Conditions: Non Small Cell Lung Cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 63
Healthy volunteers: no

Brief summary:
The purpose of this study was to evaluate the safety and efficacy of ociperlimab in combination with tislelizumab compared to durvalumab in adults with stage III unresectable PD-L1-selected non-small cell lung cancer whose disease has not progressed after cCRT.

Detailed description:
The study initiated with Protocol Amendment 1.0 (PA 1; dated on 16 April 2021). In April 2022 Protocol Amendment 2 (PA 2) was implemented. In PA 1, participants with newly diagnosed, histologically confirmed, unresectable locally advanced NSCLC and evaluable PD-L1 expression all comers were enrolled; cCRT was given within the study. In PA 2, the enrollment of the target population was revised into participants with unresectable locally advanced NSCLC whose disease has not progressed after definitive, platinum-based cCRT and with PD-L1 expression on ≥ 1% of tumor cells as assessed by the central lab; cCRT was given outside of the study.

After implementation of PA 2, participants who were randomized under PA 1 were given the option to continue assigned study treatment or to discontinue assigned treatment and begin standard of care treatment outside of the study. Participants enrolled under PA 1 were excluded from the primary and secondary analysis specified by PA 2.

This study was subsequently terminated by the Sponsor prior to enrollment of any participants under PA 2.

Arms:
arm 1: Participants enrolled under PA1 recieved two cycles of ociperlimab combined with tislelizumab and cCRT, followed by ociperlimab combined with tislelizumab up to 1 year after the cCRT phase arm 2: Participants enrolled under PA1 recieved two cycles of tislelizumab combined with cCRT, followed by tislelizumab up to 1 year after the cCRT phase arm 3: Participants enrolled under PA1 recieved two cycles of cCRT, followed by durvalumab to 1 year after the cCRT phase

Interventions: intervention 1: Tislelizumab intervention 2: Durvalumab intervention 3: Ociperlimab intervention 4: Chemotherapy intervention 5: Radiotherapy
Intervention descriptions: intervention 1: 200 mg intravenously every three weeks intervention 2: 10 milligrams per kilogram (mg/kg) intravenously once every 2 weeks (or 1500 mg intravenously once every 4 weeks where the dosage has been approved by a local health authority) intervention 3: 900 milligrams (mg) intravenously every three weeks intervention 4: The chemotherapy regimen for the study treatment was selected at the investigator's discretion and may include one of the following options:

* Cisplatin (50 mg/m²) on days 1 to 5 of each cycle, combined with etoposide (50 mg/m²) on days 1 and 8, both administered intravenously for 2 cycles. Each cycle was 28 days.
* Carboplatin (AUC 2) weekly for 6 weeks, combined with paclitaxel (40-50 mg/m²) weekly for 6 weeks, both administered intravenously.
* Cisplatin (75 mg/m²) combined with pemetrexed (500 mg/m²) on day 1 of each cycle, administered intravenously for 2 cycles. Each cycle was 21 days.
* Carboplatin (AUC 5) combined with pemetrexed (500 mg/m²) on day 1 of each cycle, administered intravenously for 2 cycles. Each cycle was 21 days.

The pemetrexed plus platinum regimen was only for participants with non-squamous histology. intervention 5: All participants recieved radiotherapy using either a standardized 3-dimensional conformal radiotherapy technique, or intensity modulated radiotherapy (IMRT) on a linear accelerator delivering a beam energy of ≥ 6 MV. The total dose of radiotherapy was 60 Gy, administered in 30 once-daily fractions of 2 Gy and 5 fractions per week for 6 weeks.

Protocol document:
Prot_000.pdf: 
BGB-A317-A1217-301 
BeiGene 
Protocol Amendment 2.0 
21 April 2022 
 
CONFIDENTIAL 
Page 1 
CLINICAL STUDY PROTOCOL 
Protocol Title:  
A Phase 3, Randomized, Open-Label Study to Compare Ociperlimab 
(BGB-A1217) Plus Tislelizumab (BGB-A317) Versus Durvalumab in 
Patients With Locally Advanced, Unresectable, PD-L1-Selected 
Non-Small Cell Lung Cancer Whose Disease Has Not Progressed 
After Concurrent Chemoradiotherapy 
Protocol Number: 
BGB-A317-A1217-301 (AdvanTIG-301) 
Phase: 
3 
Investigational Products: 
Ociperlimab and Tislelizumab 
Proposed Indication(s): 
Non-Small Cell Lung Cancer 
 
EudraCT: 
2020-004656-14 
Sponsor: 
BeiGene, Ltd. 
c/o BeiGene USA, Inc. 
2955 Campus Drive, Suite 200 
San Mateo, CA 94403 
USA 
Sponsor Medical Monitor: 
 
Telephone: 
 
Email:
 
Original Protocol 
Version 0.0: 
23 September 2020 
Amendment 1.0: 
16 April 2021 
Amendment 2.0: 
21 April 2022 
 
 
 
 
Confidentiality Statement 
This Document Is Not for Distribution – Do Not Copy 
This document contains confidential information and is the proprietary property of BeiGene, Ltd., and its 
subsidiaries. This document is for use by individuals and their designated representatives for their review, 
consideration, and/or participation in investigational trial(s). This document may not be copied or 
distributed for review by any unauthorized individuals without the prior written authorization of 
BeiGene, Ltd., or one of its subsidiaries. Your acceptance of this document constitutes agreement that you 
will not disclose the information contained herein to others without prior written authorization from 
BeiGene, Ltd., or one of its subsidiaries. 
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FINAL PROTOCOL APPROVAL SHEET 
 
A Phase 3, Randomized, Open-Label Study to Compare Ociperlimab (BGB-A1217) Plus 
Tislelizumab (BGB-A317) Versus Durvalumab in Patients With Locally Advanced, 
Unresectable, PD-L1-Selected Non-Small Cell Lung Cancer Whose Disease Has Not Progressed 
___ 
 
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INVESTIGATOR SIGNATURE PAGE 
 
Protocol Title: 
A Phase 3, Randomized, Open-Label Study to Compare Ociperlimab 
(BGB-A1217) Plus Tislelizumab (BGB-A317) Versus Durvalumab in 
Patients With Locally Advanced, Unresectable, PD-L1-Selected 
Non-Small Cell Lung Cancer Whose Disease Has Not Progressed After 
Concurrent Chemoradiotherapy 
 
Protocol Identifier: 
BGB-A317-A1217-301 (AdvanTIG-301) 
 
This protocol is a confidential communication of BeiGene, Ltd., and its subsidiaries. I confirm 
that I have read this protocol, I understand it, and I will work according to this protocol and the 
terms of the clinical study agreement governing the study. I will also work consistently with the 
ethical principles that have their origin in the Declaration of Helsinki and that are consistent with 
good clinical practices and the applicable laws and regulations. Acceptance of this document 
constitutes my agreement that no unpublished information contained herein will be published or 
disclosed without prior written approval from BeiGene, Ltd., or one of its subsidiaries. 
 
Instructions for Investigator: Please SIGN and DATE this signature page. PRINT your 
name, title, and the name and address of the center in which the study will be conducted. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
Signature of Investigator: 
_______________________________ Date: _____________ 
Printed Name: 
_______________________________ 
Investigator Title: 
_______________________________ 
Name/Address of Center: 
_______________________________ 
 
