AdvanTIG-205: A Phase 2, Randomized Study of Ociperlimab (BGB-A1217) and Tislelizumab With Chemotherapy in Patients With Previously Untreated Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer (NSCLC)
Phase: PHASE2
Conditions: Locally Advanced, Unresectable, or Metastatic Nonsmall Cell Lung Cancer (NSCLC), Nonsmall Cell Lung Cancer, Stage IIIB, Nonsmall Cell Lung Cancer, Stage IV
Sponsor: BeiGene

AdvanTIG-205 
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CLINICAL STUDY PROTOCOL  
 
Protocol Title:  
AdvanTIG-205: A Phase 2, Randomized Study of Ociperlimab 
(BGB-A1217) and Tislelizumab With Chemotherapy in Patients 
With Previously Untreated Locally Advanced, Unresectable, or 
Metastatic Non-Small Cell Lung Cancer (NSCLC)  
Brief Title 
NA 
Protocol Number: 
AdvanTIG-205 
Amendment Number: 
Amendment 4.0 Global 
Investigational Medicinal 
Product(s): 
Ociperlimab (BGB-A1217) and Tislelizumab (BGB-A317)  
Regulatory Agency 
Identification Number(s): 
EudraCT 2021-001075-17 
NCT05014815 
Sponsor: 
BeiGene, Ltd. 
c/o BeiGene USA, Inc. 
1840 Gateway Drive  
Third Floor  
San Mateo, California 94404, USA 
Approval Date: 
See electronic signature 
Contact Information: 
BeiGene Medical Officer 
Phone: 1.877.828.5568 
Email: clinicaltrials@beigene.com  
 
 
 
 
 
 
 
 
 
CONFIDENTIALITY STATEMENT 
The information contained herein is confidential and the proprietary property of BeiGene, Ltd. and its 
affiliates.  Any unauthorized use or disclosure of such information without the prior written 
authorization of BeiGene, Ltd. or any of its affiliates, or outside the cases and forms provided for by 
applicable legal provisions, is expressly prohibited. 
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INVESTIGATOR SIGNATURE PAGE  
I have read the protocol, appendices, and accessory materials related to Study AdvanTIG-205 
and agree to the following: 
• To conduct this study as described by the protocol and any accessory materials. 
• To protect the rights, safety, and welfare of the patients under my care. 
• To provide oversight to all personnel to whom study activities have been delegated. 
This includes personnel at my site as well as personnel working in any facility where 
study activities are my responsibility. 
• To control all investigational products provided by the sponsor and maintain records 
of the disposition of those products. 
• To conduct the study in accordance with all applicable laws and regulations, the 
requirements of the ethics committee of record for my clinical site, and current GCP 
as outlined by ICH E6(R2). 
• To obtain approval for the protocol and all written materials provided to patients 
before initiating the study at my site. 
• To obtain informed consent – and updated consent in the event of new information or 
amendments – from all patients enrolled at my study site before initiating any 
study-specific procedures or administering investigational products to those patients. 
• To maintain records of each patient participation and all data required by the protocol 
in an accurate and timely manner. 
Acceptance of this protocol constitutes my agreement that no confidential information contained 
herein will be published or disclosed without prior written approval from BeiGene, Ltd. or one of 
its affiliates unless and only to the extent required by applicable laws and regulations. 
Name:   
Title:   
Institution:   
  
  
  
Signature:   
Date:  
  
  
Approved Date
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DOCUMENT HISTORY  
Amendment Version Number 
Approval Date 
Type of Protocol Amendment  
AdvanTIG-205 Amendment 3.0 
23 September 2022 
Substantial 
AdvanTIG-205 Amendment 2.0 
30 March 2022 
Substantial 
AdvanTIG-205 Amendment 1.0 
11 June 2021 
Substantial 
Original protocol 
06 April 2021 
Not applicable 
 
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TABLE OF CONTENTS  
INVESTIGATOR SIGNATURE PAGE .........................................................................................2 
DOCUMENT HISTORY.................................................................................................................3 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF TABLES .........................................................................................................................12 
LIST OF FIGURES .......................................................................................................................13 
SYNOPSIS ....................................................................................................................................14 
LIST OF ABBREVIATIONS AND TERMS ................................................................................25 
1. 
INTRODUCTION ......................................................................................................28 
1.1. 
Background Information on Non-small Cell Lung Cancer ........................................28 
1.2. 
Current Treatment of Metastatic Non-small Cell Lung Cancer Without 
Actionable Mutations ..................................................................................................28 
1.2.1. 
Chemotherapy .............................................................................................................28 
1.2.2. 
Anti-PD-1/PD-L1 Therapy .........................................................................................29 
1.2.3. 
New Immunotherapy-Immunotherapy Combinations for Metastatic NSCLC: 
Anti-TIGIT and Anti-PD-1/PD-L1 .............................................................................30 
1.3. 
Background Information on Ociperlimab, a TIGIT Inhibitor ....................................31 
1.3.1. 
Nonclinical Summary .................................................................................................31 
1.3.1.1. 
Pharmacology .............................................................................................................31 
1.3.1.2. 
Toxicology ..................................................................................................................32 
1.3.2. 
Prior Clinical Experience With Ociperlimab ..............................................................33 
1.3.3. 
Ociperlimab Clinical Pharmacology ...........................................................................35 
1.4. 
Background Information on Tislelizumab ..................................................................35 
1.4.1. 
Pharmacology .............................................................................................................35 
1.4.2. 
Toxicology ..................................................................................................................36 
1.4.3. 
Clinical Pharmacology ................................................................................................36 
1.4.4. 
Prior Clinical Experience With Tislelizumab .............................................................37 
1.4.4.1. 
Treatment-Emergent Adverse Events in Chemotherapy Combination Studies .........37 
1.4.4.2. 
Treatment-Emergent Serious Adverse Events ............................................................38 
1.4.4.3. 
Immune-Mediated Adverse Events ............................................................................38 
1.4.4.4. 
Infusion-Related Reactions .........................................................................................39 
1.4.4.5. 
Liver Laboratory Abnormalities .................................................................................39 
1.4.4.6. 
Fatal Adverse Events ..................................................................................................39 
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1.4.5. 
Efficacy Assessment of Tislelizumab .........................................................................40 
1.5. 
Study Rationales .........................................................................................................44 
1.5.1. 
Rationale for Ociperlimab and Tislelizumab in the Treatment of NSCLC ................44 
1.5.2. 
Rationale for the Selection of the Ociperlimab Dose in Combination With 
Tislelizumab ...............................................................................................................45 
1.5.3. 
Rationale for the Selection of the Tislelizumab Dose ................................................45 
1.5.4. 
Rationale for Tislelizumab Plus Chemotherapy as the Comparator ...........................46 
1.5.5. 
Rationale for Biomarker Strategy ...............................................................................46 
1.6. 
Benefit-Risk Assessment ............................................................................................47 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................49 
2.1. 
Study Objectives .........................................................................................................49 
2.1.1. 
Primary Objective .......................................................................................................49 
2.1.2. 
Secondary Objectives .................................................................................................49 
2.1.3. 
Exploratory Objectives ...............................................................................................49 
2.2. 
Study Endpoints ..........................................................................................................49 
2.2.1. 
Primary Endpoint ........................................................................................................49 
2.2.2. 
Secondary Endpoints ..................................................................................................50 
2.2.3. 
Exploratory Endpoints ................................................................................................50 
3. 
STUDY DESIGN .......................................................................................................51 
3.1. 
Summary of Study Design ..........................................................................................51 
3.2. 
Screening Period .........................................................................................................52 
3.3. 
Treatment Period ........................................................................................................52 
3.4. 
End of Treatment ........................................................................................................54 
3.5. 
Safety Follow-up ........................................................................................................55 
3.6. 
Survival Follow-up .....................................................................................................55 
3.7. 
Discontinuation From the Study Treatment or From the Study .................................55 
3.7.1. 
Patient Discontinuation From Study Treatment .........................................................55 
3.7.2. 
Patient Discontinuation From Study (End of Study for an Individual Patient) ..........56 
3.8. 
End of Study ...............................................................................................................56 
4. 
STUDY POPULATION .............................................................................................58 
4.1. 
Inclusion Criteria ........................................................................................................58 
4.2. 
Exclusion Criteria .......................................................................................................59 
5. 
STUDY TREATMENT ..............................................................................................64 
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5.1. 
Formulation, Packaging, and Handling ......................................................................64 
5.1.1. 
Ociperlimab ................................................................................................................64 
5.1.2. 
Tislelizumab ...............................................................................................................64 
5.1.3. 
Chemotherapy Agents ................................................................................................64 
5.1.4. 
Ociperlimab Placebo ...................................................................................................64 
5.2. 
Dosage, Administration, and Compliance ..................................................................65 
5.3. 
Overdose or Incorrect Administration ........................................................................68 
5.4. 
Investigational Medicinal Product Accountability .....................................................68 
5.5. 
Dose Delay, Interruption, and Modification ...............................................................69 
5.5.1. 
General Guidance Regarding Dose Modifications .....................................................69 
5.5.2. 
Dose Delay or Interruption for Ociperlimab and Tislelizumab ..................................69 
5.5.3. 
Dose Delay or Modifications for Chemotherapy ........................................................70 
5.5.4. 
Criteria for Discontinuing Chemotherapy Regimens .................................................71 
5.6. 
Blinding ......................................................................................................................72 
5.6.1. 
Emergency Unblinding ...............................................................................................72 
5.6.2. 
Nonemergency Unblinding .........................................................................................73 
5.6.3. 
Inadvertent Unblinding ...............................................................................................73 
5.6.4. 
Unblinding After Primary Analysis or Completion of the Trial.................................73 
6. 
PRIOR AND CONCOMITANT THERAPY .............................................................74 
6.1. 
Prior Therapy ..............................................................................................................74 
6.2. 
Concomitant Therapy .................................................................................................74 
6.2.1. 
Permitted Concomitant Medications/Procedures .......................................................74 
6.2.1.1. 
Systemic Corticosteroids ............................................................................................74 
6.2.1.2. 
Hepatitis B Treatment .................................................................................................74 
6.2.1.3. 
Hepatitis C Treatment .................................................................................................74 
6.2.1.4. 
Radiation Therapy ......................................................................................................75 
6.2.1.5. 
COVID-19 Vaccines ...................................................................................................75 
6.2.2. 
Prohibited Concomitant Medications/Procedures ......................................................75 
6.2.3. 
Restricted Concomitant Medications/Procedures .......................................................76 
6.3. 
Potential Interactions Between the Study Drugs and Concomitant 
Medications .................................................................................................................76 
7. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................78 
7.1. 
Screening ....................................................................................................................78 
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7.1.1. 
Informed Consent and Screening Log ........................................................................78 
7.1.2. 
Patient Numbering ......................................................................................................78 
7.1.3. 
Pulmonary Function Tests ..........................................................................................79 
7.1.4. 
Demographic Data and Medical History ....................................................................79 
7.1.5. 
Contraception and Women of Childbearing Potential ................................................79 
7.1.6. 
HIV Serology Test ......................................................................................................80 
7.1.7. 
COVID-19 Test ..........................................................................................................80 
7.2. 
Enrollment ..................................................................................................................80 
7.2.1. 
Confirmation of Eligibility .........................................................................................80 
7.2.2. 
Enrollment/Randomization .........................................................................................80 
7.3. 
Study Drug Dispensation ............................................................................................80 
7.4. 
Safety Assessments .....................................................................................................80 
7.4.1. 
Vital Signs, Height, and Weight .................................................................................80 
7.4.2. 
Physical Examinations ................................................................................................81 
7.4.3. 
Eastern Cooperative Oncology Group Performance Status ........................................81 
7.4.4. 
Laboratory Safety Tests ..............................................................................................81 
7.4.4.1. 
Cardiac Enzyme Monitoring .......................................................................................82 
7.4.5. 
Electrocardiograms .....................................................................................................82 
7.4.6. 
Adverse Events ...........................................................................................................82 
7.4.7. 
Hepatitis B and C Testing ...........................................................................................82 
7.5. 
Tumor and Response Evaluations ..............................................................................83 
7.6. 
Pharmacokinetic and Antidrug Antibody Testing ......................................................84 
7.7. 
Biomarkers ..................................................................................................................84 
7.8. 
Patient-Reported Outcomes ........................................................................................85 
7.9. 
Visit Windows ............................................................................................................85 
7.10. 
Unscheduled Visits .....................................................................................................86 
8. 
SAFETY MONITORING AND REPORTING .........................................................87 
8.1. 
Risks Associated With Study Drugs ...........................................................................87 
8.1.1. 
Risks Associated With Ociperlimab and Tislelizumab ..............................................87 
8.1.2. 
Risks Associated With Chemotherapy Agents ...........................................................87 
8.2. 
General Plan to Manage Safety Concerns ..................................................................88 
8.2.1. 
Eligibility Criteria .......................................................................................................88 
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8.2.2. 
Safety Monitoring Plan ...............................................................................................88 
8.3. 
Adverse Events ...........................................................................................................88 
8.3.1. 
Definitions and Reporting ...........................................................................................88 
8.3.2. 
Assessment of Severity ...............................................................................................89 
8.3.3. 
Assessment of Causality .............................................................................................89 
8.3.4. 
Follow-up of Adverse Events .....................................................................................90 
8.3.5. 
Laboratory Test Abnormalities ...................................................................................91 
8.4. 
Definition of a Serious Adverse Event .......................................................................91 
8.5. 
Suspected Unexpected Serious Adverse Reaction .....................................................92 
8.6. 
Timing, Frequency, and Method of Capturing Adverse Events and Serious 
Adverse Events ...........................................................................................................92 
8.6.1. 
Adverse Event Recording Period ................................................................................92 
8.6.2. 
Reporting Serious Adverse Events .............................................................................93 
8.6.2.1. 
Prompt Reporting of Serious Adverse Events ............................................................93 
8.6.2.2. 
Completion and Transmission of the Serious Adverse Event Report ........................93 
8.6.2.3. 
Regulatory Reporting Requirements for Serious Adverse Events .............................94 
8.6.3. 
Eliciting Adverse Events ............................................................................................94 
8.6.4. 
Disease Progression ....................................................................................................94 
8.6.5. 
Deaths .........................................................................................................................95 
8.6.6. 
Pregnancies .................................................................................................................95 
8.6.7. 
Expedited Reporting to Health Authorities, Investigators, Institutional 
Review Boards, and Independent Ethics Committees ................................................95 
8.6.8. 
Assessing and Recording Immune-Mediated Adverse Events ...................................95 
8.6.9. 
Recording Infusion-Related Reactions .......................................................................96 
8.6.10. 
Managing Infusion-Related Reactions .......................................................................96 
8.6.11. 
Severe Hypersensitivity Reactions and Flu-Like Symptoms .....................................97 
8.6.12. 
Immune-Mediated Adverse Events ............................................................................98 
9. 
STATISTICAL METHODS AND SAMPLE SIZE DETERMINATION ...............100 
9.1. 
Statistical Analysis ....................................................................................................100 
9.1.1. 
Randomization Methods ...........................................................................................100 
9.1.2. 
Analysis Sets .............................................................................................................100 
9.1.3. 
Patient Disposition ....................................................................................................100 
9.1.4. 
Demographic and Other Baseline Characteristics ....................................................100 
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9.1.5. 
Prior and Concomitant Medications .........................................................................101 
9.2. 
Efficacy Analyses .....................................................................................................101 
9.2.1. 
Primary Efficacy Analysis ........................................................................................101 
9.2.2. 
Secondary Efficacy Analysis ....................................................................................102 
9.2.3. 
Exploratory Efficacy Analysis ..................................................................................103 
9.3. 
Safety Analyses ........................................................................................................103 
9.3.1. 
Extent of Exposure ...................................................................................................103 
9.3.2. 
Adverse Events .........................................................................................................103 
9.3.3. 
Laboratory Analyses .................................................................................................104 
9.3.4. 
Vital Signs ................................................................................................................104 
9.3.5. 
Pulmonary Function Test ..........................................................................................104 
9.4. 
Pharmacokinetic Analysis ........................................................................................104 
9.5. 
Immunogenicity Analyses ........................................................................................104 
9.6. 
Sample Size Considerations .....................................................................................105 
9.7. 
Interim Analyses .......................................................................................................105 
10. 
STUDY COMMITTEES AND COMMUNICATION ............................................106 
11. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS .............................................................................................107 
11.1. 
Access to Information for Monitoring ......................................................................107 
11.2. 
Access to Information for Auditing or Inspections ..................................................107 
12. 
QUALITY ASSURANCE AND QUALITY CONTROL .......................................108 
12.1. 
Regulatory Authority Approval ................................................................................108 
12.2. 
Quality Assurance .....................................................................................................108 
12.3. 
Study Site Inspections...............................................................................................108 
12.4. 
Drug Accountability .................................................................................................108 
13. 
ETHICS/PROTECTION OF HUMAN PATIENTS ................................................110 
13.1. 
Ethical Standard ........................................................................................................110 
13.2. 
Institutional Review Board/Independent Ethics Committee ....................................110 
13.2.1. 
Protocol Amendments ..............................................................................................110 
13.3. 
Informed Consent .....................................................................................................111 
13.4. 
Patient and Data Confidentiality ...............................................................................111 
13.5. 
Financial Disclosure .................................................................................................113 
14. 
DATA HANDLING AND RECORD KEEPING ....................................................114 
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14.1. 
Data Collection and Management Responsibilities ..................................................114 
14.1.1. 
Data Entry in the Electronic Case Report Form .......................................................114 
14.1.2. 
Data Collection .........................................................................................................114 
14.1.3. 
Data Management/Coding ........................................................................................114 
14.2. 
Data Integrity and In-house Blinding .......................................................................115 
14.3. 
Study Records Retention ..........................................................................................115 
14.4. 
Protocol Deviations ..................................................................................................116 
14.5. 
Study Report and Publications..................................................................................116 
14.6. 
Study and Study Center Closure ...............................................................................117 
14.7. 
Information Disclosure and Inventions ....................................................................117 
15. 
REFERENCES .........................................................................................................119 
APPENDIX 1. SCHEDULE OF ASSESSMENTS ..................................................................125 
APPENDIX 2. CLINICAL LABORATORY ASSESSMENTS ..............................................132 
APPENDIX 3. EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS .....................................................................................133 
APPENDIX 4. THE RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
(RECIST) GUIDELINES, VERSION 1.1 ................................................................134 
APPENDIX 5. PREEXISTING IMMUNE DEFICIENCIES OR AUTOIMMUNE 
DISEASES ................................................................................................................144 
APPENDIX 6. NEW YORK HEART ASSOCIATION FUNCTIONAL 
CLASSIFICATION ..................................................................................................145 
APPENDIX 7. IMMUNE-MEDIATED ADVERSE EVENT EVALUATION AND 
MANAGEMENT .....................................................................................................146 
APPENDIX 8. DOSE MODIFICATION FOR CHEMOTHERAPY .......................................163 
APPENDIX 9. CHRONIC KIDNEY DISEASE EPIDEMIOLOGY 
COLLABORATION (CKD-EPI) EQUATION, COCKCROFT-GAULT 
EQUATION, AND CALVERT FORMULA ...........................................................166 
APPENDIX 10. CONTRACEPTION GUIDELINES AND DEFINITIONS OF 
“WOMEN OF CHILDBEARING POTENTIAL,” “NO CHILDBEARING 
POTENTIAL” ...........................................................................................................167 
APPENDIX 11. EUROPEAN ORGANISATION FOR RESEARCH AND 
TREATMENT OF CANCER QUALITY OF LIFE CANCER 
QUESTIONNAIRE QLQ-C30 .................................................................................169 
APPENDIX 12. EUROPEAN ORGANISATION FOR RESEARCH AND 
TREATMENT OF CANCER QUALITY OF LIFE QUESTIONNAIRE 
LUNG CANCER QLQ-LC13 ..................................................................................171 
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APPENDIX 13. LIST OF PROHIBITED CHINESE HERBAL AND PATENT 
MEDICINES .............................................................................................................172 
 
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LIST OF TABLES  
Table 1: 
Overview of Treatment-Emergent Adverse Events (Safety Analysis Set) .................34 
Table 2: 
Summary of Tumor Response in Study BGB-A317-206 (Efficacy Analysis 
Set) ..............................................................................................................................41 
Table 3: 
Selection and Timing of Dose for Each Patient (Induction Phase) ............................65 
Table 4: 
Selection and Timing of Dose for Each Patient (Maintenance Phase) .......................66 
Table 5: 
Administration of Study Treatments and Monitoring Time .......................................66 
Table 6. 
Commonly and Specific Reported Toxicity of the Chemotherapeutic Agents ..........87 
Table 7: 
Guidance for Duration of Recording New or Worsening Adverse Events in 
All Treatment Arms ....................................................................................................93 
Table 8: 
Timeframes and Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee .............................................................................93 
Table 9: 
Treatment Modifications for Symptoms of Infusion-Related Reactions Due 
to Study Drug(s) .........................................................................................................96 
Table 10: 
Examples of Immune-Mediated Adverse Events .......................................................98 
Table 11: 
Hazard Ratio and Median PFS Assumption, Number Of Events, Alpha and 
Power in the Primary Hypothesis Test .....................................................................105 
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LIST OF FIGURES  
Figure 1: 
Cycles 1 and 5 Mean (+ SD) Serum Concentration-Time Profiles of 
Ociperlimab in Study AdvanTIG-105 ........................................................................35 
Figure 2: 
Study Schema .............................................................................................................52 
 
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SYNOPSIS  
Name of Sponsor/Company: BeiGene, Ltd. 
Investigational Products: Ociperlimab (BGB-A1217) and Tislelizumab (BGB-A317) 
Title of Study: AdvanTIG-205: A Phase 2, Randomized Study of Ociperlimab (BGB-A1217) and 
Tislelizumab With Chemotherapy in Patients With Previously Untreated Locally Advanced, 
Unresectable, or Metastatic Non-Small Cell Lung Cancer (NSCLC)  
Protocol Identifier: AdvanTIG-205 
Phase of Development: 2 
Number of Patients: Approximately 270 
Study Centers: Approximately 84 centers globally 
Study Objectives: 
Primary: 
• 
To compare progression-free survival (PFS) between Arm A (ociperlimab in combination with 
tislelizumab and chemotherapy) and Arm B (placebo in combination with tislelizumab and 
chemotherapy) in the Intent-to-Treat (ITT) Analysis Set, as assessed by investigators per 
Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) 
Secondary: 
• 
To evaluate overall response rate (ORR) and duration of response (DOR) in Arm A 
(ociperlimab in combination with tislelizumab and chemotherapy) versus Arm B (placebo in 
combination with tislelizumab and chemotherapy), as assessed by investigators per RECIST 
v1.1 
• 
To compare overall survival (OS) in Arm A (ociperlimab in combination with tislelizumab and 
chemotherapy) and Arm B (placebo in combination with tislelizumab and chemotherapy) 
• 
To evaluate the safety and tolerability profile of ociperlimab in combination with tislelizumab 
and chemotherapy compared to tislelizumab in combination with chemotherapy 
Exploratory: 
• 
To evaluate disease control rate (DCR), clinical benefit rate (CBR), and time to response 
(TTR) in Arm A (ociperlimab in combination with tislelizumab and chemotherapy) versus 
Arm B (placebo in combination with tislelizumab and chemotherapy), as assessed by 
investigators per RECIST v1.1 
• 
To evaluate the potential association of exploratory biomarkers with response or resistance of 
ociperlimab and tislelizumab, and patient prognosis 
• 
To compare health-related quality of life (HRQoL) between Arm A (ociperlimab in 
combination with tislelizumab and chemotherapy) and Arm B (placebo in combination with 
tislelizumab and chemotherapy) 
• 
To characterize the pharmacokinetics (PK) of ociperlimab and tislelizumab 
• 
To determine host immunogenicity to ociperlimab and tislelizumab 
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Study Endpoints: 
Primary: 
• 
PFS (time from the date of randomization to the date of the first objectively documented tumor 
progression, or death, whichever occurs first) in the ITT Analysis Set of Arm A (ociperlimab in 
combination with tislelizumab and chemotherapy) versus Arm B (placebo in combination with 
tislelizumab and chemotherapy), as assessed by investigators per RECIST v1.1  
Secondary: 
• 
ORR as assessed by investigators (proportion of patients with a documented, confirmed 
complete response [CR] or partial response [PR] per RECIST v1.1) and DOR as assessed by 
investigators (time from the first determination of an objective response per RECIST v1.1 until 
the first documentation of progression or death, whichever occurs first) in Arm A (ociperlimab 
in combination with tislelizumab and chemotherapy) and Arm B (placebo in combination with 
tislelizumab and chemotherapy) 
• 
OS (time from the date of randomization to the date of death due to any cause) in the ITT 
Analysis Set of Arm A (ociperlimab in combination with tislelizumab and chemotherapy) 
versus Arm B (placebo in combination with tislelizumab and chemotherapy) 
• 
The incidence and severity of adverse events according to National Cancer Institute Common 
Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0) 
Exploratory: 
• 
DCR (proportion of patients with confirmed CR or confirmed PR or stable disease [SD]), CBR 
(proportion of patients with confirmed CR or confirmed PR or durable SD), and TTR (time 
from randomization to the first occurrence of a documented objective response) in Arm A 
(ociperlimab in combination with tislelizumab and chemotherapy) versus Arm B (placebo in 
combination with tislelizumab and chemotherapy) as assessed by investigators per RECIST 
v1.1 
• 
Status of exploratory biomarkers, including but not limited to expression of T-cell 
immunoglobulin and ITIM domain (TIGIT), CD226, CD155, CD112, and programmed cell 
death ligand-1 (PD-L1), gene expression profiling (GEP), circulating tumor DNA (ctDNA), 
tumor mutation burden (TMB), gene mutations and microsatellite instability (MSI), tumor-
infiltrating immune cells (TILs), and extracellular vesicles (EVs) in archival and/or fresh tumor 
tissue or blood before and after study treatment or at disease progression/reoccurrence, and the 
association between these biomarkers and clinical efficacy, disease status, and resistance.  
• 
HRQoL will be assessed using 2 validated patient-reported outcomes (PRO), including 
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- 
Core 30 (EORTC-QLQ-C30) and its lung cancer module (Quality of Life Questionnaire- Lung 
Cancer 13 [QLQ-LC13]).  
• 
Serum concentrations of ociperlimab and tislelizumab at prespecified timepoints. 
• 
Immunogenic responses to ociperlimab and tislelizumab, evaluated through detection of anti-
drug antibodies (ADAs). 
 
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Study Design: 
This is a randomized, investigator- and patient-blinded, sponsor-unblinded, multicenter, Phase 2 study 
designed to evaluate the efficacy and safety of ociperlimab in combination with tislelizumab and 
histology-based chemotherapy versus placebo in combination with tislelizumab and histology-based 
chemotherapy in patients with previously untreated locally advanced, unresectable, or metastatic 
NSCLC that does not harbor epidermal growth factor receptor (EGFR) mutations, anaplastic 
lymphoma kinase (ALK) translocations, BRAF V600E mutations, or c-ROS oncogene-1 (ROS1) 
mutations. Patients with non-squamous NSCLC will receive either cisplatin or carboplatin in 
combination with pemetrexed, with the choice of platinum (cisplatin or carboplatin) selected at the 
investigator’s discretion. Patients with squamous NSCLC will receive carboplatin and either paclitaxel 
or nab-paclitaxel at the investigator’s discretion. 
Approximately 270 patients will be enrolled globally (including a minimum of 25% of non-Asian 
patients). 
The PD-L1 expression is tested centrally. Local PD-L1 results may be utilized under certain 
circumstances for enrollment. 
The study will target to enroll patients to ensure that it reflects a representative distribution of PD-L1 
expression in NSCLC (approximately 40% PD-L1 TC < 1%) and to ensure that it reflects a 
representative histology distribution in the NSCLC population without driver mutation (approximately 
30% squamous NSCLC).  
Eligible participants will be randomized in a 1:1 ratio to receive one of the following treatment 
regimens: 
Induction phase (4 to 6 cycles, every 3 weeks): 
• 
Arm A: Ociperlimab 900 mg intravenously (IV) + tislelizumab 200 mg IV + histology-based 
chemotherapy 
• 
Arm B: Placebo IV + tislelizumab 200 mg IV + histology-based chemotherapy 
For patients with squamous NSCLC, the histology-based chemotherapy regimen will be carboplatin 
area under the concentration-time curve (AUC) 5 or 6 on Day (D) 1 + paclitaxel 175 or 200 mg/m2 
(D1) or nab-paclitaxel 100 mg/m2 (D1, D8, D15) administered every 3 weeks.  
For patients with non-squamous NSCLC, the histology-based chemotherapy regimen will be cisplatin 
75 mg/m2 or carboplatin AUC 5 (D1) + pemetrexed 500 mg/m2 IV (D1) administered every 3 weeks. 
Maintenance phase (every 3 weeks): 
For patients with non-squamous NSCLC: 
• 
Arm A: Ociperlimab 900 mg IV + tislelizumab 200 mg IV + pemetrexed 500 mg/m2 once 
every 3 weeks  
• 
Arm B: Placebo IV + tislelizumab 200 mg IV + pemetrexed 500 mg/m2 once every 3 weeks 
For patients with squamous NSCLC: 
• 
Arm A: Ociperlimab 900 mg IV + tislelizumab 200 mg IV once every 3 weeks 
• 
Arm B: Placebo IV + tislelizumab 200 mg IV once every 3 weeks 
All study treatments will be administered until intolerable toxicity, withdrawal of informed consent, or 
the time point at which, in the investigator’s opinion, the patient is no longer benefiting from study 
therapy.  
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The study schema is as follows: 
 
Abbreviations: ALK, anaplastic lymphoma kinase; AUC, area under the concentration-time curve; D, day; EGFR, epidermal 
growth factor receptor; NSCLC, non-small cell lung cancer; PD-L1, programmed cell death ligand-1; R, randomization; WT, 
wild type 
Study Assessments: 
PFS and tumor response will be assessed by the investigators using RECIST v1.1. Tumor imaging 
(computed tomography [CT] with or without contrast or magnetic resonance imaging [MRI]) must be 
performed within 28 days prior to randomization. All study assessments will occur every 9 weeks 
± 7 days for the first 52 weeks and every 12 weeks ± 7 days thereafter. Patients who discontinue study 
treatment early for reasons other than radiologic disease progression (eg, toxicity) will continue to 
undergo tumor assessments following the original plan until the patient begins a subsequent anticancer 
treatment, experiences radiologic disease progression or death, withdraws consent, is lost to follow-up, 
or until the study terminates, whichever occurs first. 
Patients will be evaluated for any adverse events (AEs) and serious adverse events (SAEs) (all severity 
grades, per NCI-CTCAE v5.0). After informed consent has been signed but prior to the administration 
of the study drug(s), only SAEs should be reported. After initiation of the study drug(s), all AEs and 
SAEs, regardless of relationship to the study drug(s), will be reported until either 30 days after the last 
dose of study treatment or chemotherapy, or until the initiation of a new anticancer therapy, whichever 
occurs first. Immune-related AEs (serious or non-serious) should be reported until 90 days after the last 
dose of ociperlimab (or placebo) and/or tislelizumab, regardless of whether or not the patient starts a 
new anticancer therapy. All SAEs considered related to the study drug(s) that are brought to the 
attention of the investigator should be reported, regardless of time since the last dose of treatment. 
Duration of Patient Participation: 
The duration of the study from first patient randomized to final analysis for PFS is estimated to be 
approximately 33 months. 
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Study Population:  
Key Inclusion Criteria 
• 
Age ≥ 18 years on the day of signing the ICF (or the legal age of consent in the jurisdiction in 
which the study is taking place). 
• 
Histologically or cytologically documented locally advanced or recurrent NSCLC that is not 
eligible for curative surgery and/or definitive radiotherapy, with or without chemotherapy, or 
metastatic non-squamous or squamous NSCLC. 
• 
No prior systemic therapy for locally advanced or metastatic squamous or non-squamous 
NSCLC, including but not limited to chemotherapy or targeted therapy. Patients who have 
received prior neoadjuvant, adjuvant chemotherapy, or chemoradiotherapy with curative intent 
for nonmetastatic disease must have experienced a disease-free interval of ≥ 6 months from the 
last dose of chemotherapy and/or concurrent radiotherapy prior to randomization. 
• 
Archival tumor tissue or fresh biopsy (if archival tissue is not available) for the determination 
of PD-L1 levels and retrospective analyses of other biomarkers. If local PD-L1 testing will be 
used for patient randomization purposes, confirmation of tumor sample receipt by the central 
laboratory is required before patient randomization (preferably from the same block used for 
local PD L1 testing). Local PD-L1 testing must be performed using an approved assay (limited 
to 22C3, SP263, and 28-8) at a certified laboratory and according to the manufacturer’s 
instructions. 
• 
At least one measurable lesion by the investigator per RECIST v1.1. 
• 
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1. 
• 
Adequate organ function as indicated by the following laboratory values during screening. 
• 
For full inclusion criteria, see Section 4.1. 
Key Exclusion Criteria 
• 
Known mutations in: 
o EGFR gene  
Note: For non-squamous NSCLC, patients with unknown EGFR mutation status will 
be required to have a tissue-based EGFR test either locally or at the central laboratory 
before enrollment, or endobronchial ultrasound-guided transbronchial needle aspiration 
(EBUS-TBNA)–based EGFR test locally. Patients found to have EGFR-sensitizing 
mutations will be excluded.  
o ALK fusion oncogene.  
o BRAF V600E 
o ROS1 
• 
Prior treatment with EGFR inhibitors, ALK inhibitors, or targeted therapy for other driver 
mutations. 
• 
Any prior therapy targeting T-cell costimulation or checkpoint pathways in metastatic NSCLC.  
• 
Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of 
prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before 
randomization. 
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• 
Infection (including tuberculosis infection, etc.) requiring systemic antibacterial, antifungal, or 
antiviral therapy within 14 days before randomization. 
For full exclusion criteria, see Section 4.2. 
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Investigational Product, Dose, and Mode of Administration: 
Ociperlimab 
Ociperlimab is a monoclonal antibody formulated for intravenous infusion in a single-use vial (20 mL 
glass vial, United States Pharmacopeia [USP] Type I) containing a total of 300 mg antibody in 15 mL 
of buffered isotonic solution as available. Ociperlimab has been aseptically filled in single-use vials 
with a Flurotec-coated butyl rubber stopper and an aluminum cap. Each vial is packaged into a single 
carton box. 
The contents of the label will be in accordance with all applicable local regulatory requirements. 
The study drug must be kept at the temperature condition as specified on the label. Shaking should be 
avoided. 
Refer to the pharmacy manual for details regarding intravenous administration, accountability, and 
disposal. Refer to the Ociperlimab (BGB-A1217) Investigator’s Brochure for other details regarding 
ociperlimab. 
Tislelizumab 
Tislelizumab is a monoclonal antibody formulated for intravenous infusion in a single-use vial (20R 
glass, USP Type I), containing a total of 100 mg of antibody in 10 mL of isotonic solution. 
Tislelizumab has been aseptically filled in single-use glass vials with a rubber stopper and capped by an 
aluminum flip-off seal cap. Each vial is packaged into a single carton box. 
The contents of the label will be in accordance with all applicable local regulatory requirements. 
The study drug must be kept at the temperature condition as specified on the label. Shaking should be 
avoided. 
Refer to the pharmacy manual for details regarding intravenous administration, accountability, and 
disposal. Please also refer to the Tislelizumab (BGB-A317) Investigator’s Brochure for other details 
regarding tislelizumab. 
Dose and Mode of Administration:  
Tislelizumab 200 mg will be administered on Day 1 of each 21-day cycle (once every 3 weeks). 
Ociperlimab 900 mg will be administered on Day 1 of each 21-day cycle (once every 3 weeks) after 
tislelizumab. 
Ociperlimab and tislelizumab will be administered by intravenous infusion through an intravenous line 
containing a sterile, non-pyrogenic, low-protein-binding 0.2 or 0.22 micron in-line or add-on filter. 
Specific instructions for product preparation and administration are provided in the pharmacy manual. 
The initial infusions (Day 1 of Cycle 1 and Cycle 2) will be delivered over 60 (± 5) minutes; if this is 
well tolerated, then the subsequent infusions may be administered over 30 (± 5) minutes, which is the 
shortest time period permissible for infusion. Tislelizumab and ociperlimab/placebo must not be 
concurrently administered with any other drug (refer to Section 6). 
As a routine precaution, after the infusion of ociperlimab and tislelizumab on Day 1 of Cycle 1 and 
Cycle 2, patients must be monitored for at least 120 minutes afterward in an area with resuscitation 
equipment and emergency agents. From Cycle 3 onward, a ≥ 60-minute monitoring period is required 
in an area with resuscitation equipment and emergency agents. 
Guidelines for treatment interruption or discontinuation and for the management of immune-mediated 
adverse events (imAEs) and infusion-related reactions are provided in detail in Appendix 7. 
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Refer to the pharmacy manual for detailed instructions on drug preparation, storage, and 
administration. 
Non-Investigational Therapy, Dose, and Mode of Administration: 
Matching placebo for ociperlimab will be administered as an intravenous infusion every 3 weeks. 
Chemotherapy regimens (Section 3.3 and Section 5.1.3): 
Carboplatin AUC 5 or 6 will be administered as an intravenous infusion once every 3 weeks on Day 1 
of each cycle for 4 to 6 cycles.  
Cisplatin 75 mg/m2 will be administered as an intravenous infusion once every 3 weeks on Day 1 of 
each cycle for 4 to 6 cycles.  
Paclitaxel 175 or 200 mg/m2 will be administered as an intravenous infusion once every 3 weeks on 
Day 1 of each cycle for 4 to 6 cycles.  
Nab-paclitaxel 100 mg/m2 will be administered as an intravenous infusion once every 3 weeks on 
Day 1, Day 8, and Day 15 of each cycle for 4 to 6 cycles.  
Pemetrexed 500 mg/m2 will be administered as an intravenous infusion once every 3 weeks on Day 1 
of each cycle.  
Statistical Methods: 
PFS is the primary endpoint in the ITT Analysis Set of the study. The secondary endpoints of ORR and 
OS will be tested sequentially once PFS superiority of Arm A over Arm B has been demonstrated. 
Analysis Sets: 
• 
The ITT Analysis Set includes all randomized patients. Patients will be analyzed according to 
their randomized treatment arm. This will be the primary analysis set for efficacy and HRQoL 
analyses. 
• 
The Per-Protocol (PP) Analysis Set includes all randomized patients who received ≥ 1 dose of 
the assigned study drug and had no critical protocol deviations. Critical protocol deviations will 
be determined and documented before the database lock for the primary analyses. 
• 
The Safety Analysis Set includes all randomized patients who received ≥ 1 dose of study drug. 
This will be the analysis set for the safety analyses. 
• 
The PK Analysis Set includes all patients who received ≥ 1 dose of any component of study 
drug per the protocol and for whom any postdose PK data are available.  
• 
The Immunogenicity Analysis Set includes all patients who received ≥ 1 dose of any 
component of study drug for whom both baseline ADA and ≥ 1 postbaseline ADA results are 
available. 
Primary Efficacy Endpoint Analysis: 
The primary analyses will be performed when approximately 194 PFS events have been observed.  
PFS in ITT Analysis Set 
The null hypothesis (H0) to be tested is: 
H0: PFS in Arm A ≤ PFS in Arm B 
against the alternative hypothesis (H1): 
H1: PFS in Arm A > PFS in Arm B 
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A stratified log-rank test to compare PFS distribution between ociperlimab + tislelizumab + 
chemotherapy (Arm A) and placebo + tislelizumab + chemotherapy (Arm B) will be the primary 
efficacy analysis, stratified by PD-L1 expression (three levels: < 1% TC versus 1% to 49% TC versus 
≥ 50% TC) and histology (squamous versus non-squamous NSCLC). It will be performed once the 
targeted PFS event number is reached. A significance level of 1-sided alpha of 0.025 will be used in the 
PFS testing. 
PFS as assessed by investigators per RECIST v1.1 will be estimated using the Kaplan-Meier method in 
the ITT Analysis Set. PFS will be censored at the last adequate tumor assessment if 1 of the following 
occurs by the time of analysis: absence of event, a new anticancer therapy is given, or the event 
occurred after ≥ 2 missing tumor assessments. For cases with missing baseline tumor assessment, a 
death occurring ≤ 19 weeks from the randomization date will be considered a PFS event. Clinical or 
symptomatic progressions without supportive radiologic data will not be considered as PFS events.  
The median PFS and 2-sided 95% confidence interval (CI) using the method of Brookmeyer and 
Crowley will be summarized. The cumulative probability of PFS at every 6 months including PFS rate 
at 6 and 12 months, if estimable, will be calculated for each treatment arm and presented with 2-sided 
95% CIs. Standard error for PFS rates will be calculated based on Greenwood’s formula. Kaplan-Meier 
survival probabilities for each arm will be plotted over time.  
The treatment effect will be estimated by fitting a Cox regression model to the PFS times, including 
treatment arm as a factor and PD-L1 expression (three levels: < 1% TC versus 1% to 49% TC versus 
≥ 50% TC) and histology (squamous versus non-squamous NSCLC) as strata. From this model, the 
hazard ratio (HR) of PFS will be estimated and presented with a 2-sided 95% CI. 
Subgroup analysis of PFS will be performed by PD-L1 expression, histology, region, and other key risk 
factors that are to be described in the statistical analysis plan.  
Secondary Efficacy Endpoint Analyses: 
Best overall response (BOR) is defined as the best response per RECIST v1.1 recorded from 
randomization until data cut, progressive disease, or start of a new anticancer treatment. The null 
hypotheses of no difference in ORR per RECIST v1.1 assessed by investigators between ociperlimab + 
tislelizumab + chemotherapy (Arm A) and placebo + tislelizumab + chemotherapy (Arm B) will be 
tested in a Cochran-Mantel-Haenszel (CMH) test adjusting for stratification factors (PD-L1 expression 
[three levels: < 1% TC versus 1% to 49% TC versus ≥ 50% TC] and histology [squamous versus 
non-squamous NSCLC]) in the ITT Analysis Set. Patients with no postbaseline response assessment 
(for any reason) will be considered non-responders. The 2-sided 95% CI for the odds ratio in ORR will 
be calculated, as well as Clopper-Pearson 95% CIs of ORR for each treatment arm. 
DOR as assessed by investigators will be derived using the similar censoring rule as for PFS and 
summarized descriptively in the responders receiving ociperlimab + tislelizumab + chemotherapy 
(Arm A) versus placebo + tislelizumab + chemotherapy (Arm B). 
OS will be compared between ociperlimab + tislelizumab + chemotherapy (Arm A) and placebo + 
tislelizumab + chemotherapy (Arm B) in a 1-sided, stratified log-rank test using stratification factors of 
PD-L1 expression (three levels: < 1% TC versus 1% to 49% TC versus ≥ 50% TC) and histology 
(squamous versus non-squamous NSCLC).  
In the absence of confirmation of death, patients will be censored either at the date that the patient was 
last known to be alive or the date of data cutoff, whichever comes earlier. The median OS and 2-sided 
95% CI using the method of Brookmeyer and Crowley will be summarized. The cumulative probability 
of OS at every 6 months including OS rate at 12 months and 24 months if estimable, will be calculated 
for each treatment arm and presented with 2-sided 95% CIs. Standard error for survival rates will be 
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calculated based on Greenwood’s formula. Kaplan-Meier survival probabilities for each arm will be 
plotted over time.  
The treatment effect will be estimated by fitting a Cox regression model to the OS times including 
treatment arm as a factor and PD-L1 expression (three levels: < 1% TC versus 1% to 49% TC versus 
≥ 50% TC) and histology (squamous versus non-squamous NSCLC) as strata. From this model, the HR 
of OS will be estimated and presented with a 2-sided 95% CI. 
Exploratory Efficacy Analyses: 
The proportion and its corresponding Clopper-Pearson 95% CI for each of the response categories 
(eg, CR, PR, SD, progressive disease [PD], not evaluable [NE], and not assessable [NA]) will be 
presented for the ociperlimab + tislelizumab + chemotherapy (Arm A) and placebo + tislelizumab + 
chemotherapy (Arm B). DCR and CBR, as assessed by investigators, will be analyzed similarly to 
ORR. TTR will be summarized using descriptive statistics, such as mean, median, and standard 
deviation. Only patients who have achieved an objective response will be included in the analysis of 
TTR. 
HRQoL will be analyzed via postbaseline scores of EORTC QLQ-C30’s Global Health Status 
(GHS)/QoL and functional and symptom scale scores and single item scores and symptoms measured 
by QLQ-LC13. Observed values and changes from baseline will be summarized using descriptive 
statistics. Postbaseline scores of GHS and physical function (PF) of the QLQ-C30 and dyspnea, 
coughing, hemoptysis, pain in chest, peripheral neuropathy, and pain in the arms and shoulders 
symptoms of the QLQ-LC13 will be further analyzed using a mixed-model analysis at prespecified 
timepoints and compared between Treatment Arms A and B.  
Safety Analyses: 
Extent of exposure to each study drug will be summarized descriptively by the number of doses 
received (number and percentage of patients), duration of exposure (weeks), cumulative total dose 
received per patient (mg), dose intensity, and relative dose intensity. 
Verbatim description of AEs will be mapped to the Medical Dictionary for Regulatory Activities 
(MedDRA) terms and graded per NCI-CTCAE v5.0. A TEAE is defined as an AE that has an onset 
date or a worsening in severity from baseline (pretreatment) on or after the first dose of study drug and 
up to 30 days following study drug discontinuation or the initiation of new anticancer therapy, 
whichever occurs first. Only those AEs that were treatment emergent will be included in summary 
tables. Immune-mediated AEs (imAEs) will be identified from all AEs that had an onset date or a 
worsening in severity from baseline (pretreatment) on or after the first dose of study drug and up to 
90 days from the last dose of ociperlimab (or placebo) and/or tislelizumab, regardless of whether or not 
the patient starts a new anticancer therapy. If an imAE occurs outside of the above mentioned TEAE 
window it will not be classified as a treatment-emergent adverse event. All imAEs will be reported 
separately. All AEs, treatment emergent or otherwise, will be presented in patient data listings. SAEs, 
deaths, TEAEs of all grades, TEAEs with Grade 3 or above, treatment-related TEAEs, TEAEs that led 
to treatment discontinuation or dose modification, and imAEs will be summarized. 
Clinical laboratory data with values outside of the normal ranges will be identified. Select laboratory 
data will be summarized by grade. Changes in vital signs will also be summarized by visit. 
Pharmacokinetic Analysis 
PK samples will be collected in this study as outlined in the Schedule of Assessments in Appendix 1. 
Ociperlimab and tislelizumab serum concentration data will be tabulated and summarized by visit/cycle 
at which these concentrations are collected. Descriptive statistics will include means, medians, ranges, 
and standard deviations, as appropriate. Additional PK analyses may be conducted as appropriate. 
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Immunogenicity Analysis 
Immunogenicity samples will be collected in this study as outlined in the Schedule of Assessments in 
Appendix 1. 
The immunogenicity results will be summarized using descriptive statistics by the number and 
percentage of patients who develop detectable ADAs. The incidence of positive ADAs and neutralizing 
ADAs will be reported for evaluable patients. The effect of immunogenicity on PK, efficacy, and safety 
may be evaluated if data allow. 
Sample Size Considerations: 
The sample size calculation is driven by the primary efficacy analysis of PFS in the comparison 
between ociperlimab + tislelizumab + chemotherapy (Arm A) and placebo + tislelizumab + 
chemotherapy (Arm B) in the ITT Analysis Set. The number of PFS events needed is based on the 
assumption of an exponential distribution with the targeted median PFS improvement. The 1-sided 
overall Type I error in the study is set at 0.025. The table below summarizes the statistical assumption 
and power in the sample size calculation. Assuming an approximately 10% dropout rate for PFS, 1:1 
randomization, and 14 months enrollment time, approximately 270 patients will be enrolled in order to 
observe approximately 194 PFS events approximately 33 months after study start.  
Hazard Ratio and Median PFS Assumption, Number of Events, Alpha and Power in the Primary 
Hypothesis Test 
Endpoint 
HR 
 
