endpoints if requested by health authorities. 
Roche will retain study data for 25 years after the final Clinical Study Report has been 
completed or for the length of time required by relevant national or local health 
authorities, whichever is longer.  Study data may be used for secondary purposes. 
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 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 
Informed consent for participation must be obtained before performing any study specific 
screening tests or evaluations.  This study will use the paper consent process and the 
patient will provide a wet ink signature prior to participation at all sites.  Consent must be 
obtained per the consent process used at the investigational site.  Records of Informed 
Consent for both enrolled patients and those who are not subsequently enrolled will be 
maintained at the study site.  Copies of the study specific patient signed Informed 
Consent Forms will also be maintained at the site. 

 
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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 
IRB/EC-approved Consent Forms must be provided to the Sponsor for health authority 
submission purposes according to local requirements. 
The Informed Consent Form will contain a separate section that addresses the collection 
of optional samples and the use of remaining mandatory samples (whole blood and 
tissue) for optional exploratory research.  The investigator or authorized designee will 
explain to each patient the objectives of the exploratory research.  Patients will be told 
that they are free to refuse to participate and may withdraw their specimens at any time 
and for any reason during the storage period.  A separate, specific signature will be 
required to document a patient's agreement to allow the collection of optional samples 
and to use any remaining specimens for exploratory research.  Patients who decline to 
participate will not provide a separate signature. 
The Consent Forms must be sig
authorized representative before his or her participation in the study.  The case history or 
clinical records for each patient shall document the informed consent process and that 
written informed consent was obtained prior to participation in the study. 
The Consent Forms should be revised whenever there are changes to study procedures 
or when new information becomes available that may affect the willingness of the patient 
to participate.  The final revised IRB/EC-approved Consent Forms must be provided to 
the Sponsor for health authority submission purposes. 
Patients must be re-consented to the most current version of the Consent Forms (or to a 
significant new information/findings addendum in accordance with applicable laws and 
IRB/EC policy) during their participation in the study.  For any updated or revised 
Consent Forms, the case history or clinical records for each patient shall document the 
informed consent process and that written informed consent was obtained with use of 
the updated/revised Consent Forms for continued participation in the study. 
legally authorized representative.  All signed and dated Consent Forms must remain in 
study monitors at any time. 
For sites in the United States, each Consent Form may also include patient authorization 
to allow use and disclosure of personal health information in compliance with the 
U.S. Health Insurance Portability and Accountability Act (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, 

 
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and other processes outlined above apply except that IRB review and approval may not 
be required per study site policies. 
8.3 
INSTITUTIONAL REVIEW BOARD OR ETHICS COMMITTEE 
This protocol, the Informed Consent Forms, any information to be given to the patient, 
and relevant supporting information must be submitted to the IRB/EC by the Principal 
Investigator and reviewed and approved by the IRB/EC before the study is initiated.  
In addition, any patient recruitment materials must be approved by the IRB/EC. 
The Principal Investigator is responsible for providing written summaries of the status of 
the study to the IRB/EC annually or more frequently in accordance with the 
requirements, policies, and procedures established by the IRB/EC.  Investigators are 
also responsible for promptly informing the IRB/EC of any protocol amendments (see 
Section 9.6). 
In addition to the requirements for reporting all adverse events to the Sponsor, 
investigators must comply with requirements for reporting serious adverse events to the 
local health authority and IRB/EC.  Investigators may receive written IND safety reports 
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 
 
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. 
Medical information may be given to a pat
 
Data generated by this study must be available for inspection upon request by 
representatives of the U.S. FDA and other national and local health authorities, Sponsor 

 
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monitors, representatives, and collaborators, and the IRB/EC for each study site, as 
appropriate. 
8.5 
FINANCIAL DISCLOSURE 
Investigators will provide the Sponsor with sufficient, accurate financial information in 
accordance with local regulations to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate health authorities.  
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after the last patient has completed the study. 
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 
policies and procedures.  The Sponsor will review all protocol deviations and assess 
whether any represent a serious breach of Good Clinical Practice guidelines and require 
reporting to health authorities.  As per the Sponsor's standard operating procedures, 
prospective requests to deviate from the protocol, including requests to waive protocol 
eligibility criteria, are not allowed. 
9.3 
SITE INSPECTIONS 
Site visits will be conducted by the Sponsor or an authorized representative for 
permit national and local health authorities, Sponsor monitors, representatives, and 
collaborators, and the IRBs/ECs to inspect facilities and records relevant to this study. 
9.4 
ADMINISTRATIVE STRUCTURE 
This study will be sponsored by Roche and managed by a contract research 
organization.  Approximately 300 sites globally will participate in the study and 
approximately 1280 patients will be enrolled.  Randomization will occur through an IxRS.  
Central facilities will be used for study assessments throughout the study (e.g., specified 