_______________________________ 
 
_______________________________ 
 
_______________________________ 
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TABLE OF CONTENTS 
FINAL PROTOCOL APPROVAL SHEET ....................................................................................2 
INVESTIGATOR SIGNATURE PAGE .........................................................................................3 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF TABLES .........................................................................................................................15 
LIST OF FIGURES .......................................................................................................................16 
SYNOPSIS ....................................................................................................................................17 
LIST OF ABBREVIATIONS AND TERMS ................................................................................30 
1. 
INTRODUCTION ......................................................................................................32 
1.1. 
Background Information .............................................................................................32 
1.1.1. 
Background Information on Non-Small Cell Lung Cancer ........................................32 
1.1.2. 
Current Treatment of Locally Advanced, Unresectable Non-Small Cell Lung 
Cancer .........................................................................................................................32 
1.1.2.1. 
Concurrent Chemoradiotherapy ..................................................................................32 
1.1.2.2. 
Anti-PD-1/PD-L1 Therapy .........................................................................................34 
1.1.2.3. 
Unmet Medical Needs ................................................................................................36 
1.2. 
Compound...................................................................................................................36 
1.2.1. 
Ociperlimab as a TIGIT Inhibitor ...............................................................................36 
1.2.1.1. 
Nonclinical ..................................................................................................................39 
1.2.1.2. 
Clinical Experience .....................................................................................................41 
1.2.2. 
Tislelizumab as a PD-1 Inhibitor ................................................................................43 
1.2.2.1. 
Pharmacology .............................................................................................................43 
1.2.2.2. 
Toxicology ..................................................................................................................43 
1.2.2.3. 
Clinical Pharmacology ................................................................................................44 
1.2.2.4. 
Prior Clinical Experience With Tislelizumab .............................................................44 
1.3. 
Study Rationale ...........................................................................................................49 
1.3.1. 
Rationale for the Dose Selection ................................................................................49 
1.3.1.1. 
Rationale for the Selection of Ociperlimab Dose .......................................................49 
1.3.1.2. 
Rationale for the Selection of Tislelizumab Dose ......................................................50 
1.3.2. 
Rationale for Combination of Ociperlimab and Tislelizumab in the 
Treatment of Non-Small Cell Lung Cancer ................................................................50 
1.3.3. 
Rationale for Durvalumab as the Comparator ............................................................51 
1.3.4. 
Biomarker Strategy Rationale.....................................................................................52 
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1.4. 
Benefit-Risk Assessment ............................................................................................53 
1.5. 
Study Conduct ............................................................................................................55 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................56 
2.1. 
Study Objectives and Endpoints .................................................................................56 
2.2. 
Definition of Primary Estimand ..................................................................................58 
2.2.1. 
Primary Estimand 1 – PFS benefit in patients with LA NSCLC who have not 
progressed after cCRT and with PD-L1 ≥ 50% ..........................................................58 
2.2.2. 
Primary Estimand 2 – PFS benefit in patients with LA NSCLC whose 
disease has not progressed after cCRT and with PD-L1 ≥ 1% ...................................59 
2.3. 
Definition of Key Secondary Estimand ......................................................................60 
2.3.1. 
Key Secondary Estimand 1 – OS benefit in patients with LA NSCLC whose 
disease has not progressed after cCRT and with PD-L1 ≥ 50% .................................60 
2.3.2. 
Key Secondary Estimand 2 – OS benefit in patients with LA NSCLC whose 
disease has not progressed after cCRT and with PD-L1 ≥ 1% ...................................60 
3. 
STUDY DESIGN .......................................................................................................61 
3.1. 
Summary of Study Design ..........................................................................................61 
3.2. 
Prescreening ................................................................................................................62 
3.3. 
Screening Period .........................................................................................................63 
3.4. 
Treatment Period ........................................................................................................63 
3.5. 
End of Treatment ........................................................................................................65 
3.6. 
Safety Follow-up ........................................................................................................65 
3.7. 
Survival Follow-up .....................................................................................................65 
3.8. 
Discontinuation From the Study Treatment or From the Study .................................66 
3.8.1. 
Discontinuation From Study Treatment .....................................................................66 
3.8.2. 
Patient Discontinuation From Study (End of Study for an Individual Patient) ..........66 
3.9. 
End of Study ...............................................................................................................67 
4. 
STUDY POPULATION .............................................................................................68 
4.1. 
Inclusion Criteria ........................................................................................................68 
4.2. 
Exclusion Criteria .......................................................................................................70 
5. 
STUDY TREATMENT ..............................................................................................74 
5.1. 
Formulation, Packaging, and Handling ......................................................................74 
5.1.1. 
Ociperlimab ................................................................................................................74 
5.1.2. 
Tislelizumab ...............................................................................................................74 
5.1.3. 
Durvalumab ................................................................................................................74 
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5.2. 
Dosage, Administration, and Compliance ..................................................................74 
5.2.1. 
Ociperlimab and Tislelizumab Treatment Administration .........................................76 
5.2.2. 
Durvalumab ................................................................................................................76 
5.2.3. 
Supportive Care ..........................................................................................................77 
5.3. 
Incorrect Administration or Overdose ........................................................................77 
5.4. 
Investigational Medicinal Product Accountability .....................................................77 
5.5. 
Dose Modification ......................................................................................................77 
5.5.1. 
Dose Interruption or Delay for Ociperlimab and Tislelizumab ..................................78 
5.5.2. 
Dose Reductions for Ociperlimab and Tislelizumab ..................................................78 
5.5.3. 
Dose Interruption, Delay or Modification for Durvalumab ........................................78 
6. 
PRIOR AND CONCOMITANT THERAPY .............................................................79 
6.1. 
Prior Therapy ..............................................................................................................79 
6.2. 
Permitted Concomitant Medications/Procedures .......................................................79 
6.2.1. 
Systemic Corticosteroids ............................................................................................79 
6.2.2. 
Hepatitis B Treatment .................................................................................................79 
6.2.3. 
Hepatitis C Treatment .................................................................................................80 
6.3. 
Prohibited Concomitant Medications/Procedures ......................................................80 
6.4. 
Restricted Concomitant Medications/Procedures .......................................................80 
6.5. 
Potential Interactions Between the Study Drugs and Concomitant 
Medications .................................................................................................................81 
7. 
STUDY ASSESSMENT AND PROCEDURES ........................................................82 
7.1. 
Prescreening ................................................................................................................82 
7.2. 
Screening Period .........................................................................................................82 
7.2.1. 
Informed Consent and Prescreening and Screening Log ............................................83 
7.2.2. 
Patient Numbering ......................................................................................................83 
7.2.3. 
Demographic Data and Medical History ....................................................................83 
7.2.4. 
Females of Childbearing Potential and Contraception ...............................................83 
7.2.5. 
Pulmonary Function Tests ..........................................................................................84 
7.2.6. 
HIV Serology Test ......................................................................................................84 
7.2.7. 
COVID-19 Test ..........................................................................................................84 
7.3. 
Enrollment ..................................................................................................................84 
7.3.1. 
Confirmation of Eligibility .........................................................................................84 
7.3.2. 
Randomization ............................................................................................................84 
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7.4. 
Study Drug Dispensation ............................................................................................85 
7.5. 
Safety Assessment ......................................................................................................85 
7.5.1. 
Vital Signs ..................................................................................................................85 
7.5.2. 
Physical Examinations ................................................................................................85 
7.5.3. 
Eastern Cooperative Oncology Group Performance Status ........................................85 
7.5.4. 
Laboratory Safety Tests ..............................................................................................86 
7.5.4.1. 
Cardiac Enzyme Monitoring .......................................................................................86 
7.5.5. 
Electrocardiograms .....................................................................................................87 
7.5.6. 
Adverse Events ...........................................................................................................87 
7.5.7. 
Hepatitis B and C Testing ...........................................................................................87 
7.6. 
Tumor and Response Evaluations ..............................................................................87 
7.7. 
Pharmacokinetic and Antidrug Antibody Testing ......................................................90 
7.8. 
Biomarker ...................................................................................................................90 
7.9. 
Health-Related Quality of Life ...................................................................................91 
7.10. 
Visit Windows ............................................................................................................91 
7.11. 
Unscheduled Visits .....................................................................................................91 
8. 
SAFETY MONITORING AND REPORTING .........................................................92 
8.1. 
Risks Associated With Study Treatment ....................................................................92 
8.1.1. 