Median in 
Arm A 
(months) 
Median in 
Arm B 
(months) 
Number 
of events 
1-Sided
Alpha 
Power 
PFS 
0.65 
13.7 
8.9 
194 
0.025 
85% 
Abbreviations: HR, hazard ratio; PFS, progression-free survival. 
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LIST OF ABBREVIATIONS AND TERMS  
Abbreviation 
Definition 
ADA 
antidrug antibody 
AE 
adverse event 
ALK 
anaplastic lymphoma kinase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
BGB-A1217 
ociperlimab 
BGB-A317 
tislelizumab 
CBR 
clinical benefit rate 
CI 
confidence interval 
CR 
complete response 
CT 
computed tomography 
ctDNA 
circulating tumor DNA  
DCR 
disease control rate 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture (system) 
EGFR 
epidermal growth factor receptor 
EORTC QLQ-C30 
European Organization for Research and Treatment of Cancer Quality of 
Life Questionnaire- Core 30 
EORTC QLQ-LC13 
European Organization for Research and Treatment of Cancer Quality of 
Life Questionnaire- Lung Cancer 13 
EOT 
End-of-Treatment 
EV 
extracellular vesicle 
FDG 
fluorodeoxyglucose 
GEP 
gene expression profiling 
GHS 
Global Health Status 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
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Abbreviation 
Definition 
HIV 
human immunodeficiency virus 
HRQoL 
health-related quality of life 
ICF 
informed consent form 
ICH 
International Council for Harmonisation  
IEC 
Independent Ethics Committee 
IgG 
immunoglobulin G 
imAE 
immune-mediated adverse event 
IRB 
Institutional Review Board 
IRR 
infusion-related reaction 
IRT 
Interactive Response Technology 
ITT 
Intent-to-Treat (Analysis Set) 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
MSI 
microsatellite instability 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events 
NSCLC 
non-small cell lung cancer 
ORR 
overall response rate 
OS 
overall survival 
PD 
progressive disease 
PD-1 
programmed cell death protein-1 
PD-L1 
programmed cell death ligand-1 
PET 
positron emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PR 
partial response 
RECIST 
Response Evaluation Criteria in Solid Tumors 
ROS1 
c-ROS oncogene-1 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
TC 
tumor cell 
TEAE 
treatment-emergent adverse event 
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Abbreviation 
Definition 
TIGIT 
T-cell immunoglobulin and ITIM domain 
TIL 
tumor-infiltrating immune cell 
TMB 
tumor mutation burden 
TPS 
Tumor Proportion Score 
TTD 
time to deterioration 
TTR 
time to response 
ULN 
upper limit of normal 
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1. 
INTRODUCTION  
1.1. 
Background Information on Non-small Cell Lung Cancer  
Lung cancer is the most common cancer, with approximately 2.21 million new diagnoses and 
1.8 million deaths worldwide in 2020, which corresponds to the highest incidence among cancers 
and the most common cancer-related mortality (WHO Cancer 2021). The disease is more 
common in men than women, representing 16.8% of all cancers in men and 8.8% of all cancers 
in women. In China, lung cancer is the leading cause of cancer-related death in both men and 
women, with an estimated 610,200 deaths and an estimated 733,300 new cases in 2015 (Chen et 
al 2016). Non-small cell lung cancer (NSCLC) originates from the epithelial cells of the lung and 
accounts for 80% to 85% of all lung cancers. There are 3 main histological subtypes of NSCLC: 
adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, which constitute 40%, 
25%, and 10% of lung cancers, respectively (PDQ Adult Treatment Editorial Board [NSCLC] 
2020).  
The prognosis for lung cancer patients is relatively poor, and greatly depends on the stage at 
which the cancer is detected. Lung cancer staging is performed worldwide according to the 
tumor, lymph node, and metastasis (TNM) Classification of Malignant Tumors, Eighth Edition 
(Amin et al 2017). If lung cancer is diagnosed in its earliest stages, cure is possible through 
surgery or chemo-radiation therapy. Unfortunately, lung cancer cases are most often detected at a 
relatively late stage. Fifty-five percent of patients with newly diagnosed NSCLC have distal 
metastases (Stage IV). Stage IVA patients (any T, any N, M1) present with contralateral lung 
involvement, malignant pleural effusion, and malignant pericardial effusion (M1a) or with 
metastases in a single location outside the chest, for instance, a distal lymph node or organ such 
as brain, liver, or bone (M1b). Stage IVB patients (any T, any N) present with disease that has 
spread to multiple locations (either distal lymph nodes or organs, M1c). The 5-year survival rate 
for patients with Stage IV NSCLC is 5% (Siegel et al 2020). For NSCLC patients with 
oncogenic drivers (eg, epidermal growth factor receptor [EGFR] mutation, anaplastic lymphoma 
kinase [ALK] rearrangements), the prognosis improved a lot due to development of targeted 
therapies within the last decades, such as erlotinib, gefitinib, osimertinib, or dacomitinib for 
patients with EGFR mutation, crizotinib, ceritinib, alectinib, or brigatinib for patients with ALK 
rearrangements. Nevertheless, the prevalence of oncogenic drivers is low, with the prevalence of 
EGFR mutation ranging from 7% to 64% (Midha et al 2015), and the prevalence of ALK 
rearrangements ranging from 3% to 7% (Horn and Pao 2009; Koivunen et al 2008; Choi et al 
2008). However, patients with NSCLC without actionable mutation, still represent a population 
with unmet medical need.  
1.2. 
Current Treatment of Metastatic Non-small Cell Lung Cancer 
Without Actionable Mutations  
1.2.1. 
Chemotherapy  
Treatment of metastatic NSCLC patients depends on disease histology, the presence of 
actionable mutations, age, performance status (PS), comorbidities, and patient’s preferences. 
Patients without actionable mutations regardless of programmed cell death ligand-1 (PD-L1) 
status and with PS 0 to 2 may receive 4 to 6 cycles of platinum-based doublets with or without 
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maintenance. Patients with higher risk of neurotoxicity may receive carboplatin/nab-paclitaxel. 
Carboplatin based doublets are also considered for patients with PS2 (ESMO 2020). 
Patients with squamous NSCLC and PS 0 to 2 may receive platinum-based doublets with either 
gemcitabine, vinorelbine, or taxanes. Patients with non-squamous NSCLC are given pemetrexed-
based combination chemotherapy with carboplatin or cisplatin (ESMO 2020). Before the 
emergence of immunotherapy, platinum-based chemotherapy reached median progression-free 
survival (PFS) of less than 6 months, and median overall survival (OS) of less than 12 months 
(Kelly et al 2001; Sandler et al 2006; Scagliotti et al 2008; Schiller et al 2002). 
1.2.2. 
Anti-PD-1/PD-L1 Therapy  
Anti-programmed cell death protein-1 (PD-1) therapy has emerged as an effective treatment for 
those patients with tumors expressing varying degrees of PD-L1 (Hanna et al 2017). Anti-PD-1 
and anti-PD-L1 therapies target the programmed death receptor pathway of T lymphocytes; this 
checkpoint has been found to be activated in cancers allowing tumors to evade the host immune 
system.  
Single-agent pembrolizumab was approved by the US Food and Drug Administration (FDA) as 
first-line therapy for patients with metastatic NSCLC whose tumors expressed PD-L1 (Tumor 
Proportion Score [TPS] ≥ 1%) based on results from the KEYNOTE-024 (Reck et al 2016) and 
the KEYNOTE-042 (Mok et al 2019) studies. In the KEYNOTE-024 study, pembrolizumab 
showed a significant improvement in PFS (10.3 months versus 6 months [HR = 0.5; 95% 
confidence interval [CI]: 0.37, 0.68; p < 0.001]) and in the OS rate at 6 months (80.2% versus 
72.4% [HR = 0.6; 95% CI: 0.4, 0.9; p = 0.005]) compared to platinum-based chemotherapy. In 
the KEYNOTE-042 study, pembrolizumab showed a significant improvement in the overall 
survival (16.7 months versus 12.1 months [HR = 0.81; 95% CI: 0.71, 0.93; p = 0.0036]) 
compared to platinum-based chemotherapy. 
Single-agent atezolizumab was also approved by the FDA as first-line therapy of patients with 
metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 stained ≥ 50% of tumor 
cells [TC ≥ 50%] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 10% of the 
tumor area [IC ≥ 10%]) with no EGFR or ALK genomic tumor aberrations based on results from 
the Phase 3 Impower 110 trial. The study showed that atezolizumab monotherapy demonstrated a 
7.1-month improvement in OS versus chemotherapy, with a median OS of 20.2 months and 13.1 
months, respectively (HR = 0.59; 95% CI: 0.40, 0.89; p = 0.0106) in these patients (Herbst et al 
2020). 
Nivolumab in combination with ipilimumab was approved as first-line treatment for patients 
with metastatic NSCLC whose tumors express PD-L1 (≥ 1%), with no EGFR or ALK genomic 
tumor aberrations based on the finding of the CheckMate-227 study (Hellmann et al 2019).  
Pembrolizumab in combination with platinum-based chemotherapy were approved by the FDA 
as a first-line treatment for patients with metastatic non-squamous and squamous NSCLC with 
no EGFR or ALK genomic aberrations based on the results from KEYNOTE-189 and 
KEYNOTE-407 studies (Gadgeel et al 2020; Paz‑Ares et al 2018). In the KEYNOTE-189 study, 
pembrolizumab plus chemotherapy demonstrated a 3.9-month improvement in PFS versus 
chemotherapy, with a median PFS of 8.8 months and 4.9 months, respectively (HR = 0.52; 95% 
CI: 0.43-0.64; p < 0.0001), and significant improvement in the OS rate at 12 months (69.2% 
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versus 49.4% [HR = 0.49; 95% CI: 0.38, 0.64; p < 0.0001]). In the KEYNOTE-407 study, 
pembrolizumab plus chemotherapy demonstrated a 4.6-month improvement in OS versus 
chemotherapy, with a median OS of 15.9 months and 11.3 months, respectively (HR = 0.64; 
95% CI: 0.49, 0.85; p = 0.0017), and a 1.6- month improvement in PFS versus chemotherapy 
with a median PFS of 6.4 months and 4.8 months, respectively (HR = 0.56; 95% CI: 0.45, 0.70; 
p < 0.0001). 
Based on results from the IMpower130 trial, atezolizumab in combination with carboplatin/nab-
paclitaxel was approved as a first-line treatment of patients with metastatic non-squamous 
NSCLC who have no EGFR or ALK genomic tumor aberrations. Both median OS and median 
PFS in the intent-to-treat wild-type genotype populations (patients without EGFR or ALK 
alterations), were significantly improved in the atezolizumab arm versus the chemotherapy arm 
(OS: 18.6 months versus 13.9 months [HR = 0.80; 95% CI: 0.64, 0.99; p = 0.0384]; 
PFS: 7.2 months versus 6.5 months [HR = 0.75; 95% CI: 0.63, 0.91; p = 0.0024]) (West et al 
2019). 
Nivolumab and ipilimumab combination with platinum-doublet chemotherapy was also 
approved by the FDA as first-line treatment for metastatic or recurrent NSCLC with no EGFR or 
ALK genomic tumor aberrations, based on the finding of CheckMate-9LA (Paz-Ares et al 2021). 
1.2.3. 
New Immunotherapy-Immunotherapy Combinations for Metastatic NSCLC: 
Anti-TIGIT and Anti-PD-1/PD-L1  
Up-regulation of T-cell immunoglobulin and ITIM domain (TIGIT) expression in 
tumor-infiltrating lymphocytes (TILs) has been reported in many types of cancers, such as lung 
cancer (Tassi et al 2017). TIGIT pathway cooperates with PD-1 to maximize the suppression of 
effector TILs as well as to promote resistance to anti-PD-1 therapy. In vitro and in vivo studies 
showed that TIGIT blockade in combination with anti-PD-1/PD-L1 antibodies demonstrated 
significantly better antitumor efficacy than either monotherapy (Johnston et al 2014; Dixon et al 
2018). 
The preliminary results of several ongoing early phase clinical trials showed that anti-TIGIT 
antibody in combination with anti-PD-1/PD-L1 antibodies have potential for further improving 
ORR and PFS compared with single agent anti-PD-1/PD-L1 antibodies, and may become a novel 
therapeutic approach that could bring clinical benefit for metastatic NSCLC without actionable 
mutation 
CITYSCAPE (Rodriguez-Abreu et al 2020) is a Phase 2 randomized study evaluating the anti-
TIGIT antibody tiragolumab in combination with atezolizumab versus atezolizumab and placebo 
as a first-line therapy for PD-L1-selected NSCLC patients with no EGFR or ALK genomic 
aberrations. At the time of the report, the study had enrolled 135 patients, 58 of whom had high 
PD-L1 expression (TPS ≥ 50%). Results from this study demonstrated improvement in overall 
response rate (ORR) and median PFS in a subset of PD-L1 high patients treated with 
tiragolumab and atezolizumab (ORR: 37.3% [95% CI: 25.0, 49.6]; PFS: 5.6 months [95% CI: 
4.2, 10.4]) compared with those treated with atezolizumab and placebo (ORR: 20.6% [ 95% CI: 
10.2, 30.9]; PFS: 3.9 months [95% CI: 2.7, 4.5]). A slightly higher percentage of treatment-
related treatment-emergent adverse events (TEAEs) occurred in patients receiving tiragolumab 
and atezolizumab compared with patients receiving atezolizumab and placebo (81% versus 
72%). The most common TEAEs observed in patients treated with tiragolumab and atezolizumab 
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were low-grade fatigue, pruritus, and arthralgia; the most common imAEs were low-grade rash, 
infusion-related reactions, and hypothyroidism. Similarly, Grade 3 events were slightly more 
frequent in the tiragolumab and atezolizumab arm (19%) versus the atezolizumab and placebo 
arm (15%). Anemia and dyspnea were the most common Grade 3 events, whereas Grade 4 
pancreatitis was the most common imAE.  
A Phase 1b study is evaluating the anti-TIGIT antibody vibostolimab in combination with 
pembrolizumab in therapy naive or previously treated, advanced metastatic NSCLC patients who 
had never received anti-PD-L1 or anti PD-1 therapy (Niu et al 2020). At the time of the report, 
the study had enrolled 41 patients in this arm, out of whom 13 were considered PD-L1 positive 
(TPS ≥ 1%) and 12 had a TPS ≤ 1%. Results from this study showed a better ORR and median 
PFS in patients with TPS ≥ 1% (N = 13; confirmed ORR: 31.0%, 95% CI: 9.0, 61.03; median 
PFS: 8.4 months, 95% CI: 3.9, 10.2) compared with patients with TPS ≤ 1% (N = 12; confirmed 
ORR: 25.0%, 95% CI: 6.0, 57.0; median PFS: 4.1 months, 95% CI: 1.9, NR). Ten percent of 
patients experienced SAEs deemed related to study drug. Eighty-three percent of patients 
experienced a treatment-related TEAE of any grade, the majority of which were low grade. The 
most common treatment-related TEAEs were pruritus (34.0%), hypoalbuminemia (29.0%), 
pyrexia (20.0%), decreased lymphocyte counts (17.0%), fatigue and rash (12.0% each), and 
infusion related reactions (10.0%). Decreased lymphocyte counts (7.0%) and rash (2.0) were the 
most common ≥ Grade 3 events. 
1.3. 
Background Information on Ociperlimab, a TIGIT Inhibitor  
Refer to the Ociperlimab (BGB-A1217) Investigator’s Brochure for additional background on 
ociperlimab. 
1.3.1. 
Nonclinical Summary  
1.3.1.1. 
Pharmacology  
Ociperlimab, also known as BGB-A1217, is a humanized immunoglobulin G (IgG) 1 
monoclonal antibody against TIGIT under clinical development for the treatment of human 
malignancies. 
Ociperlimab binds to the extracellular domain of human TIGIT with high specificity and affinity 
(equilibrium dissociation constant [KD] = 0.135 nM), as demonstrated by target binding assays 
and surface plasmon resonance (SPR) characterization. Ociperlimab has shown antitumor 
activity in both the GL261 mouse glioma tumor model and the CT26.WT mouse colon cancer 
model in humanized TIGIT knock-in mice. In the MC-38 mouse colon cancer model in 
humanized TIGIT knock-in mice, ociperlimab in combination with anti-mouse PD-1 
significantly inhibited tumor growth compared with either therapy alone. 
Ociperlimab has the constant region of a wild-type human immunoglobulin G1 (IgG1) to enable 
the Fc-mediated effector functions. Ociperlimab has demonstrated competent binding to C1q and 
all FcRs and induces antibody-dependent cellular cytotoxicity against a TIGIT overexpressing 
cell line, but no antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity 
against primary T cells in the cell-based assays. 
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Refer to the Ociperlimab (BGB-A1217) Investigator’s Brochure for detailed information 
regarding pharmacology studies. 
1.3.1.2. 
Toxicology  
Humanized TIGIT knock-in mice containing human TIGIT gene and cynomolgus monkeys were 
selected for nonclinical safety evaluation of ociperlimab based on the homology of TIGIT amino 
acid sequence, binding affinity, and efficacy studies. Cynomolgus monkeys were the most 
relevant species. 
Ociperlimab demonstrated a comparable binding affinity in TIGIT receptor occupancy assays 
with CD3+ splenocytes from humanized TIGIT knock-in mice compared to CD3+ human 
peripheral blood mononuclear cells (with EC50 of 48.8 ng/ml versus 63.2 ng/ml, respectively). 
In addition, ociperlimab showed a significant inhibition of GL261 tumor growth in humanized 
TIGIT knock-in mice at a dose of ≥ 0.4 mg/kg via weekly intraperitoneal dosing. 
The toxicity and safety profile of ociperlimab was characterized in a 4-week repeated dose 
toxicology study in humanized TIGIT knock-in mice and a 13-week repeated dose toxicology 
study in cynomolgus monkeys. Ociperlimab was also evaluated in a 4-week repeated dose study 
in humanized TIGIT knock-in mice with subcutaneous MC-38 tumors. The cynomolgus monkey 
was considered the relevant species for toxicity studies based upon the target sequence homology 
and cross-species TIGIT binding activities of ociperlimab.  
No apparent toxicity was noted in monkeys following repeated dosing at 10, 30, or 100 mg/kg 
once every 2 weeks for 13 weeks. The toxicokinetic profile in the monkey study showed that 
systemic exposure appeared to be dose proportional with no sex difference. No accumulation 
was observed over the 13-week dosing period in monkeys. No immunotoxicity was apparent as 
no changes in clinical pathology or histopathology were observed. Positive ADAs against 
ociperlimab were observed in 6 of 10, 3 of 10, and 4 of 10 animals during the dosing period, and 
3 of 4, 2 of 4, and 2 of 4 animals during the recovery period, at doses of 10, 30, and 100 mg/kg, 
respectively. The anti-ociperlimab antibodies showed a rapid clearance of ociperlimab in serum 
in a few individual animals but did not appear to have an effect on the overall systemic exposure 
(area under the concentration-time curve [AUC]) or toxicity assessment. 
No specific binding of ociperlimab was noted with normal human tissues. A variety of factors 
might contribute to the negative results, including negligible target expression in normal tissues 
(Yang 2016; Human Protein Atlas 2019) and sensitivity of the immunohistochemistry method. 
No significant increase in cytokine release was observed from an in vitro cytokine release assay 
following treatment of nonactivated peripheral blood mononuclear cells with ociperlimab when 
compared to human IgG. The results suggest that ociperlimab has potentially low probability of 
causing acute cytokine release syndrome. 
Overall, no apparent toxicity was noted in the monkey toxicity study. No unexpected tissue cross 
reactivity was found in human or monkey tissues. The toxicokinetic profile showed 
dose-proportional increases in systemic exposure without apparent accumulation or sex 
difference. Immunogenicity was observed without apparent immunotoxicity or effect on the 
systemic exposure. The no-observed-adverse-effect level (NOAEL) of ociperlimab was 
100 mg/kg in the 13-week monkey toxicity study. The safety profile of ociperlimab is considered 
adequate to support first in human dosing. 
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Refer to the Ociperlimab (BGB-A1217) Investigator’s Brochure for detailed information 
regarding toxicology studies. 
1.3.2. 
Prior Clinical Experience With Ociperlimab  
As of 28 July 2023, 10 studies with ociperlimab are ongoing (Ociperlimab (BGB-A1217) 
Investigator’s Brochure). Of the 10 ongoing studies, 6 (AdvanTIG-101, AdvanTIG-105, 
AdvanTIG 202, AdvanTIG-204, AdvanTIG-206, and AdvanTIG-301) have preliminary data 
available. For more detailed information on ociperlimab safety and efficacy data refer to the 
most recent edition of the Ociperlimab (BGB-A1217) Investigator’s Brochure.  
A pooled analysis of monotherapy and combination therapies was conducted to provide a 
comprehensive safety assessment. As of the data cutoff date of 28 July 2023, a total of 
729 patients received ociperlimab treatment in 6 studies, including Study AdvanTIG 101, 
Study AdvanTIG-105, Study AdvanTIG-202, Study AdvanTIG-204, Study AdvanTIG-206 and 
Study AdvanTIG-301.  
An overview of TEAEs, including serious TEAEs, TEAEs leading to discontinuation of 
ociperlimab, and TEAEs leading to death, is shown in 
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Table 1. 
Overall, of the 729 patients in the Safety Analysis Set, 708 (97.1%) experienced ≥ 1 TEAE and 
534 patients (73.3%) experienced ≥ 1 TEAE related to ociperlimab. TEAEs ≥ Grade 3 in severity 
were experienced by 440 of 729 patients (60.4%), and 152 patients (20.9%) experienced ≥ Grade 
3 TEAE related to ociperlimab. Serious adverse events were experienced by 343 patients 
(47.1%), and 103 patients (14.1%) had serious adverse events related to ociperlimab. Adverse 
events leading to discontinuation of ociperlimab were experienced by 107 patients (14.7%).  
Adverse events leading to death were experienced by 52 patients (7.1%), and 7 patients (1.0%) 
experienced ≥ 1 ociperlimab-related adverse event leading to death. A single patient (1.4% of 69 
dose-limiting toxicity-evaluable patients) experienced a dose-limiting toxicity. 
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Table 1: 
Overview of Treatment-Emergent Adverse Events (Safety Analysis Set) 
Ociper 
Mono a 
(N = 9)  
n (%) 
Ociper + 
Tisle b 
(N = 346)  
n (%) 
Ociper + Tisle + 
Chemo a 
(N = 214)  
n (%) 
Ociper + Tisle + 
cCRT a 
(N = 63)  
n (%) 
Ociper + Tisle 
+ BAT1706 a 
(N = 62)  
n (%) 
Ociper + Tisle 
Heme 
(N = 24)  
n (%) 
Ociper + 
Ritu 
(N = 11)  
n (%) 
Total 
(N = 729)  
n (%) 
Number of Patients with 
any TEAE 
9 (100.0) 326 (94.2) 
214 (100.0) 
63 (100.0) 
62 (100.0) 
24 (100.0) 
10 (90.9) 708 (97.1) 
Related to 
Ociperlimab 
7 (77.8) 
233 (67.3) 
157 (73.4) 
57 (90.5) 
55 (88.7) 
17 (70.8) 
8 (72.7) 
534 (73.3) 
Grade ≥ 3 
4 (44.4) 
170 (49.1) 
160 (74.8) 
48 (76.2) 
44 (71.0) 
9 (37.5) 
5 (45.5) 
440 (60.4) 
Related to 
Ociperlimab 
1 (11.1) 
55 (15.9) 
46 (21.5) 
13 (20.6) 
27 (43.5) 
5 (20.8) 
5 (45.5) 
152 (20.9) 
Serious TEAE 
4 (44.4) 
144 (41.6) 
115 (53.7) 
36 (57.1) 
31 (50.0) 
9 (37.5) 
4 (36.4) 
343 (47.1) 
Related to 
Ociperlimab 
0 (0.0) 
37 (10.7) 
26 (12.1) 
20 (31.7) 
12 (19.4) 
5 (20.8) 
3 (27.3) 
103 (14.1) 
Leading to 
Discontinuation of 
Ociperlimab 
1 (11.1) 
47 (13.6) 
30 (14.0) 
11 (17.5) 
15 (24.2) 
1 (4.2) 
2 (18.2) 
107 (14.7) 
Related to 
Ociperlimab 
0 (0.0) 
16 (4.6) 
11 (5.1) 
10 (15.9) 
7 (11.3) 
0 (0.0) 
2 (18.2) 
46 (6.3) 
Leading to Death 
2 (22.2) 
22 (6.4) 
17 (7.9) 
2 (3.2) 
6 (9.7) 
2 (8.3) 
1 (9.1) 
52 (7.1) 
Related to 
Ociperlimab 
0 (0.0) 
3 (0.9) 
0 (0.0) 
2 (3.2) 
1 (1.6) 
0 (0.0) 
1 (9.1) 
7 (1.0) 
Source: ADSL, ADAE. Data cutoff: 28JUL2023. Data extraction: 28JUL2023. 
Abbreviations: AE, adverse event; TEAE, treatment-emergent adverse event; cCRT, concurrent chemoradiotherapy; Ociper, ociperlimab; Mono, monotherapy; 
Tisle, tislelizumab; Chemo, chemotherapy; Heme, hematology; Ritu, rituximab.  
A patient with multiple occurrences of an AE is counted only once in the AE category.  
All AEs are coded using MedDRA version 26.0 and graded according to NCI-CTCAE version 5.0 
Studies include AdvanTIG-105, AdvanTIG-101, AdvanTIG-202, AdvanTIG-204, AdvanTIG-206, and AdvanTIG-301 (Part I). 
Ociperlimab monotherapy, ociperlimab + tislelizumab, ociperlimab + tislelizumab + chemotherapy, ociperlimab + tislelizumab + cCRT, ociperlimab + 
tislelizumab + BAT1706 are treatments in solid tumor studies; ociperlimab + tislelizumab hematology and ociperlimab + rituximab are treatments in 
hematology study.  
a The dose level of Ociperlimab is 900 mg.  
b The dose level of Ociperlimab includes 50 mg, 150 mg, 450 mg, 900 mg and 1800 mg.  
The dose level of ociperlimab for hematology study includes 600 mg 900 mg.  
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1.3.3. 
Ociperlimab Clinical Pharmacology  
Preliminary PK data are available from a total of 52 patients treated with ociperlimab at 50 mg, 
150 mg, 450 mg, 900 mg, or 1800 mg dose levels in combination with tislelizumab 200 mg in 
the dose-escalation and dose-verification portions of Study AdvanTIG-105.  The PK data were 
analyzed using noncompartmental analyses (NCA) using nominal timepoints and nominal 
dosing information.  Ociperlimab exposures increased approximately dose proportionally from 
the 50 mg to the 1800 mg dose level for maximum observed serum concentration (Cmax) and area 
under the concentration-time curve (AUC).  There was minimal accumulation observed in 
Cycle 5 following multiple doses. The geometric mean terminal half-life estimate following the 
first dose ranged from approximately 7 to 11 days.  Postdose PK sampling duration may not be 
sufficient for robust characterization of elimination half-life using noncompartmental analysis 
and, therefore, reported half-life values should be interpreted with caution.  The mean serum 
concentration-time profiles of ociperlimab are shown in Figure 1. 
Peripheral TIGIT receptor occupancy data were available for 32 enrolled patients treated with 
ociperlimab at 50 mg, 150 mg, 450 mg, 900 mg, and 1800 mg dose levels in Study 
AdvanTIG-105.  Complete TIGIT receptor occupancy (100%) was observed on CD8+ T cells, 
CD4+ T cells, and regulatory T cells in peripheral blood at all the tested dose levels. 
Refer to the Ociperlimab (BGB-A1217) Investigator’s Brochure for detailed information on 
ociperlimab clinical pharmacokinetics and pharmacodynamics. 
Figure 1: 
Cycles 1 and 5 Mean (+ SD) Serum Concentration-Time Profiles of 
Ociperlimab in Study AdvanTIG-105 
  
Abbreviation: SD, standard deviation. 
Note: For the 1800 mg dose, only 3 concentrations were available on D28. 
1.4. 
Background Information on Tislelizumab  
1.4.1. 
Pharmacology  
Tislelizumab (also known as BGB-A317) is a humanized, immunoglobulin G4 (IgG4)-variant 
monoclonal antibody against PD-1 under clinical development for the treatment of several 
human malignancies. 
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Tislelizumab acts by binding to the extracellular domain of human PD-1 with high specificity 
and affinity (dissociation constant [KD] = 0.15 nM). It competitively blocks binding of both 
PD-L1 and PD-L2, thus inhibiting PD-1-mediated negative signaling in T cells.  
In vitro assays with tislelizumab suggest either low or no antibody-dependent cellular 
cytotoxicity, antibody-dependent cellular phagocytosis, or complement-dependent cytotoxicity 
effects in humans (Labrijn et al 2009; Zhang et al 2018). Tislelizumab was specifically 
engineered to abrogate these potential mechanisms of T-cell clearance and potential resistance to 
anti-PD-1 therapy. 
Please refer to the Tislelizumab (BGB-A317) Investigator’s Brochure for additional details 
regarding nonclinical studies of tislelizumab. 
1.4.2. 
Toxicology  
The toxicity and safety profile of tislelizumab was characterized in single-dose toxicology 
studies in mice and cynomolgus monkeys and in a 13-week, repeat-dose toxicology study in 
cynomolgus monkeys. Cynomolgus monkey was the only relevant species based on the target 
sequence homology and binding activity. 
Overall, no apparent toxicity was noted in mice or monkey toxicity studies. No tissue cross 
reactivity was found in either human or monkey tissues, nor was any effect on cytokine release 
observed in the human whole-blood assay. The toxicokinetic profile showed dose proportional 
increases in systemic exposure without apparent accumulation or sex difference. 
Immunogenicity was observed without apparent immunotoxicity or effect on the systemic 
exposure. The NOAEL of tislelizumab in the 13-week monkey toxicity study was considered to 
be 30 mg/kg. The safety profile of tislelizumab is considered adequate to support the current 
study, AdvanTIG-205. 
Please refer to the Tislelizumab (BGB-A317) Investigator’s Brochure for more detailed 
information on the toxicology of tislelizumab. 
1.4.3. 
Clinical Pharmacology  
Tislelizumab exhibited linear PK across the dose range tested in the clinical studies. A 
population PK (popPK) analysis was conducted using pooled serum concentration data from 
2596 patients enrolled in 12 tislelizumab clinical studies. The PK of tislelizumab was best 
characterized using a 3-compartmental model with a linear clearance mechanism. PK of 
tislelizumab does not appear to be time varying. The typical estimates of clearance (CL), central 
volume of distribution (Vc), and peripheral volumes 2 and 3 (V2 and V3, respectively), were 
0.153 L/day, 3.05 L, 1.27 L, and 2.10 L, respectively, with inter-individual variability in 
CL (26.3%), Vc (16.7%), V2 (74.7%), and V3 (99.9%). The elimination half-life was estimated to 
be approximately 23.8 days. 
PopPK analyses demonstrated that race, baseline alanine aminotransferase, aspartate 
aminotransferase, bilirubin, lactate dehydrogenase, estimated glomerular filtration rate, Eastern 
Cooperative Oncology Group (ECOG) performance status score at baseline did not have 
statistically significant influences on tislelizumab PK. Baseline body weight, tumor size of solid 
tumors, albumin, age, sex, immunogenicity, and tumor type were found to be statistically 
significant covariates on the PK of tislelizumab, however, the exposure changes by these 
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covariates were approximately 30% or less which is relatively small compared to the overall 
range estimated for the PK exposures, and hence are not considered clinically relevant. 
Please refer to the Tislelizumab (BGB-A317) Investigator’s Brochure for more detailed 
information on the clinical pharmacology of tislelizumab. 
1.4.4. 
Prior Clinical Experience With Tislelizumab  
Tislelizumab is being developed for the treatment of human malignancies in multiple organs and 
tissues as monotherapy or in combination with other therapies. The overall safety experience 
with tislelizumab, as a monotherapy or in combination with other therapeutics, is based on 
experience in 4588 patients (2569 patients treated with monotherapy and 2019 patients treated 
with combination therapy) as of the cutoff date 27 October 2023 (Tislelizumab (BGB-A317) 
Investigator’s Brochure). A total of 2569 patients were treated in the monotherapy studies 
included in the pooled safety analysis. Within the 9 solid tumor monotherapy studies, 2377 
patients were treated. Within the 3 hematologic malignancy monotherapy studies, 192 patients 
were treated. 
A pooled analysis of combination studies with tislelizumab and chemotherapy was conducted to 
provide a comprehensive safety assessment separately from other combination therapy studies. A 
total of 2019 patients were treated with tislelizumab in combination with chemotherapy in 
10 studies as of 27 October 2023. 
The patients in the pooled tislelizumab plus chemotherapy combination studies had a median 
tislelizumab treatment exposure duration of 7.1 months (range: 0 to 58) and a median study 
follow-up duration of 18.7 months (range: 0 to 58).  The median age of patients was 61.0 years, 
and 80.6% of the patients were male.  Most patients were Asian (89.8%).  The most common 
tumor types were NSCLC (723 patients, 35.8%), gastric or gastroesophageal junction 
adenocarcinoma (25.4%), and esophageal squamous cell carcinoma (20.2%).  Over half of 
patients had no prior systemic anticancer therapy (1340 patients, 66.4%). Refer to the 
Tislelizumab (BGB-A317) Investigator’s Brochure for more detailed information on tislelizumab 
safety data when given as monotherapy or in combination with chemotherapy. 
In addition to the safety data provided in the Tislelizumab (BGB-A317) Investigator’s Brochure, 
other ongoing studies are evaluating the safety profile of tislelizumab when used in combination 
with chemotherapy in patients with NSCLC. 
1.4.4.1. 
Treatment-Emergent Adverse Events in Chemotherapy Combination Studies  
Of the 2019 patients in the pooled tislelizumab plus chemotherapy combination studies, 
1984 (98.3%) experienced ≥ 1 TEAE, and 1451 patients (71.9%) experienced ≥ 1 TEAE 
considered related to tislelizumab treatment.  TEAEs ≥ Grade 3 in severity were experienced by 
1528 patients (75.7%) and 572 patients (28.3%) experienced a ≥ Grade 3 TEAE considered 
tislelizumab related.  Serious TEAEs were reported in 816 patients (40.4%) and 337 patients 
(16.7%) experienced a serious tislelizumab-related TEAE.  A total of 124 patients (6.1%) 
experienced ≥ 1 TEAE leading to death. 
The most commonly occurring TEAEs were Anaemia (65.0%), Neutrophil count decreased 
(50.2%), White blood cell count decreased (48.8%), Nausea (42.2%), Decreased appetite 
(39.2%), and Platelet count decreased (32.6%). 
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Of the 2019 patients in the pooled tislelizumab plus chemotherapy combination studies, 
1451 (71.9%) experienced ≥ 1 TEAE assessed as related to tislelizumab treatment.  The most 
commonly occurring tislelizumab-related TEAEs were Anaemia (16.1%), Alanine 
aminotransferase increased (15.5%), Aspartate aminotransferase increased (15.0%), Neutrophil 
count decreased (12.5%), White blood cell count decreased (12.2%), Hypothyroidism (12.0%), 
and Rash (11.2%). 
Of the 2019 patients in the pooled chemotherapy combination studies, 572 (28.3%) experienced 
≥ 1 TEAE assessed as related to tislelizumab treatment that was ≥ Grade 3 in severity.  The most 
commonly occurring ≥ Grade 3 tislelizumab-related TEAEs were Neutrophil count decreased 
(6.1%), White blood cell count decreased (3.3%), Neutropenia (3.1%), Anaemia (2.7%), and 
Platelet count decreased (2.0%). 
1.4.4.2. 
Treatment-Emergent Serious Adverse Events  
Of the 2019 patients in the pooled tislelizumab plus chemotherapy combination studies, 
816 (40.4%) experienced ≥ 1 treatment-emergent SAE.  The most commonly occurring SAEs 
were Pneumonia (4.3%), Pneumonitis (2.3%), and Platelet count decreased (2.1%). 
Of the 2019 patients treated in the pooled tislelizumab plus chemotherapy combination studies, 
337 (16.7%) experienced ≥ 1 tislelizumab-related treatment-emergent SAE.  The most 
commonly occurring SAEs were Pneumonitis (2.1%) and Pneumonia (1.0%).  All other SAEs 
occurred in < 1% of patients. 
1.4.4.3. 
Immune-Mediated Adverse Events  
Anti-PD-1 therapies are known to cause imAEs in some patients; therefore, they have been 
defined as adverse events (AEs) of special interest (AESI) in tislelizumab clinical studies and, as 
such, are monitored closely. 
Immune-mediated AEs are consistent with an immune-related mechanism or immune-related 
component for which noninflammatory etiologies (eg, infection or tumor progression) have been 
ruled out. Immune-mediated AEs can include events with an alternate etiology which were 
exacerbated by the induction of autoimmunity. There is a potential temporal relationship 
between the initiation of treatment with tislelizumab and onset of an imAE that spans a window 
of days to several months. 
All imAEs presented here are assessed as related to study drug by the investigator and 
categorized and adjudicated by the BeiGene Safety/Pharmacovigilance Team. Certain imAEs 
have multiple Medical Dictionary for Regulatory Activities (MedDRA) terms associated with the 
same category. Special categories have been created to group patients experiencing these events. 
Of the 2019 patients in the pooled tislelizumab plus chemotherapy combination studies, 
777 (38.5%) experienced ≥ 1 imAE of any grade.  The most commonly occurring imAEs were 
Rash and Hypothyroidism (13.0% each), Pneumonitis (5.5%), Hyperthyroidism (4.0%), Rash 
maculo-papular (1.3%), Immune-mediated lung disease (1.2%), and Thyroxine free decreased 
(1.0%).  The categories of imAEs experienced by ≥ 1% of patients were Immune-Mediated Skin 
Adverse Reaction (16.2%), Immune-Mediated Endocrinopathies (Hypothyroidism) (14.6%), 
Immune-Mediated Pneumonitis (7.4%), Immune-Mediated Endocrinopathies (Hyperthyroidism) 
(5.4%), Immune-Mediated Hepatitis (1.4%), Immune-Mediated Endocrinopathies (Diabetes 
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Mellitus) (1.3%), Immune-Mediated Myocarditis/Pericarditis (1.2%), and Immune-Mediated 
Colitis (1.0%). 
Of the 2019 patients in the pooled tislelizumab plus chemotherapy combination studies, 162 
(8.0%) experienced ≥ 1 imAE that was ≥ Grade 3 in severity.  The most commonly occurring 
≥ Grade 3 imAEs were Pneumonitis (31 of 2019 patients, 1.5%) and Rash (1.3%). All other 
≥ Grade 3 imAEs occurred in < 1.0% of patients. 
1.4.4.4. 
Infusion-Related Reactions  
Infusion-related reactions, including high-grade hypersensitivity reactions, following 
administration of tislelizumab are uncommon.  
Of the 2019 patients in the pooled tislelizumab plus chemotherapy combination studies, 
125 (6.2%) experienced ≥ 1 IRR.  The most commonly occurring IRRs of any grade were Rash 
(1.8%) and Chills and Infusion-related reaction (1.2% each).  All other IRRs occurred in < 1.0% 
of patients. 
1.4.4.5. 
Liver Laboratory Abnormalities  
In the pooled tislelizumab plus chemotherapy combination studies, 15 (0.8%) of 1975 patients 
treated with any dose of Tislelizumab or with any postbaseline assessment experienced alanine 
aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 3 x ULN with a concurrent 
total bilirubin level ≥ 2 x upper limit of normal (ULN).  Concurrent elevation of ALP (ie, ALP ≥ 
2 x ULN) was observed in 12 of these 15 patients.  The remaining 3 patients did not meet true 
Hy’s law criteria.  
1.4.4.6. 
Fatal Adverse Events  
Of the 2019 patients in the pooled tislelizumab plus chemotherapy combination studies, 
79 (3.9%) died ≤ 30 days after their last dose of tislelizumab.  The causes of death for these 
patients were AEs (2.4%), disease under study (1.3%), disease progression (0.1%), and “other 
reason” (1 patient; 0.0%).  A total of 1171 patients (58.0%) died > 30 days after their last dose of 
tislelizumab.  The causes of death for these patients were disease under study (37.0%), disease 
progression (10.3%), “other reason” (8.8%), and AEs (1.9%). 
Of the 2019 patients in the pooled tislelizumab plus chemotherapy combination studies, 
124 (6.1%) experienced ≥ 1 TEAE leading to death.  The most commonly occurring TEAEs 
leading to death were Death (1.0%), General physical health deterioration (0.4%), Pneumonia 
and Respiratory failure (0.3% each), and Sepsis, Gastrointestinal haemorrhage, and Depressed 
level of consciousness (0.2% each).  All other events occurred in ≤ 0.1% of patients. 
Of the 2019 patients in the pooled tislelizumab plus chemotherapy combination studies, 
34 (1.7%) experienced ≥ 1 tislelizumab-related TEAE leading to death.  The most commonly 
occurring tislelizumab-related TEAEs leading to death were Death (6 patients; 0.3%), 
Gastrointestinal haemorrhage and Pneumonitis (3 patients; 0.1% each), and Respiratory failure 
and Myocarditis (2 patients; 0.1% each).  All other events occurred in single patients. 
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1.4.5. 
Efficacy Assessment of Tislelizumab  
Efficacy data in NSCLC are summarized below from 2 completed Phase 1 monotherapy studies 
in solid tumors, Study BGB-A317_Study_001(data cutoff of May 2019)and Study BGB-A317-
102 (data cutoff of 01 December 2018), 1 Phase 2 combination study in NSCLC, 
Study BGB-A317-206 (data cutoff of 31 December 2019) and from 4 Phase 3 combination 
studies in NSCLC, Study BGB-A317-303 (data cutoff of 10 August 2020), Study BGB-A317-
304 (data cutoff of 26 October 2020), Study BGB-A317-307 (data cutoff of 30 September 2020) 
and Study BGB-A317-315 (data cutoff of 20 February 2023). Please refer to Tislelizumab 
(BGB-A317) Investigator’s Brochure for more details. 
BGB-A317_Study_001 
Study BGB-A317_Study_001 is a Phase 1a/1b study consisting of a dose escalation phase (1a) 
and a dose expansion phase (1b) designed to establish the MTD and schedule, determine the 
recommended Phase 2 dose (RP2D), and investigate the preliminary efficacy of tislelizumab in 
previously treated patients with select tumor types, including NSCLC. 
The RP2D and schedule for tislelizumab was determined to be 200 mg administered once every 
3 weeks. Across all disease cohorts (N = 451), 6 patients (1.3%) experienced a complete 
response (CR), and 54 patients (12.0%) had a partial response (PR), yielding an ORR of 13.3%. 
Additionally, 141 patients (31.3%) had a best overall response of stable disease. Disease control 
rate (DCR) was 44.6% (95% CI: 39.92, 49.29), and clinical benefit rate (CBR) was 25.9% (95% 
CI: 21.96, 30.25). Of the 49 NSCLC patients enrolled in the study, no patients experienced a CR 
(0%) and 6 patients (12.2%) had a confirmed PR. Stable disease was observed in 23 patients 
(46.9%). DCR was 59.2% (95% CI: 44.21, 73.00) and CBR was 30.8% (95% CI: 14.33, 51.79). 
BGB-A317-102 
Study BGB-A317-102 is a nonrandomized, Phase 1/2 study of tislelizumab monotherapy 
evaluating the activity and safety of tislelizumab at the RP2D and schedule of 200 mg given once 
every 3 weeks in previously treated Chinese patients with select advanced solid tumors, 
including NSCLC. 
In the NSCLC cohort (N = 56), no patients (0%) experienced a CR and 10 patients (18%) had a 
confirmed PR. Stable disease was observed in 21 patients (38%). ORR was 18% (95% CI: 8.9, 
30.4).  
BGB-A317-206 
Study BGB-A317-206 was a Phase 2, open-label, multi-cohort study to investigate the 
preliminary antitumor activity, safety, and PK of tislelizumab in combination with chemotherapy 
as first-line treatment in Chinese subjects with locally advanced or metastatic lung cancer. 
Efficacy data from BGB-A317-206 (data cutoff 31 December 2019) were presented at the 2020 
meeting of the European Society for Medical Oncology (Wang Z et al 2020).  A summary of 
tumor responses for the evaluable patients (N = 54 patients) is shown in Table 2. 
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Table 2: 
Summary of Tumor Response in Study BGB-A317-206 (Efficacy Analysis 
Set) 
Category 
Non-
squamous 
NSCLC 
n = 16 
Squamous 
NSCLC 
Cohort A 
n = 15 
Squamous 
NSCLC 
Cohort B 
n = 6 
SCLC 
n = 17 
Total 
N = 54 
ORR (CR, PR) 
 
 
 
 
 
   n (%) 
7 (43.8) 
12 (80.0) 
4 (66.7) 
13 (76.5) 
36 (66.7) 
   Exact 95% CI 
(19.8, 70.1) (51.9, 95.7) (22.3, 95.7) (50.1, 93.2) (52.5, 78.9) 
Best Overall Response – 
Confirmed, n (%) 
 