 
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laboratory tests, and PK analyses).  Accredited local laboratories will be used for routine 
monitoring; local laboratory ranges will be collected. 
A central imaging IRF will be used to perform BICR if requested by health authorities.  
BICR membership and procedures will be detailed in a BICR charter.  An IRF may 
collect, store, and review imaging data. 
9.5 
PUBLICATION OF DATA AND PROTECTION OF TRADE 
SECRETS 
Regardless of the outcome of a study, the Sponsor is dedicated to openly providing 
information on the study to healthcare professionals and to the public, both at scientific 
congresses and in peer-reviewed journals.  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 and 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.  The Sponsor will comply with all requirements for 
publication of study results.  For more information, refer to the Roche Global Policy on 
Sharing of Clinical 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 studies 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 study results within 6 months after the 
availability of the respective clinical study report.  In addition, for all clinical studies 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 studies 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 

 
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monitoring will be considered as a joint publication by the investigator and the 
appropriate Sponsor personnel. 
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of data from this study will become and remain the exclusive and unburdened 
property of the Sponsor, except where agreed otherwise. 
9.6 
PROTOCOL AMENDMENTS 
Any protocol amendments will be prepared by the Sponsor.  Protocol amendments will 
be submitted to the IRB/EC and to regulatory authorities in accordance with local 
regulatory requirements. 
Approval must be obtained from the IRB/EC and regulatory authorities (as locally 
required) before implementation of any changes, except for changes necessary to 
eliminate an immediate hazard to patients or changes that involve logistical or 
administrative aspects only (e.g., change in Medical Monitor or contact information). 

 
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10. 
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Spigel D, De Marinis F, Giaccone G, et al. IMpower110: Interim overall survival (OS) 
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Appendix 1: Schedule of Assessments for Enrollment Phase (Cisplatin-Based Chemotherapy Administration) (Cont.) 
  
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f ECG should be obtained within 14 days before enrollment if clinically indicated or if pre-operative test results showed abnormalities.  
If pre-operative ECG was normal and there is no indication of a change in cardiac condition a repeat ECG within 14 days is not 
mandatory.  Patients should be resting and in a supine position for at least 10 minutes prior to each ECG collection. 
g To include, at a minimum, sodium, potassium, chloride, BUN or urea, creatinine, AST (SGOT) and/or ALT (SGPT), total bilirubin, 
alkaline phosphatase. 
h Tests should be obtained within 24 hours prior to day of treatment with results known prior to day of treatment.  Laboratory samples that 
are drawn within 48 hours prior to treatment that are normal will be acceptable.  CBC for Day 8 is only required for chemotherapy 
regimens with Day 8 administration. 
i See Section 4.5.6 for serology tests.  All patients will be tested for HIV prior to the inclusion into the study and HIV-positive patients will 
be excluded from the clinical study.  HBV DNA must be collected on or before Cycle 1, Day 1 in patients who have negative serology for 
hepatitis B surface antigen and positive serology for hepatitis B core antibody.  HCV RNA must be collected on or before Cycle 1, Day 1 
in patients who test positive for anti-HCV. 
j To include ANC, platelet count, hemoglobin. 
k More frequent testing is indicated if there is any suspicion of elevated values (i.e., patient is on low dose anticoagulation for a venous 
access device). 
l CT scans (with oral and/or IV contrast unless contraindicated) of the chest and abdomen and a CT and/or MRI scan of the brain to rule 
out CNS metastasis, especially if patient has Stage IIIA disease.  Bone scans and CT scans of the neck should also be performed if 
clinically indicated. 
m A representative FFPE tumor specimen in paraffin block (preferred) or of 15 (or more) unstained, freshly cut, serial sections (on slides) 
from an FFPE resected tumor specimen is required for participation in this study.  This specimen must be accompanied by the 
associated pathology report.  Retrieval of archival tumor sample can occur outside the 28-day screening period. 
n Copies of the pathology report must be submitted. 
o For patients who experience an ongoing study agent-related serious adverse event upon active treatment completion, or at 
discontinuation from the study, should be contacted by the investigator or his/her designee until the event is resolved or determined to 
be irreversible
 