Risks Associated With Ociperlimab and Tislelizumab ..............................................92 
8.1.2. 
Risks Associated With Durvalumab ...........................................................................92 
8.2. 
General Plan to Manage Safety Concerns ..................................................................92 
8.2.1. 
Eligibility Criteria .......................................................................................................92 
8.2.2. 
Safety Monitoring Plan ...............................................................................................93 
8.3. 
Adverse Events ...........................................................................................................93 
8.3.1. 
Definitions and Reporting ...........................................................................................93 
8.3.2. 
Assessment of Severity ...............................................................................................94 
8.3.3. 
Assessment of Causality .............................................................................................94 
8.3.4. 
Follow-up of Adverse Events .....................................................................................95 
8.3.5. 
Laboratory Test Abnormalities ...................................................................................96 
8.4. 
Definition of a Serious Adverse Event .......................................................................96 
8.5. 
Suspected Unexpected Serious Adverse Reaction .....................................................97 
8.6. 
Timing, Frequency, and Method of Capturing Adverse Events and Serious 
Adverse Events ...........................................................................................................97 
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8.6.1. 
Adverse Event Reporting Period ................................................................................97 
8.6.2. 
Reporting Serious Adverse Events .............................................................................98 
8.6.2.1. 
Prompt Reporting of Serious Adverse Events ............................................................98 
8.6.2.2. 
Completion and Transmission of the Serious Adverse Event Report ........................98 
8.6.2.3. 
Regulatory Reporting Requirements for Serious Adverse Events .............................99 
8.6.3. 
Eliciting Adverse Events ............................................................................................99 
8.6.4. 
Disease Progression ....................................................................................................99 
8.6.5. 
Deaths .......................................................................................................................100 
8.6.6. 
Pregnancies ...............................................................................................................100 
8.6.7. 
Expedited Reporting to Health Authorities, Investigators, Institutional 
Review Boards, and Independent Ethics Committees ..............................................100 
8.6.8. 
Assessing and Recording Immune-Mediated Adverse Events .................................100 
8.6.9. 
Recording Infusion-Related Reactions .....................................................................101 
8.7. 
Management of Adverse Events of Special Interest .................................................101 
8.7.1. 
Infusion-Related Reactions .......................................................................................101 
8.7.2. 
Severe Hypersensitivity Reactions and Flu-Like Symptoms ...................................102 
8.7.3. 
Immune-Mediated Adverse Events ..........................................................................103 
8.7.4. 
Adverse Events of Special Interest of Durvalumab ..................................................104 
9. 
STATISTICAL METHODS AND SAMPLE SIZE DETERMINATION ...............105 
9.1. 
Statistical Analysis ....................................................................................................105 
9.1.1. 
Randomization Methods ...........................................................................................105 
9.1.2. 
Analysis Sets .............................................................................................................105 
9.1.3. 
Patient Disposition ....................................................................................................106 
9.1.4. 
Demographic and Other Baseline Characteristics ....................................................106 
9.1.5. 
Prior and Concomitant Medications .........................................................................106 
9.2. 
Efficacy Analyses .....................................................................................................106 
9.2.1. 
Primary Efficacy Analysis ........................................................................................107 
9.2.1.1. 
Primary Estimand .....................................................................................................107 
9.2.1.2. 
Primary Analysis for Primary Estimand ...................................................................107 
9.2.1.3. 
Handling of Missing Values Not Related to Intercurrent Event ...............................107 
9.2.1.4. 
Sensitivity Analyses/Supplementary for Primary Endpoint/Estimand .....................108 
9.2.2. 
Efficacy Analysis for Key Secondary Estimand ......................................................108 
9.2.2.1. 
Definition of Key Secondary Estimand ....................................................................108 
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9.2.2.2. 
Primary Analysis for Key Secondary Estimand .......................................................108 
9.2.2.3. 
Sensitivity Analyses/Supplementary for Key Secondary Endpoint/Estimand .........109 
9.2.3. 
Other Secondary Efficacy Analysis ..........................................................................109 
9.2.4. 
Exploratory Efficacy Analyses .................................................................................110 
9.2.5. 
Subgroup Analyses ...................................................................................................110 
9.3. 
Safety Analyses ........................................................................................................110 
9.3.1. 
Extent of Exposure ...................................................................................................110 
9.3.2. 
Adverse Events .........................................................................................................111 
9.3.3. 
Laboratory Analyses .................................................................................................111 
9.3.4. 
Vital Signs ................................................................................................................112 
9.4. 
Pharmacokinetic Analyses ........................................................................................112 
9.5. 
Immunogenicity Analyses ........................................................................................112 
9.6. 
Other Exploratory Analyses .....................................................................................112 
9.7. 
Sample Size Consideration .......................................................................................113 
9.8. 
Interim Analysis ........................................................................................................114 
10. 
STUDY COMMITTEES ..........................................................................................115 
10.1. 
Independent Review Committee ...............................................................................115 
10.2. 
Independent Data Monitoring Committee ................................................................115 
10.3. 
Steering Committee ..................................................................................................115 
11. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS .............................................................................................116 
11.1. 
Access to Information for Monitoring ......................................................................116 
11.2. 
Access to Information for Auditing or Inspections ..................................................116 
12. 
QUALITY ASSURANCE AND QUALITY CONTROL .......................................117 
12.1. 
Regulatory Authority Approval ................................................................................117 
12.2. 
Quality Assurance .....................................................................................................117 
12.3. 
Study Site Inspections...............................................................................................117 
12.4. 
Drug Accountability .................................................................................................117 
13. 
ETHICS/PROTECTION OF HUMAN PATIENTS ................................................119 
13.1. 
Ethical Standard ........................................................................................................119 
13.2. 
Institutional Review Board/Independent Ethics Committee ....................................119 
13.2.1. 
Protocol Amendments ..............................................................................................119 
13.3. 
Informed Consent .....................................................................................................120 
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13.4. 
Patient and Data Confidentiality ...............................................................................120 
13.5. 
Financial Disclosure .................................................................................................122 
14. 
DATA HANDLING AND RECORD KEEPING ....................................................123 
14.1. 
Data Collection and Management Responsibilities ..................................................123 
14.1.1. 
Data Entry in the Electronic Case Report Form .......................................................123 
14.1.2. 
Data Collection .........................................................................................................123 
14.1.3. 
Data Management/Coding ........................................................................................123 
14.2. 
Data Integrity and In-house Blinding .......................................................................124 
14.3. 
Study Records Retention ..........................................................................................124 
14.4. 
Protocol Deviations ..................................................................................................125 
14.5. 
Study Report and Publications..................................................................................125 
14.6. 
Study and Study Center Closure ...............................................................................126 
14.7. 
Information Disclosure and Inventions ....................................................................126 
15. 
REFERENCES .........................................................................................................128 
16. 
APPENDICES ..........................................................................................................139 
APPENDIX 1. SCHEDULE OF ASSESSMENTS ..................................................................140 
APPENDIX 2. CLINICAL LABORATORY ASSESSMENTS ..............................................146 
APPENDIX 3. EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE 
STATUS ...................................................................................................................148 
APPENDIX 4. PREEXISTING IMMUNE DEFICIENCIES OR AUTOIMMUNE 
DISEASES ................................................................................................................149 
APPENDIX 5. CONTRACEPTION GUIDELINES AND DEFINITIONS OF 
“WOMEN OF CHILDBEARING POTENTIAL,” “NO CHILDBEARING 
POTENTIAL” ...........................................................................................................150 
APPENDIX 6. NEW YORK HEART ASSOCIATION FUNCTIONAL 
CLASSIFICATION ..................................................................................................152 
APPENDIX 7. EUROPEAN ORGANISATION FOR RESEARCH AND 
TREATMENT OF CANCER QUALITY OF LIFE CANCER 
QUESTIONNAIRE QLQ-C30 .................................................................................153 
APPENDIX 8. EUROPEAN ORGANISATION FOR RESEARCH AND 
TREATMENT OF CANCER QUALITY OF LIFE QUESTIONNAIRE 
LUNG CANCER QLQ-LC13 ..................................................................................155 
APPENDIX 9. THE 5-LEVEL VERSION OF EUROPEAN QUALITY OF LIFE 5-
DIMENSIONAL QUESTIONNAIRE .....................................................................156 
APPENDIX 10. PATIENT GLOBAL IMPRESSION OF SEVERITY (PGI-S) .....................158 
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APPENDIX 11. PATIENT REPORTED TREATMENT-RELATD SIDE-EFFECT 
BURDEN (PRTSE) ..................................................................................................159 
APPENDIX 12. IMMUNE-MEDIATED ADVERSE EVENT EVALUATION AND 
MANAGEMENT .....................................................................................................160 
APPENDIX 13. RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
(RECIST) GUIDELINES, VERSION 1.1 ................................................................171 
APPENDIX 14. CHRONIC KIDNEY DISEASE EPIDEMIOLOGY 
COLLABORATION (CKD-EPI) AND COCKCROFT-GAULT (CG) 
EQUATION ..............................................................................................................180 
APPENDIX 15. RECOMMENDED DOSAGE MODIFICATIONS FOR ADVERSE 
REACTIONS OF DURVALUMAB ........................................................................182 
APPENDIX 16. LIST OF PROHIBITED CHINESE HERBAL AND PATENT 
MEDICINES .............................................................................................................185 