 
 
 
 
   CR 
0 
0 
0 
0 
0 
   PR 
7 (43.8) 
12 (80.0) 
4 (66.7) 
13 (76.5) 
36 (66.7) 
   SD 
8 (50.0) 
2 (13.3) 
1 (16.7) 
2 (11.8) 
13 (24.1) 
   PD 
1 (6.3) 
0 
0 
1 (5.9) 
2 (3.7) 
   Missing 
0 
1 (6.7) 
1 (16.7) 
1 (5.9) 
3 (5.6) 
DCR (CR, PR, SD) 
 
 
 
 
 
   n (%) 
15 (93.8) 
14 (93.3) 
5 (83.3) 
15 (88.2) 
49 (90.7) 
   Exact 95% CI 
(69.8, 99.8) (68.1, 99.8) (35.9, 99.6) (63.6, 98.5) (79.7, 96.9) 
CBR (CR, PR, durable SD ≥ 12 
weeks) 
 
 
 
 
 
   n (%) 
15 (93.8) 
14 (93.3) 
5 (83.3) 
15 (88.2) 
49 (90.7) 
   Exact 95% CI 
(69.8, 99.8) (68.1, 99.8) (35.9, 99.6) (63.6, 98.5) (79.7, 96.9) 
CBR (CR, PR, durable SD ≥ 24 
weeks) 
 
 
 
 
 
   n (%) 
9 (56.3) 
14 (93.3) 
4 (66.7) 
14 (82.4) 
41 (75.9) 
   Exact 95% CI 
(29.9, 80.2) (68.1, 99.8) (22.3, 95.7) (56.6, 96.2) (62.4, 86.5) 
Data cutoff 31 December 2019. 
Abbreviations: CBR, clinical benefit rate; CI, confidence interval; CR, complete response; DCR, disease control rate; NSCLC, 
non-small cell lung cancer; ORR, objective response rate; PD, progressive disease; PR, partial response; SCLC, small cell lung 
cancer; SD, stable disease. 
ORR is based on the confirmed CR or PR according to RECIST v1.1. Durable SD is defined as SD duration ≥ 12 or ≥ 24 weeks.  
Patients with no post-baseline response assessment or assessments as NE were considered as non-responders.  CIs were estimated 
by the exact method. 
The confirmation of best overall response must be at least 4 weeks after the initially observed objective response. 
BGB-A317-303 
Study BGB-A317-303 is a randomized, open-label, multicenter Phase 3 study in adult 
patients with histologically confirmed and locally advanced or metastatic NSCLC (squamous or 
nonsquamous) who have disease progression during or after receiving a platinum-containing 
regimen. 
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A total of 805 patients were randomized in the study (535 patients in the tislelizumab arm versus 
270 patients in the docetaxel arm).  At the prespecified interim analysis (data cutoff date of 
10 August 2020), the co-primary endpoint of OS in the Intent-to-Treat (ITT) Analysis Set was 
met, which demonstrated a statistically significant and clinically meaningful improvement in OS 
in the tislelizumab arm compared with the docetaxel arm (median OS 17.2 months [95% CI: 15.3 
to 20.0 months] versus 11.9 months [95% CI: 10.2 to 13.9 months]; hazard ratio = 0.64 [95% CI: 
0.53 to 0.78]; p < 0.0001). 
BGB-A317-304 (RATIONALE 304) 
BGB-A317-304 is an ongoing, open-label, randomized, multicenter Phase 3 study designed to 
compare the efficacy and safety of tislelizumab combined with platinum (cisplatin or 
carboplatin) and pemetrexed (Arm A) versus platinum and pemetrexed alone (Arm B) as 
first-line treatment in 334 patients who have Stage IIIB or IV non-squamous NSCLC.  
As of the data cutoff of 23 January 2020, an interim analysis demonstrated that the study met its 
primary endpoint of PFS. As of the data cutoff of 26 October 2020, the final PFS analysis from 
additional follow-up data showed that, compared with the chemotherapy-only arm, the risk of 
disease progression or death as assessed by the Independent Review Committee (IRC) was 
reduced by 37.26% in patients who received tislelizumab in combination with pemetrexed and 
platinum (HR = 0.628) (data on file). The IRC-assessed median PFS was 9.8 months (CI: 8.94, 
11.70 months) in the tislelizumab combination arm and 7.6 months (CI: 5.55, 8.02 months) in the 
chemotherapy-only arm. The 12-month PFS event-free rate was approximately double in the 
tislelizumab combination arm as compared with the chemotherapy arm (39.9% versus 19.5%). 
PFS improvement was consistent across all prespecified subgroups, including 
investigator-assessed PFS. ORR per IRC review was greater in Arm A than in Arm B (57.8% 
versus 36.0%). The median DOR in Arm A and Arm B were 10.6 months and 6.9 months, 
respectively.  
The health-related quality of life (HRQoL) data, based on the patient-reported outcomes, further 
confirmed the clinical benefits with tislelizumab in combination with chemotherapy in this 
patient population (Lu et al 2020). Compared with Arm B, patients in Arm A experienced a 
higher reduction of pain and cough symptoms. 
HRQoL was measured using 2 validated patient-reported outcomes (PROs): European 
Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-
Core 30 (QLQ-C30) and its lung cancer module (Quality of Life Questionnaire- Lung Cancer 13 
[QLQ-LC13]) in ITT. Changes in scores from baseline were used to compare the effects of the 
treatments between the study arms. Measures of HRQoL showed improvements in Arm A 
compared to Arm B. The Global Health Status (GHS)/QoL of the QLQ-C30 was observed with 
LS mean changes of 5.7 (95% CI [1.0, 10.5], P=0.018) at 18 weeks. Furthermore, patients in 
Arm A experienced larger reductions in lung cancer symptoms from baseline than patients in 
Arm B, with mean change (SD) in coughing (-13.4 [29.10] versus -5.5 [22.92]), chest pain (-5.7 
[22.78] versus -3.2 [20.16]), dyspnea (-1.5 [16.42] versus, 2.0 [11.32]), and pain in arm or 
shoulder (-7.3 [23.46] versus -3.2 [19.38]). 
BGB-A317-307 (RATIONALE 307) 
BGB-A317-307 is an ongoing, open-label, randomized, multicenter Phase 3 study designed to 
compare the efficacy and safety of tislelizumab combined with carboplatin and either paclitaxel 
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(Arm A) or nab-paclitaxel (Arm B), versus paclitaxel plus carboplatin alone (Arm C) as first-line 
treatment in 360 patients with untreated Stage IIIB or IV squamous NSCLC. 
As of the data cutoff of 06 December 2019, an interim analysis demonstrated that the study met 
its primary endpoint of PFS (Wang J et al 2021). Additional follow-up data for the final PFS 
analysis as of the data cutoff of 30 September 2020 are presented below. 
The updated final analysis of PFS with a median follow-up of 18.5 months showed consistent 
results. PFS in Arm A was 7.7 months (CI: 6.74, 10.41 months), which was longer than PFS in 
Arm C with 5.5 months (CI: 4.21, 5.72 months) with one-sided stratified log-rank test p-value 
< 0.0001 (data on file). The stratified HR was 0.475 (CI: 0.344, 0.654), indicating a 52.5% 
reduction in the risk of experiencing a PFS event. PFS assessed by the IRC in Arm B was 
9.7 months (CI: 7.39, 11.01 months) and significantly longer than PFS in Arm C with 
5.5 months (CI: 4.21, 5.72 months), with a one-sided stratified log-rank test p-value < 0.0001. 
The HR was 0.451 (CI: 0.324, 0.628), indicating a 54.9% reduction in the risk of experiencing a 
PFS event. 
The ORR assessed by the IRC of the latest analysis was 74.2% (CI: 65.4%, 81.7%) in Arm A 
versus 49.6% (CI: 40.4%, 58.8%) in Arm C; and 73.9% (CI: 65.1%, 81.6%) in Arm B versus 
49.6% (CI: 40.4%, 58.8%) in Arm C. 
The median OS at the time of the latest analysis with a median follow-up of 18.5 months was 
22.8 months in Arm A, not estimable in Arm B, and 20.2 months in Arm C. The stratified HR for 
OS were 0.674 (CI: 0.449, 1.010) for Arm A versus Arm C, and 0.752 (CI: 0.504 versus 1.121) 
for Arm B versus Arm C; these differences correspond to one-sided stratified log-rank test p-
values of 0.0271 and 0.08, respectively. 
HRQoL results showed that GHS/QoL scores improved for Arm A (mean change of 2.8, 
SD = 23.2) and Arm B (mean change of 3.9, SD = 18.00) but declined in Arm C (mean change 
of -1.3, SD = 19.4) by Cycle 5 (Wang J et al 2020). Arm A (mean change of -20.1, SD = 29.2) 
and Arm B (mean change of -12.7, SD = 33.8) experienced a larger reduction in coughing at 
Cycle 5 compared to Arm C (mean change of -7.3, SD = 23.2). Similarly, Arm A (mean change 
of -1.9, SD = 18.1) and Arm B (mean change of -1.8, SD = 19.9) experienced a reduction in 
dyspnea while Arm C (mean change of 2.4, SD = 15.2) experienced more symptoms. All three 
arms experienced a reduction in hemoptysis at Cycle 5 with larger reductions observed for 
Arm A (mean change of -9.4, SD = 19.8) and Arm B (mean change of -9.4, SD = 26.8) 
compared to Arm C (mean change of -2.3, SD = 19.4). No clinical differences were observed 
between the three arms in pain events, with all three reporting a reduction in pain symptoms. 
On 13 January 2021, tislelizumab received approval from the China National Medical Products 
Administration (NMPA) for use in combination with two chemotherapy regimens as a first-line 
treatment for patients with untreated Stage IIIB or IV squamous NSCLC. This tislelizumab 
combination demonstrated a clinically meaningful benefit as assessed by PFS and response rates. 
BGB-A317-315 
Study BGB-A317-315 is a randomized, double-blind, placebo-controlled, global, Phase 3 study 
to compare the efficacy and safety of neoadjuvant treatment with tislelizumab plus 
platinum-based doublet chemotherapy followed by adjuvant tislelizumab versus neoadjuvant 
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treatment with placebo plus platinum-based doublet chemotherapy followed by placebo in 
patients with resectable Stage II or IIIA NSCLC. 
Efficacy data of major pathological response rate and pathological complete response rate from 
Study BGB-A317-315 (data cutoff 20 February 2023) were presented at the 2023 European 
Society for Medical Oncology World Congress (Yue et al 2023). 
The major pathological response rate in the ITT Analysis Set was significantly improved in 
patients treated with tislelizumab plus chemotherapy before surgery (56.2%) versus those treated 
with placebo plus chemotherapy before surgery (15.0%) (difference: 41.1%; 95% CI: 33.2% to 
49.1%, p < 0.0001). Additionally, the pathological complete response rate in the ITT Analysis 
Set was significantly improved in patients treated with tislelizumab plus chemotherapy before 
surgery (40.7%) versus those treated with placebo plus chemotherapy before surgery (5.7%) 
(difference: 35.0%; 95% CI: 27.0% to 42.1%, p < 0.0001). 
1.5. 
Study Rationales  
1.5.1. 
Rationale for Ociperlimab and Tislelizumab in the Treatment of NSCLC  
Upregulation of TIGIT expression in tumor-infiltrating lymphocytes has been reported in 
NSCLC (Tassi et al 2017). Blockade of the TIGIT receptor alone or in combination with 
PD-1/PD-L1 blockade has been shown both in vitro and in vivo to rescue functionally 
“exhausted” T-cells (Johnston et al 2014; Chauvin et al 2015). In mouse models, TIGIT blockade 
in combination with anti-PD-1/PD-L1 antibodies demonstrated significantly better antitumor 
efficacy than either monotherapy (Johnston et al 2014; Dixon et al 2018).  
As discussed in Section 1.2, anti-PD-1/PD-L1 antibodies have been shown to be clinically 
efficacious in both squamous and non-squamous NSCLC; furthermore, results from other 
anti-TIGIT + PD-L1 or PD-1 combination studies in NSCLC showed significant enhancement of 
antitumor activity compared with PD-1/PD-L1 monotherapy, suggesting that anti-TIGIT 
antibodies have the potential to significantly improve and/or extend the therapeutic benefit of 
anti-PD-1 therapy in this population , especially in patients expressing higher levels of PD-L1 
(Chauvin et al 2015). Studies confirming the activity of these combinations in these patients are 
currently underway (SKYSCRAPER-01 and AdvanTIG-302). 
Unfortunately, many NSCLC patients’ tumors do not express high levels of PD-L1, and patients 
will most likely receive chemotherapy or chemotherapy combined with anti-PD-1/PD-L1 
therapy. It is unclear if combining anti-TIGIT with these regimens in patients with low or 
negative PD-L1 expression will be successful. Subset analysis of the CITYSCAPE trial suggests 
that the PD-L1 high group (TPS ≥ 50%) was the primary driver of the enhanced activity for the 
combination but it is not known if the PD-L1 low (or PD-L1-negative) patients would have had 
greater benefit from the TIGIT + PD-L1 combination if chemotherapy had also been used. As 
these patients do show some activity with PD-1 monotherapy, it is quite possible that adding 
both chemotherapy and anti-TIGIT may be superior to PD-1 + TIGIT combinations in this 
group. 
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1.5.2. 
Rationale for the Selection of the Ociperlimab Dose in Combination With 
Tislelizumab  
The ociperlimab dose of 900 mg once every 3 weeks (Q3W) combined with tislelizumab 200 mg 
Q3W was selected as the RP2D for further investigations based on clinical safety, tolerability, 
PK, and pharmacodynamic data from the ongoing Phase 1/1b Study AdvanTIG-105. 
Complete TIGIT receptor occupancy was observed in circulating T cells in peripheral blood at 
all the tested doses of ociperlimab in Study AdvanTIG-105.  However, the correlation between 
TIGIT receptor occupancy in the periphery and in tumor tissues is unknown.  In a previous 
Phase 1 study of tiragolumab, another anti-TIGIT antibody, complete peripheral receptor 
occupancy was reached at the 30 mg dose level, but the clinical dose of 600 mg was determined 
as the RP2D, which was 20 times the 30 mg dose (Bendell et al 2020).  Similarly, although 
complete peripheral receptor occupancy was observed at the 50 mg dose level of ociperlimab, 
the RP2D of 900 mg is approximately 20 times the dose of 50 mg.  As of 12 May 2021, a total of 
3 patients were assessed to have a confirmed partial response, 1 patient each in the 450 mg, 
900 mg, and 1800 mg cohorts.  Ociperlimab exposure in all 3 patients with a partial response is 
consistent with that expected at the 900 mg dose level.  The confirmed disease control rates 
observed in the 450 mg, 900 mg, and 1800 mg cohorts were 60% (3/5), 64.3% (9/14), and 
60% (3/5) of patients, respectively. 
Although the best overall response and disease control rate were numerically comparable at the 
450 mg and 900 mg dose levels, the 900 mg dose was chosen as the RP2D for the following 
reasons: 
• 900 mg was well tolerated in Study AdvanTIG-105 
• Exposure in all 3 patients with a partial response was consistent with that expected at 
the 900 mg dose 
• Lack of sufficient information on the impact of immunogenicity on ociperlimab PK 
• An overall intent to minimize exposure overlap with doses ≤ 450 mg 
1.5.3. 
Rationale for the Selection of the Tislelizumab Dose  
The tislelizumab dose of 200 mg once every 3 weeks was selected based on the totality of 
clinical safety, efficacy, and pharmacokinetic data from Study BGB-A317-001. 
• Incidence rates of various treatment-related AEs and serious AEs in patients receiving 
2 mg/kg and 5 mg/kg once every 2 weeks or once every 3 weeks were comparable, 
suggesting a lack of dose or regimen dependance (Wu et al 2019a; Wu et al 2019b). 
• The ORRs observed in patients treated with tislelizumab 2 mg/kg once every 2 weeks 
(10%) or once every 3 weeks (38%) were generally comparable with tislelizumab 
5 mg/kg once every 2 weeks (15%) or once every 3 weeks (15%), suggesting a lack of 
dose or regimen dependence.  
• Tislelizumab exhibited linear PK across the dose range of 0.5 mg/kg to 10 mg/kg and no 
PK differences were observed between 2 dose regimens (once every 2 weeks or once 
every 3 weeks). Additionally, population PK analysis indicated tislelizumab clearance is 
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not dependent on body weight, which supports administration of tislelizumab without 
regard to body weight.  
• Incidence of ADAs to tislelizumab did not appear to be related to safety events and 
efficacy.  
• Exposure-response analysis for safety events and efficacy (ORR) across a wide range of 
tumor types showed flat relationships, with tislelizumab exposure supporting selection of 
a flat dose within the exposure range of 2 mg/kg and 5 mg/kg.  
A flat dose of 200 mg, which is equivalent to 2.86 mg/kg for a 70 kg patient, was chosen based 
on the comparable safety and efficacy data at the 2 mg/kg and 5 mg/kg dose levels, and the lack 
of relationship between tislelizumab clearance and body weight. The regimen of tislelizumab 
200 mg once every 3 weeks produces tislelizumab concentrations that overlap with those 
observed with the 2 mg/kg and 5 mg/kg dose levels. The once-every-3-weeks regimen was 
selected based on the similarity in efficacy and safety data observed between the 
once-every-2-weeks and once-every-3-weeks regimens. A flat dose offers additional advantages 
such as convenience in preparation and administration of dose and avoids potential dosing errors. 
The efficacy and safety of the regimen of tislelizumab 200 mg once every 3 weeks has been 
assessed subsequently in multiple pivotal Phase 2 and 3 clinical studies. 
1.5.4. 
Rationale for Tislelizumab Plus Chemotherapy as the Comparator  
While in many countries, pembrolizumab is considered standard of care as first-line therapy for 
patients with metastatic NSCLC, tislelizumab has shown comparable activity when combined 
with chemotherapy in this population (see Section 1.4.5 for a discussion of the BGB-A317-304 
and BGB-A317-307 studies) and is expected to perform similarly in this study. As the goal of the 
study is to assess the activity of ociperlimab when combined with tislelizumab and 
chemotherapy, using tislelizumab with chemotherapy as a comparator should provide an accurate 
assessment of how the ociperlimab combination performs versus a PD-1 inhibitor alone (either 
tislelizumab or pembrolizumab) with chemotherapy and also demonstrate the contribution of 
ociperlimab to the combination. 
1.5.5. 
Rationale for Biomarker Strategy  
Biomarker analyses in tumor tissues will include but not be limited to the expression of TIGIT, 
CD226, CD155, CD112, PD-L1, gene expression profiling (GEP), tumor mutation burden 
(TMB), gene mutations, microsatellite instability (MSI), and TILs to explore potential predictive 
and prognostic biomarkers and mechanisms of resistance. For sites in mainland China, tissue 
samples will be limited to the expression of TIGIT, CD226, CD155, CD112, PD-L1, GEP, TMB, 
gene mutations, MSI, and TILs at baseline and at disease progression/reoccurrence. 
In addition, blood-based biomarkers will include but not be limited to circulating tumor DNA 
(ctDNA), TMB, MSI, gene mutations, and extracellular vesicles (EVs). For sites in mainland 
China, blood-based biomarkers will be limited to ctDNA, TMB, MSI, gene mutations, and EVs.  
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PD-L1 is expressed in tumor and TILs in advanced NSCLC, and its expression level has been 
shown to be correlated with clinical efficacy of anti-PD-1 treatment in multiple studies (Topalian 
et al 2012; Herbst et al 2014; Borghaei et al 2015; Fehrenbacher et al 2016; Herbst et al 2016; 
Rosenberg et al 2016). PD-L1 IHC 22C3 pharmDx was approved as a companion diagnostic 
(CDx) to identify patients with NSCLC for treatment with KEYTRUDA (pembrolizumab). In 
addition, higher PD-L1 expression on tumor cells has also shown to be correlated with enhanced 
ORR and PFS in anti-PD(L)-1 plus chemotherapy studies (KEYNOTE-189, KEYNOTE-407, 
IMpower131), suggesting the possible predictive value of PD-L1 in therapies combining 
anti-PD-1 and chemotherapy in NSCLC. 
However, the role of PD-L1 in predicting response to immune combination therapies in patients 
with NSCLC is still poorly understood. In the CITYSCAPE study, NSCLC patients with higher 
PD-L1 derived impressive benefit from atezolizumab (anti-PD-L1) plus tiragolumab 
(anti-TIGIT) compared to atezolizumab alone (PFS of HR 0.29 with 95% CI 0.15-0.53), 
suggesting PD-L1 could be a predictive biomarker for PD-1 and TIGIT pathway co-targeting 
treatment in NSCLC (Rodriguez-Abreu et al 2020). In this study, PD-L1 expression in tumor 
cells (three levels: < 1% versus 1% to 49% versus ≥ 50%) was designed as one of the 
stratification factors to explore its association with clinical efficacy.  
In addition to PD-L1, clinical data from various studies suggested TMB, MSI, abundance and 
location of TILs, and immune-related GEP are a few factors associated with response to 
immunotherapies including anti-PD-1 antibodies in different cancers (Vilain et al 2017; 
Goodman et al 2017; Gandara et al 2018; Jiang et al 2018). Therefore, ctDNA, TMB, MSI, gene 
mutations, TILs, EVs, and GEP will be studied in relationship with clinical response to 
ociperlimab in combination with tislelizumab treatment to explore potential predictive or 
prognosis biomarkers. 
Mechanisms of resistance to immunotherapies are also not well understood and need more 
exploration. Identification of tumor and immune-related features associated with disease 
progression or acquired resistance to ociperlimab and tislelizumab may increase the 
understanding of disease pathobiology and provide biological evidence for the combination 
strategy. In this regard, high TIGIT/CD226 ratio on Treg cells was shown to correlated with poor 
clinical outcomes in melanoma patients treated with anti-PD 1 or anti-PD-L1 antibodies 
(Fourcade et al 2018). In addition, a higher frequency of TIGIT+ T cells among PD-1+CD8+ 
T cells was associated with hyperprogressive disease during PD-1/PD-L1 blockade and inferior 
survival rate in patients with NSCLC (Kim et al 2019). These results suggest that signaling 
through the TIGIT pathway in tumor tissues might contribute to resistance to immune checkpoint 
inhibitors targeting PD-1 or PD-L1. Here, the expression levels of TIGIT pathway molecules 
including TIGIT, CD226, CD155, and CD112 will also be studied to explore its correlation with 
the clinical efficacy of ociperlimab plus tislelizumab combined treatment.  
1.6. 
Benefit-Risk Assessment  
AdvanTIG-205 will evaluate the safety and efficacy of the anti-TIGIT antibody ociperlimab in 
combination with tislelizumab and chemotherapy in patients with previously untreated locally 
advanced, unresectable, or metastatic NSCLC that does not harbor EGFR mutations, ALK 
translocations, BRAF V600E mutations, or c-ROS oncogene-1 (ROS1) mutations. There is 
extensive evidence supporting TIGIT’s role in regulating immune response. In addition, the 
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interaction between the TIGIT and PD-1 pathways has been shown to promote tumor immune 
escape. The clinical efficacy demonstrated for tislelizumab (Section 1.4.5) and preliminary 
results from an anti-TIGIT/ anti-PD-L1 competitor combination, suggests that ociperlimab has 
the potential to improve and/or extend the therapeutic benefits of tislelizumab in the treatment 
naive setting, especially in patients whose tumors express higher levels of PD-L1. By testing the 
combination with chemotherapy, there is a good chance that enhanced activity of the 
combination may be seen in a broader group of patients, including those whose tumors express 
low or no PD-L1.  
As discussed earlier (Section 1.5.1), based on the mechanism(s) of action, and the nonclinical 
and preliminary clinical data, the combined blockade of TIGIT and PD-1 by ociperlimab and 
tislelizumab, respectively, is expected to result in immune-mediated toxicities similar to what has 
been observed with tislelizumab alone or tislelizumab with chemotherapy.  
Preliminary safety results from the CITYSCAPE trial (N = 135 patients) support this hypothesis 
and show that patients treated with the anti-TIGIT/PD-L1 combination experienced less than 
10% increase in overall and Grade 3 or 4 TEAEs compared to patients treated with anti-PD-1 
and placebo. 
The risk of observing augmented safety signals as has been shown for other anti-PD-1-based 
immune-oncology combinations still remains; therefore, a monitoring plan derived from the 
European Society for Medical Oncology and American Society for Clinical Oncology has been 
established to monitor, diagnose, and manage imAEs (Appendix 7). It is important to note that 
peripheral effector T cells typically do not express TIGIT, which is in contrast to TILs stimulated 
by the antigens in the tumor microenvironment. Therefore, the combination provides an 
opportunity to specifically augment the activity of effector T cells in the tumor rather than 
periphery and/or nontumor tissue (Johnston et al 2014), which should help control toxicity. 
Blockade of the PD-1 pathway has demonstrated strong antitumor efficacy either alone or in 
combination with standard of care chemotherapy in multiple cancer indications. As of 
20 May 2020, PD-1 blockade by tislelizumab has been evaluated in more than 1917 patients with 
a safety and efficacy profile similar to what has been reported for other anti-PD-1/PD-L1 
therapies, such as nivolumab and pembrolizumab. 
Safety data will be continuously monitored by the sponsor’s study team in consultation with 
investigator(s) as needed. Refer to Section 7.4 and Section 8 for information regarding additional 
safeguards and considerations related to potential risk. 
In summary, there is a strong scientific rationale that the combined blockade of the TIGIT 
pathway and PD-1 pathway may result in enhanced antitumor activity without a major increase 
in the risk of immune-mediated toxicities to benefit a larger patient population than single agent 
anti-PD-1 therapy. 
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2. 
STUDY OBJECTIVES AND ENDPOINTS  
2.1. 
Study Objectives  
2.1.1. 
Primary Objective  
• To compare progression-free survival (PFS) in Arm A (ociperlimab in combination 
with tislelizumab and chemotherapy) and Arm B (placebo in combination with 
tislelizumab and chemotherapy) in the ITT Analysis Set, as assessed by investigators 
per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) 
2.1.2. 
Secondary Objectives  
• To evaluate overall response rate (ORR) and duration of response (DOR) in Arm A 
(ociperlimab in combination with tislelizumab and chemotherapy) versus Arm B 
(placebo in combination with tislelizumab and chemotherapy), as assessed by 
investigators per RECIST v1.1 
• To compare overall survival (OS) between Arm A (ociperlimab in combination with 
tislelizumab and chemotherapy) and Arm B (placebo in combination with 
tislelizumab and chemotherapy) 
• To evaluate the safety and tolerability profile of ociperlimab in combination with 
tislelizumab and chemotherapy compared to tislelizumab in combination with 
chemotherapy  
2.1.3. 
Exploratory Objectives  
• To evaluate disease control rate (DCR), clinical benefit rate (CBR), and time to 
response (TTR) in Arm A (ociperlimab in combination with tislelizumab and 
chemotherapy) versus Arm B (placebo in combination with tislelizumab and 
chemotherapy), as assessed by investigators per RECIST v1.1 
• To evaluate the potential association of exploratory biomarkers with response or 
resistance of ociperlimab and tislelizumab, and patient prognosis 
• To compare health-related quality-of-life (HRQoL) between Arm A (ociperlimab in 
combination with tislelizumab and chemotherapy) and Arm B (placebo in 
combination with tislelizumab and chemotherapy)  
• To characterize the pharmacokinetics (PK) of ociperlimab and tislelizumab  
• To determine host immunogenicity to ociperlimab and tislelizumab 
2.2. 
Study Endpoints  
2.2.1. 
Primary Endpoint  
• PFS (time from the date of randomization to the date of the first objectively 
documented tumor progression, or death, whichever occurs first) in the ITT Analysis 
Set of Arm A (ociperlimab in combination with tislelizumab and chemotherapy) 
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versus Arm B (placebo in combination with tislelizumab and chemotherapy), as 
assessed by investigators per RECIST v1.1  
2.2.2. 
Secondary Endpoints  
• ORR as assessed by investigators (proportion of patients with a documented, 
confirmed complete response [CR] or partial response [PR] per RECIST v1.1) and 
DOR as assessed by investigators (time from the first determination of an objective 
response per RECIST v1.1 until the first documentation of progression or death, 
whichever occurs first) in Arm A (ociperlimab in combination with tislelizumab and 
chemotherapy) and Arm B (placebo in combination with tislelizumab and 
chemotherapy) 
• OS (time from the date of randomization to the date of death due to any cause) in the 
ITT Analysis Set of Arm A (ociperlimab in combination with tislelizumab and 
chemotherapy) versus Arm B (placebo in combination with tislelizumab plus 
chemotherapy) 
• The incidence and severity of adverse events according to National Cancer Institute 
Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0) 
2.2.3. 
Exploratory Endpoints  
• DCR (proportion of patients with confirmed CR or confirmed PR or stable disease 
[SD]), CBR (proportion of patients with confirmed CR or confirmed PR or durable 
SD) and TTR (time from randomization to the first occurrence of a documented 
objective response) in Arm A (ociperlimab in combination with tislelizumab and 
chemotherapy) versus Arm B (placebo in combination with tislelizumab and 
chemotherapy) as assessed by investigators per RECIST v1.1 
• Status of exploratory biomarkers, including but not limited to expression of T-cell 
immunoglobulin and ITIM domain (TIGIT), CD226, CD155, CD112, PD-L1, GEP, 
ctDNA, TMB, gene mutations, MSI, TILs, and EVs in archival and/or fresh tumor 
tissue and blood before and after study treatment or at disease 
progression/reoccurrence, and the association between these biomarkers and clinical 
efficacy, disease status, and resistance.  
• HRQoL will be assessed using 2 validated patient-reported outcomes (PROs), 
including European Organization for Research and Treatment of Cancer Quality of 
Life Questionnaire- Core 30 (EORTC-QLQ-C30) and its lung cancer module (Quality 
of Life Questionnaire-Lung Cancer 13 [QLQ-LC13]). 
• Serum concentrations of ociperlimab and tislelizumab at specified timepoints 
• Immunogenic responses to ociperlimab and tislelizumab, evaluated through detection 
of anti-drug antibodies (ADAs) 
 
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3. 
STUDY DESIGN  
3.1. 
Summary of Study Design  
This is a randomized, investigator- and patient-blinded, sponsor-unblinded, multicenter, Phase 2 
study designed to evaluate the efficacy and safety of ociperlimab in combination with 
tislelizumab and histology-based chemotherapy versus tislelizumab in combination with placebo 
and histology-based chemotherapy in patients with previously untreated locally advanced, 
unresectable, or metastatic NSCLC whose tumors do not harbor EGFR-sensitizing mutations, 
ALK translocations, BRAF V600E mutations, ROS1 mutations, or other genetic mutations for 
which a targeted therapy is appropriate and accessible. 
Patients will be required to sign an informed consent form (ICF) to undergo collection of tissue 
samples (archival tissue or fresh biopsy) for central evaluation of status and to undergo screening 
procedures. If the assessments of PD-L1 in the local laboratory meet all requirements (refer to 
Section 4.1), the local PD-L1 results may be used for randomization. 
Approximately 270 patients will be enrolled (including a minimum of 25% of non-Asian 
patients). 
The study will target to enroll patients to ensure that it reflects a representative distribution of 
PD-L1 expression in NSCLC (approximately 40% PD-L1 TC < 1%) and to ensure that it reflects 
a representative histology distribution in the NSCLC population without driver mutation 
(approximately 30% squamous NSCLC).  
Eligible participants will be randomized in a 1:1 ratio to receive ociperlimab + tislelizumab + 
chemotherapy (Arm A) or placebo + tislelizumab + chemotherapy (Arm B). Randomization will 
be stratified by PD-L1 expression (three levels: < 1% TC versus 1% to 49% TC versus 
≥ 50% TC), and histology (squamous versus non-squamous). 
During the induction phase (4 to 6 cycles), study treatments will be given as follows: 
• Arm A: Ociperlimab 900 mg IV + tislelizumab 200 mg IV + histology-based 
chemotherapy once every 3 weeks  
• Arm B: Placebo IV + tislelizumab 200 mg IV + histology-based chemotherapy once 
every 3 weeks  
• All patients in Arms A and B will receive histology-based chemotherapy: 
o For patients with squamous NSCLC: carboplatin AUC 5 or 6 (D1) + paclitaxel 
175 or 200 mg/m2 (D1) or nab-paclitaxel 100 mg/m2 (D1, D8, D15) administered 
every 3 weeks 
o For patients with non-squamous NSCLC: cisplatin 75 mg/m2 or carboplatin AUC 
5 (D1) + pemetrexed 500 mg/m2 (D1) IV administered every 3 weeks 
During the maintenance phase, study treatments will be given as follows: 
• For patients with non-squamous NSCLC: 
o Arm A: Ociperlimab 900 mg IV + tislelizumab 200 mg IV + pemetrexed 
500 mg/m2 once every 3 weeks  
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o Arm B: Placebo IV + tislelizumab 200 mg IV + pemetrexed 500 mg/m2 once 
every 3 weeks 
• For patients with squamous NSCLC: 
o Arm A: Ociperlimab 900 mg IV + tislelizumab 200 mg IV once every 3 weeks 
o Arm B: Placebo IV + tislelizumab 200 mg IV once every 3 weeks  
The study design schematic is presented in Figure 2.  
Figure 2: 
Study Schema  
 
Abbreviations: ALK, anaplastic lymphoma kinase; D, day; AUC, area under the concentration-time curve; EGFR, 
epidermal growth factor receptor; NSCLC, non-small cell lung cancer; PD-L1, programmed cell death ligand-1; 
R, randomization; WT, wild type 
For all study procedures, see Section 7 and Appendix 1. 
3.2. 
Screening Period  
Screening evaluations will be performed within 28 days before randomization. Patients who 
agree to participate in this study will sign the main ICF before undergoing any screening 
procedure (refer to Section 7 and Appendix 1 for details). Screening evaluations may be repeated 
as needed within the screening period; the investigator is to assess preliminary patient eligibility 
according to the latest screening assessment results. 
3.3. 
Treatment Period  
After completing all screening activities, eligible patients will be randomized in a 1:1 ratio to 
receive ociperlimab + tislelizumab + chemotherapy (Arm A) or placebo + tislelizumab + 
chemotherapy (Arm B). 
The study will have 2 phases: an induction phase and a maintenance phase.  
During the induction phase (4 to 6 cycles), study treatments will be given as follows: 
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• Arm A: Ociperlimab 900 mg IV + tislelizumab 200 mg IV + histology-based 
chemotherapy once every 3 weeks  
• Arm B: Placebo IV + tislelizumab 200 mg IV + histology-based chemotherapy once 
every 3 weeks  
• All patients in Arms A and B will receive histology-based chemotherapy: 
o For patients with squamous NSCLC: carboplatin AUC 5 or 6 (D1) + paclitaxel 
175 or 200 mg/m2 (D1) or nab-paclitaxel 100 mg/m2 (D1, D8, D15) administered 
every 3 weeks 
o For patients with non-squamous NSCLC: cisplatin 75 mg/m2 or carboplatin AUC 
5 (D1) + pemetrexed 500 mg/m2 (D1) IV administered every 3 weeks 
The number of chemotherapy cycles (4 to 6 cycles) and the chemotherapy regimen selection will 
be at the investigator’s discretion. 
During the maintenance phase, study treatments will be given as follows: 
• For patients with non-squamous NSCLC: 
o Arm A: Ociperlimab 900 mg IV + tislelizumab 200 mg IV + pemetrexed 
500 mg/m2 once every 3 weeks  
o Arm B: Placebo IV + tislelizumab 200 mg IV + pemetrexed 500 mg/m2 once 
every 3 weeks 
• For patients with squamous NSCLC: 
o Arm A: Ociperlimab 900 mg IV + tislelizumab 200 mg IV once every 3 weeks 
o Arm B: Placebo IV + tislelizumab 200 mg IV once every 3 weeks 
All study treatments will be administered until intolerable toxicity, withdrawal of informed 
consent, or the timepoint at which, in the opinion of the investigator, the patient is no longer 
benefiting from study therapy.  
No crossover will be allowed between treatment arms because the treatment assignment will 
remain blinded to investigators and patients until the primary endpoint data are available.  
Treatment beyond the initial investigator-assessed, RECIST v1.1-defined disease progression is 
permitted in both arms provided that the patient has investigator-assessed clinical benefit and is 
tolerating tislelizumab in combination with ociperlimab (or placebo); the chemotherapy beyond 
initial progression will be at investigator’s discretion (see Section 7.5).  
The following criteria must be met to treat patients after initial evidence of radiologic disease 
progression: 
• Absence of clinical symptoms and signs of progressive disease (including clinically 
significantly worsening of laboratory values) 
• ECOG Performance Status ≤ 1 
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• Absence of rapid progression of disease or of progressive tumor at critical anatomical 
sites (eg, spinal cord compression) that requires urgent alternative medical 
intervention 
• Investigators must obtain written informed consent for treatment beyond radiologic 
disease progression and inform patients that this practice is not considered standard in 
the treatment of cancer. Patients must be informed that they may be forgoing 
treatment that has shown benefit by continuing treatment beyond progression 
• The decision to continue study drug(s) beyond initial investigator-assessed 
progression must be agreed upon with the sponsor medical monitor 
Patients who receive study treatment beyond progression will have tumor assessments performed 
according to the original schedule until study treatment discontinuation.  
Tumor assessments are required to be performed on schedule regardless of whether study 
treatment has been administered or held (ie, their schedule should not be adjusted for delays in 
cycles). Tumor response will be assessed by investigators using RECIST v1.1 criteria 
(Eisenhauer et al 2009). Radiologic assessment of tumor-response status will be performed 
approximately every 9 weeks (± 7 days) from randomization for the first 52 weeks and every 12 
weeks (± 7 days) thereafter. Patients who discontinue study treatment early for reasons other 
than radiologic disease progression (eg, toxicity) will continue to undergo tumor assessments 
following the original plan until the patient begins a subsequent anticancer treatment, 
experiences radiologic disease progression or death, withdraws consent, is lost to follow-up, or 
until the study terminates, whichever occurs first. Details are provided in Section 7.5. 
Patient-reported outcomes (PRO; see Section 7.8) will be collected at baseline (Day 1 of Cycle 
1), every other cycle through Cycle 13, then every 4 cycles thereafter, and at the End of 
Treatment (EOT) Visit (Section 3.4). At each visit, PRO will be collected before any procedures 
or dose administration. 
Safety will be assessed throughout the study by monitoring AEs/SAEs (toxicity grades assigned 
per NCI-CTCAE v5.0 and laboratory results. Vital signs, physical examinations, ECOG 
Performance Status change, electrocardiogram (ECG) results, and other examinations will also 
be used for safety assessment. Safety assessments are further detailed in Section 7.4 and 
Appendix 1. 
Patients will provide blood samples at Cycle 1 Day 1 and Cycle 3 Day 1 for the assessment of 
mechanism of response or resistance (Section 7.7; Appendix 1). 
3.4. 
End of Treatment  
The End of Treatment Visit will be conducted when the investigator determines that 
ociperlimab/placebo or tislelizumab will no longer be used. If routine laboratory tests (eg, 
hematology, serum chemistry) were completed within 7 days before the EOT Visit, these tests 
need not be repeated.  
All AEs, including SAEs, will be collected as described in Section 8.6. 
Patients who discontinue from study treatment before disease progression will need to undergo 
tumor assessments as outlined in Section 7.5. 
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Patients who have progressive disease will be asked to provide an optional biopsy at the EOT 
Visit for the assessment of mechanism of resistance (Section 7.7). 
Patients who have progressive disease will provide blood samples at the EOT Visit for the 
assessment of mechanism of response or resistance (Section 7.7; Appendix 1). 
See Appendix 1 for assessments to be performed at the EOT Visit. 
3.5. 
Safety Follow-up  
A Safety Follow-up Visit at 30 days (± 7 days) after the last dose of the study drug(s) is required 
to assess AEs and concomitant medications, unless the time window overlaps with the time 
window of the EOT Visit; the Safety Follow-up Visit may be a telephone call or an on-site visit 
if laboratory assessments are necessary. Two additional telephone calls with patients will occur 
in the safety follow-up period to assess imAEs and concomitant medications if appropriate at 
60 and 90 days (± 14 days) after the last dose of ociperlimab (or placebo) and/or tislelizumab 
regardless of whether the patient starts a new subsequent anticancer therapy. If a patient reports a 
suspected imAE at a safety follow-up telephone call, the investigator should arrange an 
unscheduled visit if further assessment is indicated. 
For women of childbearing potential (see Appendix 10), an additional follow-up visit for a urine 
pregnancy test will occur until 120 days after the last dose of ociperlimab and/or tislelizumab or 
180 days after the last dose of chemotherapy, whichever comes later. 
All AEs, including SAEs, will be collected as described in Section 8.6. 
See Appendix 1 for assessments to be performed at the Safety Follow-Up Visit. 
3.6. 
Survival Follow-up  
Patients will be followed for survival and to obtain information on subsequent anticancer therapy 
information after discontinuation of study treatment via telephone calls, patient medical records, 
and/or clinic visits approximately every 3 months (± 14 days) after the EOT Visit or as directed 
by the sponsor until death, withdrawal of consent, loss to follow-up, or end of study. 
3.7. 
Discontinuation From the Study Treatment or From the Study  
3.7.1. 
Patient Discontinuation From Study Treatment  
Patients have the right to discontinue study treatment at any time for any reason. In addition, the 
investigator has the right to discontinue a patient from the study treatment at any time. Patients 
who discontinue study treatment for reasons other than disease progression should be followed 
for assessments of antitumor activity (Section 7.5), safety (Section 7.4) and survival 
(Section 3.6), if possible. 
The primary reason for discontinuation from the study treatment should be documented on the 
appropriate electronic case report form (eCRF). Patients may discontinue study treatment for 
reasons that include, but are not limited to, the following: 
• Disease progression 
• Adverse event 
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• Drug withdrawal by patient 
• Pregnancy 
• Any medical condition that the investigator or sponsor determines may jeopardize the 
patient’s safety, if he or she were to continue the study treatment 
• Use of any concurrent anticancer therapy (ie, chemotherapy, hormonal therapy, 
immunotherapy, or standard or investigational agents [including Chinese (or other 
country) herbal medicine and Chinese (or other country) patent medicines] for the 
treatment of cancer) 
• Patient noncompliance 
o Investigative site staff should first counsel patients who are significantly 
noncompliant (eg, missing 2 treatment cycles) on the importance of study drug 
compliance and drug accountability. The investigator may, in consultation with 
the medical monitor, discontinue patients from treatment who are consistently 
noncompliant. 
Benefits of continuation of ociperlimab (or placebo) and/or tislelizumab beyond 2 years after the 
start of treatment should be evaluated and discussed with the sponsor’s medical monitor (Herbst 
et al 2020; Kottschade 2019) 
3.7.2. 
Patient Discontinuation From Study (End of Study for an Individual Patient)  
Patients may discontinue study for reasons which include, but are not limited to, the following:  
• Patient withdrawal of consent 
• Noncompliance 
• Death 
• Lost to follow-up 
• Patients have completed all study assessments 
3.8. 
End of Study  
The end of study is defined as the timepoint when the final data point is collected from the last 
patient in the study. This is when the last patient dies, withdraws consent, completes all study 
assessments, or is lost to follow-up. Alternatively, the end of study is when the sponsor decides 
to terminate the study. 
The sponsor has the right to terminate this study at any time. Reasons for terminating the study 
early may include, but are not limited to, the following: 
• The incidence or severity of AEs in this or other studies indicates a potential health 
hazard to patients 
• Overall patient enrollment is unsatisfactory 
• A rollover study becomes available 
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The sponsor will notify each investigator if a decision is made to terminate the study. Should this 
be necessary, prematurely discontinued patients should be seen as soon as possible for an EOT 
Visit and Safety Follow-Up Visit. 
The investigators may be informed of additional procedures to be followed to ensure that 
adequate consideration is given to the protection of the patient’s interests. The investigator will 
be responsible for informing Institutional Review Boards (IRBs)/Independent Ethics Committees 
(IECs) of the early termination of the study. 
Patients who, in the opinion of the investigator, continue to benefit from ociperlimab in 
combination with tislelizumab or tislelizumab alone at study termination will be offered the 
option to continue the treatment as permitted by applicable laws and regulations in a continuous 
access program, such as but not limited to, a Long-Term Extension study, a Post-Trial Supply 
program, a Patient Access Program, until the treatment is commercially available in the country 
of the patient’s residence. 
The sponsor has the right to close a site at any time. The decision will be notified to the site in 
advance. 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  
• Good Clinical Practice (GCP) noncompliance 
• Study activity is completed (ie, all patients have completed, and all obligations have 
been fulfilled) 
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4. 
STUDY POPULATION  
The specific eligibility criteria for selection of patients are provided in Section 4.1 and 
Section 4.2. The sponsor will not grant any eligibility waivers. 
4.1. 
Inclusion Criteria  
Each patient eligible to participate in this study must meet all the following criteria: 
1. Able to provide written informed consent and can understand and agree to comply with 
the requirements of the study and the schedule of assessments. 
2. Age ≥ 18 years on the day of signing the informed consent form (or the legal age of 
consent in the jurisdiction in which the study is taking place). 
3. Histologically or cytologically documented locally advanced or recurrent NSCLC that is 
not eligible for curative surgery and/or definitive radiotherapy, with or without 
chemotherapy, or metastatic non-squamous or squamous NSCLC. 
a. Tumors of mixed non-small cell histology will be categorized by the predominant cell 
type. 
b. If small cell elements are present, the patient is ineligible. 
c. Patients with Stage IIIa NSCLC are not eligible. 
4. No prior systemic therapy for locally advanced or metastatic squamous or non-squamous 
NSCLC, including but not limited to chemotherapy or targeted therapy. Patients who 
have received prior neoadjuvant, adjuvant chemotherapy, or chemoradiotherapy with 
curative intent for nonmetastatic disease must have experienced a disease-free interval of 
≥ 6 months from the last dose of chemotherapy and/or concurrent radiotherapy prior to 
randomization. 
5. Archival tumor tissue (formalin-fixed paraffin-embedded block containing tumor 
[preferred] or approximately 6 to 15 freshly cut unstained slides) or fresh biopsy (if 
archival tissue is not available) for the determination of PD-L1 levels and retrospective 
analyses of other biomarkers. PD-L1 expression in tumor cells will be assessed using a 
central laboratory validated PD‑L1 (SP263) assay or local PD-L1 assay. Local PD-L1 
results may be utilized under certain circumstances for enrollment. 
Note: If local PD-L1 testing will be used for patient randomization purposes, 
confirmation of tumor sample receipt by the central laboratory is required before patient 
randomization (preferably from the same block used for local PD‑L1 testing). Local 
PD-L1 testing must be performed using an approved assay (limited to 22C3, SP263, and 
28-8) at a certified laboratory and according to the manufacturer’s instructions. 
6. At least one measurable lesion by the investigator as defined per RECIST v1.1. 
Note: A lesion in an area subjected to prior locoregional therapy, including previous 
radiotherapy, is not considered measurable unless there has been demonstrated 
progression in the lesion since the therapy as defined by RECIST v1.1. 
7. ECOG Performance Status ≤ 1. 
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8. Adequate organ function as indicated by the following laboratory values during 
screening. 
Patients must not have required blood transfusion or growth factor support ≤ 14 days 
before sample collection at screening for the following: 
a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L 
b. Platelets ≥ 100 x 109/L 
c. Hemoglobin ≥ 90 g/L 
d. Estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2 by Chronic Kidney 
Disease Epidemiology Collaboration (CKD-EPI) equation or calculated creatinine 
clearance (CrCl) ≥ 45 mL/min/1.73 m2 by Cockcroft-Gault (CG) equation. If using 
cisplatin, eGFR ≥ 60 mL/min/1.73 m2 by CKD-EPI equation or CrCl 
≥ 60 mL/min/1.73 m2 by CG equation (Appendix 9). 
Note: For France only, eGFR ≥ 45 mL/min/1.73 m2 by CKD-EPI equation and CrCl 
≥ 45 mL/min/1.73 m2 by CG equation. If using cisplatin, eGFR ≥ 60 mL/min/1.73 m2 
by CKD-EPI equation and CrCl ≥ 60 mL/min/1.73 m2 by CG equation. 
e. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN for patients with 
Gilberts syndrome). 
f. AST and ALT ≤ 2.5 x ULN or < 5 x ULN if hepatic metastases present. 
9. Women of childbearing potential must be willing to use a highly effective method of 
birth control for the duration of the study, and for ≥ 120 days after the last dose of 
tislelizumab and ociperlimab/placebo, or ≥ 180 days after the last dose of chemotherapy 
(14 months after the last dose of cisplatin), whichever occurs later, and must have a 
negative urine or serum pregnancy test ≤ 7 days before randomization. See Appendix 10. 
10. Nonsterile men must be willing to use a highly effective method of birth control for the 
duration of the study and for ≥ 120 days after the last dose of tislelizumab and 
ociperlimab/placebo, or ≥ 180 days after the last dose of chemotherapy (11 months after 
the last dose of cisplatin), whichever occurs later. 
• A sterile man is defined as one for whom azoospermia has been previously 
demonstrated in a semen sample examination as definitive evidence of infertility. 
• Men with known “low sperm counts” (consistent with “subfertility”) are not to be 
considered sterile for purposes of this study. 
11. Eligibility to receive a platinum-based doublet chemotherapy regimen. 
• For patients intended to receive cisplatin: without any hearing impairment. 
4.2. 
Exclusion Criteria  
Patients who meet any of the following criteria are not eligible to enroll: 
1. Known mutations in: 
a. EGFR gene  
Note: For non-squamous NSCLC, patients with unknown EGFR mutation status will 
be required to have a tissue-based EGFR test either locally or at the central laboratory 
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before enrollment, or endobronchial ultrasound-guided transbronchial needle 
aspiration (EBUS-TBNA)–based EGFR test locally. Patients found to have 
EGFR-sensitizing mutations will be excluded. An additional ≥ 6 freshly cut unstained 
slides are required for non-squamous NSCLC patients with unknown EGFR status 
who will have EGFR testing done at the study central laboratory. 
b. ALK fusion oncogene.  
Note: However, testing for ALK fusions and EGFR mutations can be considered in 
select patients if they have never smoked, small biopsy specimens were used for 
testing, or mixed histology was reported. 
c. BRAF V600E 
d. ROS1 
Note: If no targeted therapy approved by local health authority is available for 
BRAF V600E or ROS1 mutations, then these patients are eligible.  
For France only: Patients with non-squamous NSCLC and unknown ROS1 gene 
rearrangements status should be tested locally to confirm eligibility. Testing is not 
required for patients with squamous NSCLC but can be considered if small biopsy 
samples were used to assess histology or mixed histology was reported. 
e. For other genetic mutations, if no targeted therapy approved by local health authority 
is available, then these patients are eligible. 
2. Prior treatment with EGFR inhibitors, ALK inhibitors, or targeted therapy for other driver 
mutations. 
3. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-TIGIT, or any other 
antibody or drug specifically targeting T-cell costimulation or checkpoint pathways in 
locally advanced or metastatic NSCLC. 
Note: Patients who have received prior neoadjuvant, adjuvant, or immuno-oncology 
therapies in consolidation are eligible, as long as there has been a treatment-free interval 
of ≥ 6 months from the last dose of immuno-oncology therapy prior to radiologic 
recurrence of the disease. 
4. Active leptomeningeal disease or uncontrolled, untreated brain metastasis. 
• Patients with stable central nervous system (CNS) metastases at the time of screening 
are eligible, provided they meet all the following: 
a. Brain imaging at screening shows no evidence of interim progression, patient is 
clinically stable for at least 2 weeks and without evidence of new brain 
metastases. 
b. Measurable and/or evaluable disease outside the CNS. 
c. No ongoing requirement for corticosteroids as therapy for CNS disease; off 
steroids 3 days before randomization; anticonvulsants at a stable dose are allowed. 
d. No stereotactic radiation or whole-brain radiation within 14 days before 
randomization. 
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e. Subjects with asymptomatic brain metastases (ie, no neurological symptoms, no 
requirements for corticosteroids, and no lesion > 1.5 cm) may participate but will 
require regular imaging of the brain as a site of disease. 
5. Active autoimmune diseases or history of autoimmune diseases that may relapse. 
Note: Prospective patients should be carefully questioned to determine whether they have 
any history of an acquired or congenital immune deficiency or autoimmune disease 
(Appendix 5). Patients with the following diseases are not excluded and may proceed to 
further screening: 
a. Controlled Type I diabetes. 
b. Hypothyroidism (provided it is managed with hormone replacement therapy only). 
c. Controlled celiac disease. 
d. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia). 
e. Any other disease that is not expected to recur in the absence of external triggering 
factors. 
6. Any active malignancy ≤ 5 years before randomization except for the specific cancer 
under investigation in this study and any locally recurring cancer that has been treated 
curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, 
carcinoma in situ of the cervix or breast). 
7. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily 
of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before 
randomization. 
Note: Patients who are currently or have previously been on any of the following steroid 
regimens are not excluded: 
a. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent). 
b. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal 
systemic absorption. 
c. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast 
dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type 
hypersensitivity reaction caused by contact allergen. 
8. Uncontrolled diabetes or > Grade 1 laboratory test abnormalities in potassium, sodium, or 
corrected calcium despite standard medical management or ≥ Grade 3 hypoalbuminemia 
≤ 14 days before randomization. 
9. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent 
drainage  
10. History of interstitial lung disease, noninfectious pneumonitis or uncontrolled lung 
diseases including pulmonary fibrosis, acute lung diseases, etc. Patients with significantly 
impaired pulmonary function, or who require supplemental oxygen at baseline must 
undergo an assessment of pulmonary function at screening (see Section 7.1.3). 
11. Infection (including tuberculosis infection, etc.) requiring systemic antibacterial, 
antifungal, or antiviral therapy within 14 days before randomization. 
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Note: Antiviral therapy is permitted for patients with chronic hepatitis B virus (HBV) or 
hepatitis C virus (HCV) infection. Patients with symptomatic COVID-19 infection are 
excluded. 
12. Untreated chronic hepatitis B or chronic HBV carriers with HBV DNA > 500 IU/mL 
(or > 2500 copies/mL) at screening. 
Note: Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B 
(HBV DNA < 500 IU/mL or < 2500 copies/mL) can be enrolled. Patients with detectable 
HBsAg or detectable HBV DNA should be managed per treatment guidelines. Patients 
receiving antivirals at screening should have been treated for > 2 weeks before 
randomization. 
13. Patients with active hepatitis C. 
Note: Patients with a negative HCV antibody test at screening or positive HCV antibody 
test followed by a negative HCV RNA test at screening are eligible. The HCV RNA test 
will be performed only for patients testing positive for HCV antibody. Patients receiving 
antivirals at screening should have been treated for > 2 weeks before randomization. 
14. Known history of human immunodeficiency virus (HIV) infection. 
Note: For sites where required by Health Authority or local guidance, an HIV serology 
test (including antigen and/or antibodies) will be conducted at baseline for patients with 
unknown HIV status. Patients with positive HIV test results will be excluded.  
15. Any major surgical procedure ≤ 28 days before randomization. Patients must have 
recovered adequately from the toxicity and/or complications from the intervention before 
randomization. 
16. Prior allogeneic stem cell transplantation or organ transplantation. 
17. Any of the following cardiovascular risk factors: 
a. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily 
living, ≤ 28 days before randomization. 
b. Symptomatic pulmonary embolism ≤ 28 days before randomization. 
c. Any history of acute myocardial infarction ≤ 6 months before randomization. 
d. Any history of heart failure meeting New York Heart Association (NYHA) 
Classification III or IV (Appendix 6) ≤ 6 months before randomization. 
e. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before 
randomization.  
f. Any history of cerebrovascular accident ≤ 6 months before randomization. 
g. Uncontrolled hypertension that cannot be managed by standard antihypertension 
medications ≤ 28 days before randomization. 
For France only: Systolic pressure ≥ 140 mmHg or diastolic pressure ≥ 90 mmHg on 
repeated measurements. 
h. Any episode of syncope or seizure ≤ 28 days before randomization. 
18. A history of severe hypersensitivity reactions to other monoclonal antibodies or any 
components of chemotherapy agents. 
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19. Was administered a live vaccine ≤ 28 days before randomization. 
Note: Vaccines for COVID-19 are allowed except for any live vaccine that may be 
developed. It is recommended to avoid COVID-19 vaccination within 72 hours before or 
after study drug administration during the first 2 treatment cycles and within 24 hours 
before or after study drug administration thereafter (ie, from Cycle 3 onwards). Seasonal 
vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal 
vaccines are live vaccines and are not allowed.  
20. Underlying medical conditions (including laboratory abnormalities) or alcohol or drug 
abuse or dependence that will be unfavorable for the administration of study drug, or 
affect the explanation of drug toxicity or AEs, or result in insufficient or impaired 
compliance with study conduct.  
21. Women who are pregnant, suspected of being pregnant, breastfeeding, or planning to get 
pregnant during the study. 
Note: Women who are breastfeeding and agree to stop breastfeeding before screening are 
allowed to enroll. They cannot breastfeed during the study and for at least 120 days after 
the last dose of study drugs. 
22. Concurrent participation in another therapeutic clinical study.  
Note: Concurrent participation in observational or noninterventional studies is allowed. 
In addition, patients who have completed active treatment in a clinical study and are in 
the follow-up period can be enrolled in this study. 
23. Toxicities from prior therapy that have not recovered to baseline, ≤ Grade 1, or stabilized, 
except for AEs not considered a likely safety risk (eg, alopecia, neuropathy, fatigue, or 
non-clinically significant laboratory anomalies). 
24. Has received any immunotherapy (eg, interleukin, interferon, thymosin, etc.) or any 
investigational therapies ≤ 14 days or ≤ 5 half-lives (whichever is shorter) before the first 
dose of study drug. 
25. For France, adults protected by law defined in Art. L. 1121-8 of the Public Health Code. 
 