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a Patients will be asked to return to the clinic not more than 30 days after the decision to discontinue treatment for a treatment or observation 
discontinuation visit. 
b Cycle 1, Day 1 must be performed within 5 days after the patient is randomized.  Screening assessments performed 
 96 hours before Cycle 1, 
Day 1 are not required to be repeated for Cycle 1, Day 1.  In addition, ECOG Performance Status, limited physical examination, and local 
laboratory tests may be performed 
 96 hours before Day 1 of each cycle as specified in Section 4.6.2. 
c Serum pregnancy test (for women of childbearing potential, including women who have had a tubal ligation) must be performed and 
documented as negative within 14 days prior to Day 1. 
d If a urine pregnancy test result is positive, it must be confirmed by a serum pregnancy test. 
e Complete and limited physical examinations are defined in Section 4.5.3. 
f Vital signs include heart rate, respiratory rate, blood pressures, and temperature and will be performed as standard of care for patients 
randomized to the BSC arm.  For patients randomized to the atezolizumab treatment arm, vital signs should be recorded as described in 
Table 10. 
g ECG recordings will be obtained when clinically indicated.  Patients should be resting and in a supine position for at least 10 minutes prior to 
each ECG collection. 
h Blood samples collected to monitor safety will be collected in patients randomized to both arms.  Hematology consists of CBC, including RBC 
count, hemoglobin, hematocrit, WBC count with automated differential (neutrophils, eosinophils, lymphocytes, monocytes, basophils, and other 
cells), and platelet count.  A manual differential can be done if clinically indicated.  Refer to Section 4.5.6 for a list of laboratory test results 
obtained within 14 days prior to the first dose of atezolizumab treatment. 
i Serum chemistry includes glucose, BUN or urea, creatinine, sodium, potassium, magnesium, chloride, bicarbonate or total carbon dioxide 
(if considered standard of care for the site), calcium, phosphorus, total bilirubin, ALT, AST, alkaline phosphatase, LDH, total protein, and 
albumin.  Refer to Section 4.5.6 for a list of laboratory results obtained within 14 days prior to first dose of atezolizumab treatment. 
j Urinalysis (specific gravity, pH, glucose, protein, ketones, and blood). 
k Perform if clinically indicated. 
l For patients assigned to atezolizumab treatment arm only.  See Appendix 3 for details of the ATA and PK collection schedule.  Blood samples 
should be processed to obtain serum.  A post-treatment ATA and PK sample should be collected 120 days (± 30 days) after the last dose of 
atezolizumab received during the treatment period unless the patient withdraws consent or the study closes. 
m See Appendix 3 for details of the biomarker sampling schedule. 
n Patients randomized to atezolizumab arm will receive their first dose of study drug the day of randomization if possible.  If this is not possible, 
the first dose should occur no later than 5 days after randomization.  The initial dose of atezolizumab treatment will be delivered over 
60 (
 15) minutes.  If the first infusion is well tolerated, all subsequent infusions may be delivered over 30 (
 10) minutes.  Atezolizumab 
treatment may be continued for a maximum of 16 cycles in the absence of meeting discontinuation criteria specified in Section 4.3.4.2.

Appendix 2: Schedule of Assessments for Randomized Phase (Atezolizumab or Best Supportive Care) (Cont.) 
  
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o A mandatory biopsy is required, if clinically feasible, within 40 days of disease recurrence or prior to the start of the next anti-cancer therapy, 
whichever is sooner (see Section 4.5.8.1).  After the DFS final analysis is complete, tumor samples will no longer be collected. 
p Results must be reviewed by the investigator before dosing at the next cycle (in atezolizumab treatment arm only).  Tumor assessments 
should continue for at least 5 years regardless of whether patients start new anti-cancer therapy in the absence of disease recurrence unless 
the patient withdraws consent for tumor assessments.  If there is a recurrence, it is also strongly encouraged that patients be fully restaged, 
including a CT scan of the chest and abdomen, imaging (preferably MRI, but CT is acceptable) of the brain, and a radionuclide bone scan or 
positron emission tomography (PET) scan.  Additional scans may be necessary as per investigator judgment if recurrence of primary lung 
cancer is suspected on treatment.   
q Concomitant medications include any prescription medications or over-the-counter medications.  At screening, any medications the patient has 
used within the 7 days prior to the screening visit should be documented.  At subsequent visits, changes to current medications or medications 
used since the last documentation of medications will be recorded. 
r Once randomized into the study, during both the enrollment phase (cisplatin-based chemotherapy) and randomization phase (atezolizumab or 
BSC), all serious adverse events and adverse events of special interest will be recorded during the study and for 90 days after the last dose of 
study treatment (last study assessment for patients in Arm B) or initiation of new anti-cancer therapy, whichever occurs first.  All other adverse 
events will be recorded during the study and for 30 days after the last dose of study treatment (last study assessment for patients randomized 
to Arm B) or until the initiation of another anti-cancer therapy, whichever occurs first. 
s This medical contact can be either via telephone call or formal clinic visit.  If the contact is via a formal clinic visit, additional assessments may 
be done as clinically indicated per local standard of care and at the discretion of the investigator. 
t Survival follow-up information will be collected via telephone calls, patient medical records, and/or clinic visits approximately every 6 months or 
more often until death, loss to follow-up, or study termination by Roche.  All patients (irrespective of which arm they are randomized to) will be 
followed 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 atezolizumab study, the study staff may 
use a public information source (e.g., county records) to obtain information about survival status only.  This also applies to patients randomized 
to BSC arm.  Patients assigned to either study arm who complete either the initial treatment or the initial observation period (16 cycles) will 
discontinue atezolizumab treatment or BSC and will continue follow-up tumor assessments (per the tumor assessment schedule above see 
footnote p). No patients are allowed to cross over.
 