APPENDIX 17. PATIENT CARE AND STUDY CONDUCT FOR PATIENTS 
ENROLLED WITH PA 1.0 ......................................................................................186 
1. 
STUDY DESIGN OF PA 1.0 ...................................................................................186 
1.1. 
Summary of Study Design ........................................................................................186 
1.2. 
Screening Period .......................................................................................................196 
1.3. 
Treatment Period ......................................................................................................196 
1.4. 
End of Treatment ......................................................................................................198 
1.5. 
Safety Follow-up ......................................................................................................198 
1.6. 
Survival Follow-up ...................................................................................................198 
1.7. 
Discontinuation From the Study Treatment or From the Study ...............................199 
1.7.1. 
Discontinuation From Study Treatment ...................................................................199 
1.7.2. 
Patient Discontinuation From Study (End of Study for an Individual Patient) ........199 
1.8. 
End of Study .............................................................................................................200 
2. 
STUDY TREATMENT ............................................................................................201 
2.1. 
Formulation, Packaging, and Handling ....................................................................201 
2.1.1. 
Ociperlimab ..............................................................................................................201 
2.1.2. 
Tislelizumab .............................................................................................................201 
2.1.3. 
Durvalumab ..............................................................................................................201 
2.1.4. 
Chemotherapy ...........................................................................................................202 
2.2. 
Dosage, Administration, and Compliance ................................................................202 
2.2.1. 
Ociperlimab and Tislelizumab ..................................................................................204 
2.2.2. 
Durvalumab ..............................................................................................................205 
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2.2.3. 
Chemotherapy ...........................................................................................................205 
2.2.3.1. 
Cisplatin Plus Etoposide ...........................................................................................205 
2.2.3.2. 
Carboplatin Plus Paclitaxel .......................................................................................205 
2.2.3.3. 
Cisplatin Plus Pemetrexed ........................................................................................206 
2.2.3.4. 
Carboplatin Plus Pemetrexed ....................................................................................206 
2.2.4. 
Radiation Therapy ....................................................................................................207 
2.2.4.1. 
Radiation Dose Specifications ..................................................................................208 
2.2.4.2. 
Variations of Dose Prescription ................................................................................208 
2.2.4.3. 
Simulation, Immobilization, and Treatment Imaging...............................................209 
2.2.4.4. 
Radiation Treatment Planning ..................................................................................210 
2.2.4.5. 
Radiation Treatment Documentation ........................................................................211 
2.2.4.6. 
Organs at Risk ...........................................................................................................211 
2.2.4.7. 
Quality Assurance and Compliance with Protocol-defined Radiation 
Prescription (Quality Control) ..................................................................................212 
2.2.5. 
Supportive Care ........................................................................................................213 
2.3. 
Incorrect Administration or Overdose ......................................................................213 
2.4. 
Investigational Medicinal Product Accountability ...................................................214 
2.5. 
Dose Delay or Modification .....................................................................................214 
2.5.1. 
Dose Interruption or Delay for Ociperlimab and Tislelizumab ................................214 
2.5.2. 
Dose Reductions for Ociperlimab and Tislelizumab ................................................215 
2.5.3. 
Dose Interruption, Delay or Modification for Durvalumab ......................................215 
2.5.4. 
Dose Delay or Modification for Radiotherapy .........................................................215 
2.5.5. 
Dose Modifications for Chemotherapy Treatment ...................................................218 
2.5.6. 
Criteria for Discontinuing Chemotherapy Regimens ...............................................222 
3. 
PRIOR AND CONCOMITANT THERAPY ...........................................................223 
3.1. 
Prior Therapy ............................................................................................................223 
3.2. 
Permitted Concomitant Medications/Procedures .....................................................223 
3.2.1. 
Systemic Corticosteroids ..........................................................................................223 
3.2.2. 
Hepatitis B Treatment ...............................................................................................223 
3.2.3. 
Hepatitis C Treatment ...............................................................................................224 
3.3. 
Prohibited Concomitant Medications/Procedures ....................................................224 
3.4. 
Restricted Concomitant Medications/Procedures .....................................................224 
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3.5. 
Potential Interactions Between the Study Drugs and Concomitant 
Medications ...............................................................................................................225 
4. 
STUDY ASSESSMENT AND PROCEDURES ......................................................226 
4.1. 
Screening Period .......................................................................................................226 
4.1.1. 
Informed Consent and Screening Log ......................................................................226 
4.1.2. 
Patient Numbering ....................................................................................................226 
4.1.3. 
Demographic Data and Medical History ..................................................................227 
4.1.4. 
Females of Childbearing Potential and Contraception .............................................227 
4.1.5. 
Pulmonary Function Tests ........................................................................................227 
4.1.6. 
COVID-19 Test ........................................................................................................227 
4.2. 
Enrollment ................................................................................................................227 
4.2.1. 
Confirmation of Eligibility .......................................................................................227 
4.2.2. 
Randomization ..........................................................................................................228 
4.3. 
Study Drug Dispensation ..........................................................................................228 
4.4. 
Safety Assessment ....................................................................................................228 
4.4.1. 
Vital Signs ................................................................................................................228 
4.4.2. 
Physical Examinations ..............................................................................................228 
4.4.3. 
Eastern Cooperative Oncology Group Performance Status ......................................228 
4.4.4. 
Laboratory Safety Tests ............................................................................................229 
4.4.4.1. 
Cardiac Enzyme Monitoring .....................................................................................229 
4.4.5. 
Electrocardiograms ...................................................................................................230 
4.4.6. 
Adverse Events .........................................................................................................230 
4.4.7. 
Hepatitis B and C Testing .........................................................................................230 
4.5. 
Tumor and Response Evaluations ............................................................................230 
4.6. 
Pharmacokinetic and Antidrug Antibody Testing ....................................................232 
4.7. 
Biomarker .................................................................................................................233 
4.8. 
Health-Related Quality of Life .................................................................................233 
4.9. 
Visit Windows ..........................................................................................................234 
4.10. 
Unscheduled Visits ...................................................................................................234 
5. 
SAFETY MONITORING AND REPORTING .......................................................235 
5.1. 
Risks Associated With Study Treatment ..................................................................235 
5.1.1. 
Risks Associated With Ociperlimab and Tislelizumab ............................................235 
5.1.2. 
Risks Associated With Durvalumab .........................................................................235 
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5.1.3. 
Risks Associated With Concurrent Chemotherapy ..................................................235 
5.1.4. 
Risks Associated With Radiotherapy .......................................................................236 
5.2. 
General Plan to Manage Safety Concerns ................................................................236 
5.2.1. 
Safety Monitoring Plan .............................................................................................236 
5.3. 
Adverse Events .........................................................................................................237 
5.3.1. 
Definitions and Reporting .........................................................................................237 
5.3.2. 
Assessment of Severity .............................................................................................237 
5.3.3. 
Assessment of Causality ...........................................................................................238 
5.3.4. 
Follow-up of Adverse Events ...................................................................................239 
5.3.5. 
Laboratory Test Abnormalities .................................................................................239 
5.4. 
Definition of a Serious Adverse Event .....................................................................240 
5.5. 
Suspected Unexpected Serious Adverse Reaction ...................................................240 
5.6. 
Timing, Frequency, and Method of Capturing Adverse Events and Serious 
Adverse Events .........................................................................................................241 
5.6.1. 
Adverse Event Reporting Period ..............................................................................241 
5.6.2. 
Reporting Serious Adverse Events ...........................................................................241 
5.6.2.1. 
Prompt Reporting of Serious Adverse Events ..........................................................241 
5.6.2.2. 
Completion and Transmission of the Serious Adverse Event Report ......................242 
5.6.2.3. 
Regulatory Reporting Requirements for Serious Adverse Events ...........................242 
5.6.3. 
Eliciting Adverse Events ..........................................................................................243 
5.6.4. 
Disease Progression ..................................................................................................243 
5.6.5. 
Deaths .......................................................................................................................243 
5.6.6. 
Pregnancies ...............................................................................................................243 
5.6.7. 
Expedited Reporting to Health Authorities, Investigators, Institutional 
Review Boards, and Independent Ethics Committees ..............................................243 
5.6.8. 
Assessing and Recording Immune-Mediated Adverse Events .................................244 
5.6.9. 
Recording Infusion-Related Reactions .....................................................................244 
5.7. 
Management of Adverse Events of Special Interest .................................................244 
5.7.1. 
Infusion-Related Reactions .......................................................................................245 
5.7.2. 
Severe Hypersensitivity Reactions and Flu-Like Symptoms ...................................246 
5.7.3. 
Immune-Mediated Adverse Events ..........................................................................246 
5.7.4. 
Adverse Events of Special Interest of Durvalumab ..................................................247 
 