 
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5. 
STUDY TREATMENT  
5.1. 
Formulation, Packaging, and Handling  
5.1.1. 
Ociperlimab  
Ociperlimab is a monoclonal antibody formulated for intravenous infusion in a single-use vial 
(20 mL glass vial, United States Pharmacopeia [USP] Type I) containing a total of 300 mg 
antibody in 15 mL of buffered isotonic solution as available. Ociperlimab has been aseptically 
filled in single-use vials with a Flurotec-coated butyl rubber stopper and an aluminum cap. Each 
vial is packaged into a single carton box. 
The contents of the label will be in accordance with all applicable local regulatory requirements. 
The study drug must be kept at the temperature condition as specified on the label. Shaking 
should be avoided. 
Refer to the pharmacy manual for details regarding intravenous administration, accountability, 
and disposal. Refer to the Ociperlimab (BGB-A1217) Investigator’s Brochure for other details 
regarding ociperlimab. 
5.1.2. 
Tislelizumab  
Tislelizumab is a monoclonal antibody formulated for intravenous infusion in a single-use vial 
(20R glass, USP type I), containing a total of 100 mg of antibody in 10 mL of isotonic solution. 
Tislelizumab has been aseptically filled in a single-use glass vial with a rubber stopper and 
capped by an aluminum flip-off seal cap. Each vial is packaged into a single carton box. 
The contents of the label will be in accordance with all applicable local regulatory requirements. 
The study drug must be kept at the temperature condition as specified on the label. Shaking 
should be avoided. 
Refer to the pharmacy manual for details regarding intravenous administration, accountability, 
and disposal. Refer to the Tislelizumab (BGB-A317) Investigator’s Brochure for other details 
regarding tislelizumab. 
5.1.3. 
Chemotherapy Agents  
Management (ie, handling, storage, administration, and disposal) of these products will be in 
accordance with the relevant local guidelines and/or prescribing information.  
For further details, see the manufacturer’s prescribing information. 
5.1.4. 
Ociperlimab Placebo  
Ociperlimab placebo is a sterile, preservative-free solution for infusion formulated in the same 
buffer as ociperlimab. All excipients used for the manufacture of placebo are of pharmacopeial 
grade. No animal-derived components are used in the manufacture of placebo. Each vial is 
packaged into a single carton box. 
As with ociperlimab, the contents of the label will be in accordance with all applicable local 
regulatory requirements. 
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The study drug must be kept at the temperature condition as specified on the label.  
Refer to the pharmacy manual for details regarding intravenous administration, accountability, 
and disposal. 
5.2. 
Dosage, Administration, and Compliance  
Dosing schedules for all arms, broken out by individual treatment arm, are provided in Table 3 
for the induction phase and Table 4 for the maintenance phase. Dosing administration and 
monitoring times, broken out by individual treatment arm, are provided in Table 5. 
The first dose of study drug is to be administered within 2 business days of randomization.  
Patients should receive antiemetics and intravenous hydration for chemotherapy according to the 
standard of care and manufacturer’s instructions. Due to their immunomodulatory effects, 
premedication with steroids should be limited when clinically feasible. In addition, in the event 
of chemotherapeutic agent-related skin rash, topical steroid use is recommended as treatment 
whenever it is clinically feasible. 
In special situations (eg, when the administration is prolonged to allow for management of 
adverse events or in the case of an infusion-related reaction), administration of the subsequent 
study drugs might be delayed to the second day of each cycle. 
Chemotherapy regimen may be switched in consideration of a patient’s ability to tolerate the 
treatment. The reasons for intolerability should be documented. 
All patients will be monitored continuously for AEs. Treatment modifications (eg, dose delay, 
interruption, or discontinuation) will be based on specific laboratory and AE criteria, as 
described in Section 5.5. 
Table 3: 
Selection and Timing of Dose for Each Patient (Induction Phase) 
Treatment 
arm 
Study treatment 
Dose 
Frequency and sequence of 
administration 
Route of 
administration 
Duration of 
treatment 
Arm A 
Tislelizumab 
200 mg 
Day 1 of each cycle (21 days) 
Administer first 
Intravenous 
See 
Section 3.3 
Ociperlimab 
900 mg 
Day 1 of each cycle (21 days) 
Administer after tislelizumab 
Intravenous 
See 
Section 3.3 
Histology-based 
Chemotherapy 
* 
Administer after ociperlimab * 
Intravenous 
See 
Section 3.3 
Arm B 
Tislelizumab 
200 mg 
Day 1 of each cycle (21 days) 
Administer first 
Intravenous 
See 
Section 3.3 
Placebo infusion 
N/A 
Day 1 of each cycle (21 days) 
Administer after tislelizumab 
Intravenous 
See 
Section 3.3 
Histology-based 
Chemotherapy 
* 
Administer after placebo * 
Intravenous 
See 
Section 3.3 
Abbreviations: AUC, area under the concentration-time curve; D, day; NA, not applicable 
* For patients with squamous NSCLC: carboplatin AUC 5 or 6 (D1) + paclitaxel 175 or 200 mg/m2 (D1) or nab-
paclitaxel 100 mg/m2 (D1, D8, D15) administered every 3 weeks. For patients with non-squamous NSCLC: cisplatin 
75 mg/m2 or carboplatin AUC 5 (D1) + pemetrexed 500 mg/m2 IV (D1) administered every 3 weeks. 
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Table 4: 
Selection and Timing of Dose for Each Patient (Maintenance Phase)  
Treatment 
arm 
Study treatment Dose 
Frequency and sequence of 
administration 
Route of 
administration 
Duration of 
treatment 
Patients with non-squamous NSCLC 
Arm A 
Tislelizumab 
200 mg 
Day 1 of each cycle (21 days) 
Administer first 
Intravenous 
See 
Section 3.3 
Ociperlimab 
900 mg 
Day 1 of each cycle (21 days) 
Administer after tislelizumab 
Intravenous 
See 
Section 3.3 
Pemetrexed 
500 
mg/m2 
Day 1 of each cycle (21 days) 
Administer after ociperlimab 
Intravenous 
See 
Section 3.3 
Arm B 
Tislelizumab 
200 mg 
Day 1 of each cycle (21 days) 
Administer first 
Intravenous 
See 
Section 3.3 
Placebo infusion 
N/A 
Day 1 of each cycle (21 days) 
Administer after tislelizumab 
Intravenous 
See 
Section 3.3 
Pemetrexed 
500 
mg/m2 
Day 1 of each cycle (21 days) 
Administer after placebo infusion 
Intravenous 
See 
Section 3.3 
Patients with squamous NSCLC 
Arm A 
Tislelizumab 
200 mg 
Day 1 of each cycle (21 days) 
Administer first 
Intravenous 
See 
Section 3.3 
Ociperlimab 
900 mg 
Day 1 of each cycle (21 days) 
Administer after tislelizumab 
Intravenous 
See 
Section 3.3 
Arm B 
Tislelizumab 
200 mg 
Day 1 of each cycle (21 days) 
Administer first 
Intravenous 
See 
Section 3.3 
Placebo infusion 
N/A 
Day 1 of each cycle (21 days) 
Administer after tislelizumab 
Intravenous 
See 
Section 3.3 
Abbreviations: NSCLC, non-small cell lung cancer. 
Table 5: 
Administration of Study Treatments and Monitoring Time 
Cycle 
Treatment 
arm 
Study treatment administration and monitoring times 
C1D1 and C2D1 
Arm A 
Tislelizumab infusion over 60 (± 5) minutes followed by 
ociperlimab infusion over 60 (± 5) minutes  
Patient monitoring for ≥ 120 minutes 
Arm B 
Tislelizumab infusion over 60 (± 5) minutes followed by 
placebo infusion over 60 (± 5) minutes 
Patient monitoring for ≥ 120 minutes 
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Cycle 
Treatment 
arm 
Study treatment administration and monitoring times 
C3D1 onwards 
Arm A 
Tislelizumab infusion over 30 (± 5) minutes followed by 
ociperlimab infusion over 30 (± 5) minutes  
Patient monitoring for ≥ 60 minutes 
Arm B 
Tislelizumab infusion over 30(± 5) minutes followed by placebo 
infusion over 30 (± 5) minutes Patient monitoring for 
≥ 60 minutes 
Abbreviations: C1D1, Cycle 1 Day 1; C2D1, Cycle 2 Day 1; C3D1, Cycle 3 Day 1 
Treatment Administration 
During the induction phase: 
• In Arm A, tislelizumab 200 mg will be administered followed by ociperlimab 900 mg 
and histology-based chemotherapy on Day 1 of each 21-day cycle (once every 
3 weeks). 
• In Arm B, tislelizumab 200 mg will be administered followed by a placebo infusion 
and histology-based chemotherapy on Day 1 of each 21-day cycle (once every 
3 weeks). 
During the maintenance phase in patients with non-squamous NSCLC: 
• In Arm A, tislelizumab 200 mg will be administered followed by ociperlimab 900 mg 
and pemetrexed 500 mg/m2 on Day 1 of each 21-day cycle (once every 3 weeks). 
• In Arm B, tislelizumab 200 mg will be administered followed by a placebo infusion 
and pemetrexed 500 mg/m2 on Day 1 of each 21-day cycle (once every 3 weeks). 
During the maintenance phase in patients with squamous NSCLC: 
• In Arm A, tislelizumab 200 mg will be administered followed by ociperlimab 900 mg 
on Day 1 of each 21-day cycle (once every 3 weeks). 
• In Arm B, tislelizumab 200 mg will be administered followed by a placebo infusion 
on Day 1 of each 21-day cycle (once every 3 weeks). 
All drugs will be administered by intravenous infusion through an intravenous line containing a 
sterile, non-pyrogenic, low-protein-binding 0.2 or 0.22 micron in-line or add-on filter. Specific 
instructions for product preparation and administration are provided in the pharmacy manual. 
The initial infusions (Day 1 of Cycle 1 and Cycle 2) of tislelizumab will be delivered over 
60 (± 5) minutes followed by ociperlimab/placebo delivered over 60 (± 5) minutes; if this is well 
tolerated, then the subsequent infusions of tislelizumab and ociperlimab/placebo may be 
administered over 30 (± 5) minutes, which is the shortest time period permissible for infusion. 
Tislelizumab and ociperlimab/placebo must not be concurrently administered with any other 
drug (Section 6). 
Use of a volumetric pump is recommended to control the infusion speed and to avoid potential 
infusion reactions associated with too rapid administration. The pump may not be needed if the 
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infusion speed is controlled through alternative means and consistent with approved institutional 
procedures.  
At the end of each infusion period, the line will be flushed with enough normal saline to make 
sure the complete doses of study drugs are administered. 
As a routine precaution, after infusion of all study treatment is complete on Day 1 of Cycle 1 and 
Cycle 2, patients must be monitored for ≥ 120 minutes afterward in an area with resuscitation 
equipment and emergency agents. From Cycle 3 onward, a ≥ 60-minute monitoring period is 
required in an area with resuscitation equipment and emergency agents. 
The length of the infusion period for cisplatin, carboplatin, pemetrexed, paclitaxel and 
nab-paclitaxel may also follow the approved label or local practice. The administered dose may 
be adjusted within ± 5% of the calculated dose at the investigator’s discretion. 
If the infusions of tislelizumab, ociperlimab/placebo, chemotherapy, and the premedication for 
chemotherapy cannot be managed in 1 day, it is acceptable to administer the chemotherapy drug 
infusions on Day 2 of the cycle.  
Guidelines for treatment interruption or discontinuation and for the management of imAEs and 
infusion-related reactions are provided in detail in Section 8.6 and Appendix 7. 
Refer to the pharmacy manual for detailed instructions on drug preparation, storage, and 
administration. 
5.3. 
Overdose or Incorrect Administration  
Any incorrect administration of any study drug or overdose of ociperlimab (defined as 
≥ 1800 mg in a 24-hour period) or tislelizumab (defined as ≥ 600 mg in a 24-hour period) should 
be noted in the patient’s chart and on the appropriate eCRF. AEs associated with an overdose or 
incorrect administration of study drug will be recorded on the AE eCRF. Any SAEs associated 
with an overdose or incorrect administration must be reported within 24 hours of awareness via 
the SAE reporting process described in Section 8.6.2. Supportive care measures should be 
administered as appropriate. 
5.4. 
Investigational Medicinal Product Accountability  
The investigational medicinal products (IMPs) required for completion of this study are 
ociperlimab, ociperlimab placebo, and tislelizumab. Ociperlimab, ociperlimab placebo, and 
tislelizumab will be provided by the sponsor, as required by local or country-specific guidance. 
The investigational site will acknowledge receipt of IMPs. Any damaged shipments will be 
replaced. 
Accurate records of all IMP received, dispensed, returned, and disposed of should be recorded on 
the site’s Drug Inventory Log. Refer to the pharmacy manual for details of IMP management. 
Chemotherapy drugs (ie, paclitaxel, nab-paclitaxel, carboplatin, cisplatin, pemetrexed) may be 
locally sourced by the investigational site or, in some circumstances, provided by the sponsor. 
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5.5. 
Dose Delay, Interruption, and Modification  
A dose delay is a deviation from the prescribed dosing schedule (ie, the drug is withheld beyond 
visit window). A dose interruption is an interruption of an infusion. 
Every effort should be made to administer the study drugs according to the planned dose and 
schedule. In the event of significant toxicities, dosing may be delayed and/or reduced based on 
the guidelines below. Reasons for dose reductions or delays, the supportive measures taken, and 
the outcome will be documented in the patient’s source documents and recorded in the eCRF. 
The dose modification guidelines in this section are not intended to be a substitute for clinical 
judgment. Investigators may delay or modify doses for other reasons (eg, AEs, declining body 
weight, laboratory findings) as appropriate. 
5.5.1. 
General Guidance Regarding Dose Modifications  
• Dose modifications for chemotherapy will be performed per local practice and per 
prescribing information according to the treating physician’s clinical judgment 
(Section 5.5.3). 
• Tislelizumab and ociperlimab/placebo might be delayed as defined in Section 5.5.2. 
• For any events already apparent at baseline, the dose modifications will apply 
according to the corresponding shift in toxicity grade, if the investigator considers it 
is appropriate. For example, if a patient has Grade 1 asthenia at baseline that turns to 
Grade 2 during treatment, this will be considered a shift of 1 grade and treated as 
Grade 1 toxicity for dose modification purposes. 
• If in the opinion of the investigator, a toxicity is considered to be solely due to 1 
component of the study treatment and the dose of that component is delayed or 
modified in accordance with the guidelines below, other components may be 
administered if there is no contraindication. 
• When treatment is temporarily interrupted because of toxicity, the treatment cycles 
will be restarted such that the tislelizumab and ociperlimab/placebo infusions ideally 
remain synchronized and aligned with the chemotherapy schedule.  
Dose modification guidelines for chemotherapy, as described below (Section 5.5.3), will depend 
on the severity of toxicity and an assessment of the risk versus benefit for the patient, with the 
goal of maximizing the patient’s compliance and access to supportive care. 
5.5.2. 
Dose Delay or Interruption for Ociperlimab and Tislelizumab  
There will be no dose reduction for ociperlimab or tislelizumab in this study.  
In all treatment arms, treatment with study drugs may be temporarily suspended if the patient 
experiences adverse events and requires a dose to be withheld. If temporary suspension is 
required, both study drugs (ociperlimab [or placebo] and tislelizumab) must be suspended. 
Treatment with study drugs should resume as soon as possible after the AEs recover to Grade 1 
or baseline (whichever is more severe) and within 12 weeks after the last dose of study drugs. 
Here the AEs (that cause temporary suspension as mentioned above) refer to AEs related to 
tislelizumab or ociperlimab as assessed by investigators. If an AE is not related to tislelizumab or 
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ociperlimab, the decision to delay study drugs is at the discretion of the investigators. If the 
administration of study drugs can resume within ≤ 10 days of the Day 1 of the cycle, study drugs 
should be administered in the current cycle. If study drugs need to be withheld for > 10 days 
within the cycle, study drugs should be omitted from the current cycle and administration should 
restart in the next cycle. If the toxicity is assessed as not related to chemotherapy, the 
chemotherapy regimen(s) may be administered as scheduled in the current cycle.  
If the patient is unable to resume study drugs within 12 weeks after the last dose of study drugs, 
then the patient should be discontinued from study treatment. If the patient is not able to resume 
study drugs ≤ 12 weeks after the last dose for unforeseen non-drug-related reasons, continued 
treatment may be allowed if approved by the medical monitor. 
If a patient is benefiting from the study treatment while meeting the discontinuation criteria, 
resumption of study treatment may occur after discussion and agreement with the medical 
monitor. 
Specific treatment modifications to manage study drug-related toxicities, such as to imAEs and 
infusion-related reactions, are described in Section 8.6 and Appendix 7. 
5.5.3. 
Dose Delay or Modifications for Chemotherapy  
Dose modifications for chemotherapy should be performed per prescribing information and per 
local practice according to the treating physician’s clinical judgment. 
If temporary suspension is required for one component of the chemotherapy regimen, the 
investigator will decide whether the remaining chemotherapy regimen(s) will be administered, 
taking into consideration the benefits and risks of continuing the regimen(s). Baseline body 
weight is used to calculate the required chemotherapy doses. Dose modifications are required if 
the patient’s body weight changes by > 10% from baseline (or the new reference body weight). 
The dose is not recommended to be modified for any body weight change of less than 10% 
except for carboplatin. Dosage of carboplatin should be calculated based on the most recent 
blood creatinine value per the local approved label.  
Chemotherapy-related toxicities must be resolved to baseline or Grade 1 prior to administering 
the next dose, except for alopecia or Grade 2 fatigue. A maximum of 2 dose reductions is 
permitted for each chemotherapeutic agent, except for carboplatin for which only one dose 
reduction is permitted. Once the dose has been decreased, it should remain reduced for all 
subsequent administrations or further reduced if necessary. If additional reductions are required, 
that chemotherapeutic agent must be discontinued. Chemotherapy treatment may be delayed up 
to 21 days if the reason for the delay is toxicity/adverse event. All subsequent chemotherapy 
should be rescheduled according to the start date of the last chemotherapy cycle. 
Patients will be allowed to switch from cisplatin to carboplatin chemotherapy if they become 
ineligible for cisplatin due to toxicity and if all of the following criteria are met (no more than 
6 cycles of chemotherapy will be administered).  
• Patients have completed at least one cycle of cisplatin treatment. 
• The switch is not due to the reason of suspected of confirmed disease progression by 
RECIST v1.1. 
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Switching is allowed only once during the whole study. No switch from carboplatin to cisplatin 
is allowed. If a dose delay is required for the patients to recover from the cisplatin-related 
toxicity, carboplatin should be started within 1 cycle (3 weeks) from the anticipated treatment 
date.  
Reasons for platinum switch should be documented in source documents and eCRF. 
SELECTED PRECAUTIONS: 
• Neutropenia: Fever or other evidence of infection must be assessed promptly and 
treated aggressively following the local clinical practice and/or the guidelines. 
• Renal toxicity:  
o Carboplatin should not be administered to patients whose creatinine clearance is 
< 45 mL/min.  
o Nephrotoxicity is common with cisplatin. Encourage oral hydration. Avoid 
nephrotoxic drugs such as aminoglycoside antibiotics. 
o Pemetrexed should not be administered to patients whose creatinine clearance is  
< 45 mL/min.  
• Ototoxicity and sensory neural damage should be assessed prior to each cycle.  
• For toxicities not listed above, dose modifications are permitted per local standards.  
Guidance regarding dose modifications for certain toxicities is presented in detail in Appendix 8. 
These serve as guidelines and do not replace investigator judgment and applicable local label 
recommendations. 
For anemia and thrombocytopenia that have not recovered to baseline or ≤ Grade 1 (whichever is 
more severe), chemotherapy should be given as planned when the patient can tolerate it and will 
have clinical benefit as assessed by the investigator per local practice. 
For other situations besides the above, please contact the sponsor medical monitor. 
5.5.4. 
Criteria for Discontinuing Chemotherapy Regimens  
The drug assessed as not related to the adverse reaction may be continued at the investigator’s 
discretion, provided the current toxicity is resolved. Except where specified above, 
chemotherapy drug(s) in the platinum-based doublet regimen should be discontinued for any of 
the following: 
• Any Grade 3 or 4 peripheral neuropathy 
• Persistent Grade 3 paresthesia 
• Grade 3 or 4 drug-related thrombocytopenia associated with clinically significant 
bleeding 
• Any drug-related liver function test abnormality value that meets any of the following 
criteria requires discontinuation: 
o AST or ALT > 5 to 10 x ULN for > 2 weeks  
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o AST or ALT > 10 x ULN 
o Total bilirubin > 5 x ULN  
o Concurrent AST or ALT > 3 x ULN and total bilirubin > 2 x ULN 
• Any cisplatin-related decrease in CrCL to < 30 mL/min requires discontinuation of 
cisplatin. 
• Any drug-related AE that recurs after 2 prior dose reductions (or 1 prior reduction for 
carboplatin) for the same drug-related AE requires discontinuation of the drug(s). 
• Any Grade 3 or 4 drug-related hypersensitivity reaction or infusion reaction requires 
discontinuation of the drug(s) assessed to be causing the reaction. The drug assessed 
as not related to the hypersensitivity reaction or infusion reaction may be continued. 
• Any Grade 4 AE that the investigator considers related to study drug and 
inappropriate to be managed by dose reduction(s) requires discontinuation of drug(s). 
The drug not assessed to be related to the event may be continued. 
For toxicities not listed above, the investigator would determine whether the chemotherapy 
regimen should be discontinued per clinical judgment, patient’s well-being, and local standards. 
5.6. 
Blinding  
This is a randomized, investigator- and patient-blinded, sponsor-unblinded, Phase 2 study. 
Patients will be randomized in a 1:1 ratio to receive ociperlimab + tislelizumab + chemotherapy 
(Arm A) or placebo + tislelizumab + chemotherapy (Arm B). Patients, investigators, and site 
staff will remain blinded to study treatments but the sponsor will be unblinded. 
Every effort should be made to avoid unblinding the patient’s treatment assignment unless 
necessary. Unblinding may be indicated and permissible only in specific situations as described 
below and if necessary for the patient’s welfare. Unblinding would occur through Interactive 
Response Technology (IRT) as per the instructions in the IRT site user manual. If unblinding has 
occurred, the sponsor must be notified immediately using the Unblinding Event Form. To ensure 
the continued blinding of blinded study personnel, this form will not include the treatment 
assignment. Patients will remain on study for safety follow-up and, if applicable, for survival 
follow-up. 
5.6.1. 
Emergency Unblinding  
In case of an emergency, such as when a patient has an AE suspected to be related to the 
investigational drug product and for which management of the AE with one or more drug 
products with substantial toxicity or invasive procedures is being considered, unblinding can 
occur. The investigator has the sole responsibility for determining if unblinding of a patient’s 
treatment assignment is warranted. Patient safety must always be the first consideration in 
making such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every effort to inform the medical monitor of their intent before 
unblinding a patient’s treatment assignment unless this could delay emergency treatment of the 
patient. If a patient’s treatment assignment is unblinded, the sponsor must be notified 
immediately. 
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The investigator performs the emergency unblinding for AEs through an IRT System. Unblinded 
patients may remain on study treatment at the discretion of the investigator in consultation with 
the medical monitor and only as permissible per definitions in the study protocol. 
5.6.2. 
Nonemergency Unblinding  
Nonemergency unblinding to study treatment administration may occur on an individual patient 
basis when a new anticancer treatment is being considered and only after consultation with and 
written approval from the medical monitor at the time of 1) confirmed disease progression and 
EOT, or 2) EOT due to toxicity. 
Nonemergency unblinding must be formally requested from the sponsor via the BeiGene 
Unblinding Form.  
5.6.3. 
Inadvertent Unblinding  
Every effort will be made to blind both the patient and the investigator/site staff to the identity of 
the treatment assignment (ie, ociperlimab + tislelizumab + chemotherapy [Arm A] or placebo + 
tislelizumab + chemotherapy [Arm B]), but the inadvertent unblinding of a patient may occur. 
Inadvertent unblinding events must be reported using the BeiGene Unblinding Form within 
1 business day of awareness. To ensure the continued blinding of study personnel, this form and 
subsequent CRFs must not include the treatment assignment.  
If an investigator, site personnel (eg, those performing assessments), or patient is unblinded, the 
unblinding will not be a sufficient cause (in and of itself) for that patient to be discontinued from 
study therapy or excluded from any safety or efficacy analyses. 
Additionally, there may be ethical reasons to have the patient remain on the study treatment. For 
patients to continue study treatment in the event of unblinding, the investigator must obtain 
specific approval from the medical monitor. 
5.6.4. 
Unblinding After Primary Analysis or Completion of the Trial  
Investigators, site personnel, and patients will be unblinded to treatment arms and PD-L1 results 
at the time of primary analysis or the sponsor’s decision to close the trial for safety or non-safety 
reasons. Placebo administration will be discontinued after unblinding.  
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6. 
PRIOR AND CONCOMITANT THERAPY  
6.1. 
Prior Therapy  
As specified in Section 4, patients should not have received prior chemotherapy, targeted 
therapy, biologic therapy, immunotherapy, or investigational agent used to control locally 
advanced or metastatic NSCLC, or prior therapy targeting T-cell costimulation or checkpoint 
pathways in locally advanced or metastatic NSCLC.  
6.2. 
Concomitant Therapy  
6.2.1. 
Permitted Concomitant Medications/Procedures  
Most concomitant medications and therapies deemed necessary and in keeping with local 
standards of medical care at the discretion of the investigator for supportive care (eg, antiemetics, 
antidiarrheals) and in a patient’s interest are allowed. Opiates and other medication required for 
palliative management of patients are allowed. Patients must notify the investigator of all 
concurrent medications including herbal remedies used during the study. 
6.2.1.1. 
Systemic Corticosteroids  
Systemic corticosteroids given for the control of imAEs must be tapered gradually (see 
Appendix 7) and be at non-immunosuppressive doses (≤ 10 mg/day of prednisone or equivalent) 
before the next study drug(s) administration. The short-term use of steroids as prophylactic 
treatments (eg, patients with contrast allergies to diagnostic imaging contrast dyes) is permitted. 
6.2.1.2. 
Hepatitis B Treatment  
Patients with active hepatitis B, defined as HBV DNA ≥ 500 IU/mL at screening, must initiate 
antiviral treatment 2 weeks before randomization, and continue until 6 months after the last dose 
of study drug(s). Patients should continue effective antiviral treatment during the study to 
decrease potential viral reactivation risk. Tenofovir and entecavir are recommended in the 
American Association for the Study of Liver Disease (AASLD) guideline because they lack 
resistance with long-term use (Terrault et al 2016). The investigator may use other antiviral 
agents, if appropriate, following local guidelines. However, interferon-based therapy for hepatitis 
B is not permitted on study. 
Management of prophylactic antiviral therapy for patients with inactive, treated, and stable 
hepatitis B (HBV DNA < 500 IU/mL) is at the discretion of the investigator, as aligned with 
local guidance. Such medications must be documented in the patient’s chart and recorded in the 
eCRF. Patients receiving antivirals at Screening should be treated for > 2 weeks before 
randomization and continue treatment during the study and for 6 months after study drug 
treatment discontinuation. 
6.2.1.3. 
Hepatitis C Treatment  
Patients with detectable HCV RNA who are receiving treatment at screening should remain on 
continuous, effective antiviral therapy during the study. Investigators can consider treatment with 
sofosbuvir alone or in combination with other antivirals following the AASLD guideline or the 
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local guidelines as appropriate (AASLD/IDSA HCV Guidance Panel 2021). However, 
interferon-based therapy for HCV is not permitted on study. Patients who are given antiviral 
therapy must initiate treatment > 2 weeks before randomization. 
6.2.1.4. 
Radiation Therapy  
Palliative (limited-field) radiation therapy is permitted, but only for pain control or prophylaxis 
of bone fracture to sites of bone disease present at baseline provided the following criteria are 
met: 
• Repeat imaging demonstrates no new sites of bone metastases 
• The lesion being considered for palliative radiation is not a target lesion for RECIST 
v1.1 
• The case is discussed with the medical monitor, and the medical monitor agrees that 
the conditions required to receive palliative radiation are met 
Additionally, palliative radiation or other focally ablative therapy for other nontarget sites of the 
disease is permitted if clinically indicated per investigators’ discretion. The medical monitor 
should be informed of the on-study radiotherapy. These patients should have a tumor assessment 
of the lesion(s) before receiving the radiotherapy in order to rule out progression of disease. 
It is not required to withhold study treatment during palliative radiotherapy. 
6.2.1.5. 
COVID-19 Vaccines  
Vaccines for COVID-19 are allowed except for any live vaccine that may be developed. It is 
recommended to avoid COVID-19 vaccination within 72 hours before or after study drug 
administration during the first 2 treatment cycles, and within 24 hours before or after study drug 
administration thereafter (ie, from Cycle 3 onwards). 
Vaccinations are considered a concomitant medication and hence should be entered on the eCRF. 
Instead of generic language (eg, “COVID-19 vaccination”), the specific COVID-19 vaccine 
should be recorded eg, mRNA-1273 vaccine (Moderna), BioNTech vaccine (Pfizer), etc. 
6.2.2. 
Prohibited Concomitant Medications/Procedures  
The following medications are prohibited during screening and through the EOT visit: 
• Live vaccines ≤ 28 days before randomization and ≤ 60 days after the last dose of 
study drug(s) are prohibited. 
Note: Seasonal vaccines for influenza are generally inactivated vaccines and are 
allowed. Intranasal vaccines are live vaccines and are not allowed.  
• Any concurrent anti-cancer therapy, including chemotherapy, hormonal therapy, 
immunotherapy, standard anticancer agents, or investigational anticancer agents 
• Herbal remedies for the treatment of cancer or Chinese patent medicines for use as 
anticancer treatment (regardless of cancer type) (Appendix 13). 
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• Herbal remedies with immune-stimulating properties (eg, mistletoe extract) or that 
are known to potentially interfere with liver or other major organ functions 
(eg, hypericin) 
6.2.3. 
Restricted Concomitant Medications/Procedures  
The following medications are restricted during the study: 
• Immunosuppressive agents (except to treat a drug-related AE) 
• Systemic corticosteroids > 10 mg daily (prednisone or equivalent), except to treat or 
control a drug-related AE (per protocol) or for short-term use as prophylactic 
treatment 
• Patients should not abuse alcohol or other drugs during the study 
• Use of potentially hepatotoxic drugs in patients with impaired hepatic function should 
be carefully monitored 
• Radiation therapy is not allowed, except for palliative radiation therapy described in 
Section 6.2.1.4 
• Non-steroidal anti-inflammatory drugs (eg, aspirin, ibuprofen, diclofenac, celecoxib, 
naproxen, indomethacin, or piroxicam) are prohibited ≤ 5 days before and 2 days 
after pemetrexed therapy. If concomitant administration of a non-steroidal 
anti-inflammatory drug is necessary, patients should be monitored closely for 
toxicity, especially myelosuppression, renal, and gastrointestinal toxicity. 
6.3. 
Potential Interactions Between the Study Drugs and Concomitant 
Medications  
The potential for drug-drug interactions between the study drugs (ociperlimab and tislelizumab), 
standard chemotherapy, and small-molecule drug products is very low, given that the study drugs 
are therapeutic monoclonal antibodies. The study drugs are unlikely to have an effect on 
drug-metabolizing enzymes or transporters because they are expected to degrade into amino 
acids and recycle into other proteins. 
Refer to the drug-drug interaction section in the manufacturer’s prescribing information for the 
influence of the respective chemotherapy agents on drug metabolizing enzymes or transporters. 
For example, the metabolism of paclitaxel is catalyzed by cytochrome P-450(CYP)2C8 and 
CYP3A4. Caution should be exercised when administering paclitaxel or nab-paclitaxel 
concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4 
(eg, inhibitors ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, 
gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir, or inducers rifampicin, 
carbamazepine, phenytoin, efavirenz, and nevirapine). When strong CYP2C8 and CYP3A4 
inhibitors are co-administered with nab-paclitaxel, the toxicities may be exacerbated and the 
investigator should closely monitor for them. Please refer to the list of strong CYP2C8 and 
CYP3A4 inhibitors (Flockhart 2007; FDA Drug Development and Drug Interactions) and the 
prescribing information of paclitaxel and nab-paclitaxel for more information. 
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Renal function decreases would result in an increase in systemic exposure of pemetrexed. 
Pemetrexed should not be administered to patients whose creatinine clearance is < 45 mL/min. 
Caution should be exercised when administering pemetrexed concurrently with non-steroidal 
anti-inflammatory drugs to patients whose creatinine clearance is < 80 mL/min.  
The major route of elimination of carboplatin is renal excretion. The renal effects of nephrotoxic 
compounds may be potentiated by carboplatin. 
Refer to the drug-drug interaction section in the manufacturer’s prescribing information for the 
influence of the respective chemotherapy agents on drug-metabolizing enzymes or transporters. 
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7. 
STUDY ASSESSMENTS AND PROCEDURES  
A table of scheduled study assessments is provided in Appendix 1. Patients will be closely 
monitored for safety and tolerability throughout the study. All assessments must be performed 
and documented in the medical record for each patient. 
Dosing will occur only if the clinical assessment and local laboratory test values (that must be 
available before any dosing) have been reviewed and found to be acceptable per protocol 
guidelines.  
7.1. 
Screening  
Screening evaluations will be performed within 28 days before randomization. The screening 
period begins on the first day a screening procedure is conducted. Screening evaluations may be 
repeated as needed within the screening period; the investigator is to assess patient eligibility 
according to the latest screening assessment results. 
Results of standard-of-care tests or examinations performed before obtaining informed consent 
and ≤ 28 days before randomization may be used for the purposes of screening rather than 
repeating the standard-of-care tests unless otherwise indicated. 
Procedures conducted only during the Screening Visit are described in this section. For the 
description of other assessments that are conducted during screening, as well as throughout the 
study, refer to the Safety Assessments (Section 7.4), Tumor and Response Evaluations 
(Section 7.5) and Biomarkers (Section 7.7) sections. The PK sampling schedule is shown in 
Appendix 1. 
Rescreening under limited conditions may be allowed after consultation with the sponsor, 
eg, when a patient narrowly misses a laboratory criterion and it is correctable and not due to 
rapidly deteriorating condition or disease progression. Rescreening is allowed only once. 
7.1.1. 
Informed Consent and Screening Log  
Voluntary, written informed consent for participation in the study must be obtained before 
performing any study-specific procedures at the Screening Visit (Section 7.1, main ICF). 
Informed consent forms for enrolled patients and for patients who are screened but not enrolled 
will be maintained at the study site.  
All screening evaluations must be completed and reviewed to confirm that patients meet all 
eligibility criteria before randomization or first dose of study drug. 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. 
7.1.2. 
Patient Numbering  
After obtaining informed consent, study site personnel will access the IRT system to assign a 
unique patient number to a potential study participant. Patients who are rescreened (see 
Section 7.1) will be assigned a new patient number. Screening numbers assigned to the same 
patient within the IRT system will be linked.  
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7.1.3. 
Pulmonary Function Tests  
Pulmonary function testing including spirometry and assessment of oxygenation, at a minimum, 
pulse oximetry at rest and with exercise, or alternatively, assessment of diffusion capacity, are to 
be performed for all patients during the screening period to assist the determination of suitability 
on the study. Respective test results need to be submitted to the sponsor. 
For test results indicative of significantly impaired pulmonary function, eg, resting pulse 
oximetry < 90% on room air and further desaturation upon exercise, forced expiratory volume 
(FEV1) < 60% or diffusing capacity of the lungs for carbon monoxide (DLCO) (if performed) 
< 60% of age and sex adjusted predicted performance levels (Pellegrino et al 2005). 
Tests may be repeated as clinically indicated while on study. 
7.1.4. 
Demographic Data and Medical History  
Demographic data will include age or date of birth, sex, and self-reported race/ethnicity.  
Ethnic factors could influence the effects (safety and efficacy) of medicines and the risk/benefit 
assessment in different populations. Race and Ethnicity data are collected in the Clinical Data 
Interchange Standards Consortium (CDISC) Study Data Tabulation Model (SDTM, 
Implementation Guide v3.2), in accordance with ICH guidance (ICH E5 1998, ICH E17 2017) 
adopted by the EMA and FDA, to support population PK analysis, which is a well-established, 
quantitative method that can quantify and explain the variability in drug concentrations among 
patients. Variability can be attributed to intrinsic factors (eg, body weight, age, sex, 
race/ethnicity), or to extrinsic factors (eg, concomitant medications). In some cases, intrinsic or 
extrinsic factors lead to clinically relevant changes in drug concentrations that require a change 
in the dose or dosing regimen. Results from population PK analyses will be incorporated into 
drug product labeling to provide guidance on the dose or dosing regimen including any potential 
dose adjustment in some subpopulations (eg, race or ethnic group). Therefore, collecting 
race/ethnicity data in the study is essential to understand whether race/ethnicity could influence 
the PK, safety, and/or efficacy. 
Medical history includes any history of clinically significant disease, surgery, or cancer history; 
reproductive status (ie, of childbearing potential or no childbearing potential); history of alcohol 
and/or tobacco consumption (ie, former or current or never); and all medications (eg, 
prescription drugs, over-the-counter drugs, herbal or homeopathic remedies, nutritional 
supplements) used by the patient within 28 days before randomization.  
Cancer history will include an assessment of prior surgery, prior radiotherapy, and prior drug 
therapy including start and stop dates, best response, and reason for discontinuation. Data from 
radiographic studies performed before study entry may be collected for review by the 
investigator. 
7.1.5. 
Contraception and Women of Childbearing Potential  
Childbearing potential is defined as being physiologically capable of becoming pregnant (ie, 
fertile, following menarche and until becoming postmenopausal unless permanently sterile). 
Refer to Appendix 10 for contraception guidelines and definitions of “women of childbearing 
potential” and “no childbearing potential.” 
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7.1.6. 
HIV Serology Test  
An HIV serology test (antigen and/or antibodies) will be conducted at baseline for patients with 
unknown HIV status. 
7.1.7. 
COVID-19 Test  
A COVID-19 test may be conducted according to local practice 
7.2. 
Enrollment  
7.2.1. 
Confirmation of Eligibility  
Prior to enrollment, the investigator is responsible for assessing and confirming that each patient 
meets all inclusion eligibility criteria for this study and that none of the exclusion criteria apply. 
All results from the screening procedures and relevant medical history must be available and 
reviewed by the investigator before eligibility can be determined.  No eligibility waivers will be 
granted. 
Sponsor verification of patient eligibility will be managed by way of source data verification in 
accordance with International Council for Harmonisation (ICH) E6. 
The sponsor’s medical monitor will support the investigator and/or site staff by answering any 
queries or questions relating to protocol eligibility criteria.  
7.2.2. 
Enrollment/Randomization  
Site personnel will access the IRT system to randomize to treatment assignment and to enable 
study drug dispensation. Study treatment must start within 2 business days after 
randomization/treatment assignment.  
7.3. 
Study Drug Dispensation  
All study drugs will be dispensed and administered as described in Section 5.2. 
7.4. 
Safety Assessments  
7.4.1. 
Vital Signs, Height, and Weight  
Vital signs will include measurements of body temperature (˚C), pulse rate, and blood pressure 
(systolic and diastolic). Pulse rate and blood pressure will be collected in patients after resting for 
10 minutes. Vital signs will be recorded at screening, on Day 1 of each cycle, and at the EOT 
Visit (Appendix 1). 
The patient’s vital signs are required to be recorded within 60 minutes before, during, and 
30 minutes after completion of study drug infusion on Cycle 1 Day 1. For subsequent infusions, 
vital signs will be collected within 60 minutes before infusion and, if clinically indicated, during 
and 30 minutes after the completion of infusion. 
Height will be recorded at screening only. Weight will be recorded at screening, on Day 1 of 
each cycle, and at the EOT Visit. 
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7.4.2. 
Physical Examinations  
During the Screening Visit, a complete physical examination will be conducted including 
evaluations of 1) head, eyes, ears, nose, throat, 2) cardiovascular, 3) dermatological, 
4) musculoskeletal, 5) respiratory, 6) gastrointestinal, and 7) neurological systems. Any 
abnormality identified during screening will be graded according to NCI-CTCAE v5.0 and 
recorded on the medical history eCRF with appropriate disease/condition terms. 
At subsequent visits (and as clinically indicated), limited, symptom-directed physical 
examinations will be performed. New or worsened clinically significant abnormalities are to be 
recorded as AEs on the eCRF. Refer to Section 8.3 regarding AE definitions and reporting and 
follow-up requirements. 
7.4.3. 
Eastern Cooperative Oncology Group Performance Status  
ECOG Performance Status (Appendix 3) will be assessed during the study as specified in 
Appendix 1. 
7.4.4. 
Laboratory Safety Tests  
Local laboratory assessments of serum chemistry, hematology, coagulation, and urinalysis 
described in Appendix 2 will be conducted and collected at the timepoints shown in Appendix 1. 
If laboratory tests of serum chemistry (including liver function), hematology, and coagulation at 
screening are performed > 7 days before randomization, these tests must be repeated within 
3 days prior to Cycle 1 Day 1. Hematology, serum chemistry (including liver function tests), and 
coagulation as specified in Appendix 2 should be performed on Day 1 of each cycle, and at the 
EOT Visit (Appendix 1).  
In addition, for patients with squamous NSCLC receiving nab-paclitaxel during the induction 
phase (first 4 to 6 cycles), hematology will also be performed weekly on Day 8 and Day 15 of 
each cycle before the administration of nab-paclitaxel.  
The required weekly hematology and serum chemistry tests may take place at an alternative 
hospital/clinic near the patient’s home, at the investigator’s discretion. The investigator’s 
permission and choice of hospital/clinic should be documented in the patient’s source documents 
and the medical monitor must be notified. Only test results from previously approved 
hospitals/clinicals will be accepted. 
After Cycle 1, lab assessments are to be done, results are to be reviewed within 48 hours before 
study drug administration. 
Furthermore, the following tests will be performed as specified in Appendix 1: 
• Urine or serum pregnancy test 
• Thyroid function testing (thyroid stimulating hormone [TSH], free T3, free T4) 
• Hepatitis serology (Section 7.4.7) 
• Cardiac enzyme monitoring (Section 7.4.4.1) 
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Details about sample collection and shipment will be provided in a separate instruction manual. 
Investigators may use results from local laboratories for assessing eligibility, safety monitoring, 
and dosing decision. 
7.4.4.1. 
Cardiac Enzyme Monitoring  
Although immune-related myocarditis is a rare complication of immune checkpoint inhibitors, 
serum creatinine kinase (CK) and CK cardiac muscle isoenzyme (CK-MB) is monitored 
(Appendix 2) to protect study participants and to quantify the risk of muscle inflammation (see 
Appendix 1 for the blood collection schedule and Appendix 7 for guidelines for management of 
suspected immune-related myocarditis). If laboratory tests of cardiac enzymes at screening are 
performed > 7 days before randomization, these tests must be repeated within 3 days prior to 
Cycle 1 Day 1. Serum troponins may be substituted per local guidelines if used consistently 
throughout the study. 
7.4.5. 
Electrocardiograms  
For safety monitoring purposes, the investigator must review, sign, and date all ECG tracings. 
Paper or electronic copies of ECG tracings will be kept as part of the patient's permanent study 
file at the site. 
The ECG recordings will be obtained during screening, the EOT Visit, and as clinically indicated 
at other timepoints (Appendix 1). When coinciding with blood draws at the same timepoint, ECG 
assessment should be performed before blood draws. Patients should rest in a semi-recumbent 
supine position for at least 10 minutes before ECG collection. 
7.4.6. 
Adverse Events  
AEs will be graded and recorded throughout the study according to NCI-CTCAE v5.0. 
Characterization of toxicities will include severity, duration, and time to onset. 
All AEs, including SAEs, will be collected as described in Section 8.6. 
7.4.7. 
Hepatitis B and C Testing  
Testing will be performed by a local laboratory at screening and will include HBV/HCV 
serology (HBsAg, hepatitis B surface antibody [HBsAb], hepatitis B core antibody [HBcAb], 
and HCV antibody). In the case of active HBV or HCV infection, these tests will be followed by 
viral load assessment (HBV DNA and HCV RNA). 
Inactive hepatitis B surface antigen (HBsAg) carriers and patients with treated and stable 
hepatitis B (HBV DNA < 500 IU/mL or < 2500 copies/mL) can be enrolled. Patients with 
detectable HBsAg or detectable HBV DNA should be managed per treatment guidelines. 
Patients receiving antivirals at screening should have been treated for > 2 weeks before 
randomization. Patients who have detectable HBV DNA at screening will perform a viral load 
test every 4 cycles (eg, Day 1 of Cycles 5, 9, 13). 
Patients with a negative HCV antibody test at screening or positive HCV antibody test followed 
by a negative HCV RNA test at screening can be enrolled. The HCV RNA test will be performed 
only for patients testing positive for HCV antibody. Patients receiving antivirals at screening 
should have been treated for > 2 weeks before randomization. Patients who had a positive 
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antibody test at screening will perform a viral load test every 4 cycles (eg, Day 1 of Cycles 5, 
9, 13). 
7.5. 
Tumor and Response Evaluations  
Tumor imaging will be performed within 28 days before randomization. Radiologic images 
captured as standard of care before obtaining written informed consent and ≤ 28 days before 
randomization may be used rather than repeating tests. During the study, tumor imaging will be 
performed every 9 weeks (± 7 days) from randomization for the first 52 weeks and then every 
12 weeks (± 7 days) based on RECIST v1.1. Tumor assessments are required to be performed on 
schedule regardless of whether study treatment has been administered or held; they should not be 
adjusted for possible delays in cycles. Tumor assessments should continue until radiologic 
disease progression as determined by the investigators. Patients who discontinue study treatment 
early for reasons other than radiologic disease progression (eg, toxicity) will continue to undergo 
tumor assessments following the original plan until the patient begins a subsequent anticancer 
treatment, experiences radiologic disease progression or death, withdraws consent, is lost to 
follow-up, or until the study terminates, whichever occurs first. 
Screening assessments and each subsequent assessment of the tumor must include CT scans 
(with oral/intravenous contrast, unless contraindicated) or MRI of the chest, abdomen, and 
pelvis. Other known or suspected sites of disease must be included in the imaging assessments 
(eg, neck or extremities). 
All measurable and evaluable lesions should be assessed and documented at the Screening Visit 
and reassessed at each subsequent tumor evaluation. The same radiographic procedure used to 
assess disease sites at screening is required to be used throughout the study (eg, the same contrast 
protocol for CT scans or MRI). 
• Imaging of the brain (preferably MRI) at baseline is required for all screened patients. 
Screening evaluations will be performed within 28 days before randomization. 
• If a patient is known to have a contraindication to CT contrast media or develops a 
contraindication during the study, a non-contrast CT of the chest plus a 
contrast-enhanced MRI (if possible) of the abdomen and pelvis should be performed. 
• If a CT scan for tumor assessment is performed on a positron emission tomography 
(PET)/CT scanner, the CT acquisition must be consistent with the standards of a 
diagnostic CT scan. 
• Bone scans (Technetium-99m [Tc-99m]) or PET should be performed at screening if 
clinically indicated. If bone metastases are present at screening and cannot be seen on 
CT or MRI scans, Tc-99m or PET bone scans should be repeated when a CR is 
suspected in target lesion or when progression in bone is suspected. 
• CT scans of the neck or extremities should be performed at screening only if 
clinically indicated and should be followed throughout the study if there is evidence 
of metastatic disease in these regions at screening. 
• At the investigator’s discretion, other methods of assessment of target lesions and 
nontarget lesions per RECIST v1.1 may be used. 
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Response will be assessed by the investigators using RECIST v1.1 (see Appendix 4). The same 
evaluator should perform assessments, if possible, to ensure internal consistency across visits. 
After first documentation of response (CR or PR), confirmation of tumor response should occur 
at 4 weeks or later after the first response or at the next scheduled assessment timepoint.  
At the investigator’s discretion, patients may continue their assigned treatment after PD has been 
confirmed by the investigator per RECIST v1.1. To continue treatment, the criteria for treatment 
beyond disease progression in Section 3.3 must be met. In both arms, tislelizumab in 
combination with ociperlimab (or placebo) treatment beyond the initial investigator-assessed, 
RECIST v1.1-defined PD is permitted provided that the patient has investigator-assessed clinical 
benefit and is tolerating the treatment. Continuation of chemotherapy treatment after initial 
disease progression will be at the discretion of the investigator. 
Tumor assessment should continue as planned in patients receiving tislelizumab in combination 
with ociperlimab (or placebo) beyond initial investigator-assessed progression. Tumor 
assessment in such patients should continue until study treatment discontinuation. 
Tumor assessments are required to be performed on schedule regardless of whether study 
treatment has been administered or held. That is, assessments should not be adjusted for delays 
in cycles. 
7.6. 
Pharmacokinetic and Antidrug Antibody Testing  
Blood samples will be collected for characterization of ociperlimab and tislelizumab PK. The 
serum samples will be assayed for ociperlimab and tislelizumab concentrations using validated 
immunoassays. Checkpoint inhibitor drugs may elicit an immune response. Patients with signs of 
any potential immune response to study drug will be closely monitored (Appendix 7). Validated 
screening and confirmatory assays will be employed to detect ADAs at multiple timepoints 
throughout the study (see Appendix 1). The immunogenicity evaluation will utilize a risk-based 
immunogenicity strategy (Koren et al 2008; Worobec and Rosenberg 2004a; Worobec and 
Rosenberg 2004b) to characterize ADA responses to tislelizumab and ociperlimab in support of 
the clinical development program.  
Shipping, storage, and handling of samples for the assessment of ociperlimab and tislelizumab 
PK and ADA assays will be managed through a central laboratory. Refer to the laboratory 
manual for instructions.  
PK and ADA samples will be collected at the timepoints indicated in Appendix 1. 
7.7. 
Biomarkers  
Shipping, storage, and handling of blood, archival tumor, fresh tumor, and leftover tumor tissue 
for the assessment of biomarkers will be managed through a central laboratory. Refer to the 
laboratory manual for details of sample handling. 
Biomarker analyses in tumor tissues will include but not be limited to the expression of TIGIT, 
CD226, CD155, CD112, PD-L1, GEP, TMB, gene mutations, MSI, and TILs to explore potential 
predictive and prognostic biomarkers and mechanisms of resistance. For sites in mainland China, 
tissue sample testing will be limited to the expression of TIGIT, CD226, CD155, CD112, PD-L1, 
GEP, TMB, gene mutations, MSI, and TILs at baseline and at disease progression/reoccurrence. 
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Archival tumor tissues (formalin-fixed paraffin-embedded blocks or approximately 6 to 
15 freshly cut unstained slides) need to be sent to the central laboratory during Screening for 
central immunohistochemistry assay of PD-L1 status using the central laboratory-validated 
PD-L1 (SP263) assay (preferably from the same block used for local PD-L1 testing). Archival 
tissue sample for retrospective biomarkers testing can be delivered after the screening period. An 
additional ≥ 6 freshly cut unstained slides are required if non-squamous NSCLC patients with 
unknown EGFR status will be tested at a central laboratory. 
If no archival samples are available, a fresh tumor biopsy at baseline is mandatory. For fresh 
biopsy specimens, acceptable samples include core needle biopsies for deep tumor tissue or 
excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal 
lesions.  
Tumor tissue should be of good quality based on total and viable tumor content. Fine-needle 
aspiration, brushing, cell pellets from pleural effusion, and lavage samples are not acceptable. 
Patients who have progressive disease will be asked to provide an optional biopsy at the EOT 
Visit (Appendix 1) from accessible tumor sites to obtain samples to explore the mechanism of 
resistance. If feasible, any follow-up biopsy should be ideally taken from the same tumor lesion 
as the baseline biopsy if one was provided. Written patient consent is required for fresh tumor 
biopsies. 
Blood samples will be taken predose on Day 1 of Cycle 1, predose on Day 1 of Cycle 3, and at 
the EOT Visit after disease progression to evaluate biomarkers including, but not limited to, 
circulating tumor DNA (ctDNA), TMB, MSI, gene mutations, and EVs in blood (Appendix 1). 
For sites in mainland China, blood-based biomarkers will be limited to ctDNA, TMB, MSI, gene 
mutations, and EVs.  
7.8. 
Patient-Reported Outcomes  
Patients will be asked to complete questionnaires before any clinical activities (including blood 
draws or imaging scans) are performed during on-study clinic visits according to the schedule in 
Appendix 1. These questionnaires will include the EORTC-QLQ-C30 (Appendix 11) and its 
lung cancer module QLQ-LC13 (Appendix 12). The questionnaires will be provided in the 
patient’s preferred language. 
7.9. 
Visit Windows  
All visits must occur within ± 3 days from the scheduled date, unless otherwise noted 
(see Appendix 1). All assessments will be performed on the day of the specified visit unless an 
acceptable time window is specified. Assessments scheduled on the day of study treatment 
administration (Day 1) of each cycle should be performed before study treatment infusion/dose 
unless otherwise noted. Laboratory results are required to be reviewed before dosing. 
If the timing of a protocol-mandated study visit coincides with a holiday, weekend, or other 
event, the visit should be scheduled on the nearest feasible date (the visit window is provided in 
Appendix 1). 
A cycle is defined as every 21 days. In the induction phase, subsequent visits should be 
conducted according to a new 21-day schedule based on the starting date of the patient’s last 
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cycle of chemotherapy. In the maintenance phase, subsequent visits should be conducted 
according to the last tislelizumab infusion in the induction phase. 
7.10. 
Unscheduled Visits  
Unscheduled visits may be performed at any time at the patient’s or the investigator’s request 
and may include vital signs/focused physical examination; ECOG Performance Status; AE 
review; concomitant medications and procedures review; radiographic assessments; physical 
examination; disease-related constitutional symptoms; and hematology and chemistry laboratory 
assessments. The date and reason for the unscheduled visit must be recorded in the source 
documentation. 
If an unscheduled visit is necessary to assess toxicity or for suspected disease progression, then 
diagnostic tests may be performed based on the investigator assessment as appropriate, and the 
results of these tests should be entered on the unscheduled visit eCRF. 
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8. 
SAFETY MONITORING AND REPORTING  
The investigator is responsible for the monitoring and documentation of events that meet the 
criteria and definition of an AE or SAE as provided in this protocol. 
8.1. 
Risks Associated With Study Drugs  
8.1.1. 
Risks Associated With Ociperlimab and Tislelizumab  
Ociperlimab and tislelizumab are investigational agents that are currently in clinical 
development. The following recommendation is based on results from nonclinical and clinical 
studies with ociperlimab and tislelizumab and published data on other molecules within the same 
biologic class. 
The PD-L1/PD-1 pathway is involved in peripheral immune tolerance; therefore, such therapy 
may increase the risk of imAEs, specifically the induction or enhancement of autoimmune 
conditions. AEs observed with anti PD-1 therapy are presented in Section 8.6.12. 
Although most imAEs observed with immunomodulatory agents have been mild and self-
limiting, such events should be recognized early and treated promptly to avoid potential major 
complications. Suggested evaluation and management guidelines for suspected imAEs are 
provided in Appendix 7. 
8.1.2. 
Risks Associated With Chemotherapy Agents  
For NSCLC patients who were treated with paclitaxel in a first-line setting, frequent (> 5%) 
Grade 3 or 4 drug-related toxicities were neutropenia, anemia, nausea, vomiting, and fatigue 
(Scagliotti et al 2008). For NSCLC patients who were treated with carboplatin in a first-line 
setting, frequent (> 5%) Grade 3 or 4 toxicities were leukopenia, neutropenia, anemia, 
thrombocytopenia, febrile neutropenia, nausea, vomiting, anorexia and constipation 
(Ohe et al 2007). Although not life threatening, these AEs can severely impact the physical, 
psychological, and social well-being of patients receiving chemotherapy and can lead to dose 
reductions and discontinuations.  
Please refer to Table 6 below for the reported toxicity of the respective chemotherapeutic agents. 
Table 6. 
Commonly and Specific Reported Toxicity of the Chemotherapeutic Agents  
Agents 
Common toxicity 
Specific toxicity 
Cisplatin 
Myelosuppression with leukopenia, 
thrombocytopenia, and anemia; infectious 
complications; nausea/vomiting and other 
gastrointestinal toxicity; hepatic impairment; 
fatigue; anorexia; constipation 
Nephrotoxicity, ototoxicity, 
peripheral neuropathies 
Carboplatin 
Ototoxicity and peripheral 
neuropathies 
Paclitaxel 
Hypersensitivity reaction, 
peripheral neuropathy, myalgia, 
arthralgia, cardiovascular 
disorders 
Pemetrexed 
Nephrotoxicity, skin rash, 
pneumonitis, radiation recall 
Nab-paclitaxel 
Peripheral neuropathy, alopecia 
Refer to the manufacturer’s prescribing information for additional details. 
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8.2. 
General Plan to Manage Safety Concerns  
8.2.1. 
Eligibility Criteria  
Eligibility criteria were selected to guard the safety of patients in this study. Results from the 
nonclinical toxicology studies and clinical data with ociperlimab and tislelizumab as well as the 
nonclinical/clinical data from other PD-L1/PD-1 and TIGIT inhibitors were considered. 
Specifically, patients who are at risk for study-emergent active autoimmune diseases or with a 
history of autoimmune diseases that may relapse, patients who have undergone allogeneic stem 
cell or organ transplantation, and patients who have received a live vaccine ≤ 28 days before 
randomization are excluded from the study (see Section 4.2 for the full list of exclusion criteria). 
8.2.2. 
Safety Monitoring Plan  
Safety will be evaluated in this study through the monitoring of all AEs, which will be defined 
and graded according to NCI-CTCAE v5.0. All enrolled patients will be evaluated clinically and 
with standard laboratory tests at regular intervals during their participation in this study. Safety 
evaluations will consist of medical interviews, recording of AEs (see Table 7), physical 
examinations, laboratory measurements (eg, hematology or chemistry) and other assessments 
including those listed in Appendix 1. In addition, patients will be closely monitored for the 
development of any signs or symptoms of infections or autoimmune conditions. 
At the start of each cycle, study drugs will be administered only after clinical laboratory results 
have been reviewed. Administration of study drugs will be performed in a setting where 
emergency medical equipment and staff who are trained to respond to medical emergencies are 
available (Section 5.2). 
Investigators are instructed to report all AEs (including pregnancy-related AEs). 
The potential safety issues anticipated in this study, as well as measures intended to avoid or 
minimize such toxicities, are outlined in Section 8.6. 
8.3. 
Adverse Events  
8.3.1. 
Definitions and Reporting  
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study 
drug, whether considered related to study drug or not. 
Examples of AEs include: 
• Worsening of a chronic or intermittent preexisting condition, including an increase in 
severity, frequency, duration, and/or has an association with a significantly worse 
outcome 
• Detection or diagnosis of a new condition after study drug administration, even 
though the condition may have been present before the start of the study 
• Signs, symptoms, or the clinical sequelae of a suspected interaction 
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• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug 
or a concurrent medication (overdose per se should not be reported as an AE or SAE) 
When an AE or SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory results, and diagnostics reports) relative to 
the AE or SAE. The investigator will then record all relevant information regarding an AE or 
SAE in the eCRF. However, there may be instances when copies of medical records for certain 
cases are requested by the sponsor. In this instance, all patient identifiers will be blinded on the 
copies of the medical records prior to submission to the sponsor. 
8.3.2. 
Assessment of Severity  
The investigator will assess the severity of each AE and SAE reported during the study. AEs and 
SAEs should be assessed and graded based upon the NCI-CTCAE v5.0. 
Toxicities that are not specified in the NCI-CTCAE will be defined as follows: 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated 
• Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (ADL) 
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
selfcare ADL 
• Grade 4: Life-threatening consequences; urgent intervention indicated 
• Grade 5: Death related to AE 
Note: The terms “severe” and “serious” are not synonymous. Severity is a measure of intensity 
(eg, grade of a specific AE, mild [Grade 1], moderate [Grade 2], severe [Grade 3], or 
life-threatening [Grade 4]), whereas seriousness is classified by the criteria based on the 
regulatory definitions. Seriousness serves as the guide for defining regulatory reporting 
obligations from the sponsor to applicable regulatory authorities as described in Section 8.6.2. 
8.3.3. 
Assessment of Causality  
The investigator is obligated to assess the relationship between the study drug and the occurrence 
of each AE or SAE, using best clinical judgment. Alternative causes, such as natural history of 
the underlying diseases, concomitant therapy, other risk factors, and the temporal relationship of 
the AE or SAE to the study drug should be considered and investigated. The investigator should 
consult the Tislelizumab (BGB-A317) Investigator’s Brochure, the Ociperlimab (BGB-A1217) 
Investigator’s Brochure, and chemotherapy prescribing information in the determination of 
his/her assessment. 
There may be situations when an SAE has occurred, and the investigator has only limited 
information to include in the initial report to the sponsor. However, it is very important that the 
investigator always assesses causality for every SAE before transmission of the SAE report to 
the sponsor, because the causality assessment is one of the criteria used when determining 
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regulatory reporting requirements. The investigator may subsequently change his/her opinion of 
causality considering follow-up information and may amend the SAE report accordingly. 
The causality of each AE should be assessed and classified by the investigator as “related” or 
“not related” based on all information available at the time of reporting. An AE is considered 
related if there is “a reasonable possibility” that the AE may have been caused by the study drug 
(ie, there are facts, evidence, or arguments to suggest possible causation). A number of factors 
should be considered in making this assessment, including: 
• Temporal relationship of the AE to the administration of study treatment/study 
procedure 
• Whether an alternative etiology has been identified 
• Mechanism of action of the study drug 
• Biological plausibility 
• An AE should be considered “related” to study drug if any of the following criteria 
are met, otherwise the event should be assessed as “not related”: 
o There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out 
o There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely 
o There is some evidence to suggest a causal relationship (eg, the AE occurred 
within a reasonable time after administration of the study drug). However, the 
influence of other factors may have contributed to the AE (eg, the patient’s 
clinical condition or other concomitant AEs). 
8.3.4. 
Follow-up of Adverse Events  
After the initial AE or SAE report, the investigator is required to proactively follow each patient 
and provide further information to the sponsor on the patient’s condition. 
All AEs and SAEs documented at a previous visit/contact and designated as ongoing will be 
reviewed at subsequent visits/contacts.  
All AEs and SAEs (only SAEs in case of patients who did not meet screening criteria) will be 
followed until resolution, the condition stabilizes or is considered chronic, the AE or SAE is 
otherwise explained, the patient is lost to follow-up or the patient withdraws consent. The 
investigator will ensure that follow-up includes any supplemental investigations as may be 
indicated to elucidate the nature and/or causality of the AE or SAE. This may include additional 
laboratory tests or investigations, histopathological examinations, radiographic imaging, or 
consultation with other health care professionals. 
The sponsor may request that the investigator perform or arrange for the conduct of supplemental 
measurements and/or evaluations to elucidate as fully as possible the nature and/or causality of 
the AE or SAE. The investigator is obligated to assist. If a patient dies during participation in the 
study or during a recognized follow-up period, the sponsor will be provided with a copy of any 
postmortem findings, including histopathology. 
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New or updated information should be reported to the sponsor according to the SAE instructions 
provided by the sponsor within the time frames outlined in Section 8.6.2. 
8.3.5. 
Laboratory Test Abnormalities  
Abnormal laboratory findings (eg, clinical chemistry, complete blood count [CBC], coagulation, 
or urinalysis) or other abnormal assessments (eg, ECGs, x-rays, or vital signs) that are judged by 
the investigator as clinically significant will be recorded as AEs or SAEs. This includes clinically 
significant abnormal laboratory findings or other abnormal assessments that are present at 
baseline and significantly worsen during the study. The definition of clinically significant is left 
to the judgment of the investigator. In general, these are the laboratory test abnormalities or other 
abnormal assessments that: 
• are associated with clinical signs or symptoms, or 
• require active medical intervention, or 
• lead to dose interruption or discontinuation, or 
• require close observation, more frequent follow-up assessments, or further diagnostic 
investigation. 
If a clinically significant laboratory abnormality is a sign of a disease or syndrome (eg, alkaline 
phosphatase and bilirubin 5 x ULN associated with cholestasis), only the diagnosis 
(ie, cholestasis) should be recorded on the Adverse Event eCRF. 
If the laboratory abnormality can be characterized by a precise clinical term per standard 
definitions, the clinical term should be recorded as the AE. For example, an elevated serum 
potassium level of 7.0 mEq/L should be recorded as “hyperkalemia.” 
Observations of the same clinically significant laboratory abnormality from visit to visit should 
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. 
8.4. 
Definition of a Serious Adverse Event  
An SAE is any untoward medical occurrence that, at any dose: 
• Results in death 
• Is life-threatening 
Note: The term “life-threatening” in the definition of “serious” refers to an AE in 
which the patient was at risk of death at the time of the AE. It does not refer to an AE 
that hypothetically might have caused death if it were more severe. 
• Requires hospitalization or prolongation of existing hospitalization 
Note: In general, hospitalization signifies that the patient was admitted (usually 
involving at least an overnight stay) to the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the physician’s 
office or outpatient setting. 
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• Results in disability/incapacity 
Note: The term “disability” means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include experiences 
of relatively minor medical significance, such as uncomplicated headache, nausea, 
vomiting, diarrhea, influenza, and accidental trauma (eg, sprained ankle), which may 
interfere with or prevent everyday life functions, but do not constitute a substantial 
disruption. 
• Is a congenital anomaly/birth defect 
• Is considered a significant medical AE by the investigator based on medical 
judgement (eg, may jeopardize the patient or may require medical/surgical 
intervention to prevent one of the outcomes listed above) 
The following are NOT considered to be SAEs: 
• Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline 
• Hospitalization for social/convenience considerations 
• Scheduled therapy for the target disease of the study, including admissions for 
transfusion support or convenience 
8.5. 
Suspected Unexpected Serious Adverse Reaction  
A suspected unexpected serious adverse reaction (SUSAR) is a serious adverse reaction that is 
both unexpected (ie, not present in the product’s Reference Safety Information [RSI]) and meets 
the definition of a serious adverse drug reaction (SADR), the specificity or severity of which is 
not consistent with those noted in the Tislelizumab (BGB-A317) Investigator’s Brochure, 
Ociperlimab (BGB-A1217) Investigator’s Brochure, and chemotherapy prescribing information. 
8.6. 
Timing, Frequency, and Method of Capturing Adverse Events and 
Serious Adverse Events  
8.6.1. 
Adverse Event Recording Period  
After informed consent has been signed but prior to the administration of the study drug(s), only 
SAEs should be reported. 
After initiation of the study drug(s), all AEs and SAEs, regardless of the relationship to the study 
drug(s), will be reported until either 30 days after last dose of study drug(s) (including 
chemotherapy) or the initiation of new anticancer therapy, whichever occurs first. 
Immune-mediated AEs (serious or nonserious) should be reported until 90 days after the last 
dose of ociperlimab (or placebo) and/or tislelizumab, regardless of whether or not the patient 
starts a new anticancer therapy. All SAEs considered related to the study drugs that are brought 
to the attention of the investigator should be reported regardless of time since the last dose of 
treatment. 
AEs and SAEs should be recorded according to the details in Table 7. For the follow-up period 
for AEs, see Section 8.3.4. For the definition of TEAEs, see Section 9.3.2. 
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Table 7: 
Guidance for Duration of Recording New or Worsening Adverse Events in 
All Treatment Arms  
Event type 
Record new or worsening events that occur during this period 
Begin 
End  
SAEs a 
Signing of 
informed consent 
Up to 30 days after last dose, initiation of new 
anticancer therapy, death, withdrawal of consent, or 
loss to follow-up, whichever occurs first 
Nonserious AEs due to 
PD 
Do not record (see Section 8.6.4) 
All nonserious AEs, 
except those due to PD 
First dose of study 
drug 
Up to 30 days after last dose, initiation of new 
anticancer therapy, death, withdrawal of consent, or 
loss to follow-up, whichever occurs first 
Immune-mediated AEs 
(serious or nonserious) 
First dose of study 
drug 
Up to 90 days after last dose of ociperlimab (or 
placebo) and/or tislelizumab (regardless of initiation of 
new anticancer therapy), death, withdrawal of consent, 
or loss to follow-up, whichever occurs first 
Abbreviations: AE, adverse event; PD, progressive disease; SAE, serious adverse event. 
a All SAEs considered related to the study drug(s) that are brought to the attention of the investigator should be 
reported regardless of time since the last dose of treatment. 
8.6.2. 
Reporting Serious Adverse Events  
8.6.2.1. 
Prompt Reporting of Serious Adverse Events  
As soon as the investigator determines that an AE meets the protocol definition of an SAE, the 
event must be reported promptly (within 24 hours) to the sponsor or designee as described in 
Table 8. 
Table 8: 
Timeframes and Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee  
 