 
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Appendix 4  
Anti PD-L1 (SP142) Immunohistochemistry 
OVERVIEW 
The Ventana anti-programmed death ligand 1 (PD-L1) (SP142) rabbit monoclonal 
primary antibody immunohistochemistry (IHC) assay will be used to determine PD-L1 
IHC status.  The anti PD-L1 (SP142) rabbit monoclonal antibody IHC assay is currently 
being developed by Ventana Medical Systems as a companion diagnostic to 
atezolizumab.  For Study GO29527, the anti PD-L1 (SP142) IHC assay will be used for 
investigational purposes only. 
The Ventana anti PD-L1 (SP142) rabbit monoclonal primary antibody is intended for 
laboratory use in the semi-quantitative immunohistochemical assessment of the PD-L1 
protein in formalin-fixed, paraffin-embedded non small cell lung cancer (NSCLC) tissue 
stained on a Ventana BenchMark ULTRA automated slide stainer.  It is indicated as an 
aid in the selection of patients with NSCLC with locally advanced or metastatic disease 
who might benefit from treatment with atezolizumab. 
This assay is for investigational use only.  The performance characteristics of this 
product have not been established. 
DEVICE DESCRIPTION 
The Ventana anti PD-L1 (SP142) rabbit monoclonal primary antibody is a pre-dilute, 
ready to use antibody product optimized for use with the Ventana Medical Systems 
OptiView DAB IHC Detection Kit and the OptiView Amplification Kit on Ventana Medical 
Systems automated BenchMark ULTRA platforms.  One 5 mL dispenser of anti PD-L1 
(SP142) rabbit monoclonal primary antibody contains approximately 36 g of rabbit 
monoclonal antibody directed against the PD-L1 protein and contains sufficient reagent 
for 50 tests.  The reagents and the IHC procedure are optimized for use on the 
BenchMark ULTRA automated slide stainer, utilizing Ventana system software (VSS). 
SCORING SYSTEM 
PD-L1 staining with anti PD-L1 (SP142) rabbit monoclonal primary antibody in NSCLC 
can be observed in both tumor cells and tumor-infiltrating immune cells. 