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LIST OF TABLES 
Table 1: Statistical Assumptions, Sample Size, and Power ...........................................................28 
Table 2: 
Event Number and Testing Boundaries of Interim Analyses and Final 
Analysis ......................................................................................................................29 
Table 3: 
Primary Objectives and Endpoints .............................................................................56 
Table 4: 
Secondary Objectives and Endpoints .........................................................................56 
Table 5: 
Exploratory Objectives and Endpoints .......................................................................58 
Table 6: 
Planned Dose, Frequency of Administration, and Route of Administration 
for Study Drugs ...........................................................................................................75 
Table 7: 
Administration of Ociperlimab and Tislelizumab and Monitoring Time ...................75 
Table 8:  
Guidance for Duration of Recording New or Worsening Adverse Events in 3 
Arms ...........................................................................................................................98 
Table 9: 
Time Frames and Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee .............................................................................98 
Table 10: Treatment Modification for Symptoms of Infusion-Related Reactions Due to 
Study Drugs ..............................................................................................................101 
Table 11: Immune-Mediated Adverse Events ..........................................................................103 
Table 12: Statistical assumptions, sample size and power ..........................................................113 
Table 13: Event number, and Testing Boundaries of Interim Analyses and Final 
Analysis ....................................................................................................................114 
Table 14: Schedule of Assessment for PA 1.0 ..........................................................................187 
Table 15: Planned Dose, Frequency of Administration, and Route of Administration 
for Study Drugs .........................................................................................................203 
Table 16: Administration of Ociperlimab and Tislelizumab and Monitoring Time .................204 
Table 17: Carboplatin Dose Calculation ...................................................................................207 
Table 18: Summary of Dose Prescription Variations ...............................................................209 
Table 19: Credentialing Procedure ...........................................................................................212 
Table 20: CTCAE Scale: Acute Esophagitis Related to Radiation ..........................................217 
Table 21: Dietary and Nutritional Support Recommendations for Acute Radiation 
Esophagitis ................................................................................................................217 
Table 22: Recommendations for Medication Management of Radiation Esophagitis .............217 
Table 23: Dose Modification of Chemotherapy .......................................................................219 
Table 24: The summary of the commonly and specific reported toxicity of the 
chemotherapeutic agents ...........................................................................................236 
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Table 25:  Guidance for Duration of Recording New or Worsening Adverse Events in 3 
Arms .........................................................................................................................241 
Table 26: Time Frames and Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee ...........................................................................242 
Table 27: Treatment Modification for Symptoms of Infusion-Related Reactions Due to 
Study Drugs ..............................................................................................................245 
Table 28: Immune-Mediated Adverse Events ..........................................................................247 
 