Timeframe for sending 
initial/follow-up a 
report 
Documentation 
method 
Reporting method 
All SAEs 
Within 24 hours of first 
knowledge of the SAE 
SAE Report 
Electronic submission of 
SAE Form to safety portal b 
Abbreviations: EDC, electronic data capture; IMP, investigational medicinal product; SAE, serious adverse event. 
a Report follow-up information that is clinically relevant and pertaining to the SAE which includes but is not limited 
to the following: Update to the SAE, new additional SAE, outcome, seriousness criteria, investigator causality, event 
start date/date of onset, date of death, relationship to each IMP. Follow-up information will also be reported as per 
the discretion of the investigator if the new or updated information changes the medical assessment of the case. 
b SAE reports should be submitted to the sponsor safety database electronically from within the EDC. If the 
electronic submission is not available for any reason, a paper SAE form should be submitted by email or fax. 
8.6.2.2. 
Completion and Transmission of the Serious Adverse Event Report  
Once an investigator becomes aware that an SAE has occurred in a patient, the investigator is to 
report the information to the sponsor within 24 hours as outlined above in Section 8.6.2.1. The 
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SAE Report will always be completed as thoroughly as possible with all available details of the 
event and forwarded to the sponsor or designee within the designated time frames. 
If the investigator does not have all information regarding an SAE, he/she is not to wait to 
receive additional information before notifying the sponsor or designee of the SAE and 
completing the form. The form will be updated when additional information is received. 
The investigator must always provide an assessment of causality for each SAE as described in 
Section 8.3.3. 
The sponsor will provide contact information for SAE receipt. 
8.6.2.3. 
Regulatory Reporting Requirements for Serious Adverse Events  
The investigator will report all SAEs to the sponsor in accordance with the procedures detailed in 
Section 8.6.2.1. The sponsor has a legal responsibility to notify, as appropriate, both the local 
regulatory authority and other regulatory agencies about the safety of a product under clinical 
investigation. 
The investigator, or responsible person according to local requirements, will comply with the 
applicable local regulatory requirements related to the reporting of SAEs to regulatory authorities 
and the IRB/IEC. 
All SUSARs (as defined in Section 8.5), will be submitted to all applicable regulatory authorities 
and investigators for ociperlimab and tislelizumab studies. 
When a study center receives an initial or follow-up safety report or other safety information 
(eg, revised Investigator’s Brochure) from the sponsor, the investigator or designated responsible 
person is required to promptly notify his/her IRB or IEC. The investigator should place copies of 
Safety Reports from the sponsor in the Investigator Site File. 
8.6.3. 
Eliciting Adverse Events  
The investigator or designee will ask patients about AEs by asking the following standard 
questions: 
• How are you feeling? 
• Have you had any medical problems since your last visit? 
• Have you taken any new medicines since your last visit? 
8.6.4. 
Disease Progression  
Disease progression, which is expected in this study population and is measured as an efficacy 
endpoint, should not be recorded as an AE term. Similarly, nonserious AEs that are clearly 
consistent with the pattern of progression of the underlying disease and are considered 
unequivocally due to disease progression should not be recorded. However, if there is any 
uncertainty as to whether a nonserious AE is due to disease progression, it should be recorded as 
an AE. All SAEs and deaths regardless of relatedness to disease progression should be recorded 
and reported (see Section 8.6.2). 
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8.6.5. 
Deaths  
Death is an outcome and is not usually considered an event. If the only information available is 
death and the cause of death is unknown, then the death is reported as an AE, eg, “death,” “death 
of unknown cause,” or “death unexplained.” 
8.6.6. 
Pregnancies  
If a female patient or the partner of a male patient becomes pregnant while receiving study drug 
treatment or within 120 days after the last dose of ociperlimab and/or tislelizumab or 180 days 
after the last dose of chemotherapy, a pregnancy report form is required to be completed and 
expeditiously submitted to the sponsor to facilitate outcome follow-up. Information on the status 
of the mother and child will be forwarded to the sponsor. Generally, follow-up will be no longer 
than 6 to 8 weeks following the estimated delivery date. Any premature termination of the 
pregnancy will be reported. 
While pregnancy itself is not considered to be an AE, any pregnancy complication or elective 
termination of a pregnancy for medical reasons will be recorded as an AE or SAE. 
An abortion, whether accidental, therapeutic, or spontaneous, should be always reported as an 
SAE. Similarly, any congenital anomaly/birth defect in a child born to a patient exposed to the 
study drug should be recorded and reported as an SAE. 
8.6.7. 
Expedited Reporting to Health Authorities, Investigators, Institutional Review 
Boards, and Independent Ethics Committees  
The sponsor will promptly assess all SAEs against cumulative study drug experience to identify 
and expeditiously communicate new safety findings to regulatory authorities, investigators, 
IRBs, and IECs based on applicable legislation. 
To determine the reporting requirements for individual SAEs, the sponsor will assess the 
expectedness of the SAEs using the following RSI documents: 
• Tislelizumab (BGB-A317) Investigator’s Brochure 
• Ociperlimab (BGB-A1217) Investigator’s Brochure 
• Nab-paclitaxel label 
• Cisplatin label 
• Carboplatin label 
• Paclitaxel label 
• Pemetrexed label 
8.6.8. 
Assessing and Recording Immune-Mediated Adverse Events  
Because treatment with anti-PD-1 or immune checkpoint inhibitors can cause autoimmune 
disorders, AEs considered by the investigator to be immune-mediated (see Section 8.6.12) 
should be classified as imAEs and identified as such on the eCRF AE page until 90 days after the 
last dose of ociperlimab (or placebo) and/or tislelizumab. 
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Investigators should consult the guidance on diagnostic evaluation and management of imAEs, 
which are commonly seen with immune checkpoint inhibitors, in Appendix 7. 
An extensive list of potential imAEs appears in Section 8.6.12, Table 10. All conditions like 
those listed should be evaluated to determine whether they are imAEs based on a similar 
diagnostic process to those reactions that are presented in more detail in Appendix 7. 
8.6.9. 
Recording Infusion-Related Reactions  
The symptoms of infusion-related reactions may include but are not limited to fever, chills/rigor, 
nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, 
myalgia, dizziness, or hypertension. Severe reactions may include acute respiratory distress 
syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. Each individual 
sign and symptom of an infusion reaction should be recorded as a separate AE in the eCRF and 
identified as an infusion-related reaction. Refer to the eCRF completion guidelines for details. 
As a routine precaution, after completing the infusion of study drugs on Day 1 of Cycle 1 and 
Cycle 2, patients must be monitored for ≥ 120 minutes afterward in an area with resuscitation 
equipment and emergency agents. From Cycle 3 onward, a ≥ 60-minute monitoring period is 
required in an area with resuscitation equipment and emergency agents. 
The management of infusion-related reactions, severe hypersensitivity reactions, and imAEs 
according to the NCI-CTCAE v5.0 criteria are outlined below. 
8.6.10. 
Managing Infusion-Related Reactions  
Patients should be closely monitored for infusion-related reactions. Immediate access to an 
Intensive Care Unit (ICU) or equivalent environment and appropriate medical therapy (including 
epinephrine, corticosteroids, intravenous antihistamines, bronchodilators, and oxygen) must be 
available to treat infusion-related reactions. 
Treatment modifications for symptoms of infusion-related reactions due to study drug(s) is 
provided in Table 9. 
Table 9: 
Treatment Modifications for Symptoms of Infusion-Related Reactions Due to 
Study Drug(s) 
NCI-CTCAE grade 
Treatment modification for all study arms 
Grade 1 – mild 
Mild transient reaction; infusion interruption not 
indicated; intervention not indicated. 
Decrease infusion rate by 50%. Any worsening is 
closely monitored. Medical management as 
needed. 
Subsequent infusions should be given after 
premedication and at the reduced infusion rate. 
Grade 2 – moderate 
Therapy or infusion interruption indicated but 
responds promptly to symptomatic treatment (eg, 
antihistamines, NSAIDS, narcotics, intravenous 
fluids); prophylactic medications indicated for 
≤ 24 hours. 
Stop infusion. Infusion may be resumed at 50% of 
previous rate once infusion-related reaction has 
resolved or decreased to Grade 1 in severity. Any 
worsening is closely monitored. Proper medical 
management should be instituted as described 
below. 
Subsequent infusions should be given after 
premedication and at the reduced infusion rate. 
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Grade 3 – severe 
Prolonged (eg, not rapidly responsive to 
symptomatic medication and/or brief interruption 
of infusion); recurrence of symptoms following 
initial improvement; hospitalization indicated for 
clinical sequelae. 
Immediately stop the infusion. Proper medical 
management should be instituted as described 
below. 
The patient should be withdrawn from study 
drug(s) treatment. 
Grade 4 – life threatening 
Life-threatening consequences; urgent 
intervention indicated. 
Immediately stop the infusion. Proper medical 
management should be instituted as described 
below. 
The patient should be withdrawn from study 
drug(s) treatment. 
Hospitalization is recommended. 
Abbreviations: NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Event; NSAIDs, 
nonsteroidal anti-inflammatory drugs. 
Once the study drug infusion rate has been decreased by 50% or suspended due to an infusion 
related reaction, it must remain decreased for all subsequent infusions and be administered with 
premedication. If the patient has a second infusion-related reaction (≥ Grade 2) on the slower 
infusion rate, infusion should be discontinued, and the patient should be withdrawn from study 
drug treatment. 
NCI-CTCAE Grade 1 or 2 infusion reaction: Proper medical management should be instituted 
as indicated per the type of reaction. This includes, but is not limited to, an antihistamine 
(eg, diphenhydramine or equivalent), antipyretic (eg, paracetamol or equivalent), and if 
considered indicated, oral or intravenous glucocorticoids, epinephrine, bronchodilators, and 
oxygen. In the next cycle, patients should receive oral premedication with an antihistamine 
(eg, diphenhydramine or equivalent) and an antipyretic (eg, paracetamol or equivalent), and they 
should be closely monitored for clinical signs and symptoms of an infusion reaction. 
NCI-CTCAE Grade 3 or 4 infusion reaction: Proper medical management should be instituted 
immediately, as indicated per type and severity of the reaction. This includes, but is not limited 
to, oral or intravenous antihistamines, antipyretics, glucocorticoids, epinephrine, bronchodilators, 
and oxygen. 
8.6.11. 
Severe Hypersensitivity Reactions and Flu-Like Symptoms  
If hypersensitivity reaction occurs, the patient must be treated according to the best available 
medical practice as described in the complete guideline for emergency treatment of anaphylactic 
reactions according to the Working Group of the Resuscitation Council (UK) (Soar et al 2008). 
Patients should be instructed to report any delayed reactions to the investigator immediately. 
In the event of a systemic anaphylactic/anaphylactoid reaction the infusion must be immediately 
stopped, and the patient discontinued from the study treatment. Systemic 
anaphylactic/anaphylactoid reactions typically manifest within minutes following administration 
of the drug/antigen and are characterized by respiratory distress, laryngeal edema, and/or intense 
bronchospasm and often followed by vascular collapse or shock without antecedent respiratory 
difficulty, cutaneous manifestations such as pruritus and urticaria with/without edema, and 
gastrointestinal manifestations such as nausea, vomiting, crampy abdominal pain, and diarrhea. 
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The patient will be administered epinephrine injection and dexamethasone infusion if 
hypersensitivity reaction is observed. The patient should then be placed on monitoring 
immediately, and the ICU should be alerted for possible transfer if needed. 
For prophylaxis of flu-like symptoms, a dose of 25 mg indomethacin or a comparable dose of 
nonsteroidal anti-inflammatory drugs (ie, 600 mg ibuprofen and 500 mg naproxen sodium) may 
be administered 2 hours before and 8 hours after the start of each dose of study drugs(s) infusion. 
Alternative treatments for fever (ie, paracetamol) may be given to patients at the discretion of the 
investigator. 
8.6.12. 
Immune-Mediated Adverse Events  
Immune-mediated AEs are of special interest in this study. If the events listed below or similar 
events occur, the investigator should exclude alternative explanations (eg, combination drugs, 
infectious disease, metabolic, toxin, disease progression, or other neoplastic causes) with 
appropriate diagnostic tests that may include, but are not limited to, serologic, immunologic, and 
histologic (biopsy) data. The imAE indicator in the eCRF AE page should be checked if 
alternative causes have been ruled out; the AE required the use of systemic steroids, other 
immunosuppressants, or endocrine therapy; and is consistent with an immune-mediated 
mechanism of action. 
A list of potential imAEs is shown below in Table 10. All conditions similar to those listed 
should be evaluated in patients receiving study drugs to determine whether they are immune-
mediated. 
Recommendation for diagnostic evaluation and management of imAEs is based on European 
Society for Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) 
guidelines (Haanen et al 2017; Brahmer et al 2018), and common immune-mediated toxicities 
are detailed in Appendix 7. For any AEs not included in Appendix 7, please refer to the ASCO 
Clinical Practice Guideline (Brahmer et al 2018) for further guidance on diagnostic evaluation 
and management of immune-mediated toxicities. 
Table 10: 
Examples of Immune-Mediated Adverse Events 
Body system affected 
Events 
Skin (mild-common) 
pruritus or maculopapular rash; vitiligo 
Skin (moderate) 
follicular or urticarial dermatitis; erythematous/lichenoid rash; Sweet 
syndrome 
Skin (severe-rare) 
full-thickness necrolysis/Stevens-Johnson syndrome 
Gastrointestinal 
colitis (includes diarrhea with abdominal pain or 
endoscopic/radiographic evidence of inflammation); pancreatitis; 
hepatitis; aminotransferase (ALT/AST) elevation; bowel perforation 
Endocrine 
thyroiditis, hypothyroidism, hyperthyroidism; hypophysitis with features 
of hypopituitarism, eg, fatigue, weakness, weight gain; 
insulin-dependent diabetes mellitus; diabetic ketoacidosis; adrenal 
insufficiency 
Respiratory 
pneumonitis/diffuse alveolitis 
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Eye 
episcleritis; conjunctivitis; iritis/uveitis 
Musculoskeletal 
arthritis; arthralgia; myalgia; neuropathy; myasthenic 
syndrome/myasthenia gravis, myositis 
Blood 
anemia; leukopenia; thrombocytopenia 
Renal 
interstitial nephritis; glomerulonephritis; acute renal failure 
Cardiac 
pericarditis; myocarditis; heart failure 
Neurologic 
encephalitis, meningitis, meningoradiculitis, meningoencephalitis, 
Guillain-Barré syndrome 
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase. 
Recommendations for managing imAEs are detailed in Appendix 7. 
If a toxicity does not resolve to ≤ Grade 1 within 12 weeks, study drug(s) should be discontinued 
after consultation with the sponsor. Patients who experience a recurrence of any event at the 
same or higher severity grade after restart of study drug should permanently discontinue 
treatment. 
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9. 
STATISTICAL METHODS AND SAMPLE SIZE 
DETERMINATION  
The statistical analyses will be performed by the sponsor or designee after the data collection is 
completed and the database is locked and released. Details of the statistical analyses will be 
included in a separate Statistical Analysis Plan (SAP). 
9.1. 
Statistical Analysis  
9.1.1. 
Randomization Methods  
As discussed in Section 7.2.2 , patients will be randomized using the IRT system for this study 
by stratified permuted block randomization.  
9.1.2. 
Analysis Sets  
The ITT Analysis Set includes all randomized patients. Patients will be analyzed according to 
their randomized treatment arm. This will be the primary analysis set for efficacy and HRQoL 
analyses. 
The Per-Protocol (PP) Analysis Set includes all randomized patients who received ≥ 1 dose of 
the assigned study drug and had no critical protocol deviations. Critical protocol deviations will 
be determined and documented before the database lock for the primary analyses. 
The Safety Analysis Set includes all randomized patients who received ≥ 1 dose of study drug. 
This will be the analysis set for the safety analyses. 
The PK Analysis Set includes all patients who received ≥ 1 dose of any component of study drug 
per the protocol and for whom any postdose PK data are available. 
The Immunogenicity Analysis Set includes all patients who received ≥ 1 dose of any component 
of study drug and for whom both baseline ADA and at least 1 postbaseline ADA result are 
available. 
9.1.3. 
Patient Disposition  
The number of patients who are randomized, treated, discontinued from study drug and/or study, 
and those with important protocol deviations will be counted. The primary reason for study drug 
and/or study discontinuation will be summarized according to the categories in the eCRF. The 
end-of-study status (alive, dead, withdrew consent, or lost to follow-up) at the data cutoff date 
will be summarized using the data from the eCRF. 
Important protocol deviations will be summarized and listed by each category. 
9.1.4. 
Demographic and Other Baseline Characteristics  
Demographic and other baseline characteristics of patients in the ITT Analysis Set will be 
summarized using descriptive statistics. Continuous variables include age, weight, vital signs, 
time since initial cancer diagnosis, and time since advanced/metastatic disease diagnosis. 
Categorical variables include sex, ECOG Performance Status at study entry, geographical region, 
country, race, histological subtype, metastatic site, PD-L1 expression, and tobacco use. 
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9.1.5. 
Prior and Concomitant Medications  
Concomitant medications will be coded using the World Health Organization (WHO) Drug 
Dictionary drug codes. Concomitant medications will be further coded to the appropriate 
Anatomical Therapeutic Chemical (ATC) code indicating therapeutic classification. Prior and 
concomitant medications will be summarized and listed by drug and drug class in the Clinical 
Study Report (CSR) for this protocol. Prior medications will be defined as medications that 
stopped before the day of first dose of study drug. Concomitant medications will be defined as 
medications that 1) started before the first dose of study drug and were continuing at the time of 
the first dose of study drug, or 2) started on or after the date of the first dose of study drug up to 
30 days after the patient’s last dose (as of the 30-day Safety Follow-Up). In addition, telephone 
contacts with patients should be conducted to assess imAEs and concomitant medications (if 
appropriate, ie, associated with an imAE or is a new anticancer therapy) at 60 and 90 days 
(± 14 days) after the last dose of ociperlimab (or placebo) and/or tislelizumab regardless of 
whether or not the patient starts a new anticancer therapy. 
9.2. 
Efficacy Analyses  
The primary analyses will be performed when approximately 194 PFS events have been 
observed. 
9.2.1. 
Primary Efficacy Analysis  
PFS in ITT Analysis Set: 
The null hypothesis (H0) to be tested is: 
H0: PFS in Arm A ≤ PFS in Arm B 
against the alternative hypothesis (H1): 
H1: PFS in Arm A > PFS in Arm B 
A stratified log-rank test to compare PFS distribution between ociperlimab + tislelizumab + 
chemotherapy (Arm A) and placebo + tislelizumab + chemotherapy (Arm B) will be the primary 
efficacy analysis, stratified by PD-L1 expression (three levels: < 1% TC versus 1% to 49% TC 
versus ≥ 50% TC) and histology (squamous versus non-squamous NSCLC). It will be performed 
once the targeted PFS event number is reached. A significance level of 1-sided alpha of 0.025 
will be used in the PFS testing. 
PFS as assessed by the investigators per RECIST v1.1 will be estimated using the Kaplan-Meier 
method in the ITT Analysis Set. PFS will be censored at the last adequate tumor assessment if 
one of the following occurs by the time of analysis: absence of event, a new anticancer therapy is 
given, or the event occurred after ≥ 2 missing tumor assessments. For cases with missing 
baseline tumor assessment, a death occurring ≤ 19 weeks from the randomization date will be 
considered a PFS event. Clinical or symptomatic progressions without supportive radiologic data 
will not be considered as PFS events. 
The median PFS and 2-sided 95% CI using the method of Brookmeyer and Crowley will be 
summarized. The cumulative probability of PFS at every 6 months including PFS rate at 6 and 
12 months, if estimable, will be calculated for each treatment arm and presented with 2-sided 
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95% CIs. Standard error for PFS rates will be calculated based on Greenwood’s formula. 
Kaplan-Meier survival probabilities for each arm will be plotted over time.  
The treatment effect will be estimated by fitting a Cox regression model to the PFS times, 
including treatment arm as a factor and PD-L1 expression (three levels: < 1% TC versus 1% to 
49% TC versus ≥ 50% TC) and histology (squamous versus non-squamous NSCLC) as strata. 
From this model, the HR of PFS will be estimated and presented with a 2-sided 95% CI. 
Subgroup analysis of PFS will be performed by PD-L1 expression, histology, region, and other 
key risk factors that are to be described in the SAP. 
9.2.2. 
Secondary Efficacy Analysis  
Best overall response (BOR) is defined as the best response per RECIST v1.1 recorded from 
randomization until data cut, progressive disease, or start of a new anticancer treatment. The null 
hypotheses of no difference in ORR per RECIST v1.1 assessed by the investigators between 
ociperlimab + tislelizumab + chemotherapy (Arm A) and placebo + tislelizumab + chemotherapy 
(Arm B) will be tested in a Cochran-Mantel-Haenszel (CMH) test adjusting for stratification 
factors (PD-L1 expression [three levels: < 1% TC versus 1% to 49% TC versus ≥ 50% TC] and 
histology [squamous versus non-squamous NSCLC]) in the ITT Analysis Set. Patients with no 
postbaseline response assessment (for any reason) will be considered non-responders. The odds 
ratio in ORR and its 2-sided 95% CI will be calculated, as well as ORR and its Clopper‑Pearson 
95% CIs for each treatment arm. 
DOR as assessed by the investigators will be derived using the similar censoring rule as for PFS 
and summarized descriptively in the responders receiving ociperlimab + tislelizumab + 
chemotherapy (Arm A) versus placebo + tislelizumab + chemotherapy (Arm B). 
OS will be compared between ociperlimab + tislelizumab + chemotherapy (Arm A) and placebo 
+ tislelizumab + chemotherapy (Arm B) in a 1- sided, stratified log-rank test using stratification 
factors of PD-L1 expression (three levels: < 1% TC versus 1% to 49% TC versus ≥ 50% TC) and 
histology (squamous versus non-squamous NSCLC).  
In absence of confirmation of death, patients will be censored either at the date that the patient 
was last known to be alive or the date of data cutoff, whichever comes earlier. The median OS 
and 2-sided 95% CI using the method of Brookmeyer and Crowley will be summarized. The 
cumulative probability of OS at every 3 months including OS rate at 12 months and 24 months if 
estimable, will be calculated for each treatment arm and presented with 2-sided 95% CIs. 
Standard error for survival rates will be calculated based on Greenwood’s formula. 
Kaplan-Meier survival probabilities for each arm will be plotted over time.  
The treatment effect will be estimated by fitting a Cox regression model to the OS times 
including treatment arm as a factor and PD-L1 expression (three levels: < 1% TC versus 1% to 
49% TC versus ≥ 50% TC) and histology (squamous versus non-squamous NSCLC) as strata. 
From this model, the HR of OS will be estimated and presented with a 2-sided 95% CI. 
The secondary endpoints of ORR and OS will be tested sequentially once PFS superiority of 
Arm A over Arm B has been demonstrated. 
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9.2.3. 
Exploratory Efficacy Analysis  
The proportion and its corresponding Clopper-Pearson 95% CI for each of the response 
categories (eg, CR, PR, SD, PD, NE, and NA) will be presented for ociperlimab + tislelizumab + 
chemotherapy (Arm A) and placebo + tislelizumab + chemotherapy (Arm B). DCR and CBR as 
assessed by the investigators will be analyzed similarly to ORR. Proportion of response 
categories with unconfirmed CR and PR may be presented as well. TTR will be summarized 
using descriptive statistics, such as mean, median, and standard deviation. Only patients who 
have achieved an objective response will be included in the analysis of TTR. 
HRQoL is assessed via EORTC QLQ-C30’s global health status/QoL (GHS) and functional and 
symptom scale scores and single item scores and symptoms measured by QLQ-LC13. Observed 
values and changes from baseline will be summarized using descriptive statistics. Graphic 
method will be used for treatment comparison.  
Postbaseline scores of GHS and physical function (PF) of the QLQ-C30 and dyspnea, coughing, 
hemoptysis, pain in chest, peripheral neuropathy, and pain in the arms and shoulders symptoms 
of the QLQ-LC13 will be furthered analyzed using a mixed-model analysis at prespecified 
timepoints and compare between the Treatment Arms A and B.  
9.3. 
Safety Analyses  
9.3.1. 
Extent of Exposure  
Extent of exposure to each study drug will be summarized descriptively by the number of doses 
received (number and percentage of patients), duration of exposure (weeks), cumulative total 
dose received per patient (mg), dose intensity, and relative dose intensity. 
The number (percentage) of patients requiring dose interruption, dose delay, and drug 
discontinuation by reason will be summarized for each study drug. Frequency of the above dose 
adjustments and discontinuation will be summarized by category. 
Patient data listings will be provided for all dosing records and for calculated summary statistics. 
9.3.2. 
Adverse Events  
Verbatim description of AEs will be mapped to the MedDRA terms and graded per 
NCI-CTCAE v5.0. A TEAE is defined as an AE that has an onset date or a worsening in severity 
from baseline (pretreatment) on or after the first dose of study drug and up to 30 days following 
study drug discontinuation or the initiation of new anti-cancer therapy, whichever occurs first. 
Only those AEs that were treatment emergent will be included in summary tables of TEAEs. 
Immune-mediated AEs will be identified from all AEs that had an onset date or a worsening in 
severity from baseline (pretreatment) on or after the first dose of study drug and up to 90 days 
from the last dose of ociperlimab (or placebo) and/or tislelizumab, regardless of whether the 
patient starts a new anticancer therapy. If an imAE occurs outside of the above mentioned TEAE 
window, it will not be classified as a TEAE. All imAEs will be reported separately. All AEs, 
treatment emergent or otherwise, will be presented in patient data listings. 
The incidence of TEAEs will be reported as the number (percentage) of patients with TEAEs by 
System Organ Class and Preferred Term. A patient will be counted only once by the highest 
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severity grade per NCI-CTCAE v5.0 within a System Organ Class and Preferred Term, even if 
the patient experienced more than 1 TEAE within a specific System Organ Class and Preferred 
Term. The number (percentage) of patients with TEAEs will also be summarized by relationship 
to the study drug. Treatment-related AEs include those events considered by the investigator to 
be related to a study drug or with missing assessment of the causal relationship. SAEs, deaths, 
TEAEs of all grades, TEAEs with ≥ Grade 3 severity, imAEs, treatment-related TEAEs, and 
TEAEs that led to treatment discontinuation or dose modification will be summarized. 
9.3.3. 
Laboratory Analyses  
Clinical laboratory (eg, hematology and serum chemistry) values will be evaluated for each 
laboratory parameter as appropriate. Abnormal laboratory values will be flagged and identified 
as those outside (above or below) the normal range. Reference (normal) ranges for laboratory 
parameters will be provided. Descriptive summary statistics (eg, n, mean, standard deviation, 
median, minimum, maximum for continuous variables; and n [%] for categorical variables) for 
laboratory parameters and their changes from baseline will be calculated. Laboratory values will 
be summarized by visit and by worst postbaseline visit. 
Laboratory parameters that are graded by NCI-CTCAE v5.0 will be summarized by 
NCI-CTCAE Grade. In the summary of laboratory parameters by NCI-CTCAE Grade, 
parameters with NCI-CTCAE grading in both high and low directions (glucose, potassium, and 
sodium) will be summarized separately. 
9.3.4. 
Vital Signs  
Descriptive statistics for vital sign parameters (body temperature, pulse rate, and systolic and 
diastolic blood pressure) and changes from baseline will be presented by visit for all visits. Vital 
signs will be listed by patient and visit. 
9.3.5. 
Pulmonary Function Test  
Pulmonary function test results will be listed by patient. 
9.4. 
Pharmacokinetic Analysis  
Ociperlimab and tislelizumab serum concentration data will be tabulated and summarized by 
visit/cycle at which these concentrations are collected. Descriptive statistics will include means, 
medians, ranges, and standard deviations, as appropriate. Additional PK analyses may be 
conducted as appropriate. 
9.5. 
Immunogenicity Analyses  
The immunogenicity results from patients will be summarized using descriptive statistics by the 
number and percentage of patients who develop detectable ADAs. The incidence of positive 
ADAs and neutralizing ADAs will be reported for evaluable patients. The effect of 
immunogenicity on PK, efficacy, and safety may be evaluated if data allow and reported 
separately from the main study report. 
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9.6. 
Sample Size Considerations  
The sample size calculation is driven by the primary efficacy analysis of PFS in the comparison 
between ociperlimab + tislelizumab + chemotherapy (Arm A) and placebo + tislelizumab + 
chemotherapy (Arm B) in the ITT Analysis Set. The number of PFS events needed is based on 
the assumption of an exponential distribution with the targeted median PFS improvement. The 
1-sided overall Type I error in the study is set at 0.025. Table 11 summarizes the statistical 
assumption and power in the sample size calculation. Assuming an approximately 10% dropout 
rate for PFS, 1:1 randomization and 14 months enrollment time, approximately 270 patients will 
be enrolled in order to observe targeted PFS events approximately 33 months after study start.  
Table 11: 
Hazard Ratio and Median PFS Assumption, Number Of Events, Alpha and 
Power in the Primary Hypothesis Test  
Endpoint 
HR 
Median in Arm A 
(months) 
Median in Arm B 
(months) 
Number 
of events 
1-Sided 
Alpha 
Power 
PFS 
0.65 
13.7 
8.9 
194 
0.025 
85% 
Abbreviations: HR, hazard ratio; PFS, progression-free survival 
9.7. 
Interim Analyses  
No formal interim analyses will be conducted. Summaries of efficacy and safety data may be 
generated to inform subsequent clinical development planning. 
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10. 
STUDY COMMITTEES AND COMMUNICATION  
Not applicable. 
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11. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS  
The investigator must maintain adequate and accurate records to ensure that the conduct of the 
study may be fully documented. Such records include, but are not limited to, the protocol, 
protocol amendments, ICFs, and documentation of IRB/IEC and governmental approvals. In 
addition, at the end of the study, the investigator will receive patient data, which will include an 
audit trail containing a complete record of all changes to such data. 
11.1. 
Access to Information for Monitoring  
In accordance with International Council for Harmonisation (ICH) GCP guidelines, the study 
monitor must have direct access to the investigator’s source documentation in order to verify the 
data recorded in the eCRFs for consistency. 
The study monitor is responsible for routine review of the eCRFs at regular intervals throughout 
the study to verify adherence to the protocol and the completeness, consistency, and accuracy of 
the data being entered on them. The study monitor should have access to any patient records 
needed to verify the entries on the eCRFs. The investigator agrees to cooperate with the study 
monitor to ensure that any problems detected during these monitoring visits are resolved. 
11.2. 
Access to Information for Auditing or Inspections  
Representatives of regulatory authorities or of the sponsor may conduct inspections or audits any 
time during or after completion of this clinical study. If the investigator is notified of an 
inspection by a regulatory authority, the investigator agrees to notify the sponsor or its designee 
immediately. The investigator agrees to provide access to records, facilities, and personnel to 
representatives of a regulatory agency or the sponsor for the effective conduct of any inspection 
or audit. 
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12. 
QUALITY ASSURANCE AND QUALITY CONTROL  
12.1. 
Regulatory Authority Approval  
The sponsor will obtain approval to conduct the study from the appropriate regulatory agency in 
accordance with any applicable country-specific regulatory requirements or file the protocol to 
the appropriate regulatory agency before the study is initiated at a study center in that country. 
12.2. 
Quality Assurance  
To ensure compliance with GCP and all applicable regulatory requirements, the sponsor may 
conduct a quality assurance audit. Regulatory agencies may also conduct a regulatory inspection 
of this study. Such audits/inspections can occur at any time during or after completion of the 
study. If an audit or inspection occurs, the investigator and institution agree to allow the 
auditor/inspector direct access to all relevant documents and to allocate his/her time and the time 
of his/her personnel to the auditor/inspector to discuss findings and any relevant issues. 
12.3. 
Study Site Inspections  
This study will be organized, performed, and reported in compliance with the protocol, standard 
operating procedures, working practice documents, and applicable regulations and guidelines. 
Site audits may be performed periodically by the sponsor’s or the contract research 
organization’s qualified compliance auditing team, which is an independent function from the 
study team responsible for conduct of the study. 
Site visits will be conducted by the sponsor or an authorized representative to inspect study data, 
patients’ medical records, and eCRFs. The investigator is to permit national and local health 
authorities; sponsor’s study monitors, representatives, and collaborators; and IRB/IEC members 
to inspect all facilities and records relevant to this study. 
12.4. 
Drug Accountability  
The investigator or designee (ie, pharmacist) is responsible for ensuring adequate accountability 
of all used and unused study drug. This includes acknowledgment of receipt of each shipment of 
study product (quantity and condition), patient drug dispensation records, and returned or 
destroyed study product. Dispensation records will document quantities received from the 
sponsor’s designated depot or its designee and quantities dispensed to patients, including 
batch/lot number, date dispensed, patient identifier number, and the initials of the person 
dispensing the medication. 
At study initiation, the monitor will evaluate the site’s standard operating procedure for study 
drug disposal/destruction to ensure that it complies with sponsor’s requirements specified in the 
pharmacy manual. At appropriate times during the conduct of the study or at the end of the study 
following final drug inventory reconciliation by the monitor, the study site will dispose of and/or 
destroy all unused study drug supplies, including empty containers, according to these 
procedures. If the site cannot meet the sponsor’s requirements specified in the pharmacy manual 
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for disposal, arrangements will be made between the site and the sponsor or its representative for 
destruction or return of unused study drug supplies. 
All drug supplies and associated documentation will be periodically reviewed and verified by the 
study monitor over the course of the study. 
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13. 
ETHICS/PROTECTION OF HUMAN PATIENTS  
13.1. 
Ethical Standard  
This study will be conducted by the principal investigator and the study center 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 patient. The study will also comply 
with the requirements of the ICH E2A guideline (Clinical Safety Data Management: Definitions 
and Standards for Expedited Reporting). 
13.2. 
Institutional Review Board/Independent Ethics Committee  
This protocol, the ICFs, any information to be given to the patient, and any relevant supporting 
information must be submitted, reviewed, and approved by the IRB/IEC before the study is 
initiated. In addition, any patient recruitment materials must be approved by the IRB/IEC. Copies 
of the IEC/IRB correspondence and approval of the amended ICF/other information and the 
approved amended ICF/other information must be forwarded to the sponsor promptly. 
The principal investigator is responsible for providing written summaries of the status of the 
study to the IRB/IEC annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/IEC. Investigators are also responsible for promptly 
informing the IRB/IEC of any protocol amendments. In addition to the requirements for 
reporting all AEs to the sponsor, investigators must comply with requirements for reporting 
SAEs to the local health authority and IRB/IEC. Investigators may receive written 
investigational new drug (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/IEC and archived in the site’s study file. 
13.2.1. 
Protocol Amendments  
Any protocol amendments will be prepared by the sponsor. All protocol modifications must be 
submitted to competent authorities according to local requirements and to the IRB/IEC together 
with, if applicable, a revised model ICF in accordance with local requirements. Written 
documentation from competent authorities (according to local requirements) and from the 
IRB/IEC and required site approval must be obtained by the sponsor before changes can be 
implemented, except for changes necessary to eliminate an immediate hazard to patients or 
changes that involve logistical or administrative aspects only (eg, change in medical monitor or 
contact information). 
Information on any change in risk and/or change in scope must be provided to patients already 
actively participating in the study, and they must read, understand, and sign each revised ICF 
confirming their willingness to remain in the study. 
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13.3. 
Informed Consent  
The sponsor’s sample ICF will be provided to each site. If applicable, it will be provided in a 
certified translation of the local language. The final IRB/IEC-approved ICFs must be provided to 
the sponsor for health authority submission purposes according to local requirements. 
The ICFs must be signed and dated by the patient or the patient’s legally authorized 
representative before his or her participation in the study. The case history or clinical records for 
each patient shall document the informed consent process and that written informed consent was 
obtained prior to participation in the study. 
The ICFs will 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-/IEC-approved consent forms must be provided to the sponsor for health 
authority submission purposes. 
Patients must be reconsented to the most current version of the ICFs (or to a significant new 
information/findings addendum in accordance with applicable laws and IRB/IEC policy) during 
their participation in the study. For any updated or revised ICFs, the case history or clinical 
records for each patient shall document the informed consent process and that written informed 
consent was obtained using the updated/revised ICFs for continued participation in the study. 
A copy of each signed ICF must be provided to the patient or the patient’s legally authorized 
representative. All signed and dated ICFs must remain in each patient’s study file or in the site 
file and must be available for verification by study monitors at any time. 
13.4. 
Patient and Data Confidentiality  
The investigator, institution, sponsor, and site will maintain confidentiality and privacy standards 
for the collection, storage, transmission, and processing of patients’ personal and medical 
information by following applicable laws and regulations related to the confidentiality, use, and 
protection of such information, including the ICH Good Clinical Practice Guideline, as 
implemented locally. Such laws may be more stringent than the requirements in this protocol. 
The investigator and site shall code the personal and medical information obtained during the 
study with a unique patient identification number assigned to each patient enrolled in the study.  
The investigator must ensure that patients’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Unless required to be provided by laws or 
regulations or specifically requested in exceptional circumstances by the sponsor or its 
representatives, the investigator and site must ensure that any personal and medical information 
transmitted to sponsor or its service providers is: 1) required by the protocol, and 2) 
appropriately de-identified (eg, via redaction and/or coding with the patient identification 
number) to ensure the following information about patients are NOT shared: 
• names or initials (full or partial); 
• full dates of birth; 
• contact information (such as phone numbers or home or email addresses);  
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• numerical identifiers (eg, hospital or medical record, government, health insurance, or 
financial account numbers) other than patient identification numbers assigned as part 
of this study; 
• geographic identifiers smaller than a state, province, or local equivalent (such as city, 
county, zip code, or other equivalent geographic identifiers); or  
• information about marital status, family, or household members; employment, sex 
life, sexual preference, or other sensitive data that is not relevant to the study. 
Patient personal and medical information obtained during this study is confidential and may only 
be disclosed to third parties as permitted by the signed ICF (or a separate authorization for the 
use and disclosure of personal health information that has been signed by the patient), unless 
permitted or required by law. 
In limited circumstances, such as in connection with insurance purposes or patient support 
services ancillary to certain study sites (eg, for patient travel or reimbursement), the investigator 
and site may provide certain of this personal information to the sponsor or its representatives.  
Such personal information may not be provided as part of the study protocol (eg, as part of the 
eCRF, on samples or reports submitted to the central lab, on safety reporting forms [except in 
China], or on product dispensing logs provided to the sponsor, etc.). 
Investigator and site must use only the specific forms and clinical trial systems, (eg, the 
electronic data capture [EDC] system and any secure file transfer platforms [SFTPs]) designated 
by sponsor for sharing and transfers of personal and medical information.  
In the event of a breach of the confidentiality of a patient’s personal and medical information, the 
investigator, site, and sponsor, as appropriate, shall fulfill all mediation steps and reporting 
obligations under applicable laws. If the sponsor identifies personal or medical information that 
was not properly de-identified, it may be required to report the disclosure under local applicable 
laws. 
Medical information may be given to a patient’s personal physician or other appropriate medical 
personnel responsible for the patient’s welfare for treatment purposes where allowed by local 
law or the patient’s signed ICF. 
Information generated during this study must be available for inspection upon request by 
representatives of the United States Food and Drug Administration (US FDA), the China 
National Medical Products Administration (China NMPA), and all other national and local 
health authorities; by sponsor monitors, representatives, and collaborators; and by the IRBs/IECs 
for each study site, as appropriate. 
The investigator agrees that all information received from the sponsor, including but not limited 
to the Investigator’s Brochure, this protocol, eCRFs, the investigational drugs, and any other 
study information, are confidential and remain the sole and exclusive property of the sponsor 
during the conduct of the study and thereafter. This information is not to be disclosed to any third 
party (except employees or agents directly involved in the conduct of the study or as required by 
law) without prior written consent from the sponsor. The investigator further agrees to take all 
reasonable precautions to prevent the disclosure by any employee or agent of the study site to 
any third party or otherwise into the public domain. 