 
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Appendix 5  
Anti PD-L1 (SP263) Immunohistochemistry 
OVERVIEW 
The Ventana PD-L1 (SP263) CDx Assay will be used to determine PD-L1 
immunohistochemical (IHC) status.  The assay uses an anti PD-L1 rabbit monoclonal 
primary antibody (Ventana PD-L1 (SP263) antibody) to recognize the programmed 
death-ligand 1 (PD-L1) also known as B7 homolog 1 (B7-H1) or CD274.  The Ventana 
PD-L1 (SP263) CDx Assay is currently being developed by Ventana Medical Systems as 
a companion diagnostic to atezolizumab.  For Study GO29527, the Ventana PD-L1 
(SP263) Assay will be used for investigational purposes only. 
Ventana PD-L1 (SP263) CDx Assay is intended for the qualitative immunohistochemical 
assessment of the programmed death ligand 1 (PD-L1) protein in formalin-fixed, 
paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC) tissue stained with a 
BenchMark ULTRA IHC/ISH automated staining instrument.  It is indicated as an aid in 
identifying patients eligible for treatment with PD-L1 or PD-1 targeted therapy. 
This assay is for investigational use only.  The performance characteristics of this 
product have not been established. 
DEVICE DESCRIPTION 
The VENTANA PD-L1 (SP263) rabbit monoclonal primary antibody is a pre-dilute, 
ready-to-use antibody product optimized for use with the Ventana Medical Systems 
OptiView DAB IHC Detection Kit on Ventana Medical Systems automated BenchMark 
ULTRA platforms.  One 5-mL dispenser of anti-PD-L1 (SP263) rabbit monoclonal 
primary antibody contains approximately 8.05 g of rabbit monoclonal antibody directed 
against the PD-L1 protein and contains sufficient reagent for 50 tests.  The reagents and 
the IHC procedure are optimized for use on the BenchMark ULTRA automated slide 
stainer, utilizing Ventana system software (VSS). 
SCORING SYSTEM 
NSCLC neoplastic cells labeled with the Ventana PD-L1 (SP263) Assay are evaluated 
for percent positivity of the tumor cells with membrane staining at any intensity of the 
diaminobenzidine (DAB) signal.  The immunohistochemical staining in NSCLC is 
membranous and/or cytoplasmic, and may be expressed homogeneously or 
heterogeneously throughout the neoplasm. 
 

 
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Appendix 6  
Preexisting Autoimmune Diseases 
Patients should be carefully questioned regarding their history of acquired or congenital 
immune deficiencies or autoimmune disease.  Patients with any history of immune 
deficiencies or autoimmune disease 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-mediated 
hypothyroidism on a stable dose of thyroid replacement hormone are 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 for patients who have 
previously experienced a severe or life threatening skin adverse reaction or pericardial 
disorder while receiving another immunostimulatory anticancer agent.  The Medical 
Monitor is available to advise on any uncertainty over autoimmune exclusions. 
Acute disseminated 
encephalomyelitis 
Addison disease 
Ankylosing spondylitis 
Antiphospholipid antibody 
syndrome 
Aplastic anemia 
Autoimmune hemolytic anemia 
Autoimmune hepatitis 
Autoimmune hypoparathyroidism 
Autoimmune hypophysitis 
Autoimmune myelitis 
Autoimmune myocarditis 
Autoimmune oophoritis 
Autoimmune orchitis 
Autoimmune thrombocytopenic 
purpura 
Behçet disease 
Bullous pemphigoid 
Chronic fatigue syndrome 
Chronic inflammatory 
demyelinating polyneuropathy 
Chung-Strauss syndrome 
Crohn disease 
Dermatomyositis 
Diabetes mellitus type 1 
Dysautonomia 
Epidermolysis bullosa 
acquisita 
Gestational pemphigoid 
Giant cell arteritis 
Goodpasture syndrome 
Granulomatosis with 
polyangiitis 
Graves disease 
Guillain-Barré syndrome 
Hashimoto disease 
IgA nephropathy 
Inflammatory bowel disease 
Interstitial cystitis 
Kawasaki disease 
Lambert-Eaton myasthenia 
syndrome 
Lupus erythematosus 
Lyme disease - chronic 
Meniere syndrome 
Mooren ulcer 
Morphea 
Multiple sclerosis 
Myasthenia gravis 
Neuromyotonia 
Optic neuritis 
Opsoclonus myoclonus 
syndrome 
Ord thyroiditis 
Pemphigus 
Pernicious anemia 
Polyarteritis nodosa 
Polyarthritis 
Polyglandular autoimmune 
syndrome 
Primary biliary cholangitis 
Psoriasis 
Reiter syndrome 
Rheumatoid arthritis 
Sarcoidosis 
Scleroderma 
Sjögren syndrome 
Stiff-Person syndrome 
Takayasu arteritis 
Ulcerative colitis 
Vitiligo 
Vogt-Koyanagi-Harada 
disease 

 
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Appendix 7  
Anaphylaxis Precautions 
Equipment Needed 
 
Oxygen 
 
Epinephrine for subcutaneous, intravenous (IV), and/or endotracheal use in 
accordance with standard practice 
 
Antihistamines 
 
Corticosteroids 
 
IV infusion solutions, tubing, catheters, and tape 
 
Procedures 
1. 
In the event of a suspected anaphylactic reaction during study drug infusion, 
the following procedures should be performed: 
2. 
Stop the study drug infusion. 
3. 
Maintain an adequate airway. 
4. 
Administer antihistamines, epinephrine, or other medications as required by patient 
status and directed by the physician in charge. 
5. 
Continue to observe the patient and document observations. 