LIST OF FIGURES 
Figure 1:  Study Schema ...........................................................................................................21 
Figure 2: 
Fixed-Sequence Testing Strategy for Primary and Key Secondary Endpoints ..........26 
Figure 3: 
Study Schema .............................................................................................................61 
Figure 4: 
Fixed-Sequence Testing Strategy for Primary and Key Secondary Endpoints ........107 
 
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SYNOPSIS 
Name of 
Sponsor/Company: 
BeiGene, Ltd. 
Investigational 
Product(s): 
Ociperlimab (BGB-A1217) and tislelizumab (BGB-A317) 
Protocol Identifier: 
BGB-A317-A1217-301 (AdvanTIG-301) 
The context below in the synopsis applies to study conduction since Protocol Amendment (PA) 2.0 
implementation only, unless specified otherwise. 
Title of Study: 
A Phase 3, Randomized, Open-Label Study to Compare Ociperlimab 
(BGB-A1217) Plus Tislelizumab (BGB-A317) Versus Durvalumab in Patients 
With Locally Advanced, Unresectable, PD-L1-Selected Non-Small Cell Lung 
Cancer Whose Disease Has Not Progressed After Concurrent 
Chemoradiotherapy 
Planned Number of 
Patients: 
Approximately 700 patients in total 
Study Centers: 
Approximately 235 centers globally 
Study Duration: 
Prescreening (archival or fresh tumor tissue collected prior 
to cCRT for evaluation of programmed cell death protein 
ligand-1[PD-L1] status; up to 120 days), screening (up to 
28 days), treatment (immunotherapy until a maximum of 
12 months, or disease progression, intolerable toxicity, or 
treatment discontinuation for other reasons), safety 
follow-up (approximately 30, 60, 90, and 120 days after the 
last dose of study treatment), and survival follow-up 
(approximately every 3 months ± 14 days after the Safety 
Follow-up Visit). 
Phase: 3 
Study Objectives and Endpoints: 
Primary: 
Objectives 
Endpoints 
Compare progression-free survival (PFS) as 
assessed by the Independent Review Committee 
(IRC) per Response Evaluation Criteria in Solid 
Tumors (RECIST) Version (v) 1.1 in ociperlimab 
plus tislelizumab (Arm A) versus durvalumab 
(Arm C) among patients with Local Advanced 
Non-Small Cell Lung Cancer (LA NSCLC) 
whose disease has not progressed after concurrent 
chemoradiotherapy (cCRT) and with 
PD-L1 ≥ 50% 
PFS by the IRC, defined as the time from the date 
of randomization to the date of first 
documentation of disease progression as assessed 
by the IRC per RECIST v1.1 or death, whichever 
occurs first 
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Compare PFS as assessed by the IRC per RECIST 
v1.1 in ociperlimab plus tislelizumab (Arm A) 
versus durvalumab (Arm C) among patients with 
LA NSCLC whose disease has not progressed 
after cCRT and with PD-L1 ≥ 1% 
Secondary: 
Objectives 
Endpoints 
Compare overall survival (OS) in Arm A versus 
Arm C among patients with PD-L1 ≥ 50% 
OS defined as the time from the date of 
randomization until the date of death due to any 
cause 
Compare OS in Arm A versus Arm C among 
patients with PD-L1 ≥ 1% 
Evaluate overall response rate (ORR) and duration 
of response (DOR) as assessed by both the IRC 
and investigators in Arm A versus Arm C among 
patients with PD-L1 ≥ 50% and ≥ 1% 
ORR, defined as the proportion of patients who 
achieve a complete response (CR) or partial 
response (PR) assessed by both the IRC and 
investigators per RECIST v1.1 
DOR, defined as the time from the first 
determination of a confirmed objective response 
as assessed by both the IRC and investigators per 
RECIST v1.1 until the first documentation of 
disease progression or death, whichever occurs 
first 
Evaluate time to death or distant metastasis 
(TTDM) in Arm A versus Arm C among patients 
with PD-L1 ≥ 50% and ≥ 1% 
TTDM, defined as the time from the date of 
randomization until the first date of distant 
metastasis as assessed by both the IRC and 
investigators, or death. Distant metastasis is 
defined as any new lesion that is outside of the 
radiation field per RECIST v1.1 or proven by 
biopsy 
Evaluate PFS2 in Arm A versus Arm C among 
patients with PD-L1 ≥ 50% and ≥ 1% 
PFS2, defined as the time from randomization to 
the disease progression after next line of 
treatment, or death from any cause, whichever 
occurs first 
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Evaluate safety and tolerability in 3 treatment 
arms among patients with PD-L1 ≥ 50% and ≥ 1%  
Safety and tolerability, defined as adverse events 
(AEs) (using NCI-CTCAE v5.0), laboratory tests, 
vital signs, Eastern Cooperative Oncology Group 
(ECOG) Performance Status, physical 
examinations, concomitant medications, and dose 
modifications 
Compare the impact of treatments on patient 
health-related quality of life (HRQoL) in Arm A 
versus Arm C among patients with PD-L1 ≥ 50% 
and PD-L1 ≥ 1% 
HRQoL, measured via patient-reported outcomes 
(PROs) using European Organization for 
Research and Treatment of Cancer Quality of Life 
Questionnaire Core 30 (EORTC QLQ-C30), 
European Organization for Research and 
Treatment of Cancer Quality of Life 
Questionnaire Lung Cancer 13 (EORTC 
QLQ-LC13), and the 5-Level EuroQol 
5-Dimension (EQ-5D-5L) 
Characterize the pharmacokinetics (PK) of 
ociperlimab and tislelizumab 
Serum concentrations of ociperlimab and 
tislelizumab at specified timepoints 
Assess host immunogenicity to ociperlimab and 
tislelizumab 
Immunogenic responses to ociperlimab and 
tislelizumab evaluated through detection of anti-
drug antibodies 
Evaluate the association of PD-L1 and T-cell 
immunoglobulin and ITIM domain (TIGIT) 
expression with clinical efficacy to ociperlimab 
plus tislelizumab or tislelizumab or durvalumab 
only 
PD-L1 and TIGIT expression in archival and/or 
fresh tumor tissues before study treatment or at 
disease progression/reoccurrence, and their 
association with clinical efficacy 
Exploratory: 
Objectives 
Endpoints 
Evaluate PFS, ORR, DOR, TTDM by the IRC and 
investigators per RECIST v1.1 and OS, PFS2, and 
HRQoL in Arm A versus Arm B among patients 
with PD-L1 ≥ 50% and ≥ 1% 
PFS, ORR, DOR, TTDM by IRC and 
investigators per RECIST v1.1; 
OS, PFS2, HRQoL 
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Evaluate the potential association of exploratory 
biomarkers with response or resistance to 
ociperlimab plus tislelizumab or tislelizumab or 
durvalumab only, and with patient prognosis 
Status of exploratory biomarkers including but not 
limited to the expression of CD226, CD155, and 
CD112, gene expression profiling (GEP), 
circulating tumor DNA (ctDNA), tumor mutation 
burden (TMB), microsatellite instability (MSI), 
gene mutation profiles, extracellular vesicle 
(EVs), and tumor-infiltrating lymphocytes (TILs) 
in archival and/or fresh tumor tissues and blood 
before and after study treatment, and the 
association between these biomarkers and clinical 
efficacy, disease status, response, and resistance 
mechanisms 
Evaluate patient-reported global impression of 
severity (PGI-S) and patient-reported treatment 
side-effect burden (PRTSE) 
PGI-S and PRTSE 
Evaluate the efficacy of patients who have 
finished definitive cCRT treatment and received at 
least 1 consolidation treatment among patients 
enrolled under PA 1.0 
PFS by investigators 
Study Design 
This is an open-label, randomized, multicenter, Phase 3 study to compare the efficacy and safety of 
anti-T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains 
(anti-TIGIT) monoclonal antibody ociperlimab plus tislelizumab versus durvalumab in patients with 
unresectable LA NSCLC whose disease has not progressed after definitive, platinum-based cCRT and 
with PD-L1 expression on ≥ 1% of tumor cells (TC) as assessed by the central lab using the VENTANA 
PD-L1 (SP263) assay. 
The primary endpoints are PFS by the IRC per RECIST v1.1 in the PD-L1 ≥ 50% Analysis Set in Arm A 
and Arm C, and PFS by the IRC per RECIST v1.1 in the PD-L1 ≥ 1% Analysis Set in Arm A and 
Arm C. Patients with histologically or cytologically confirmed, unresectable LA NSCLC whose disease 
has not progressed after cCRT and with PD-L1 ≥ 1% are eligible. 
Approximately 700 patients will be randomized in a 3:1:3 ratio to receive the study treatment in the 
following 3 arms: 
• 
Arm A: ociperlimab (900 mg intravenously [IV]) combined with tislelizumab (200 mg IV) every 
3 weeks (Q3W) 
• 
Arm B: tislelizumab 200 mg IV Q3W 
• 
Arm C: durvalumab 10 mg/kg IV once every 2 weeks (Q2W) (or 1500 mg every 4 weeks [Q4W] 
where the dosage has been approved by the local health authority) 
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Study drugs will be given starting from Cycle 1 Day 1 (C1D1) and continued for up to 12 months, or 
until progressive disease (PD) per RECIST v1.1, unacceptable toxicity, or death, or until another 
discontinuation criterion is met, whichever occurs first. 
Randomization will be stratified by age (< 65 years versus ≥ 65 years), PD-L1 expression on TC (≥ 50% 
versus < 50%), and histology (squamous versus nonsquamous). The ITT and PD-L1 ≥ 50% populations 
are defined as patients with PD-L1 expression on ≥ 1% and ≥ 50% of TC, respectively, with membrane 
positivity for PD-L1 at any intensity above background staining as determined using the VENTANA 
PD-L1 (SP263) assay. 
The PD-L1 expression status will be closely monitored. For enrolled patients with PD-L1 1% to 49% of 
TC will be stopped as necessary through Interactive Response Technology (IRT) upon reaching around 
50% to ensure that the population reflects the natural PD-L1 expression prevalence. 
Safety and efficacy will be monitored by an Independent Data Monitoring Committee (IDMC). The 
IDMC may recommend study modification including early termination of the study due to safety 
concerns, or for evidence of compelling efficacy at a preplanned interim analysis. There is 1 planned 
interim analysis in this study for superiority. Full details of the interim analysis can be found in 
Section 9.8. The first IDMC safety assessment will be conducted after approximately 42 patients 
(approximately 18 patients each for Arm A and C, approximately 6 patients for Arm B) have been 
randomized and treated for ≥ 30 days from C1D1 or no later than 6 months after the first patient enrolled. 
The subsequent IDMC safety assessment will be conducted as determined by the IDMC, or 
approximately every 6 months thereafter. Full details of the IDMC procedures and processes can be 
found in the IDMC charter. Enrollment may continue during these IDMC safety reviews. 
The study conduct will be overseen by a Steering Committee (SC) composed of selected investigators. 
The study will be conducted in compliance with International Council for Harmonisation (ICH) Good 
Clinical Practice (GCP) guidelines. 
The study schema is summarized as below (Figure 1). 
Figure 1: 
 