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If a written contract for the conduct of the study that includes confidentiality or privacy 
provisions inconsistent with this section is executed, that contract’s provisions shall apply to the 
extent they are inconsistent with this section. 
13.5. 
Financial Disclosure  
Investigators are required to provide the sponsor with sufficient accurate financial information in 
accordance with regulations to allow the sponsor to submit complete disclosure or certification to 
the absence of certain financial interest of the clinical investigators, and/or disclose those 
financial interests, as required, to the appropriate health authorities. This is intended to ensure 
financial interests and arrangements of the clinical investigators with the sponsor that could 
affect reliability of data submitted to health authorities are identified and disclosed by the 
sponsor. Investigators are responsible for providing information about their financial interests 
before participation in the study and to update this information if any relevant changes occur 
during the study and for 1 year after completion of the study (ie, last patient, last visit). 
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14. 
DATA HANDLING AND RECORD KEEPING  
14.1. 
Data Collection and Management Responsibilities  
14.1.1. 
Data Entry in the Electronic Case Report Form  
All study-related data collected or received by the investigator or study team shall be promptly 
entered into the eCRFs. In no event should the entry of the study data into the eCRF be later than 
what is stipulated in the site contract after the data are collected or received by the investigator or 
study team without prior communication with and approval by the sponsor. 
14.1.2. 
Data Collection  
Data required by the protocol will be entered into an electronic data capture (EDC) system. 
Data collection in the eCRF should follow the instructions described in the eCRF Completion 
Guidelines. The investigator has ultimate responsibility for the collection and reporting of all 
clinical data entered in the eCRF. The electronic signature of the investigator or designee must 
be provided in the EDC system to attest to its accuracy, authenticity, and completeness. 
Data contained in the eCRFs are the sole property of the sponsor and should not be made 
available in any form to third parties without written permission from the sponsor, except for 
authorized representatives of the sponsor or appropriate regulatory authorities. 
14.1.3. 
Data Management/Coding  
All final patient data, both eCRF and external data (eg, laboratory data), collected according to 
the protocol will be stored by the sponsor at the end of the study. 
Standard procedures (including following data review guidelines, computerized validation to 
produce queries, and maintenance of an audit file that includes all database modifications) will 
be followed to support accurate data collection. Data will be reviewed for outliers, logic, data 
inconsistencies, and completeness. 
During the study, a study monitor (clinical research associate) will make site visits to review 
protocol compliance, compare eCRFs against individual patient’s medical records, and ensure 
that the study is being conducted according to pertinent regulatory requirements. 
The eCRF entries will be verified with source documentation. The review of medical records 
will be performed in a manner to ensure that patient confidentiality is maintained. Checking the 
eCRFs for completeness, clarity, and cross-checking with source documents is required to 
monitor the progress of the study. Direct access to source data is also required for inspections 
and audits and will be carried out with due consideration given to data protection and medical 
confidentiality. 
The AE verbatim descriptions (the investigator’s description from the eCRF) will be coded using 
MedDRA. AEs will be coded to MedDRA by Lowest Level Term, Preferred Term, and primary 
System Organ Class (SOC). Concomitant medications will be coded using the WHO Drug 
Dictionary. Concomitant diseases/medical history will be coded using MedDRA. 
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14.2. 
Data Integrity and In-house Blinding  
Functions/persons with access to the EDC system shall be prohibited from using the EDC system 
to generate unnecessary listings/summaries that may introduce unwanted bias or to share such 
outputs from the EDC system with other functions/persons who do not have access to the EDC 
system. Analyses or summaries generated by randomized treatment assignment and actual 
treatment received will be limited and documented. 
14.3. 
Study Records Retention  
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least 1 of the following 2 categories: 1) investigator’s study file, and/or 2) 
patient clinical source documents. 
The investigator’s study file will contain the protocol/amendments, eCRF and query forms, 
IRB/IEC and governmental approval with correspondence, ICFs, drug records, staff curriculum 
vitae and authorization forms, and other appropriate documents and correspondence. 
Patient clinical source documents (usually defined by the project in advance to record key 
efficacy/safety parameters independent of the eCRFs) would include documents such as 
(although not be limited to) the following: patient hospital/clinic records, physician’s and nurse’s 
notes, appointment book, original laboratory reports, ECG, electroencephalogram, x-ray, 
pathology and special assessment reports, consultant letters, screening and enrollment logs, etc. 
Following closure of the study, the investigator must maintain all study records in a safe and 
secure location. The records must be maintained to allow easy and timely retrieval when needed 
(eg, audit or inspection) and, whenever feasible, to allow any subsequent review of data in 
conjunction with assessment of the facility, supporting systems, and personnel. Where permitted 
by local laws/regulations or institutional policy, some or all of these records can be maintained in 
a format other than hard copy (eg, microfiche, scanned, electronic); however, caution needs to be 
exercised before such action is taken. The investigator must ensure that all reproductions are 
legible, are a true and accurate copy of the original, and meet accessibility and retrieval 
standards, including regenerating a hard copy, if required. Furthermore, the investigator must 
ensure there is an acceptable backup of these reproductions and that an acceptable quality control 
process exists for making these reproductions. 
The sponsor will inform the investigator of the time period for retaining these records to comply 
with all applicable regulatory requirements. The minimum retention time will meet the strictest 
standard applicable to that study center for the study, as dictated by any institutional 
requirements, local laws or regulations, or the sponsor’s standards/procedures; otherwise, the 
retention period will default to 15 years. 
The investigator must notify the sponsor of any changes in the archival arrangements, including 
but not limited to the following: archival at an off-site facility, or transfer of ownership of or 
responsibility for the records in the event the investigator leaves the study center. 
If the investigator cannot guarantee this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and the sponsor to 
store these in sealed containers outside of the site so that they can be returned sealed to the 
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investigator in case of a regulatory audit. When source documents are required for the continued 
care of the patient, appropriate copies should be made for storage outside of the site. 
Biological samples at the conclusion of this study may be retained as outlined in the agreement 
with the Contract Research Organization managing the biological samples, for the shorter of a 
period of up to 10 years or as allowed by your IRB/IEC. 
14.4. 
Protocol Deviations  
The investigator is responsible for ensuring that the study is conducted in accordance with the 
procedures and evaluations described in this protocol. Investigators assert they will apply due 
diligence to avoid protocol deviations and shall report all protocol deviations to sponsor. 
The investigator is to document and explain any deviations from the approved protocol. The 
investigator must promptly report any major deviations that might impact patient safety and/or 
data integrity to the sponsor and to the IRB/IEC, in accordance with established IRB/IEC 
policies and procedures. 
14.5. 
Study Report and Publications  
A clinical study report will be prepared and provided to the regulatory agency(ies). The sponsor 
will ensure that the report meets the standards set out in the ICH Guideline for Structure and 
Content of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in 
certain cases. 
The results of this study will be published or presented at scientific meetings in a timely, 
objective, and clinically meaningful manner that is consistent with good science, industry and 
regulatory guidance and the need to protect the intellectual property of the sponsor, regardless of 
the outcome of the study. The data generated in this clinical study are the exclusive property of 
the sponsor and are confidential. As this is a multicenter study, the first publication or disclosure 
of study results shall be a complete, joint multicenter publication or disclosure coordinated by 
the sponsor. Thereafter, any secondary publications will reference the original publication(s). 
Authorship will be determined by mutual agreement and all authors must meet the criteria for 
authorship established by the International Committee of Medical Journal Editors Uniform 
Requirements for Manuscripts or stricter local criteria (International Committee of Medical 
Journal Editors 2018). 
Each investigator agrees to submit all manuscripts, abstracts, posters, publications, and 
presentations (both oral and written) to the sponsor for review before submission or presentation 
in accordance with the clinical study agreement. This allows the sponsor to protect proprietary 
information, provide comments based on information from other studies that may not yet be 
available to the investigator, and ensure scientific and clinical accuracy. The details of the 
processes of producing and reviewing reports, manuscripts, and presentations based on the data 
from this study will be presented in the investigator’s clinical study agreement. Each investigator 
agrees that, in accordance with the terms of the clinical study agreement, a further delay of the 
publication/presentation may be requested by the sponsor to allow for patent filings and/or 
protection in advance of the publication/presentation. 
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14.6. 
Study and Study Center Closure  
Upon completion of the study, the monitor will conduct the following activities in conjunction 
with the investigator or study center personnel, as appropriate: 
• Return of all study data to the sponsor 
• Resolution and closure of all data queries 
• Accountability, reconciliation, and arrangements for unused study drug(s) 
• Review of study records for completeness 
• Collection of all study documents for the trial master file filing according to GCP and 
local regulation 
• Shipment of samples (including, but not limited to, those for PK, ADA, and 
biomarkers) to the assay laboratory for central laboratory analysis according to 
protocol and laboratory manual requirements  
In addition, the sponsor reserves the right to suspend the enrollment or prematurely discontinue 
this study either at a single study center or at all study centers at any time for any reason. 
Potential reasons for suspension or discontinuation include but are not limited to safety or ethical 
issues or noncompliance with this protocol, GCP, the sponsor’s written instructions, the clinical 
study agreement, or applicable laws and regulations. If the sponsor determines that such action is 
needed, the sponsor will discuss this with the investigator (including the reasons for taking such 
action) at that time. When feasible, the sponsor will provide advance notification to the 
investigator of the impending action before it takes effect. 
The sponsor will promptly inform all other investigators and/or institutions conducting the study 
if the study is suspended or terminated for safety reasons. The sponsor will also inform the 
regulatory authorities of the suspension or termination of the study and the reason(s) for the 
action. If required by applicable regulations, the investigator must inform the IEC/IRB promptly 
and provide the reason for the suspension or termination. 
If the study is prematurely discontinued, all study data must still be provided to the sponsor. In 
addition, arrangements will be made for the return of all unused study drug(s) in accordance with 
the applicable sponsor procedures for the study.  
Financial compensation to the investigators and/or institutions will be in accordance with the 
clinical study agreement established between the investigator and/or institutions and the sponsor. 
14.7. 
Information Disclosure and Inventions  
All rights, title, and interests in any inventions, know-how, or other intellectual or industrial 
property rights that are conceived or reduced to practice by the study center personnel during the 
course of or as a result of the study are the sole property of the sponsor and are hereby assigned 
to the sponsor. 
If a written contract for the conduct of the study, which includes ownership provisions 
inconsistent with this statement, is executed between the sponsor and the study center, that 
contract’s ownership provisions shall apply rather than this statement. 
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All information provided by the sponsor and all data and information generated by the study 
center as part of the study (other than a patient’s medical records) are the sole property of the 
sponsor and will be kept confidential by the investigator and other study center personnel. 
This information and data will not be used by the investigator or other study center personnel for 
any purpose other than conducting the study without the prior written consent of the sponsor. 
These restrictions do not apply to: 
• Information that becomes publicly available through no fault of the investigator or 
study center personnel 
• Information that is necessary to disclose in confidence to an IEC/IRB solely for the 
evaluation of the study 
• Information that is necessary to disclose to provide appropriate medical care to a 
patient 
• Study results that may be published as described in Section 14.5 
If a written contract for the conduct of the study, which includes provisions inconsistent with this 
statement is executed, that contract’s provisions shall apply rather than this statement. 
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15. 
REFERENCES  
American Association for the Study of Liver Diseases and the Infectious Diseases Society of 
America HCV guidance panel. HCV Guidance: Recommendations for Testing, Managing, and 
Treating Hepatitis C. 2021. Accessed May 27, 2021. https://www.hcvguidelines.com.  
Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: 
continuing to build a bridge from a population-based to a more “personalized” approach to 
cancer staging. CA Cancer J Clin. 2017;67:93-99.  
BeiGene Investigator’s Brochure, Ociperlimab (BGB-A1217). Edition 5.0, November 2023.  
BeiGene Investigator’s Brochure, Tislelizumab (BGB-A317). Edition 11.0, January 2024.  
Bendell JC, Bedard P, Bang Y-J, et al. Phase Ia/Ib dose-escalation study of the anti-TIGIT 
antibody tiragolumab as a single agent and in combination with atezolizumab in patients with 
advanced solid tumors [AACR abstract CT302]. Cancer Res. 2020;80(suppl 16).  
Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab Versus Docetaxel in Advanced Nonsquamous 
Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373:1627-39.  
Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of Immune-Related Adverse Events 
in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical 
Oncology Clinical Practice Guideline. J Clin Oncol. 2018;36(17):1714-68.  
Chauvin J, Pagliano O, Fourcade J, et al. TIGIT and PD-1 Impair Tumor Antigen-Specific 
Cd8(+) T Cells in Melanoma Patients. J Clin Invest. 2015;125:2046-58.  
Chen W, Zheng R, Baade PD, et al. Cancer Statistics in China, 2015. CA Cancer J Clin. 
2016;66(2):115-32.  
Choi YL, Takeuchi K, Soda M, et al. Identification of novel isoforms of the EML4-ALK 
transforming gene in non-small cell lung cancer. Cancer Res. 2008;68(13):4971–76.  
Clinical Trials Facilitation and Coordination Group (CTFG). Recommendations Related to 
Contraception and Pregnancy Testing in Clinical Trials. Published September 21, 2020. 
Available at: https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2020_09_HMA_CTFG_Contraception_guidance_Versio
n_1.1_updated.pdf.  
Dixon KO, Schorer M, Nevin J, et al. Functional Anti-TIGIT Antibodies Regulate Development 
of Autoimmunity and Antitumor Immunity. J Immunol. 2018;200:3000-7.  
Dolgin M, Association NYH, Fox AC, Gorlin R, et al. Nomenclature and Criteria for Diagnosis 
of Diseases of the Heart and Great Vessels. 9th ed. Boston, MA: Lippincott Williams and 
Wilkins; March 1, 1994.  
Eisenhauer EA, Therasse P, Bogaerts J, et al. New Response Evaluation Criteria in Solid 
Tumours: Revised Recist Guideline (Version 1.1). Eur J Cancer. 2009;45(2):228-47.  
European Society for Medical Oncology (ESMO) Clinical Practice Guidelines. Metastatic 
Non-Small Cell Lung Cancer: ESMO Clinical Practice Guidelines For Diagnosis, Treatment and 
Follow-Up. 2020. Available from: https://www.esmo.org/guidelines/lung-and-chest-
tumours/clinical-practice-living-guidelines-metastatic-non-small-cell-lung-cancer. Accessed 01 
June 2021.  
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European Society for Medical Oncology (ESMO) Guidelines Committee. eUpdate-Early and 
Locally Advanced Non-Small-Cell Lung Cancer (NSCLC) Treatment Recommendations. 
Published 04 May 2020. Available from: https://www.esmo.org/guidelines/guidelines-by-
topic/lung-and-chest-tumours/early-stage-and-locally-advanced-non-metastatic-non-small-cell-
lung-cancer/eupdate-early-and-locally-advanced-non-small-cell-lung-cancer-nsclc-treatment-
recommendations.  
Fehrenbacher L, Spira A, Ballinger M, et al. Tislelizumab Versus Docetaxel for Patients With 
Previously Treated Non-Small-Cell Lung Cancer (POPLAR): a Multicentre, Open-Label, Phase 
2 Randomised Controlled Trial. Lancet. 2016;387:1837-46.  
Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University 
School of Medicine (2007). https://drug-interactions.medicine.iu.edu/ Accessed 09 March 2021.  
Food and Drug Administration. Drug Development and Drug Interactions: Table of Substrates, 
Inhibitors and Inducers. U.S. Department of Health and Human Services, Food and Drug 
Administration. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-
anddrug-interactions-table-substrates-inhibitors-and-inducers. Accessed 09 March 2021.  
Fourcade J, Sun Z, Chauvin J, et al. CD226 Opposes TIGIT to Disrupt Tregs in Melanoma JCI 
Insight. 2018;3(14):e121157.  
Gadgeel S, Rodríguez-Abreu D, Speranza G, et al. Updated Analysis From KEYNOTE-189: 
Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic 
Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2020;38(14):1505-17.  
Gandara D, Paul S, Kowanetz M, et al. Blood-Based Tumor Mutational Burden as a Predictor of 
Clinical Benefit in Non-Small-Cell Lung Cancer Patients Treated With Atezolizumab. Nat Med. 
2018 Sep;24(9):1441-8.  
Goodman A, Kato S, Bazhenova L, et al. Tumor Mutational Burden as an Independent Predictor 
of Response to Immunotherapy in Diverse Cancers. Mol Cancer Ther. 2017 Nov;16(11):2598-
2608.  
Haanen JBAG, Carbonnel F, Robert C, et al. Management of Toxicities From Immunotherapy: 
ESMO Clinical Practice Guidelines for Diagnosis, Treatment, and Follow-Up. Ann Oncol. 
2017:28 (suppl 4):iv119-42.  
Hanna N, Johnson D, Temin S, et al. Systemic Therapy for Stage IV Non–Small-Cell Lung 
Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin 
Oncol. 2017;35(30):3484-515.  
Hellmann MD, Paz-Ares L, Caro RB, et al. Nivolumab plus Ipilimumab in Advanced Non–
Small-Cell Lung Cancer. N Engl J Med. 2019;381:2020-31.  
Herbst RS, Baas P, Kim D-W, et al. Pembrolizumab Versus Docetaxel for Previously Treated 
PD-L1-Positive, Advanced Non-Small-Cell Lung Cancer (KEYNOTE-010): a Randomised 
Controlled Trial. Lancet. 2016;387;1540-50.  
Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for First-Line Treatment of PD-L1-
Selected Patients with NSCLC. New Engl J Med. 2020;383:1328-39.  
Herbst RS, Soria JC, Kowanetz M, et al. Predictive Correlates of Response to the Anti-PD-L1 
Antibody Tislelizumab in Cancer Patients. Nature. 2014;515:563-7.  
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Horn L, Pao W. EML4-ALK: honing in on a new target in non-small cell lung cancer. J Clin 
Oncol. 2009;27(26):4232-35.  
Human Protein Atlas. https://www.proteinatlas.org/ENSG00000181847-TIGIT/tissue. Accessed 
02 January 2019.  
International Committee of Medical Journal Editors. Recommendations for the Conduct, 
Reporting, Editing, and Publication of Scholarly Work in Medical Journals. 2018. 
http://www.icmje.org/icmje-recommendations.pdf. Published December 2018. Accessed 10 
September 2019.  
Jiang P, Gu S, Pan D, et al. Signatures of T Cell Dysfunction and Exclusion Predict Cancer 
Immunotherapy Response. Nat Med. 2018;24(10):1550-8.  
Johnston R, Comps-Agrar L, Hackney J, et al. The Immunoreceptor TIGIT Regulates Antitumor 
and Antiviral CD8(+) T Cell Effector Function. Cancer Cell. 2014;26:923-37.  
Kelly K, Crowley J, Bunn Jr PA, et al. Randomized phase III trial of paclitaxel plus carboplatin 
versus vinorelbine plus cisplatin in the treatment of patients with advanced non–small-cell lung 
cancer: A Southwest Oncology Group trial. J Clin Oncol. 2001:19(13):3210-18.  
Kim CG, Kim KH, Pyo K-H, et al. Hyperprogressive Disease During PD-1/PD-L1 Blockade in 
Patients With Non-Small-Cell Lung Cancer. Ann of Oncol. 2019;30:1104-13.  
Koivunen JP, Mermel C, Zejnullahu K, et al. EML4-ALK fusion gene and efficacy of an ALK 
kinase inhibitor in lung cancer. Clin Cancer Res. 2008;14(13):4275-83.  
Koren E, Smith HW, Shores E, et al. Recommendations on Risk-Based Strategies for Detection 
and Characterization of Antibodies Against Biotechnology Products. J Immunol Methods. 
2008;333(1-2):1-9.  
Kottschade LA. The future of immunotherapy in the treatment of cancer. Seminars in Oncology 
Nursing. 2019; 35(5):150934.  
Labrijn AF, Buijsse AO, van den Bremer ET, et al. Therapeutic IgG4 Antibodies Engage in 
Fab-Arm Exchange With Endogenous Human IgG4 In Vivo. Nat Biotechnol. 2009;27(8):767-
71.  
Levey AS, Stevens LA, Schmid CH, et al. A New Equation to Estimate Glomerular Filtration 
Rate. Ann Intern Med. 2009;150(9):604-12.  
Lu S, Yu, Y, Barnes G, et al. Health related quality of life in patients with non-squamous 
NSCLC. North America Conference on Lung Cancer. October 15-17, 2020.  
Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of 
adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). 
Am J Cancer Res. 2015;5(9):2892-911.  
Mok T, Wu Y-L, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, 
PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): 
a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393(10183):1819-30.  
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National Cancer Institute Common Toxicity Criteria for Adverse Events Version 5.0. 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_5x7.pdf. Published 27 November 2017. Accessed 19 March 2021.  
Niu J, Nagrial A, Voskoboynik M, et al. Safety and Efficacy of Vibostolimab, an Anti-TIGIT 
Antibody, Plus Pembrolizumab in Patients With Anti-PD-1/PDL1-Naive NSCLC. European 
Society for Medical Oncology (ESMO), September 2020, 1410P.  
Ohe Y, Ohashi Y, Kubota K, et al. Randomized Phase 3 study of cisplatin plus irinotecan versus 
carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for 
advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol. 
2007;18(2):317-23.  
Oken MM, Creech RH, Tormey DC, et al. Toxicity and Response Criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-55.  
Paz-Ares L, Luft A, Vicente D, et al. Pembrolizumab plus Chemotherapy for Squamous Non–
Small-Cell Lung Cancer. N Engl J Med. 2018;379:2040-51.  
Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with 
two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an 
international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(2):198-211.  
PDQ Adult Treatment Editorial Board. Non-Small Cell Lung Cancer Treatment (PDQ®): Health 
Professional Version. 2020 May 20. In: PDQ Cancer Information Summaries [Internet]. National 
Cancer Institute (US); 2002. https://www.ncbi.nlm.nih.gov/books/NBK65917/. Accessed 01 
September 2020.  
Pellegrino R, Viegi G, Brusasco V, et al. Interpretative Strategies for Lung Function Tests. Eur 
Respir J. 2005;25(5):948-68.  
Reck M, Rodríguez-Abreu D, et al. KEYNOTE-024 Investigators. Pembrolizumab Versus 
Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 
2016;375(19):1823-33.  
Rodriguez-Abreu D, Johnson ML, Hussein MA, et al. Primary Analysis of a Randomized, 
Double-Blind, Phase II Study of the Anti-TIGIT Antibody Tiragolumab (Tira) Plus 
Atezolizumab (Atezo) Versus Placebo Plus Atezo as First-Line Treatment in Patients With 
PD-L1-Seleceted NSCLC (CITYSCAPE). J Clin Oncol. 2020;38(suppl; abstr 9503).  
Rosenberg JE, Hoffman-Censits J, Powles T, et al. Tislelizumab in Patients With Locally 
Advanced and Metastatic Urothelial Carcinoma Who Have Progressed Following Treatment 
With Platinum-Based Chemotherapy: a Single-Arm, Multicentre, Phase 2 Trial. Lancet. 
2016;387:1909-20.  
Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-
small-cell lung cancer. N Engl J Med. 2006;355(24):2542-50.  
Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine 
with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-
cell lung cancer. J Clin Oncol. 2008; 26:3543-51.  
Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for 
advanced non-small-cell lung cancer. N Engl J Med. 2002;346(2):92-8.  
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Siegel RL, Miller KD, Jemal A. Cancer Statistics 2020. CA: A Cancer Journal for Clinicians. 
2020;70(1):7-30.  
Soar J, Pumphrey R, Cant A, et al. Emergency Treatment of Anaphylactic Reactions--Guidelines 
for Healthcare Providers. Resuscitation. 2008;77(2):157-69.  
Tassi E, Grazia G, Vegetti C, et al. Early Effector T Lymphocytes Coexpress Multiple Inhibitory 
Receptors in Primary Non-Small Cell Lung Cancer. Cancer Res. 2017;77: 851-61.  
Terrault NA, Bzowej NH, Chang KM, et al. AASLD Guidelines for Treatment of Chronic 
Hepatitis B. Hepatology. 2016;63(1):261-83.  
Topalian SL, Hodi FS, Brahmer JR, et al. Safety, Activity, and Immune Correlates of Anti-PD-1 
Antibody in Cancer. N Engl J Med. 2012;366:2443-54.  
Vilain R, Menzies A, Wilmott J, et al. Dynamic Changes in PD-L1 Expression and Immune 
Infiltrates Early During Treatment Predict Response to PD-1 Blockade in Melanoma. Clin 
Cancer Res. 2017;23(17):5024-33.  
Wang J, Yu X, Barnes G, et al. Tislelizumab plus standard chemotherapy and health-related 
quality of life in patients with advanced squamous non-small cell lung cancer. North America 
Conference on Lung Cancer. October 15-17, 2020.  
Wang J, Lu S, Yu XM, et al. Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as First-
line Treatment for Advanced Squamous Non–Small-Cell Lung Cancer: A Phase 3 Randomized 
Clinical Trial. JAMA Oncology. 2021;7(5):709-17.  
Wang Z, Zhao J, Ma Z, et al. Tislelizumab plus chemotherapy as first-line treatment for lung 
cancer in Chinese Patients [ESMO-IO Abstract 66P]. Ann Oncol. 2020;31(7_suppl):S1441-51.  
West H, McCleod M, Hussein M, et al. Atezolizumab in Combination With Carboplatin Plus 
nab-Paclitaxel Chemotherapy Compared With Chemotherapy Alone as First-Line Treatment for 
Metastatic Non-Squamous Non-Small-Cell Lung Cancer (IMpower130): a Multicentre, 
Randomised, Open-Label, Phase 3 Trial. Lancet Oncol. 2019;20(7):924-37.  
World Health Organization. Cancer, https://www.who.int/news-room/fact-sheets/detail/cancer. 
Accessed on 19 February 2021.  
Worobec AS, Rosenberg AS. A Risk-Based Approach to Immunogenicity Concerns of 
Therapeutic Protein Products, Part 1: Considering Consequences of the Immune Response to a 
Protein. BioPharm Intl. 2004a;17(11).  
Worobec AS, Rosenberg AS. A Risk-Based Approach to Immunogenicity Concerns of 
Therapeutic Protein Products, Part 2: Considering Host-Specific and Product-Specific Factors 
Impacting Immunogenicity. BioPharm Intl. 2004b;17(12).  
Wu CY, Budha N, Gao Y, et al. Tislelizumab Exposure-Response Analyses of Efficacy and 
Safety in Patients with Advanced Tumors [ESMO Abstract 482P]. Ann Oncol. 
2019a;30(suppl 5):mdz244.044.  
Wu CY, Tang Z, Liu L, et al. Population Pharmacokinetics of Tislelizumab in Patients with 
Advanced Tumors [ESMO Abstract 483P]. Ann Oncol. 2019b;30(suppl 5):mdz244.045.  
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Yang Z. Expression and Function of TIGIT in B-Cell Non-Hodgkin Lymphoma. Blood. 
2016;128:4138.  
Yue D, Wang W, Liu H, et al. Pathological response to neoadjuvant tislelizumab plus 
platinum-doublet chemotherapy in resectable stage II-IIIA NSCLC patients in the phase 3 
RATIONALE-315 trial [Abstract LBA-58]. Abstract presented at the European Society for 
Medical Oncology World Congress. October 20-24, 2023. Madrid, Spain.  
Zhang T, Song X, Xu L, et al. The Binding of an Anti-PD-1 Antibody to FcγRΙ has a Profound 
Impact on its Biological Functions. Cancer Immunol Immunother. 2018;67(7):1079-90.  
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NCI-CTCAE v5.0, National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0; NSCLC, non-small cell lung cancer; PD-L1, 
programmed cell death ligand-1; PET, positron emission tomography; PK, pharmacokinetic(s); RECIST v1.1, Response Evaluation Criteria in Solid Tumors, 
Version 1.1; SAE, serious adverse event; ctDNA, circulating tumor DNA; TMB, tumor mutation burden; TSH, thyroid-stimulating hormone; v, version. 
a Written informed consent is required before performing any study-specific tests or procedures. Results of standard-of-care tests or examinations that were 
performed before obtaining informed consent and within 28 days before randomization may be used for screening assessments rather than repeating such tests. 
b The End of Treatment Visit will be conducted when the investigator determines that ociperlimab or tislelizumab will no longer be used. (Section 3.4). If routine 
laboratory tests (eg, hematology, serum chemistry) are completed within 7 days before the EOT Visit, tests need not be repeated.  
c A Safety Follow-Up Visit at 30 days (± 7 days) after the last dose of the study drug(s) is required to assess AEs and concomitant medications, unless the time 
window overlaps the time window of the EOT Visit; the Safety Follow-Up Visit may be a telephone call or an on-site visit if laboratory assessments are 
necessary. Two additional telephone calls with patients will occur in the safety follow-up period to assess imAEs and concomitant medications if appropriate 
(ie, if associated with an imAE or a new anticancer therapy) at 60 and 90 days (± 14 days) after the last dose of ociperlimab (or placebo) and/or tislelizumab 
regardless of whether the patient starts a new subsequent anticancer therapy. If a patient reports a suspected imAE at a safety follow-up telephone call, the 
investigator should arrange an unscheduled visit if further assessment is indicated. Patients who discontinue study treatment before disease progression will 
need to undergo tumor assessments as outlined in Section 7.5.   
d Survival follow-up information will be collected via telephone calls, patient medical records, and/or clinic visits approximately every 3 months (± 14 days) 
after the EOT Visit or as directed by the sponsor until death, loss to follow-up, withdrawal of consent, or study termination by sponsor. All patients will be 
followed for survival and subsequent anticancer therapy information unless a patient requests to be withdrawn from survival follow-up. 
e Patients will be randomized in a 1:1 ratio to either Arm A (ociperlimab + tislelizumab + chemotherapy) or Arm B (placebo + tislelizumab + chemotherapy via 
IRT. All patients are required to receive study treatment within 2 business days of randomization. 
f Includes age or year of birth, sex, and self-reported race/ethnicity, and history of treatment for the primary diagnosis, including prior medication, loco-regional 
treatment(s), and surgical treatment(s). Information on radiographic studies performed before study entry may be collected for review by the investigator. 
Pre-existing AEs at baseline should be recorded as medical history. 
g EGFR, ALK, BRAF V600E, and ROS1 mutational status, if known, will be collected. Patients with non-squamous NSCLC and unknown EGFR mutational 
status will be required to have a tissue-based EGFR test performed either locally or centrally at screening. Local PD-L1 testing may be used for patient 
randomization purposes, in which case, the local PD-L1 testing results will be collected in the eCRF. If local PD-L1 testing will not be used for patient 
randomization purposes, local PD-L1 testing results, if available, will not be collected in the eCRF. 
h Vital signs collected on study include body temperature (°C), pulse rate, and blood pressure (systolic and diastolic) after patients have rested for 10 minutes. 
Vital signs will be recorded at screening, on Day 1 of each cycle, and at the EOT Visit. The patient’s vital signs are required to be recorded within 60 minutes 
before, during, and 30 minutes after completion of study drug infusion on Cycle 1 Day 1. For subsequent infusions, vital signs will be collected within 60 
minutes before infusion and, if clinically indicated, during and 30 minutes after the infusion. Height will be recorded at screening only. Weight will be recorded 
at screening, on Day 1 of each cycle, and at the EOT Visit. 
i A complete physical examination is required at screening; subsequent visits will entail limited, symptom-directed physical examinations (as detailed in 
Section 7.4.2). For patients with squamous NSCLC receiving nab-paclitaxel during the induction phase (first 4-6 cycles), a symptom-directed physical 
examination will also be performed weekly on Day 8 and Day 15 of each of these cycles.  
j The ECG recordings will be obtained during screening, the EOT Visit, and as clinically indicated at other timepoints. Patients should be resting in a 
semi-recumbent supine position for at least 10 minutes before each ECG collection. 
k The AEs and laboratory abnormalities will be graded per NCI-CTCAE v5.0. All AEs will also be evaluated for seriousness. After the main ICF has been 
signed, but before the first administration of the study drug(s), only SAEs should be recorded. After the initiation of the study drug(s), all AEs and SAEs, 
regardless of relationship to study drug(s), will be reported until either 30 days after last dose of all study drug(s) or the initiation of new anticancer therapy, 
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whichever occurs first. Immune-mediated AEs (serious or non-serious) should be reported until 90 days after the last dose of ociperlimab and tislelizumab, 
regardless of whether or not the patient starts a new anticancer therapy. All SAEs considered related to the study drug(s) that are brought to the attention of the 
investigator should be reported regardless of time since the last dose of treatment. For non-squamous NSCLC receiving nab-paclitaxel, review of AEs and 
concomitant medications may be conducted by telephone on Days 8 and 15. The patient should be asked if any new symptoms have been observed or existing 
symptoms may have worsened, and if there have been any changes to medications. The investigators should remind patients to return to the clinical study site 
for further assessment if new AEs arise or worsen.  
l Local laboratory assessments of serum chemistry, hematology, coagulation, and urinalysis will be conducted, of which certain elements will be collected as 
specified in Appendix 2. If laboratory tests of serum chemistry (including liver function), hematology, and coagulation at screening are performed > 7 days 
before randomization, these tests must be repeated within 3 days prior to Cycle 1 Day 1. Hematology and serum chemistry (data collected as specified in 
Appendix 2) will be performed on Day 1 of each cycle. For patients with squamous NSCLC receiving nab-paclitaxel during the induction phase (first 4 to 6 
cycles), hematology will also be performed weekly on Day 8 and Day 15 of each of these cycles before the administration of nab-paclitaxel. After Cycle 1, 
results are to be reviewed within 48 hours before study drug administration. Coagulation assays will be performed at screening, on Day 1 of each cycle, and at 
the EOT Visit. Urinalysis is to be conducted during the treatment period only if clinically warranted. Refer to Section 8.3.5 for additional information regarding 
clinical assessment and management of clinical laboratory abnormalities. 
m All patients will have CK and CK-MB testing at screening, each cycle assessments, the EOT Visit, and the safety follow-up visits. If laboratory tests of cardiac 
enzymes at screening are performed > 7 days before randomization, these tests must be repeated within 3 days prior to Cycle 1 Day 1. If CK-MB fractionation 
is not available, troponin I and/or troponin T may be tested instead. Refer to Section 8.3.5 for additional information regarding clinical assessment and 
management of clinical laboratory abnormalities. 
n Urine or serum pregnancy test (for women of childbearing potential, including women who have had a tubal ligation) must be performed and documented as 
negative within 7 days before randomization. Urine pregnancy tests will be performed at each visit before dosing, and at the EOT Visit, until 120 days after the 
last dose of ociperlimab and/or tislelizumab or 180 days after the last dose of chemotherapy, whichever comes later. A serum pregnancy test must be performed 
if the urine pregnancy test is positive or equivocal. 
o Analysis of FT3 (or total T3 for sites where free T3 testing is not performed), FT4, and TSH will be performed by a local study site laboratory. Thyroid 
function tests will be performed at screening or on C1D1 prior to dosing, and then every 2 cycles (ie, Day 1 of Cycles 3, 5, and 7, etc.), and at the EOT Visit.  
p A COVID-19 test may be conducted according to local practice. 
q At screening, patients will be tested for HIV serology (antigen and/or antibodies) for patients with unknown HIV status, hepatitis B surface antigen, hepatitis B 
surface antibody, total hepatitis B core antibody (HBcAb), and HCV antibody. Viral load assessment (HBV DNA or HCV RNA) will be performed only when 
HBsAg or HCV antibody is positive, respectively. Patients who have detectable HBV DNA or HCV RNA at screening will perform the respective viral load 
test every 4 cycles (ie, Day 1 of Cycle 5, 9, and 13, etc.).  
r Pulmonary function testing including spirometry and assessment of oxygenation, at a minimum, pulse oximetry at rest and with exercise, or alternatively, 
assessment of diffusion capacity, are to be performed for all patients during the screening period to assist the determination of suitability on the study. 
Respective test results need to be submitted to the sponsor. For test results indicative of significantly impaired pulmonary function, eg, resting pulse oximetry 
< 90% on room air and further desaturation upon exercise, FEV1 < 60% or DLCO (if performed) < 60% of age and sex adjusted predicted performance levels 
(Pellegrino et al 2005), the medical monitor needs to be consulted to confirm eligibility. Tests may be repeated as clinically indicated while on study. 
s Procedures for collection of blood samples to evaluate ociperlimab and tislelizumab PK are described in the laboratory manual. Predose samples (within 
60 minutes before starting infusion) are required to be collected on Day 1 of Cycles 1, 2, 5, 9, and 17. Postdose samples (within 30 minutes after completing 
study drug infusion) are required to be collected on Day 1 of Cycles 1 and 5. An additional PK sample is required to be collected at the EOT Visit. Should a 
patient present with any ≥ Grade 3 imAE, an additional blood PK sample may be taken. These tests are required when it is allowed by local 
regulations/IRBs/IECs. 
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t Blood used to test for anti-ociperlimab and anti-tislelizumab antibodies will be collected within 60 minutes before beginning the Day 1 infusion of Cycles 1, 2, 
5, 9, and 17 and at the EOT Visit. All samples should be collected at the same time as blood collection for predose PK analysis. These tests are required when it 
is allowed by local regulations/IRBs/IECs. 
u Radiologic images that are captured as standard of care before obtaining written informed consent and ≤ 28 days before randomization may be used rather than 
repeating tests. All measurable and evaluable lesions are required to be assessed and documented at the Screening Visit and reassessed at each subsequent 
tumor evaluation. The same radiographic procedure used to assess disease sites at Screening is required to be used throughout the study (eg, the same imaging 
protocol for CT or MRI). Imaging of the brain (preferably MRI) is required for all patients during screening. Bone scan or PET is required if clinically 
indicated. During the study, tumor imaging will be performed every 9 weeks (± 7 days) from randomization for the first 52 weeks and then every 12 weeks 
(± 7 days) based on RECIST v1.1. Tumor assessments are required to be performed on schedule regardless of whether study treatment has been administered or 
held; they should not be adjusted for possible delays in cycles. Tumor assessment should continue until radiologic disease progression as determined by the 
investigator. Patients who discontinue study treatment early for reasons other than radiologic disease progression (eg, toxicity) will continue to undergo tumor 
assessments following the original plan until the patient experiences disease progression or death, withdraws consent, is lost to follow-up, or until the study 
terminates, whichever occurs first. See also Section 7.5. 
v Patients are required to provide archival tumor tissues during screening period if available (FFPE blocks or approximately 6 to 15 freshly cut unstained slides) 
for prospective analysis of PD-L1 status, or retrospective analysis of PD-L1 status for subjects that are randomized using the local PD-L1 results, and for 
retrospective analysis of other biomarkers (Section 7.7) and for EGFR testing if the patient has non-squamous NSCLC and unknown EGFR status. Note: For 
sites in mainland China, tissue samples will be obtained to test biomarkers limited to the expression of TIGIT, CD226, CD155, CD112, and PD-L1, GEP, 
TMB, gene mutations and MSI, and TILs at baseline and at disease progression/reoccurrence. 
w In the absence of archival tumor tissues, a fresh biopsy of a tumor lesion at baseline is required. See Section 7.7 for more information. Patients who have 
progressive disease will be asked to provide an optional biopsy at the EOT Visit for the assessment of mechanism of resistance (written informed consent is 
required before obtaining an optional fresh tumor biopsy). 
x Blood samples are required to be collected predose on Day 1 of Cycle 1, predose on Day 1 of Cycle 3, and at the EOT Visit after disease progression to 
evaluate biomarkers including, but not limited to, ctDNA, TMB, MSI, gene mutations, and EVs in blood. Note: Blood-based biomarkers, including ctDNA, 
TMB, MSI, gene mutations, and EVs will be explored for blood samples collected at sites in mainland China.  
y Ociperlimab will be given intravenously once every 3 weeks in Arm A. On Day 1 of Cycles 1 and 2, ociperlimab will be delivered over 60 minutes. If well 
tolerated, subsequent infusions can be administered over ≥ 30 minutes. The first dose will be given on Cycle 1 Day 1 and subsequent dosing will continue on 
the scheduled 21-day intervals. Ociperlimab infusion must always occur after the infusion of tislelizumab has been completed. Patients must be monitored after 
study treatment infusions are complete as shown in Table 5. 
z Tislelizumab will be given intravenously once every 3 weeks. On Day1 of Cycles 1 and 2, tislelizumab will be delivered over 60 (± 5) minutes. If well 
tolerated, subsequent infusions can be administered over ≥ 30 (± 5) minutes. The first dose will be given on Cycle 1 Day 1 and subsequent dosing will continue 
on the scheduled 21-day intervals. Note: Tislelizumab must not be concurrently administered with any other drug. Patients must be monitored after study 
treatment infusions are complete as shown in Table 5. 
aa Ociperlimab placebo infusions will be given intravenously once every 3 weeks in Arm B. On Day 1 of Cycles 1 and 2, placebo infusions will be delivered over 
60 (± 5) minutes. If well tolerated, subsequent infusions can be administered over 30 (± 5) minutes. The first dose will be given on Cycle 1 Day 1 and 
subsequent dosing will continue on the scheduled 21-day intervals. Placebo infusions must always occur after the infusion of tislelizumab has been completed. 
Patients must be monitored after study treatment infusions are complete as shown in Table 5. 
bb Doublet chemotherapy will be given for 4 cycles (pemetrexed plus platinum will be given for 4 to 6 cycles for patients with non-squamous NSCLC, 
paclitaxel/nab-paclitaxel plus platinum will be given for 4 to 6 cycles for patients with squamous NSCLC). For patients with non-squamous NSCLC whose 
disease has not progressed after 4 to 6 cycles of doublet chemotherapy, maintenance treatment of pemetrexed is permitted. For patients with squamous NSCLC, 
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the histology-based chemotherapy regimen will be carboplatin AUC 5 or 6 (D1) + paclitaxel 175 or 200 mg/m2 (D1) or nab-paclitaxel 100 mg/m2 (D1, D8, 
D15) administered every 3 weeks. For patients with non-squamous NSCLC, the histology-based chemotherapy regimen will be cisplatin 75 mg/m2 or 
carboplatin AUC 5 (D1) + pemetrexed 500 mg/m2 (D1) IV administered every 3 weeks. 
During maintenance, patients with non-squamous NSCLC only will receive pemetrexed 500 mg/m2 (D1) IV administered every 3 weeks. 
cc To be completed before any clinical activities during on-study site visits. EORTC QLQ-C30 and QLQ-LC13will be completed at baseline (Day 1 of Cycle 1), 
at every other cycle through Cycle 13, then every 4 cycles thereafter, and at the EOT Visit, whichever comes first. 
 