 
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Appendix 8  
Cockcroft and Gault Formula 
Creatinine Clearance 
The standard Cockcroft and Gault (1976) formula or the measured glomerular filtration 
rate, using the appropriate radiolabeled method (51-CrEDTA or Tc99m-DTPA), must be 
used to calculate creatinine clearance (CRCL) for screening and/or dosing.  The same 
method used at baseline should be used throughout the study. 
 
                                   (140 - age in years) 
 body weight (kg) 
 0.85 
CRCL (Female)               72 
 serum creatinine (mg/dL) 
 
 
 
                            (140 - age in years) 
 body weight (kg) 
CRCL (Male)                   72 
 serum creatinine (mg/dL) 

 
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Appendix 9  
Risks Associated with Atezolizumab and Guidelines for 
Management of Adverse Events Associated with Atezolizumab 
Although toxicities observed with atezolizumab have been mild and self-limiting, they 
should be recognized early and treated promptly to avoid potential major complications.  
Discontinuation of 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. 
DOSE MODIFICATIONS  
There will be no dose modifications for atezolizumab in this study. 
TREATMENT INTERRUPTION 
Atezolizumab treatment may be temporarily suspended in patients experiencing toxicity 
considered to be related to study treatment.  Management guidelines for patients who 
experience adverse events associated with atezolizumab are provided in Table A9-1.  
Atezolizumab treatment may be suspended for reasons other than toxicity (e.g., surgical 
procedures).  The acceptable length of treatment interruption must be based on the 
investigator's benefit risk assessment 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. 

Appendix 9: Risks Associated with Atezolizumab and Guidelines for Management of 
Adverse Events Associated with Atezolizumab (Cont.) 
  
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REFERENCES 
La Rosée P. Treatment of hemophagocytic lymphohistiocytosis in adults. Hematology 
Am Soc Hematol Educ Program 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 [resource 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. 
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. 
Schram AM, Berliner N. How I treat hemophagocytic lymphohistiocytosis in the adult 
patient. Blood 2015;125:2908 14. 
 

 
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Appendix 10  
Investigational, Non-Investigational, and Auxiliary Medicinal 
Product Designations (for Use in European Economic Area and 
United Kingdom) 
Table A10-1 Investigational and Non-Investigational Medicinal Product 
Designations for United Kingdom 
Product Name 
IMP/NIMP Designation 
Marketing 
Authorization Status 
in U.K.  
Used within Marketing 
Authorization 
Atezolizumab 
(RO5541267) 
IMP (test product) 
Authorized
No a 
Vinorelbine
NIMP (background therapy) 
Authorized
No b 
Docetaxel
NIMP (background therapy) 
Authorized
No b 
Gemcitabine
NIMP (background therapy)
Authorized
No b 
Pemetrexed
NIMP (background therapy)
Authorized
No b 
Cisplatin 
NIMP (background therapy)
Authorized 
No b 
IMP 
 investigational medicinal product; NIMP 
  non-investigational medicinal product; U.K. 
 United 
Kingdom. 
a Atezolizumab holds a Marketing Authorization in the U.K. but is not fully approved for the way in 
which it is used within this study.    
b Vinorelbine, docetaxel, gemcitabine, pemetrexed and cisplatin are not approved for the adjuvant 
treatment indication but are recommended in the clinical treatment guidelines.  
  
Table A10-2 Investigational and Authorized Auxiliary Medicinal Product 
Designations for European Economic Area  
Product Name 
IMP/AxMP Designation 
Marketing 
Authorization Status 
in EEA  
Used within Marketing 
Authorization 
Atezolizumab 
(RO5541267) 
IMP (test product) 
Authorized
No a 
Vinorelbine
AxMP (background therapy) 
Authorized
No b 
Docetaxel
AxMP (background therapy) 
Authorized
No b 
Gemcitabine
AxMP (background therapy)
Authorized
No b 
Pemetrexed
AxMP (background therapy)
Authorized
No b 
Cisplatin 
AxMP (background therapy) 
Authorized 
No b 
AxMP 
 auxiliary medicinal product; EEA 
 European Economic Area; IMP 
 investigational medicinal 
product. 
a Atezolizumab holds a Marketing Authorization in the EEA but is not fully approved for the way in 
which it is used within this study. 
b Vinorelbine, docetaxel, gemcitabine, pemetrexed and cisplatin are not approved for adjuvant 
treatment indication but are recommended in the clinical treatment guidelines.
 

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