Study Schema 
 
Abbreviations: ALK, anaplastic lymphoma kinase; C1D1, Cycle 1 Day 1; cCRT, concurrent chemoradiotherapy; 
ECOG PS, Eastern Cooperative Oncology Group Performance Status; EGFR, epidermal growth factor receptor; 
NSCLC, non-small cell lung cancer; PD-L1, programmed cell death protein ligand-1; R, randomization; TC, tumor 
cells; TIGIT, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain. 
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Note, the study was initially implemented with Protocol Amendment 1.0 (PA 1.0, dated on 16 Apr 2021). 
In the PA 1.0, patients with newly diagnosed, histologically confirmed, unresectable locally advanced 
NSCLC and evaluable PD-L1 expression all comers were enrolled; cCRT was given within the study. In 
Protocol Amendment 2.0 (PA 2.0, date 21 Apr 2022), the enrollment of the target population has been 
revised into patients with unresectable locally advanced NSCLC whose disease has not progressed after 
definitive, platinum-based cCRT and with PD-L1 expression on ≥ 1% of TC as assessed by the central 
lab; cCRT was given outside of the study; the eligibility criteria have been updated to reflect the study 
patient population changes. The enrollment of PA 1.0 will be stopped before PA 2.0 implementation. 
Patients recruited into the study prior to PA 2.0 will not be included in the primary and secondary 
analysis but would be included in exploratory analysis defined by PA 2.0. 
For all patients randomized with PA 1.0 (defined as Concurrent Part of the study): 
Patients who are still on study treatment will be informed of the substantial change from PA 1.0 to 
PA 2.0, the rationale for this change, and the following treatment options. Investigators will discuss the 
local available standard-of-care with the patients, and patients have the right to discontinue from the 
assigned study treatment and receive standard-of-care treatment outside of the study proposed by their 
physician. However, after discussion of benefit-risk of the study treatment with the treating physician, 
patients who are still willing to continue the assigned study treatment will be offered the assigned 
treatment until PA 1.0 defined treatment discontinuation point. 
All patients (including those who choose to stop the assigned study treatment) are requested to continue 
the study for follow-up visits unless the study discontinuation criterion is met. 
The care of patients enrolled with PA 1.0, including but not limited to treatment, safety management, and 
visits, will follow the details in Appendix 17, which are mostly consistent with those defined in PA 1.0 
except for minor updates. 
Study Assessments: 
Tumor Assessment: 
Tumor imaging will be performed ≤ 28 days before randomization. During the study, tumor imaging will 
be performed approximately every 9 weeks (± 7 days) from randomization, for the first 54 weeks and 
every 12 weeks (± 7 days) thereafter based on RECIST v1.1. Tumor assessments are required to be 
performed on schedule regardless of whether the study treatment has been administered or held; that is, 
tumor assessments should not be adjusted for delays in cycles. 
Administration of study drugs will continue for up to 12 months, or until PD as assessed by investigator 
per RECIST v1.1, unacceptable toxicity, death, or another discontinuation criterion is met, whichever 
occurs first. Once PD is assessed by investigators, the IRC is required to complete central image review 
and convey the results to the investigator as soon as possible. If the investigator-assessed PD is NOT 
confirmed by IRC, the medical monitor will discuss the findings with the investigator and the study 
treatment is recommended to continue as long as this is considered to be in the best interest of the patient. 
In the situation where the investigator believes the patient must urgently begin subsequent systemic 
therapy without waiting for confirmation of PD by IRC, the investigator must contact the medical 
monitor to inform them of the plan to urgently discontinue study treatment. 
A patient who discontinues study treatment for reasons other than PD assessed by the IRC (eg, toxicity, 
PD by the investigator but not confirmed by the IRC, completion of the 12-month treatment) will 
continue to undergo tumor assessments following the original plan until the patient experiences PD by 
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the IRC per RECIST v1.1, withdraws consent, is lost to follow-up, dies, or until the study terminates, 
whichever occurs first. 
If at the investigator’s discretion a patient could continue to benefit from ociperlimab and tislelizumab 
combination treatment or tislelizumab or durvalumab after PD assessed by the IRC or investigator per 
RECIST v1.1, the patient may continue their assigned treatment. The criteria must be met in order to 
treat patients who may continue to benefit from study treatment after PD are detailed in Section 3.4. The 
decision to continue study treatment beyond initial PD assessed by the IRC or investigator per RECIST 
v1.1 must be agreed upon with the medical monitor and documented in the study records. 
Tumor assessments should continue as planned in patients receiving study drug(s) beyond initial PD per 
RECIST v1.1 assessed by the IRC or investigator. Tumor assessments in such patients should continue 
until study treatment discontinuation. 
Safety assessment: 
Patients will be evaluated for any adverse events (AEs) and serious adverse events (SAEs) (all severity 
grades, per NCI-CTCAE v5.0). After main 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 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, tislelizumab, or durvalumab, 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. All AEs and SAEs 
(only SAEs in case of screen failure subjects) 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. All AEs, treatment emergent or otherwise, will be presented in patient data 
listings. SAEs, deaths, TEAEs with Grade 3 or above, treatment-related TEAEs, TEAEs that led to 
treatment discontinuation, dose interruption or dose delay, and imAEs will be summarized. 
Key Inclusion and Exclusion Criteria (Full Details in Section 4): 
Key Inclusion criteria: 
Each patient eligible to participate in this study must meet all the following criteria: 
• 
Histologically or cytologically confirmed, unresectable locally advanced Stage III NSCLC 
(AJCC Cancer Staging Manual 2017, derived from International Association for the Study of 
Lung Cancer [IASLC]) prior to cCRT. 
• 
Have completed ≥ 2 cycles of platinum-based chemotherapy concurrent with radiotherapy. 
For patients who are recovering from toxicities associated with the prior treatment, the first 
dose of study drug(s) may be delayed by up to 42 days from the end of the cCRT. It is 
recommended to screen the patients within 14 days after the completion of cCRT. 
• 
Have not experienced PD following definitive, platinum-based cCRT. 
• 
Agree to provide archival 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 prospective central evaluation of PD-L1 levels and retrospective 
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analysis of other biomarkers. PD-L1 status will be assessed centrally in either a previously 
obtained archival tumor tissue or fresh tissue obtained from a biopsy collected prior to the 
first dose of cCRT via VENTANA PD-L1 (SP263) assay. Only patients with PD-L1 
expression on ≥ 1% of TC are eligible. 
Exclusion criteria: 
Patients who meet any of the following criteria are NOT eligible to enroll: 
• 
Prior therapy with an anti-programmed cell death-1(PD-1), anti-PD-L1, anti-PD-L2, 
anti-T-cell immunoglobulin and ITIM domain (TIGIT), or any other antibody or drugs 
specifically targeting T-cell co-stimulation or checkpoint pathways. 
• 
Diagnosed with NSCLC that harbors an epidermal growth factor receptor (EGFR)-
sensitizing mutation, anaplastic lymphoma kinase (ALK) gene translocation, ROS1 gene 
translocation, or RET gene rearrangement. 
• 
Distant metastasis identified by imaging assessment and/or other examinations after 
definitive, platinum-based cCRT. 
• 
Have received chemotherapy and radiotherapy with ≤ 1 cycle overlap for LA NSCLC. 
• 
Have received systemic anticancer treatment besides the specified cCRT. 
• 
Any unresolved toxicity CTCAE > Grade 2 from the prior cCRT. Patients with irreversible 
toxicity that is not reasonably expected to be exacerbated by study treatment may be 
included (eg, hearing loss) after consultation with the medical monitor. 
• 
Any grade pneumonitis from prior cCRT. 
• 
Active autoimmune diseases or history of autoimmune diseases that may relapse. 
• 
Any active malignancy ≤ 2 years before the first dose of study drug(s) except for the specific 
cancer under investigation in this study and any locally recurring cancer that has been treated 
curatively. 
• 
Any conditions that required systemic treatment with either corticosteroids (> 10 mg daily of 
prednisone [in Japan, prednisolone] or equivalent) or other immunosuppressive medication 
≤ 14 days before the first dose of study drug(s). 
• 
History of interstitial lung disease, non-infectious pneumonitis, or uncontrolled lung diseases 
including pulmonary fibrosis, acute lung diseases, etc. 
• 
Infections (including tuberculosis infection, etc) that required systemic antibacterial, 
antifungal, or antiviral therapy within 14 days before the first dose of study drug(s). 
• 
A history of severe hypersensitivity reactions to other monoclonal antibodies or history of 
hypersensitivity to the ingredients of tislelizumab or ociperlimab. 
• 
Receipt of any immunotherapy (eg, interleukin, interferon, thymosin [not approved in 
Japan], etc) or any investigational therapies within 14 days or 5 half-lives (whichever is 
longer) before the first dose of study treatment. 
Test Product, Dose and Mode of Administration 
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Ociperlimab, 300 mg/15 mL, 900 mg Q3W administered by intravenous infusion. 
Tislelizumab, 100 mg/10 mL, 200 mg Q3W administered by intravenous infusion. 
Durvalumab, 120 mg/2.4 mL (50 mg/mL) and 500 mg/10 mL (50 mg/mL), 10 mg/kg Q2W (or 1500 mg 
Q4W where the dosage has been approved by the local health authority) administered by intravenous 
infusion. 
Statistical Methods 
Analysis Sets 
• 
The ITT Analysis Set includes all randomized patients with PD-L1 expression on ≥ 1% of TC. 
Patients will be analyzed according to the treatment assigned at randomization. This will be one 
of the primary analysis sets for demography and efficacy analyses. 
• 
The PD-L1 ≥ 50% Analysis Set is a subset of the ITT Analysis Set including patients with PD-L1 
≥ 50% of TCs as determined using the VENTANA PD-L1 (SP263) assay. Patients will be 
analyzed according to the treatment assigned at randomization. This will be the other primary 
analysis set for demography and efficacy analyses. 
• 
The Safety Analysis Set (SAS) includes all randomized patients who receive ≥ 1 dose of study 
drug(s). This will be the primary analysis set for all safety analyses. 
• 
PD-L1 ≥ 50% Safety Analysis Set is a subset of the Safety Analysis Set including patients with 
PD-L1 ≥ 50%. This will be analysis set for the safety analyses in patients with PD-L1 ≥ 50%. 
• 
The PK Analysis Set includes all patients who receive any dose of any component of study drugs 
per the protocol and for whom any postdose PK data are available. 
• 
The Immunogenicity Analysis Set includes all patients who receive any dose of any component 
of study drugs and for whom both baseline antidrug antibody (ADA) and at least 1 postbaseline 
ADA result are available. 
Analysis Methods: 
The familywise type I error will be strongly controlled at 1-sided level of 0.025. PFS analysis in Arm A 
versus Arm C will be carried out in the PD-L1 ≥ 50% Analysis Set first. A formal statistical test of PFS 
in the ITT Analysis Set will be performed only if the PFS analysis in the PD-L1 ≥ 50% Analysis Set is 
statistically significant favoring ociperlimab + tislelizumab. If the null hypothesis for PFS in Arm A 
versus Arm C in the ITT Analysis Set is rejected, the secondary endpoint OS in the PD-L1 ≥ 50% and 
ITT Analysis Sets in Arm A versus Arm C will be tested sequentially. There is 1 interim analysis 
planned at around 75% information fraction of PFS events in each analysis set across Arm A and Arm C. 
See Figure 2 for the fixed-sequence testing strategy diagram of the study. 
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Figure 2: 
Fixed-Sequence Testing Strategy for Primary and Key Secondary Endpoints 
Abbreviations: ITT: Intent-To-Treat; PFS, progression-free survival; OS, overall survival. 
Primary Efficacy Analysis 
PFS comparison in Arm A versus Arm C in the PD-L1 ≥ 50% and ITT Analysis Sets: 
The null hypothesis to be tested: HR (A vs C) ≥ 1 
against the alternative: HR (A vs C) < 1 
The primary efficacy analyses of PFS will be performed using a stratified log-rank test, stratified by 
stratification factors at randomization (age, PD-L1 expression [for the ITT Analysis Set only], and 
histology) in the PD-L1≥ 50% and ITT analysis sets. 
PFS distribution will be estimated using the Kaplan-Meier method in the PD-L1 ≥ 50% and ITT Analysis 
Sets. 
The median PFS and the cumulative probability of PFS at every 3 months including PFS-6m and 
PFS-12m if estimable, will be calculated for each treatment arm and presented with 2-sided 95% CIs. 
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 including the 
treatment arm as a factor and stratification factors at randomization (age, PD-L1 expression [in the ITT 
Analysis Set only], and histology) as strata. From this model, the HR of PFS will be estimated and 
presented with a 2-sided 95% CI. 
Key Secondary Efficacy Analysis 
OS comparison in Arm A versus Arm C in the PD-L1 ≥ 50% and ITT Analysis Sets: 
The null hypothesis to be tested: HR (A vs C) ≥ 1 
against the alternative: HR (A vs C) < 1 
The primary efficacy analyses of OS will be performed using a stratified log-rank test, stratified by 
stratification factors at randomization (age, PD-L1 expression [for ITT only] and histology). OS test in 
the PD-L1 ≥ 50% and ITT Analysis Sets will be conducted sequentially at a 1-sided significance level of 
0.025, after both null hypotheses of PFS are rejected. 
OS distribution will be estimated using the Kaplan-Meier method in the PD-L1 ≥ 50% and ITT Analysis 
Sets. The treatment effect will be estimated by fitting a Cox regression model to OS, similar to the 
analyses in PFS. 
Other Secondary Efficacy Analysis 
ORR by both the IRC and investigators per RECIST v1.1 in both the PD-L1 ≥ 50% and ITT Analysis 
Sets will be summarized, in Arm A versus Arm C. Two-sided 95% CIs of ORR will be calculated using 
the Clopper-Pearson method in the ITT Analysis Set. The odds ratio for ORR between treatment arms 
 