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APPENDIX 2. CLINICAL LABORATORY ASSESSMENTS  
Serum chemistry 
Hematology 
Coagulation 
Urinalysis 
(screening and as 
clinically 
indicated) 
Cardiac enzyme 
testing a 
Alkaline 
phosphatase 
Hemoglobin 
Prothrombin time 
pH 
Creatine kinase 
Alanine 
aminotransferase 
Hematocrit 
Partial 
thromboplastin time 
or activated partial 
thromboplastin time 
Specific gravity 
CK-MB 
Aspartate 
aminotransferase 
White blood cell 
count 
International 
normalized ratio 
Glucose 
Troponin 
Albumin 
Neutrophil count 
 
Protein 
Total bilirubin 
Lymphocyte count 
 
Ketones 
Direct bilirubin 
Platelet count 
 
Blood 
Blood urea nitrogen 
or urea 
 
 
24-hour protein c  
Potassium 
 
 
 
 
Sodium 
 
 
 
 
Calcium b 
 
 
 
 
Creatinine 
 
 
 
 
Glucose 
 
 
 
 
Lactate 
dehydrogenase 
 
 
 
 
Total protein 
 
 
 
 
Magnesium 
 
 
 
 
Phosphorus 
 
 
 
 
Chloride 
 
 
 
 
Abbreviations: CK-MB, creatine kinase cardiac muscle isoenzyme. 
a Cardiac enzyme testing has been added to monitor for potential event of immune-related myocarditis. In the event 
that CK-MB fractionation is not available, assess troponin I and/or troponin T instead. Investigators should make 
every effort to perform either CK-MB, troponin I and/or troponin T consistently at screening and at follow-up 
visits. 
b Calcium values will be corrected for patients with hypoalbuminemia. 
c On routine urinalysis, if urine protein is ≥ 2+ by dipstick, obtain a 24-hour urine sample for total protein or a 
random urine sample for total protein and creatinine to determine a protein-to-creatinine ratio. 
 
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APPENDIX 3. EASTERN COOPERATIVE ONCOLOGY GROUP 
(ECOG) PERFORMANCE STATUS  
Grade 
Description 
0 
Fully active, able to carry on all predisease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, eg, light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities; up and 
about more than 50% of waking hours 
3 
Capable of only limited self-care; confined to bed or chair more than 50% of waking hours 
4 
Completely disabled; cannot carry on any self-care; totally confined to bed or chair 
5 
Dead 
Source: Oken et al 1982. Eastern Cooperative Oncology Group, Robert Comis MD, Group Chair. 
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APPENDIX 4. THE RESPONSE EVALUATION CRITERIA IN SOLID 
TUMORS (RECIST) GUIDELINES, VERSION 1.1  
Source: Eisenhauer et al 2009. 
Definitions  
Response and progression will be evaluated in this trial using the international criteria proposed 
by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee (v1.1). Changes in 
only the largest diameter (uni-dimensional measurement) of the tumor lesions are used in the 
RECIST criteria. 
Note: Lesions are either measurable or nonmeasurable using the criteria provided below. The 
term “evaluable” in reference to measurability will not be used because it does not provide 
additional meaning or accuracy. 
Measurable Disease 
Tumor lesions: Must be accurately measured in at least 1 dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of: 
• 10 mm by computed tomography (CT) and magnetic resonance imaging (MRI) (no 
less than double the slice thickness and a minimum of 10 mm). Assumes a scan slice 
thickness no greater than 5 mm. 
• 10 mm caliper measurement by clinical exam (when superficial) 
• 20 mm by chest X-ray (if clearly defined and surrounded by aerated lung) 
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph 
node must be ≥ 15 mm in short axis when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis will 
be measured and followed. 
Nonmeasurable Disease 
All other lesions (or sites of disease), including small lesions (longest diameter < 10 mm or 
pathological lymph nodes with ≥ 10 to < 15 mm short axis), are considered nonmeasurable 
disease. Leptomeningeal disease, ascites, pleural, or pericardial effusion, inflammatory breast 
disease, lymphangitic involvement of skin or lung, abdominal masses/abdominal organomegaly 
identified by physical examination that is not measurable by reproducible imaging techniques are 
all nonmeasurable. 
Bone lesions: 
• Bone scan, positron emission tomography (PET) scan, or plain films are not 
considered adequate imaging techniques to measure bone lesions. However, these 
techniques can be used to confirm the presence or disappearance of bone lesions. 
• Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue 
components, that can be evaluated by cross sectional imaging techniques such as CT 
or MRI can be considered as measurable lesions if the soft tissue component meets 
the definition of measurability described above. 
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• Blastic bone lesions are nonmeasurable. 
Cystic lesions: 
• Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor nonmeasurable) since they 
are, by definition, simple cysts. 
• Cystic lesions thought to represent cystic metastases can be considered as measurable 
lesions, if they meet the definition of measurability described above. However, if 
noncystic lesions are present in the same patient, these are preferred for selection as 
target lesions. 
Lesions with prior local treatment: 
• Tumor lesions situated in a previously irradiated area, or in an area subjected to other 
loco-regional therapy, are usually not considered measurable unless there has been 
demonstrated progression in the lesion. Trial protocols should detail the conditions 
under which such lesions would be considered measurable. 
Target Lesions 
All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total, should be 
identified as target lesions and recorded and measured at baseline. Target lesions should be 
selected on the basis of their size (lesions with the longest diameter), be representative of all 
involved organs, but in addition should be those that lend themselves to reproducible repeated 
measurements. 
Lymph nodes merit special mention since they are normal anatomical structures which may be 
visible by imaging even if not involved by tumor. Pathological nodes which are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
≥ 15 mm by CT scan. Only the short axis of these nodes will contribute to the baseline sum. The 
short axis of the node is the diameter normally used by radiologists to judge if a node is involved 
by solid tumor. Nodal size is normally reported as 2 dimensions in the plane in which the image 
is obtained (for CT scan, this is almost always the axial plane; for MRI the plane of acquisition 
may be axial, sagittal, or coronal). The smaller of these measures is the short axis. For example, 
an abdominal node which is reported as being 20 mm by 30 mm has a short axis of 20 mm and 
qualifies as a malignant, measurable node. In this example, 20 mm should be recorded as the 
node measurement. All other pathological nodes (those with short axis ≥ 10 mm but < 15 mm) 
should be considered nontarget lesions. Nodes that have a short axis < 10 mm are considered 
nonpathological and should not be recorded or followed. 
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease. 
Nontarget Lesions 
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
nontarget lesions and should also be recorded at baseline. Measurements are not required and 
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these lesions should be followed as “present,” “absent,” or in rare cases “unequivocal 
progression” (more details to follow). In addition, it is possible to record multiple nontarget 
lesions involving the same organ as a single item on the case record form (eg, “multiple enlarged 
pelvic lymph nodes” or “multiple liver metastases”). 
Guidelines for Evaluation of Measurable Disease  
All measurements should be recorded in metric notation, using calipers if clinically assessed. All 
baseline evaluations should be performed as close as possible to the treatment start and never 
more than 4 weeks before the beginning of the treatment. 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation should 
always be done rather than clinical examination unless the lesion(s) being followed cannot be 
imaged but are assessable by clinical examination. 
• Clinical lesions: Clinical lesions will only be considered measurable when they are 
superficial and ≥ 10 mm diameter as assessed using calipers (eg, skin nodules). For 
the case of skin lesions, documentation by color photography including a ruler to 
estimate the size of the lesion is suggested. As noted above, when lesions can be 
evaluated by both clinical examination and imaging, imaging evaluation should be 
undertaken since it is more objective and may also be reviewed at the end of the trial. 
• Chest X-ray: Chest CT scan is preferred over chest X-ray, particularly when 
progression is an important endpoint, since CT is more sensitive than X-ray, 
particularly in identifying new lesions. However, lesions on chest X-ray may be 
considered measurable if they are clearly defined and surrounded by aerated lung. 
• CT, MRI: CT is the best currently available and reproducible method to measure 
lesions selected for response assessment. This guideline has defined measurability of 
lesions on CT scan based on the assumption that CT slice thickness is 5 mm or less. 
When CT scans have slice thickness greater than 5 mm, the minimum size for a 
measurable lesion should be twice the slice thickness. MRI is also acceptable in 
certain situations (eg, for body scans). 
• Ultrasound: Ultrasound is not useful in assessment of lesion size and should not be 
used as a method of measurement. Ultrasound examinations cannot be reproduced in 
their entirety for independent review at a later date, and because they are operator 
dependent, it cannot be guaranteed that the same technique and measurements will be 
taken from one assessment to the next. If new lesions are identified by ultrasound in 
the course of the study, confirmation by CT or MRI is advised. If there is concern 
about radiation exposure at CT, MRI may be used instead of CT in selected instances. 
• Endoscopy, laparoscopy: The utilization of these techniques for objective tumor 
evaluation is not advised. However, they can be useful to confirm complete 
pathological response when biopsies are obtained or to determine relapse in trials 
where recurrence following complete response (CR) or surgical resection is an 
endpoint. 
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• Tumor markers: Tumor markers alone cannot be used to assess objective tumor 
response. If markers are initially above the upper normal limit, however, they must 
normalize for a patient to be considered in CR. Because tumor markers are disease 
specific, instructions for their measurement should be incorporated into protocols on a 
disease specific basis. Specific guidelines for both CA125 response (in recurrent 
ovarian cancer) and prostate-specific antigen response (in recurrent prostate cancer), 
have been published. In addition, the Gynecologic Cancer Intergroup has developed 
CA125 progression criteria which are to be integrated with objective tumor 
assessment for use in firstline trials in ovarian cancer. 
• Cytology, histology: These techniques can be used to differentiate between partial 
response (PR) and CR in rare cases if required by protocol (for example, residual 
lesions in tumor types such as germ cell tumors, where known residual benign tumors 
can remain). When effusions are known to be a potential adverse effect of treatment 
(eg, with certain taxane compounds or angiogenesis inhibitors), the cytological 
confirmation of the neoplastic origin of any effusion that appears or worsens during 
treatment can be considered if the measurable tumor has met criteria for response or 
stable disease in order to differentiate between response (or stable disease) and 
progressive disease. 
Response Criteria  
Evaluation of Target Lesions 
• Complete Response (CR): Disappearance of all target lesions. Any pathological 
lymph nodes (whether target or nontarget) must have reduction in short axis to 
< 10 mm. 
• Partial Response (PR): At least a 30% decrease in the sum of diameters of target 
lesions, taking as reference the baseline sum diameters 
• Progressive Disease (PD): At least a 20% increase in the sum of diameters of target 
lesions, taking as reference the smallest sum on study (this includes the baseline sum 
if that is the smallest on study). In addition to the relative increase of 20%, the sum 
must also demonstrate an absolute increase of at least 5 mm. (Note: The appearance 
of one or more new lesions is also considered progression). 
• Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD, taking as reference the smallest sum diameters while on 
study 
• Lymph nodes: Lymph nodes identified as target lesions should always have the actual 
short axis measurement recorded (measured in the same anatomical plane as the 
baseline examination), even if the nodes regress to below 10 mm on study. This 
means that when lymph nodes are included as target lesions, the “sum” of lesions 
may not be zero even if CR criteria are met, since a normal lymph node is defined as 
having a short axis of < 10 mm. Case report form may be designed to have target 
nodal lesions recorded in a separate section where, in order to qualify for CR, each 
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node must achieve a short axis < 10 mm. For PR, SD and PD, the actual short axis 
measurement of the nodes is to be included in the sum of target lesions. 
• Target lesions that become “too small to measure.” While on study, all lesions (nodal 
and nonnodal) recorded at baseline should have their actual measurements recorded at 
each subsequent evaluation, even when very small (eg, 2 mm). However, sometimes 
lesions or lymph nodes which are recorded as target lesions at baseline become so 
faint on CT scan that the radiologist may not feel comfortable assigning an exact 
measure and may report them as being “too small to measure.” 
When this occurs, it is important that a value be recorded on the electronic case report 
form (eCRF). If it is the opinion of the radiologist that the lesion has likely 
disappeared, the measurement should be recorded as 0 mm. If the lesion is believed to 
be present and is faintly seen but too small to measure, a default value of 5 mm 
should be assigned. (Note: It is less likely that this rule will be used for lymph nodes 
since they usually have a definable size when normal and are frequently surrounded 
by fat, such as in the retroperitoneum; however, if a lymph node is believed to be 
present and is faintly seen but too small to measure, a default value of 5 mm should 
be assigned in this circumstance as well). This default value is derived from the 5 mm 
CT slice thickness (but should not be changed with varying CT slice thickness). The 
measurement of these lesions is potentially nonreproducible; therefore, providing this 
default value will prevent false responses or progressions based upon measurement 
error. To reiterate, however, if the radiologist is able to provide an actual measure, 
that measurement should be recorded, even if it is below 5 mm. 
• Lesions that split or coalesce on treatment: When non-nodal lesions “fragment,” the 
longest diameters of the fragmented portions should be added together to calculate the 
target lesion sum. Similarly, as lesions coalesce, a plane between them may be 
maintained that would aid in obtaining maximal diameter measurements of each 
individual lesion. If the lesions have truly coalesced such that they are no longer 
separable, the vector of the longest diameter in this instance should be the maximal 
longest diameter for the “coalesced lesion.” 
Evaluation of Nontarget Lesions 
While some nontarget lesions may actually be measurable, they need not be measured and 
instead should be assessed only qualitatively at the time points specified in the protocol. 
• CR: Disappearance of all nontarget lesions and normalization of tumor marker level. 
All lymph nodes must be nonpathological in size (< 10 mm short axis). 
• NonCR/NonPD: Persistence of one or more nontarget lesion(s) and/or maintenance of 
tumor marker level above the normal limits 
• PD: Unequivocal progression (as detailed below) of existing nontarget lesions. (Note: 
The appearance of one or more new lesions is also considered progression.) 
• When the patient also has measurable disease: In this setting, to achieve “unequivocal 
progression” on the basis of the nontarget disease, there must be an overall level of 
substantial worsening in nontarget disease such that, even in presence of SD or PR in 
target disease, the overall tumor burden has increased sufficiently to merit 
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discontinuation of therapy. A modest “increase” in the size of one or more nontarget 
lesions is usually not sufficient to qualify for unequivocal progression status. The 
designation of overall progression solely on the basis of change in nontarget disease 
in the face of SD or PR of target disease will therefore be extremely rare. 
• When the patient has only nonmeasurable disease: This circumstance arises in some 
phase 3 trials when it is not a criterion of trial entry to have measurable disease. The 
same general concept applies here as noted above; however, in this instance there is 
no measurable disease assessment to factor into the interpretation of an increase in 
nonmeasurable disease burden. Because worsening in nontarget disease cannot be 
easily quantified (by definition: if all lesions are truly nonmeasurable) a useful test 
that can be applied when assessing patients for unequivocal progression is to consider 
if the increase in overall disease burden based on the change in nonmeasurable 
disease is comparable in magnitude to the increase that would be required to declare 
PD for measurable disease: ie, an increase in tumor burden representing an additional 
73% increase in “volume” (which is equivalent to a 20% increase diameter in a 
measurable lesion). 
• Examples include an increase in a pleural effusion from “trace” to “large,” an 
increase in lymphangitic disease from localized to widespread, or may be described in 
protocols as “sufficient to require a change in therapy.” If “unequivocal progression” 
is seen, the patient should be considered to have had overall PD at that point. While it 
would be ideal to have objective criteria to apply to nonmeasurable disease, the very 
nature of that disease makes it impossible to do so; therefore, the increase must be 
substantial. 
New Lesions 
The appearance of new malignant lesions denotes disease progression; therefore, some 
comments on detection of new lesions are important. There are no specific criteria for the 
identification of new radiographic lesions; however, the finding of a new lesion should be 
unequivocal: ie, not attributable to differences in scanning technique, change in imaging 
modality or findings thought to represent something other than tumor (for example, some “new” 
bone lesions may be simply healing or flare of preexisting lesions). This is particularly important 
when the patient’s baseline lesions show partial or complete response. For example, necrosis of a 
liver lesion may be reported on a CT scan report as a “new” cystic lesion, which it is not. 
A lesion identified on a follow-up trial in an anatomical location that was not scanned at baseline 
is considered a new lesion and will indicate disease progression. An example of this is the patient 
who has visceral disease at baseline and while on study has a CT or MRI brain scan ordered that 
reveals metastases. The patient’s brain metastases are considered to be evidence of PD even if 
he/she did not have brain imaging at baseline. 
If a new lesion is equivocal, for example because of its small size, continued therapy and 
follow-up evaluation will clarify if it represents truly new disease. If repeat scans confirm there 
is definitely a new lesion, then progression should be declared using the date of the initial scan. 
While fluorodeoxyglucose (FDG)-PET response assessments need additional study, it is 
sometimes reasonable to incorporate the use of FDG-PET scanning to complement CT scanning 
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in assessment of progression (particularly possible “new” disease). New lesions on the basis of 
FDG-PET imaging can be identified according to the following algorithm: 
• Negative FDGPET at baseline, with a positive FDGPET at follow-up, is a sign of PD 
based on a new lesion. 
• No FDGPET at baseline and a positive FDGPET at follow-up: If the positive 
FDGPET at follow-up corresponds to a new site of disease confirmed by CT, this is 
PD. If the positive FDGPET at follow-up is not confirmed as a new site of disease on 
CT, additional follow-up CT scans are needed to determine if there is truly 
progression occurring at that site (if so, the date of PD will be the date of the initial 
abnormal FDGPET scan). If the positive FDGPET at follow-up corresponds to a 
preexisting site of disease on CT that is not progressing on the basis of the anatomic 
images, this is not PD. 
• Timepoint Response 
• It is assumed that at each protocol specified time point, a response assessment occurs. 
The following table provides a summary of the overall response status calculation at 
each time point for patients who have measurable disease at baseline: 
Target Lesions 
Nontarget Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all evaluated 
No 
PR 
SD 
Non-PD or not all evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Abbreviations: CR, complete response; NE, not evaluable; PD, progressive disease; PR, partial response; 
SD, stable disease. 
When patients have nonmeasurable (therefore nontarget) disease only, the following table is to 
be used: 
Nontarget Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
SD (Non-CR/non-PD) 
Not all evaluated 
No 
NE 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
Abbreviations: CR, complete response; NE, not evaluable; PD, progressive disease; SD, stable 
disease. 
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Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the study drug treatment 
until the end of treatment taking into account any requirement for confirmation. On occasion, a 
response may not be documented until after the end of therapy so protocols should be clear if 
post-treatment assessments are to be considered in determination of best overall response. 
Protocols must specify how any new therapy introduced before progression will affect best 
response designation. The patient’s best overall response assignment will depend on the findings 
of both target and nontarget disease and will also take into consideration the appearance of new 
lesions. Furthermore, depending on the nature of the trial and the protocol requirements, it may 
also require confirmatory measurement. Specifically, in nonrandomized trials where response is 
the primary endpoint, confirmation of PR or CR is needed to deem either one the “best overall 
response.” 
The best overall response is determined once all the data for the patient is known. 
Best response determination in trials where confirmation of complete or partial response IS NOT 
required: Best response in these trials is defined as the best response across all time points (for 
example, a patient who has SD at first assessment, PR at second assessment, and PD on last 
assessment has a best overall response of PR). When SD is believed to be best response, it must 
also meet the protocol specified minimum time from baseline. If the minimum time is not met 
when SD is otherwise the best time point response, the patient’s best response depends on the 
subsequent assessments. For example, a patient who has SD at first assessment, PD at second 
and does not meet minimum duration for SD, will have a best response of PD. The same patient 
lost to follow-up after the first SD assessment would be considered inevaluable. 
Best response determination in trials where confirmation of complete or partial response IS 
required: Complete or partial responses may be claimed only if the criteria for each are met at a 
subsequent time point as specified in the protocol (generally 4 weeks later). 
When nodal disease is included in the sum of target lesions and the nodes decrease to “normal” 
size (< 10 mm), they may still have a measurement reported on scans. This measurement should 
be recorded even though the nodes are normal in order not to overstate progression should it be 
based on increase in size of the nodes. As noted earlier, this means that patients with CR may not 
have a total sum of “zero.” 
In trials where confirmation of response is required, repeated “NE” (not evaluable) time point 
assessments may complicate best response determination. The analysis plan for the trial must 
address how missing data/assessments will be addressed in determination of response and 
progression. For example, in most trials it is reasonable to consider a patient with time point 
responses of PR-NE-PR as a confirmed response. 
Patients with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be reported as 
“symptomatic deterioration”. Every effort should be made to document objective progression 
even after discontinuation of treatment. Symptomatic deterioration is not a descriptor of an 
objective response: it is a reason for stopping trial therapy. 
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Conditions that define “early progression, early death, and inevaluability” are trial specific and 
should be clearly described in each protocol (depending on treatment duration, treatment 
periodicity). 
In some circumstances it may be difficult to distinguish residual disease from normal tissue. 
When the evaluation of CR depends upon this determination, it is recommended that the residual 
lesion be investigated (fine needle aspirate/biopsy) before assigning a status of CR. FDG-PET 
may be used to upgrade a response to a CR in a manner similar to a biopsy in cases where a 
residual radiographic abnormality is thought to represent fibrosis or scarring. The use of 
FDG-PET in this circumstance should be prospectively described in the protocol and supported 
by disease specific medical literature for the indication. However, it must be acknowledged that 
both approaches may lead to false positive CR due to limitations of FDG-PET and biopsy 
resolution/ sensitivity. 
For equivocal findings of progression (eg, very small and uncertain new lesions, cystic changes, 
or necrosis in existing lesions), treatment may continue until the next scheduled assessment. If 
progression is confirmed at the next scheduled assessment, the date of progression should be the 
earlier date when progression was suspected. 
Confirmation of Measurement/Duration of Response  
Confirmation 
In nonrandomized trials where response is the primary endpoint, confirmation of PR and CR is 
required to ensure responses identified are not the result of measurement error. This will also 
permit appropriate interpretation of results in the context of historical data where response has 
traditionally required confirmation in such trials. However, in all other circumstances, ie, in 
randomized trials (phase 2 or 3) or trials where stable disease or progression are the primary 
endpoints, confirmation of response is not required since it will not add value to the 
interpretation of trial results. However, elimination of the requirement for response confirmation 
may increase the importance of central review to protect against bias, in particular in trials which 
are not blinded. 
In the case of SD, measurements must have met the SD criteria at least once after trial entry at a 
minimum interval (in general not less than 6 weeks). 
Duration of Overall Response 
The duration of overall response is measured from the time measurement criteria are first met for 
CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is 
objectively documented (taking as reference for progressive disease the smallest measurements 
recorded on study). 
The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that recurrent disease is objectively documented. 
Duration of Stable Disease 
Stable disease is measured from the start of the treatment (in randomized trials, from date of 
randomization) until the criteria for progression are met, taking as reference the smallest sum on 
study (if the baseline sum is the smallest, this is the reference for calculation of PD). 
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The clinical relevance of the duration of stable disease varies in different studies and diseases. If 
the proportion of patients achieving stable disease for a minimum period of time is an endpoint 
of importance in a particular trial, the protocol should specify the minimal time interval required 
between 2 measurements for determination of stable disease. 
Note: The duration of response and stable disease as well as the progression-free survival are 
influenced by the frequency of follow-up after baseline evaluation. It is not in the scope of this 
guideline to define a standard follow-up frequency. The frequency should take into account 
many parameters including disease types and stages, treatment periodicity, and standard practice. 
However, these limitations of the precision of the measured endpoint should be taken into 
account if comparisons between trials are to be made. 
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APPENDIX 5. PREEXISTING IMMUNE DEFICIENCIES OR 
AUTOIMMUNE DISEASES  
Prospective patients should be carefully questioned to determine whether they have any history 
of an acquired or congenital immune deficiency or autoimmune disease. 
Please contact the medical monitor regarding any uncertainty about immune 
deficiency/autoimmune disease exclusions. 
Acute disseminated encephalomyelitis 
Addison disease 
Ankylosing spondylitis 
Antiphospholipid antibody syndrome 
Aplastic anemia 
Autoimmune hemolytic anemia 
Autoimmune hepatitis 
Autoimmune hypoparathyroidism 
Autoimmune hypophysitis 
Autoimmune myocarditis 
Autoimmune oophoritis 
Autoimmune orchitis 
Autoimmune thrombocytopenic purpura 
Behcet disease 
Bullous pemphigoid 
Chronic inflammatory demyelinating polyneuropathy 
Chung-Strauss syndrome 
Crohn disease 
Dermatomyositis 
Dysautonomia 
Epidermolysis bullosa acquisita 
Gestational pemphigoid 
Giant cell arteritis 
Goodpasture syndrome 
Granulomatosis with polyangiitis 
Graves disease 
Guillain-Barré syndrome 
Hashimoto disease 
Immunoglobulin A (IgA) neuropathy 
Inflammatory bowel disease 
Interstitial cystitis 
Kawasaki disease 
Lambert-Eaton myasthenic syndrome 
Lupus erythematosus 
Lyme disease (chronic) 
Mooren ulcer 
Morphea 
Multiple sclerosis 
Myasthenia gravis 
Neuromyotonia 
Opsoclonus myoclonus syndrome 
Optic neuritis 
Ord thyroiditis 
Pemphigus 
Pernicious anemia 
Polyarteritis nodosa 
Polyarthritis 
Polyglandular autoimmune syndrome 
Primary biliary cirrhosis 
Psoriasis 
Reiter syndrome 
Rheumatoid arthritis 
Sarcoidosis  
Sjögren syndrome 
Stiff person syndrome 
Takayasu arteritis 
Ulcerative colitis 
Vogt-Kovangai-Harada disease 
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APPENDIX 6. NEW YORK HEART ASSOCIATION FUNCTIONAL 
CLASSIFICATION  
Class 
Symptoms 
I 
No limitation of physical activity. Ordinary physical activity does not cause undue 
fatigue, palpitation, dyspnea (shortness of breath). 
II 
Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity 
results in fatigue, palpitation, dyspnea (shortness of breath). 
III 
Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity 
causes fatigue, palpitation, or dyspnea. 
IV 
Unable to carry on any physical activity without discomfort. Symptoms of heart failure at 
rest. If any physical activity is undertaken, discomfort increases. 
Adapted from Dolgin et al 1994. 
Original source: Criteria Committee, New York Heart Association, Inc. Diseases of the Heart and Blood Vessels. 
Nomenclature and Criteria for diagnosis, 6th edition Boston, Little, Brown and Co. 1964, p 114. 
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APPENDIX 7. IMMUNE-MEDIATED ADVERSE EVENT EVALUATION 
AND MANAGEMENT  
The recommendations below for the diagnosis and management of any immune-mediated AE 
(imAE) are intended as a guidance. This document should be used in conjunction with expert 
clinical judgement (by specialist physicians experienced in the treatment of cancer using 
immunological agents), and individual institutional guidelines or policies. 
Criteria used to diagnose imAEs include blood tests, diagnostic imaging, histopathology, and 
microbiology assessments to exclude alternative causes such as infection, disease progression, 
and adverse effects of concomitant drugs. In addition to the results of these tests, the following 
factors should be considered when making an imAE diagnosis: 
• What was the temporal relationship between initiation of study drug and the AE? 
• How did the patient respond to withdrawal of study drugs? 
• Did the event recur when study drugs were reintroduced? 
• Was there a clinical response to corticosteroids? 
• Is the event an autoimmune endocrinopathy? 
• Is disease progression or an alternative diagnosis a more likely explanation? 
When alternative explanations to autoimmune toxicity have been excluded, the imAE field 
associated with the AE in the eCRF should be checked. If further diagnostic evaluations change 
the assessment, the eCRF should be updated accordingly. 
Recommended Diagnostic Tests in the Management of 
Possible Immune-mediated Adverse Events 
Immune-mediated 
Toxicity 
Diagnostic Evaluation Guideline 
Thyroid disorders 
Scheduled and repeated thyroid function tests (TSH and T4). 
Hypophysitis 
Check visual fields and consider pituitary endocrine axis blood profile. 
Perform pituitary and whole brain MRI in patients with headache, visual 
disturbance, unexplained fatigue, asthenia, weight loss, and unexplained 
constitutional symptoms. 
Consider consultation with an endocrinologist if an abnormality is 
detected. 
Pneumonitis 
All patients presenting with new or worsened pulmonary symptoms or 
signs, such as an upper respiratory infection, new cough, shortness of 
breath, or hypoxia should be assessed by high-resolution CT. Consider 
pulmonary function test including DLCO. 
Radiographic appearance is often nonspecific. Depending on the location 
of the abnormality, bronchoscopy and bronchoalveolar lavage or lung 
biopsy may be considered. Consult with a respiratory medicine physician 
for cases of uncertain cause.  
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Recommended Diagnostic Tests in the Management of 
Possible Immune-mediated Adverse Events 
Immune-mediated 
Toxicity 
Diagnostic Evaluation Guideline 
Neurological toxicity 
Perform a comprehensive neurological examination and brain MRI for all 
CNS symptoms; review alcohol history and other medications. Conduct a 
diabetic screen and assess blood B12/folate, HIV status, TFTs, and 
consider autoimmune serology. Consider the need for brain/spine 
MRI/MRA and nerve conduction study for peripheral neuropathy. Consult 
with a neurologist if there are abnormal findings. 
For France only: 
Guillain-Barré syndrome 
Clinical findings resemble classical ascending Guillain-Barré syndrome 
symptoms, including bilateral proximal weakness, ataxia, distal sensory, 
autonomic disturbances, and cranial nerve involvement. Referral to a 
neurologist should be considered for symptoms of Guillain-Barré 
syndrome. Consider checking for antiganglioside antibodies. 
Colitis 
Review dietary intake and exclude steatorrhea. Consider comprehensive 
testing, including the following: FBC, UEC, LFTs, CRP, TFTs, stool 
microscopy and culture, viral PCR, Clostridium difficile toxin, and 
cryptosporidia (drug-resistant organism). 
In case of abdominal discomfort, consider imaging, eg, X-ray, CT scan. If 
a patient experiences bleeding, pain, or distension, consider colonoscopy 
with biopsy and surgical intervention as appropriate. 
Eye disorders 
If a patient experiences acute, new onset, or worsening of eye 
inflammation; blurred vision; or other visual disturbances, refer the patient 
urgently to an ophthalmologist for evaluation and management. 
Hepatitis 
Check ALT/AST/total bilirubin, INR/albumin; the frequency will depend 
on severity of the AE (eg, daily if Grade 3 to 4; every 2 to 3 days if 
Grade 2, until recovering). Review medications (eg, statins, antibiotics) 
and alcohol history. Perform liver screen including Hepatitis A/B/C 
serology, Hepatitis E PCR and assess anti-ANA/SMA/LKM/SLA/LP/LCI, 
iron studies. Consider imaging (eg, ultrasound scan for metastases or 
thromboembolism). Consult with a hepatologist and consider liver biopsy. 
Renal toxicity 
Review hydration status and medication history. Test and culture urine. 
Consider renal ultrasound scan, protein assessment (dipstick/24-hour urine 
collection), or phase-contrast microscopy. Refer to a nephrologist for 
further management assistance. 
Dermatology 
Consider other causes by conducting a physical examination. Consider 
dermatology referral for skin biopsy. 
For France only: 
Toxic epidermal 
necrolysis and Stevens-
Johnson syndrome 
For signs or symptoms of Stevens-Johnson syndrome or toxic epidermal 
necrolysis, withhold study drugs and refer the patient for specialized 
assessment and treatment.  
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Recommended Diagnostic Tests in the Management of 
Possible Immune-mediated Adverse Events 
Immune-mediated 
Toxicity 
Diagnostic Evaluation Guideline 
Joint or muscle 
inflammation 
Conduct musculoskeletal history and perform complete musculoskeletal 
examination. Consider joint X-ray and other imaging as required to exclude 
metastatic disease. Perform autoimmune serology and refer to rheumatology for 
further management assistance. 
For suspected myositis/rhabdomyolysis/myasthenia include: CK, ESR, 
CRP, troponin, and consider a muscle biopsy. 
Myocarditis 
Perform ECG, echocardiogram, CK/CK-MB, troponin (I and/or T), and refer to a 
cardiologist. 
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; ANA, antinuclear antibody; AST, aspartate 
aminotransferase; CK, creatine kinase; CK-MB, creatine kinase cardiac muscle isoenzyme; CNS, central nervous 
system; CRP, C-reactive protein; CT, computed tomography; DLCO, diffusing capacity for carbon monoxide; ECG, 
electrocardiogram; ESR, erythrocyte sedimentation rate; FBC, full blood count; HIV, human immunodeficiency 
virus; INR, international normalized ratio; LCI, liver cytosolic antigen; LFT, liver function test; LKM, liver kidney 
microsomal antibody; LP, liver pancreas antigen; MRA, magnetic resonance angiogram; MRI, magnetic resonance 
imaging; PCR, polymerase chain reaction; SLA, soluble liver antigen; SMA, smooth muscle antibody; T4, 
thyroxine; TFT, thyroid function tests; TSH, thyroid-stimulating hormone; UEC, urea electrolytes and creatinine. 
Treatment of Immune-Mediated Adverse Events  
• Immune-mediated AEs can escalate quickly. Study treatment interruption, close 
monitoring, timely diagnostic work-up, and treatment intervention as appropriate is 
required. 
• Immune-mediated AEs should improve promptly after introduction of 
immunosuppressive therapy. If this does not occur, review the diagnosis, seek further 
specialist advice, and contact the study medical monitor. 
• For some Grade 3 toxicities that resolve quickly, rechallenge with study drug may be 
considered if there is evidence of a clinical response to study treatment, after 
consultation with the study medical monitor. 
• Steroid dosages in the table below are for oral or intravenous (methyl)prednisolone. 
Equivalent dosages of other corticosteroids can be substituted. For steroid-refractory 
imAEs, consider use of steroid-sparing agents (eg, mycophenolate mofetil [MMF]). 
• Consider prophylactic antibiotics for opportunistic infections if the patient is 
receiving long-term immunosuppressive therapy. 
 
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Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
Thyroid 
Disorders 
1-2 
Asymptomatic TFT abnormality or 
mild symptoms 
Replace thyroxine if 
hypothyroid, until 
TSH/T4 levels return 
to normal range. 
Thyrotoxic patients 
should be referred to 
an endocrinologist. In 
cases with systemic 
symptoms: withhold 
study treatment, treat 
with a beta blocker, 
and consider oral 
prednisolone 
0.5 mg/kg/day for 
thyroid pain. 
Taper corticosteroids 
over 2-4 weeks. 
Monitor thyroid 
function regarding the 
need for hormone 
replacement. 
Continue study treatment 
or withhold both study 
drugs in cases with 
systemic symptoms. 
3-4 
Severe symptoms, hospitalization 
required 
Refer patient to an 
endocrinologist. 
If hypothyroid, replace 
with thyroxine 
0.5-1.6 µg/kg/day (for 
the elderly or those 
with comorbidities, the 
suggested starting dose 
is 0.5 µg/kg/day). Add 
oral prednisolone 
0.5 mg/kg/day for 
thyroid pain. 
Thyrotoxic patients 
require treatment with 
a beta blocker and may 
require carbimazole 
until thyroiditis 
resolves. 
Hold study treatment; 
resume when 
resolved/improved to 
Grade 0-1.  
 
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Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
Hypophysitis 
1-2 
Mild-moderate symptoms 
Refer patient to an 
endocrinologist for 
hormone replacement. 
Add oral prednisolone 
0.5-1 mg/kg/day for 
patients with pituitary 
inflammation. Taper 
corticosteroids over at 
least 1 month. 
If there is no 
improvement in 
48 hours, treat as 
Grade 3-4. 
Continue study treatment. 
3-4 
Severe or life-threatening 
symptoms 
Refer patient to an 
endocrinologist for 
assessment and 
treatment. 
Initiate pulse 
intravenous 
methylprednisolone 
1 mg/kg for patients 
with headache/visual 
disturbance due to 
pituitary inflammation. 
Convert to oral 
prednisolone and taper 
over at least 1 month. 
Maintain hormone 
replacement according 
to endocrinologist’s 
advice. 
Hold study treatment for 
patients with 
headache/visual 
disturbance due to pituitary 
inflammation until 
resolved/improved to 
≤ Grade 2. Discontinuation 
is usually not necessary.  
 
Pneumonitis 
1 
Radiographic changes only 
Monitor symptoms 
every 2-3 days.  
If appearance worsens, 
treat as Grade 2. 
Consider holding both 
study drugs until 
appearance improves and 
cause is determined. 
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Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
2 
Symptomatic: exertional 
breathlessness 
Commence antibiotics 
if infection suspected. 
Add oral prednisolone 
1 mg/kg/day if 
symptoms/appearance 
persist for 48 hours or 
worsen. 
Consider 
Pneumocystis 
infection prophylaxis. 
Taper corticosteroids 
over at least 6 weeks. 
Consider prophylaxis 
for adverse steroid 
effects: eg, blood 
glucose monitoring, 
vitamin D/calcium 
supplement. 
Hold both study drugs. 
Retreatment is acceptable if 
symptoms resolve 
completely or are 
controlled on prednisolone 
≤ 10 mg/day. Discontinue 
study treatment if 
symptoms persist with 
corticosteroid treatment. 
3-4 
Severe or life-threatening 
symptoms: breathless at rest 
Admit to a hospital 
and initiate treatment 
with intravenous 
methylprednisolone 
2-4 mg/kg/day. If there 
is no improvement, or 
worsening after 
48 hours, add 
infliximab 5 mg/kg (if 
no hepatic 
involvement). 
Convert to oral 
prednisolone and taper 
over at least 2 months. 
Cover with empiric 
antibiotics and 
consider prophylaxis 
for Pneumocystis 
infection and other 
adverse steroid effects, 
eg, blood glucose 
monitoring, vitamin 
D/calcium supplement. 
Discontinue both study 
drugs. 
Neurological 
Toxicity 
1 
Mild symptoms 
– 
Continue study treatment. 
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Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
2 
Moderate symptoms 
Treat with oral 
prednisolone 
0.5-1 mg/kg/day. 
Taper over at least 
4 weeks. 
Obtain neurology 
consultation. 
Hold both study drugs; 
resume both study drugs 
when resolved/improved to 
Grade 0-1. 
3-4 
Severe/life-threatening symptoms 
Initiate treatment with 
oral prednisolone or 
intravenous 
methylprednisolone 
1-2 mg/kg/day, 
depending on 
symptoms. Taper 
corticosteroids over at 
least 4 weeks. 
Consider azathioprine, 
MMF, cyclosporine if 
no response within 
72-96 hours. 
Discontinue both study 
drugs. 
For France only: 
Guillain-Barré 
syndrome 
All grade 
There is no Grade 1 
symptoms. For Grade 
2 symptoms, consider 
oral or intravenous 
methylprednisolone (2 
to 4 mg/kg/day) 
followed by a slow 
taper. For grade 3 or 4 
symptoms, more 
intensive immune 
modulation may be 
required in addition to 
Corticosteroids or by 
exchanging CSs for 
IVIG (0.4 g/kg/day for 
5 days) or plasma 
exchange or selective 
separation. 
Monitor for concurrent 
autonomic 
dysfunction. 
Referral to a 
neurologist should be 
considered for 
symptoms of 
Guillain-Barré 
syndrome.  
Discontinue both study 
drugs. 
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Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
Colitis/Diarrhea 
1 
Mild symptoms: ≤ 3 liquid stools 
per day over baseline and feeling 
well 
Symptomatic 
management: fluids, 
loperamide, avoid high 
fiber/lactose diet. 
If Grade 1 persists 
for > 14 days, manage 
as a Grade 2 event. 
Continue study treatment. 
2 
Moderate symptoms: 4-6 liquid 
stools per day over baseline, or 
abdominal pain, or blood in stool, 
or nausea, or nocturnal episodes 
Oral prednisolone 
0.5 mg/kg/day 
(nonenteric coated). 
Do not wait for any 
diagnostic tests to start 
treatment. Taper 
steroids over 
2-4 weeks. 
Consider endoscopy if 
symptoms are 
recurring. 
Hold both study drugs; 
resume both study drugs 
when resolved/improved to 
baseline grade. 
3 
Severe symptoms: > 6 liquid stools 
per day over baseline, or if 
episodic within 1 hour of eating 
Initiate intravenous 
methylprednisolone 
1-2 mg/kg/day. 
Convert to oral 
prednisolone and taper 
over at least 4 weeks. 
Consider prophylaxis 
for adverse steroid 
effects, eg, blood 
glucose monitoring, 
vitamin D/calcium 
supplement. 
If no improvement in 
72 hours or symptoms 
worsen, consider 
infliximab 5 mg/kg if 
no perforation, sepsis, 
TB, hepatitis, NYHA 
Class III/IV CHF or 
other 
immunosuppressive 
treatment: MMF or 
tacrolimus. 
Consult 
gastroenterologist to 
conduct colonoscopy/ 
sigmoidoscopy. 
Hold both drugs; 
retreatment with both study 
drugs may be considered 
when resolved/improved to 
baseline grade and after 
discussion with the study 
medical monitor. 
 
4 
Life-threatening symptoms 
Discontinue both study 
drugs. 
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Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
Skin reactions 
1 
Skin rash, with or without 
symptoms, < 10% BSA 
Avoid skin irritants 
and sun exposure; 
topical emollients 
recommended.  
For France only: 
Topical steroids (mild 
to moderate strength) 
and oral antihistamines 
for itch. 
Continue study treatment. 
2 
Rash covers 10%-30% of BSA 
Avoid skin irritants 
and sun exposure; 
topical emollients 
recommended. 
Topical steroids 
(moderate strength 
cream once a day or 
potent cream twice a 
day) ± oral or topical 
antihistamines for itch. 
Consider a short 
course of oral steroids. 
Continue study treatment. 
For France only: Consider 
holding both study drugs. 
Re-treat when AE is 
resolved or improved to 
mild rash (Grade 1). 
3 
Rash covers > 30% BSA or Grade 
2 with substantial symptoms 
Avoid skin irritants 
and sun exposure; 
topical emollients 
recommended. 
Initiate steroids as 
follows based on 
clinical judgement: 
For moderate 
symptoms: oral 
prednisolone 
0.5-1 mg/kg/day for 
3 days then taper 
over 2-4 weeks. 
For severe 
symptoms: 
intravenous 
methylprednisolone 
0.5-1 mg/kg/day; 
convert to oral 
prednisolone and 
taper over at least 
4 weeks. 
Hold both study drugs. 
Re-treat when AE is 
resolved or improved to 
mild rash (Grade 1-2, for 
France only: Grade 1) after 
discussion with the study 
medical monitor. 
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Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
4 
Skin sloughing > 30% BSA with 
associated symptoms (eg, 
erythema, purpura, epidermal 
detachment) 
Initiate intravenous 
methylprednisolone 
1-2 mg/kg/day. 
Convert to oral 
prednisolone and taper 
over at least 4 weeks. 
Admit to a hospital 
and seek urgent 
dermatology 
consultation. 
Discontinue both study 
drugs. 
For France only: 
Permanently discontinue 
both study drugs. 
For France only:  
Toxic epidermal 
necrolysis and 
Stevens-Johnson 
syndrome 
Any grade 
Refer the patient for 
specialized assessment 
and treatment.  
Permanently discontinue 
both study drugs. 
Hepatitis 
1 
ALT or AST > ULN to 3 x ULN 
Check LFTs within 
1 week and before the 
next dose; check LFTs 
to verify that there has 
been no worsening. 
If LFTs are worsening, 
recheck every 
48-72 hours until 
improvement is seen. 
Continue study treatment if 
LFTs are unchanged or 
improving. 
Hold both study drugs if 
LFTs are worsening until 
improvement is seen. 
2 
ALT or AST 3-5 x ULN 
Recheck LFTs every 
48-72 hours. 
For persistent 
ALT/AST elevation: 
consider oral 
prednisolone 
0.5-1 mg/kg/day for 
3 days, then taper over 
2-4 weeks. 
For rising ALT/AST: 
start oral prednisolone 
1 mg/kg/day and taper 
over 2-4 weeks; 
re-escalate dose if 
LFTs worsen, 
depending on clinical 
judgement.  
Hold both study drugs; 
treatment with both study 
drugs may be resumed 
when resolved/improved to 
baseline Grade and 
prednisolone tapered to 
≤ 10 mg. 
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Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
3 
ALT or AST 5-20 x ULN 
ALT/AST < 400 IU/L 
and normal 
bilirubin/INR/albumin: 
Initiate oral 
prednisolone 1 mg/kg 
and taper over at least 
4 weeks. 
ALT/AST > 400 IU/L 
or raised 
bilirubin/INR/low 
albumin: Initiate 
intravenous 
(methyl)prednisolone 
2 mg/kg/day. 
When LFTs improve 
to Grade 2 or lower, 
convert to oral 
prednisolone and taper 
over at least 4 weeks.  
Hold study treatment until 
improved to baseline grade; 
reintroduce only after 
discussion with the study 
medical monitor.  
For France only: 
Reintroduce only after a 
positive advice of a 
hepatologist and after 
discussion with the study 
medical monitor.  
4 
ALT or AST > 20 x ULN 
Initiate intravenous 
methylprednisolone 
2 mg/kg/day. Convert 
to oral prednisolone 
and taper over at least 
6 weeks.  
Discontinue both study 
drugs. 
For France only: For patients with Grade 3 or 4 immune-related liver injury, hospitalization 
and initiation of corticosteroid 1-2 mg/kg/day should be considered. 
If there is no response to corticosteroid within 2-3 days, alternative immunosuppressive 
therapy should be considered, such as MMF (1000 mg twice daily), tocilizumab (8 mg/kg), 
tacrolimus, azathioprine, cyclosporine, or anti-thymocyte globulin. 
Global:  
Worsening LFTs despite steroids: 
• 
If on oral prednisolone, change to pulsed intravenous methylprednisolone. 
• 
If on intravenous methylprednisolone, add mycophenolate mofetil (MMF) 
500 to 1000 mg twice a day. 
• 
If worsens on MMF, consider addition of tacrolimus. 
Duration and dose of steroid required will depend on severity of event. 
Nephritis 
1 
Creatinine 1.5 x baseline 
or > ULN to 1.5 x ULN 
Repeat creatinine 
weekly. 
If symptoms worsen, 
manage as per criteria 
below. 
Continue study treatment. 
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Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
2 
Creatinine > 1.5-3 x baseline 
or > 1.5-3 x ULN 
Ensure hydration and 
review creatinine in 
48-72 hours; if not 
improving, consider 
creatinine clearance 
measurement by 
24-hour urine 
collection. 
Discuss with 
nephrologist the need 
for kidney biopsy. 
If attributed to study 
drug, initiate oral 
prednisolone 
0.5-1 mg/kg and taper 
over at least 2 weeks. 
Repeat 
creatinine/U&E every 
48-72 hours. 
Hold study treatment. 
If not attributed to drug 
toxicity, restart treatment. 
If attributed to study drug 
and resolved/improved to 
baseline grade: Restart 
study drug if tapered to 
< 10 mg prednisolone. 
3 
Creatinine > 3 x baseline 
or > 3-6 x ULN 
Hospitalize patient for 
monitoring and fluid 
balance; repeat 
creatinine every 
24 hours; refer to a 
nephrologist and 
discuss need for 
biopsy. 
If worsening, initiate 
intravenous 
(methyl)prednisolone 
1-2 mg/kg. Taper 
corticosteroids over at 
least 4 weeks. 
Hold study treatment until 
the cause is investigated.  
If study drug suspected: 
Discontinue study 
treatment. 
 
4 
Creatinine > 6 x ULN 
As per Grade 3, 
patient should be 
managed in a hospital 
where renal 
replacement therapy is 
available. 
Discontinue study 
treatment. 
Diabetes/ 
Hyperglycemia 
1 
Fasting glucose value ULN to 
160 mg/dL; ULN to 8.9 mmol/L 
Monitor closely and 
treat according to local 
guideline. Check for 
C-peptide and 
antibodies against 
glutamic acid 
decarboxylase and 
islet cells are 
recommended. 
Continue study treatment. 
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Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
2 
Fasting glucose value 
160-250 mg/dL; 8.9-13.9 mmol/L 
Obtain a repeat blood 
glucose level at least 
every week. Manage 
according to local 
guideline. 
Continue study treatment 
or hold treatment if 
hyperglycemia is 
worsening. Resume 
treatment when blood 
glucose is stabilized at 
baseline or Grade 0-1. 
3 
Fasting glucose value 
250-500 mg/dL; 13.9-27.8 mmol/L 
Admit patient to 
hospital and refer to a 
diabetologist for 
hyperglycemia 
management. 
Corticosteroids may 
exacerbate 
hyperglycemia and 
should be avoided. 
Hold both study drugs until 
patient is hyperglycemia 
symptom-free, and blood 
glucose has been stabilized 
at baseline or Grade 0-1. 
 
4 
Fasting glucose 
value > 500 mg/dL; > 27.8 mmol/L 
Admit patient to 
hospital and institute 
local emergency 
diabetes management. 
Refer the patient to a 
diabetologist for 
insulin maintenance 
and monitoring. 
Hold study treatment until 
patient is hyperglycemia 
symptom-free, and blood 
glucose has been stabilized 
at baseline or Grade 0-1. 
 
Ocular Toxicity 
1 
Asymptomatic eye 
examination/test abnormality 
Consider alternative 
causes and prescribe 
topical treatment as 
required. 
Continue study treatment. 
2 
Anterior uveitis or mild symptoms 
Refer patient to an 
ophthalmologist for 
assessment and topical 
corticosteroid 
treatment. 
Consider a course of 
oral steroids. 
Continue study treatment 
or hold both drugs if 
symptoms worsen or if 
there are symptoms of 
visual disturbance. 
3 
Posterior uveitis/panuveitis or 
significant symptoms 
Refer patient urgently 
to an ophthalmologist. 
Initiate oral 
prednisolone 
1-2 mg/kg and taper 
over at least 4 weeks. 
Hold both study drugs until 
improved to Grade 0-1; 
reintroduce only after 
discussion with the study 
medical monitor. 
 
4 
Blindness (at least 20/200) in the 
affected eyes 
Initiate intravenous 
(methyl)prednisolone 
2 mg/kg/day. Convert 
to oral prednisolone 
and taper over at least 
4 weeks. 
Discontinue both study 
drugs. 
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Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
Pancreatitis 
2 
Asymptomatic, blood test 
abnormalities 
Monitor pancreatic 
enzymes. 
Continue study treatment. 
3 
Abdominal pain, nausea and 
vomiting 
Admit to hospital for 
urgent management. 
Initiate intravenous 
(methyl)prednisolone 
1-2 mg/kg/day. 
Convert to oral 
prednisolone when 
amylase/lipase 
improved to Grade 2 
and taper over at least 
4 weeks. 
Hold both study drugs; 
reintroduce both study 
drugs only after discussion 
with the study medical 
monitor. 
 
4 
Acute abdominal pain, surgical 
emergency 
Admit to hospital for 
emergency 
management and 
appropriate referral.  
Discontinue both study 
drugs. 
Arthritis 
1 
Mild pain with inflammation, 
swelling 
Management per local 
guideline.  
Continue study treatment. 
2 
Moderate pain with inflammation, 
swelling, limited instrumental (fine 
motor) activities 
Management as per 
local guideline. 
Consider referring 
patient to a 
rheumatologist. 
If symptoms worsen 
on treatment, manage 
as a Grade 3 event. 
Continue treatment or, if 
symptoms continue to 
worsen, hold both study 
drugs until symptoms 
improve to baseline or 
Grade 0-1. 
3 
Severe pain with inflammation or 
permanent joint damage, daily 
living activity limited 
Refer patient urgently 
to a rheumatologist for 
assessment and 
management. 
Initiate oral 
prednisolone 
0.5-1 mg/kg and taper 
over at least 4 weeks. 
Hold both study drugs 
unless improved to 
Grade 0-1; reintroduce only 
after discussion with the 
study medical monitor. 
 
Mucositis/ 
stomatitis 
1 
Test findings only or minimal 
symptoms 
Consider topical 
treatment or analgesia 
as per local guideline. 
Continue study treatment. 
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Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
2 
Moderate pain, reduced oral 
intake, limited instrumental 
activities 
As per local 
guidelines, treat with 
analgesics, topical 
treatments, and oral 
hygiene care. 
Ensure adequate 
hydration. 
If symptoms worsen or 
there is sepsis or 
bleeding, manage as a 
Grade 3 event. 
Continue study treatment. 
3 
Severe pain, limited food and fluid 
intake, daily living activity limited 
Admit to hospital for 
appropriate 
management. 
Initiate intravenous 
(methyl)prednisolone 
1-2 mg/kg/day. 
Convert to oral 
prednisolone when 
symptoms improve to 
Grade 2 and taper over 
at least 4 weeks. 
Hold both study drugs until 
improved to Grade 0-1. 
 
4 
Life-threatening complications or 
dehydration 
Admit to hospital for 
emergency care. 
Consider intravenous 
corticosteroids if not 
contraindicated by 
infection. 
Discontinue both study 
drugs. 
Myositis/ 
Rhabdomyolysis 
1 
Mild weakness with/without pain 
Prescribe analgesics. 
If CK is significantly 
elevated and patient 
has symptoms, 
consider oral steroids 
and treat as Grade 2. 
Continue study treatment. 
2 
Moderate weakness with/without 
pain 
If CK is 3 x ULN or 
worse, initiate oral 
prednisolone 
0.5-1 mg/kg and taper 
over at least 4 weeks. 
Hold both study drugs until 
improved to Grade 0-1. 
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Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
3-4 
Severe weakness, limiting self-care 
Admit to hospital and 
initiate oral 
prednisolone 1 mg/kg. 
Consider bolus 
intravenous 
(methyl)prednisolone 
and 1-2 mg/kg/day 
maintenance for severe 
activity restriction or 
dysphagia. 
If symptoms do not 
improve, add 
immunosuppressant 
therapy. 
Taper oral steroids 
over at least 4 weeks. 
For Grade 3: Hold study 
treatment until improved to 
Grade 0-1. Discontinue 
upon any evidence of 
myocardial involvement. 
 
Myocarditis a 
< 2 
Asymptomatic but significantly 
increased CK-MB or increased 
troponin OR clinically significant 
intraventricular conduction delay 
Initiate cardiac 
evaluation under close 
monitoring with repeat 
serum testing and 
including ECG, 
cardiac echo/MUGA, 
and/or other 
interventions per 
institutional 
guidelines; consider 
referral to a 
cardiologist. 
If diagnosis of 
myocarditis is 
confirmed, treat as 
Grade 2. 
Hold both study drugs. 
If a diagnosis of 
myocarditis is confirmed 
and considered immune-
mediated, permanently 
discontinue study treatment 
in patients with moderate 
or severe symptoms. 
Patients with no symptoms 
or mild symptoms may not 
restart study drugs unless 
cardiac parameters have 
returned to baseline and 
after discussion with the 
study medical monitor. 
 
2 
Symptoms on mild-moderate 
exertion 
Admit to hospital and 
initiate oral 
prednisolone or 
intravenous 
(methyl)prednisolone 
at 1-2 mg/kg/day. 
Consult with a 
3 
Severe symptoms with mild 
exertion 
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Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug Management 
(All Arms) 
4 
Life-threatening 
cardiologist and 
manage symptoms of 
cardiac failure 
according to local 
guidelines. 
If no immediate 
response, change to 
pulsed doses of 
(methyl)prednisolone 
1 g/day and add MMF, 
infliximab, or anti-
thymocyte globulin. 
Other 
immune-mediated 
adverse events 
≤ 2 
Clinical management 
per local guideline 
based on adverse event 
type and severity. 
Continue study treatment. 
3 
Hold study treatment until 
improved to Grade 0-1. 
For recurrent Grade 3: 
Discontinue study 
treatment. 
4 
Discontinue study 
treatment. 
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BSA, body 
surface area; CS, corticosteroid; CHF, congestive heart failure; CK, creatine kinase; CK-MB, creatine kinase cardiac 
muscle isoenzyme; ECG, electrocardiogram; INR, international normalized ratio; IVIG, intravenous 
immunoglobulin; LFT, liver function test; MMF, mycophenolate mofetil; MUGA, multigated acquisition scan; 
NYHA, New York Heart Association; T4, thyroxine; TB, tuberculosis; TFT, thyroid function test; TSH, 
thyroid-stimulating hormone; U&E, urea and electrolytes; ULN, upper limit of normal. 
a If clinically significant cardiac enzyme abnormalities are detected during laboratory assessment and serial cardiac 
enzyme assessments pose logistical hardship for the patient, then patient hospitalization should strongly be 
considered until immune-mediated myocarditis has been ruled out. 
 
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APPENDIX 8. DOSE MODIFICATION FOR CHEMOTHERAPY  
Recommended Dose Modifications for Hematologic Toxicity 
Dose adjustments are based on nadir blood counts since the preceding chemotherapy 
administration. Dose level adjustments are relative to that of the preceding administration. 
Recommended dose modifications for hematologic toxicity are provided in the following table. 
Chemotherapy Dose Modificationa for Hematological Toxicity 
Adverse Event 
Treatment 
Febrile neutropenia; documented infection 
The first episode of febrile neutropenia or 
documented infection will result in antibiotic 
treatment and reduction by 20% of both drugs 
doses 
If there is a second episode despite dose 
reduction, the patient must receive 
prophylactic antibiotics during the subsequent 
cycles 
If there is a third episode, the chemotherapy 
will be discontinued 
Neutropenia 
Grade 3 
(0.5-0.99 x 109/L) 
Chemotherapy delay until ≤ Grade 1  
(≥ 1.5 x 109/L); restart with the full dose 
Grade 4 
(< 0.5 x 109/L) 
Chemotherapy delay until recovered to ≤ 
Grade 1; dose reduction of all further doses by 
20% 
Thrombocytopenia 
Grade 1 
Chemotherapy delay until recovered to 
normal; restart with the full dose 
≥ Grade 2 
Chemotherapy delay until recovered to 
normal; dose reduction of all further doses by 
20% 
a If considered in the best interest of the patient and consistent with local practice, investigators may decide to use 
supportive measures/treatment and/or secondary prophylaxis instead of dose reductions for the next cycle. The 
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Recommended Dose Modifications for Non-hematologic Toxicities 
The dose adjustments of chemotherapy for non-hematologic toxicity are described in the 
following table. All dose modifications should be made based on the worst grade toxicity.  
Chemotherapy Dose Modifications for Non-Hematological Toxicity 
Toxicity 
Grade 
Treatment  
Hyper-creatinemia 
≥ Grade 1 
Delay chemotherapy until 
recovered to Grade 0 or 
baseline, change cisplatin to 
carboplatin, if possible; dose 
reduction by 20% for other drug; 
if recur, stop chemotherapy 
Ototoxicity  
Grade 2 
Dose reduction of all further 
doses of cisplatin by 20% 
 
Grade 3-4 
Delay chemotherapy until 
recovered to ≤ Grade 2, change 
cisplatin to carboplatin 
Sensory neuropathy 
Grade 2 
Dose reduction for all further 
doses of cisplatin and/or 
paclitaxel by 20% 
 
Grade 3 
Stop cisplatin, change cisplatin 
to carboplatin; stop paclitaxel 
 
Grade 4 
Stop cisplatin/carboplatin, 
and/or paclitaxel 
Other organ toxicity 
Grade 2 
Delay chemotherapy until  
≤ Grade 1 or baseline a 
  
Grade 3-4 
Delay chemotherapy until 
recovered to ≤ Grade 1 or 
baseline a, dose reduction of all 
further dose by 20% 
a Skin reactions, paronychia, alopecia, fatigue, nausea/vomiting which may have resolved to Grade 2 or baseline. 
Note: If considered in the best interest of the patient and consistent with local practice, investigators may decide to 
use supportive measures/treatment, and/or secondary prophylaxis instead of dose reductions for the next cycle. The 
provided triggers for dose modifications are recommendations only.  
Recommended Dose Modifications for Nab-paclitaxel 
The dose adjustment of nab-paclitaxel refers to approved product labels for dose modifications 
regarding this regimen. Do not administer nab-paclitaxel on Day 1 of a cycle until absolute 
neutrophil count (ANC) is at least 1500 cells/mm3 and platelet count is at least 100,000 
cells/mm3.  
• In patients who develop severe neutropenia or thrombocytopenia withhold treatment 
until counts recover to an absolute neutrophil count of at least 1500 cells/mm3 and 
platelet count of at least 100,000 cells/mm3 on Day 1 or to an absolute neutrophil 
count of at least 1500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on 
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Days 8 or 15 of the cycle. If nab-paclitaxel cannot be administered on Day 15 of the 
cycle, the next dose of nab-paclitaxel should be administered with carboplatin on Day 
1 of the following cycle provided ANC and platelets counts have recovered to 
permissible levels. 
• Withhold nab-paclitaxel for Grade 3-4 peripheral neuropathy. Resume nab-paclitaxel 
and carboplatin at reduced doses when peripheral neuropathy improves to Grade 1 or 
completely resolves. 
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APPENDIX 9. CHRONIC KIDNEY DISEASE EPIDEMIOLOGY 
COLLABORATION (CKD-EPI) EQUATION, 
COCKCROFT-GAULT EQUATION, AND CALVERT 
FORMULA  
In adults, the most widely-used equations for estimating glomerular filtration rate (GFR) from 
serum creatinine are the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 
equation (Levey et al 2009) and the Modification of Diet in Renal Disease (MDRD) Study 
equation. The National Kidney Disease Education Program (NKDEP) calculators rely on 
creatinine determinations which are isotope dilution mass spectrometry (IDMS) traceable. All 
laboratories should be using creatinine methods calibrated to be IDMS traceable. 
This CKD-EPI equation calculator should be used when serum creatinine (Scr) is reported in 
mg/dL. This equation is recommended when eGFR values above 60 mL/min/1.73 m2 are desired. 
GFR = 141 × min (Scr /κ, 1)α × max(Scr /κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if 
black] 
where: 
Scr is serum creatinine in mg/dL,  
κ is 0.7 for females and 0.9 for males,  
α is -0.329 for females and -0.411 for males,  
min indicates the minimum of Scr /κ or 1, and 
max indicates the maximum of Scr /κ or 1. 
The equation does not require weight because the results are reported normalized to 1.73 m2 
body surface area, which is an accepted average adult surface area. 
The online calculator for CKD-EPI can be found here: 
https://www.niddk.nih.gov/health-information/communication-programs/nkdep/laboratory-
evaluation/glomerular-filtration-rate-calculators 
COCKCROFT-GAULT  EQUATION: 
 
CALVERT FORMULA: 
Total Dose (mg) = (target AUC) x (CrCl + 25) 
The CrCl used in the Calvert formula should not exceed 125 mL/min.  
When using eGFR instead of CrCl for calculation, generate with actual body surface area (BSA) 
instead of 1.73 m2. 
Maximum carboplatin dose (mg) = target AUC 5 (mg•min/mL) x (125 + 25) = 5 x 
150 mL/min = 750 mg 
Abbreviations: AUC, area under the concentration-time curve; BSA, body surface area; CrCl, creatinine clearance; 
eGFR, estimated glomerular filtration rate; GFR, glomerular filtration rate; Scr, serum creatinine concentration. 
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APPENDIX 10. CONTRACEPTION GUIDELINES AND DEFINITIONS 
OF “WOMEN OF CHILDBEARING POTENTIAL,” “NO 
CHILDBEARING POTENTIAL”  
Contraception Guidelines 
The Clinical Trials Facilitation Group recommendations related to contraception and pregnancy 
testing in clinical trials include the use of highly effective forms of birth control (Clinical Trials 
Facilitation and Coordination Group 2020). These methods include the following: 
• Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with the inhibition of ovulation 
o Oral, intravaginal, or transdermal 
• Progestogen-only hormonal contraception associated with the inhibition of ovulation 
o Oral, injectable, implantable 
Note: Oral birth control pills are not considered a highly effective form of birth 
control, and if they are selected, they must be used with a second, barrier method 
of contraception such as condoms with or without spermicide. 
• An intrauterine device 
• Intrauterine hormone-releasing system 
• Bilateral tubal occlusion 
• Vasectomized partner 
Note: This is only considered a highly effective form of birth control when the 
vasectomized partner is the sole partner of the study participant and there has been a 
medical assessment confirming surgical success. 
o A sterile male is one for whom azoospermia, in a semen sample, has been 
demonstrated as definitive evidence of infertility. 
• Sexual abstinence (defined as refraining from heterosexual intercourse during the 
entire period of risk associated with the study treatment) 
Note: Total sexual abstinence should only be used as a contraceptive method if it is in 
line with the patients’ usual and preferred lifestyle. Periodic abstinence (eg, calendar, 
ovulation, sympto-thermal, post-ovulation methods), declaration of abstinence for the 
duration of exposure to study drug, and withdrawal are not acceptable methods of 
contraception. 
Of note, barrier contraception (including male and female condoms with or without spermicide) 
is not considered a highly effective method of contraception, and if used, this method must be 
used in combination with one of the highly effective forms of birth control listed above. 
Definitions of “Women of Childbearing Potential,” “Women of No Childbearing Potential” 
As defined in this protocol, “women of childbearing potential” are female patients who are 
physiologically capable of becoming pregnant (ie, fertile, following menarche and until 
becoming postmenopausal unless permanently sterile). 
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Conversely, “women of no childbearing potential” are defined as female patients meeting any of 
the following criteria: 
• Surgically sterile (ie, through bilateral salpingectomy, bilateral oophorectomy, or 
hysterectomy) 
• Postmenopausal, defined as: 
o ≥ 55 years of age with no spontaneous menses for ≥ 12 months OR 
o < 55 years of age with no spontaneous menses for ≥ 12 months AND with 
postmenopausal follicle-stimulating hormone (FSH) concentration > 30 mIU/mL 
and all alternative medical causes for the lack of spontaneous menses for 
≥ 12 months have been ruled out, such as polycystic ovarian syndrome, 
hyperprolactinemia, etc. 
If an FSH measurement is required to confirm postmenopausal state, concomitant use of 
hormonal contraception or hormonal replacement therapy should be excluded. 
Adapted from Clinical Trials Facilitation and Coordination Group (CTFG) 2020. 
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APPENDIX 11. EUROPEAN ORGANISATION FOR RESEARCH AND 
TREATMENT OF CANCER QUALITY OF LIFE CANCER 
QUESTIONNAIRE QLQ-C30  
 
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APPENDIX 12. EUROPEAN ORGANISATION FOR RESEARCH AND 
TREATMENT OF CANCER QUALITY OF LIFE 
QUESTIONNAIRE LUNG CANCER QLQ-LC13  
 
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APPENDIX 13. LIST OF PROHIBITED CHINESE HERBAL AND 
PATENT MEDICINES  
The following table provides examples of Chinese herbal and patent medications that may be 
used to treat cancer or have immune-stimulating properties. This list is not intended to be all-
inclusive. These medications require a 14-day wash-out and should be prohibited during the 
study. 
Drug Name (Chinese)  
Drug Name (English) 
Rg3 参一胶囊 
Ginsenoside-Rg3 capsule 
养正消积胶囊 
Yangzheng Xiaoji Jiaonang 
化癥回生口服液  
Huazheng Huisheng Koufuye 
十全大补汤  
Juzentaihoto 
华蟾素注射液  
Cinobufacini/Huachansu injection 
华蟾素片/胶囊 
Cinobufacini/Huachansu Pian/Capsules 
博尔宁胶囊  
Boerning capsule 
去甲斑蝥素片  
Norcantharidin Pian 
参丹散结胶囊  
Shendan Sanjie Jiaonang 
参芪扶正注射液  
Shengqi Fuzheng Zhusheye 
参莲胶囊/颗粒  
Shen Lian Jiao Nang/Ke Li 
吗特灵注射液  
Ma Te Ling injection 
回生口服液  
Hui Sheng Kou Fu Ye 
复方斑蝥胶囊  
Fufang Banmao Jiaonang 
复方红豆杉胶囊  
Fufang Hongdoushan Jiaonang 
复方苦参注射液  
Fufang Kushen Zhusheye 
天仙胶囊  
Tian Xian capsule 
奇宁注射液  
Qining injection 
威麦宁胶囊  
Weimaining Jiao Nang 
安尔欣注射液  
Anerxin/Ginseng polysaccharide injection 
安康欣胶囊  
Ankangxin Jiaonang 
安替可胶囊  
Antike capsule 
岩舒注射液  
Yanshu injection 
平消片/胶囊  
Ping Xiao Pian/Jiao Nang 
康力欣胶囊  
Kanglixin Jiaonang 
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Drug Name (Chinese)  
Drug Name (English) 
康艾注射液  
Kang’ai Zhusheye 
康莱特注射液  
Kanglaite Injection 
康莱特软胶囊  
Kanglaite Soft Capsules 
慈丹胶囊  
CIDAN Capsule 
槐耳颗粒  
Huaer Keli 
海生素注射液  
Haishengsu injection 
消癌平丸/片/胶囊/颗粒  
Xiaoaiping Wan/Pian/Jiao Nang/Ke Li 
消癌平注射液  
Xiaoaiping Zhusheye 
牛黄醒消丸  
Niuhuang Xingxiao pill 
猪苓多糖注射液  
Polyporus polysaccharide injection 
白花蛇舌草注射液  
Hedyotis Dissusa wild injection 
紫龙金片 
Zi Long jin pian 
肝复乐片/胶囊  
Ganfule Jiaonang/GFL tablet 
肿节风片 
Zhongjiefeng tablet 
胃复春片  
Weifuchun pill 
艾迪注射液  
Ai Di Zhu She Ye 
芪珍胶囊  
Qizhen Jiaonang 
莪术油注射液  
Zedoary turmeric oil injection 
金复康口服液  
Kanglixin Jiaonang 
金蒲胶囊  
Jinpu capsule 
金龙胶囊  
Jinlong Capsules 
香菇多糖  
Lentinan 
鸦胆子油乳注射液  
Yadanzi/Brucea javanica Youru Zhusheye 
鸦胆子油软胶囊/口服乳液  
Yadanziyou Ruan jiao nang/Kou Fu Ru Ye 
Terminology list: Pian = tablet; Jiao Nang/Jiaonang = capsule; Ke Li/Keli = granules; Zhue She ye/Zhusheye = 
injections; Kou Fu Ye/koufuye = oral liquid; Wan = Pill/bolus; He Ji/Heji = mixture; Gao = ointment. 
 
 
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