 
 
1 
1 
Primary 
Primary 
Secondary 
 
Secondary 
𝐻1 PFS in PD-L1 ≥ 50% 
analysis set 
(Arm A vs. C) 
α = 2.5% 
 
𝐻2 PFS in ITT 
(Arm A vs. C) 
α = 0 
 
𝐻3 OS in PD-L1 ≥ 50% 
analysis set 
(Arm A vs. C) 
α = 0 
 
𝐻4 OS in PD-L1 ITT 
(Arm A vs. C) 
α = 0 
 
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will be calculated using the Cochran-Mantel-Haenszel (CMH) method adjusting for stratification factors 
at randomization (age, PD-L1 expression [for the ITT Analysis Set only], and histology), and its 2-sided 
95% CIs will be calculated. The Mantel-Haenszel common risk difference in ORR will be estimated, 
with its 95% CI constructed by a normal approximation and Sato’s variance estimator. The proportion for 
each of the response categories including CR will be presented by treatment arm. 
DOR will be analyzed among the responders in the PD-L1 ≥ 50% and ITT Analysis Sets based on 
assessment by the IRC and investigators, in Arm A versus Arm C. All the censoring rules for PFS 
primary analysis would be applied to DOR as well. 
TTDM by both the IRC and investigators per RECIST v1.1 in the PD-L1 ≥ 50% and ITT Analysis Sets 
in Arm A versus Arm C will be analyzed. 
HRQoL will be analyzed and compared in Arm A versus Arm C in the PD-L1 ≥ 50% and ITT Analysis 
Sets via the postbaseline scores of EORTC QLQ-C30’s Global Health Status/QoL (GHS), functional 
scales and symptom scales and symptoms single item scores, EORTC QLQ-LC13’s index scores and 
symptoms scales and single item scores, and EQ-5D-5L descriptive scale scores as well as the Visual 
Analogue Scale (VAS) scores. Observed values and changes from baseline will be summarized using 
descriptive statistics. 
A mixed model repeated measure (MMRM) will be performed using prespecified PRO endpoints of 
global health status/QoL (GHS), physical function, and fatigue domains of QLQ-C30, and dyspnea, 
coughing, hemoptysis and pain in chest, pain in arms and shoulders and peripheral neuropathy domains 
of QLQ-LC13 to evaluate and compare changes from baseline in Arm A and Arm C in pre-specified key 
clinical visits Week 25 and 43. 
Time to deterioration in the PRO endpoint scales will be estimated using the Kaplan-Meier method, with 
predefined deterioration thresholds, in Arm A and Arm C. 
PD-L1 and TIGIT expression will be evaluated before, after study treatment, or at disease 
progression/reoccurrence, and their association with clinical efficacy will be assessed when appropriate 
and data allow. 
Safety Analysis 
Extent of exposure to each study drug will be summarized by duration, dosage, and dose intensity for 
each arm. 
Verbatim description of AEs will be mapped to the Medical Dictionary for Regulatory Activities 
(MedDRA) terms and graded per NCI-CTCAE v5.0. All treatment-emergent AEs (TEAEs) will be 
summarized. A TEAE is defined as an AE that had an onset date or a worsening in severity from baseline 
(pretreatment) on or after the first dose of study drug(s) up to 30 days following last dose of study 
drug(s) or initiation of a new anticancer therapy, whichever occurs first. 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(s) and up to 90 days from the last dose of study 
drug(s), 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 TEAE. All imAEs will be 
reported separately. All AEs, treatment emergent or otherwise, will be presented in patient data listings. 
SAEs, deaths, ≥ Grade 3 TEAEs, treatment-related TEAEs, TEAEs that led to treatment discontinuation 
or dose modification, and imAEs will be summarized. 
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Clinical laboratory data with values outside of the normal ranges will be identified. Selected laboratory 
data will be summarized by grade. Changes in vital signs will also be summarized by visit. 
Pharmacokinetic Analyses 
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. 
Sample Size 
The sample size calculation is based on the number of events regarding primary efficacy analyses of PFS 
between Arm A and Arm C for comparisons in both the PD-L1 ≥ 50% and ITT Analysis Sets. 
Exponential distribution is assumed for PFS. To demonstrate efficacy with regard to PFS, the estimates 
of the number of events required are based on the following assumptions: 
• 
The randomization ratio for Arm A versus Arm B versus Arm C is 3:1:3. 
• 
A steady-state enrollment rate of 20 patients per month and an enrollment ramp-up 
duration of 12 months. 
• 
PFS evaluation dropout rate of 5% per 12 months. 
• 
The prevalence of patients with PD-L1 ≥ 50% of TC in the ITT Analysis Set is 
approximately 50%. Enrollment of patients with PD-L1 < 50% on TCs might be 
stopped, if necessary, to ensure that the population reflects the natural PD-L1 expression 
prevalence. 
• 
Sequential testing procedure is implemented to control the overall alpha at a 2.5% 
one-sided level. PFS analysis in Arm A versus Arm C in the PD-L1 ≥ 50% Analysis Set 
will be performed first, and PFS analysis in Arm A versus Arm C in the ITT Analysis 
Set will be carried out only if the PFS analysis in the PD-L1 ≥ 50% Analysis Set yields a 
statistically significant between-arm difference favoring Arm A. 
• 
One interim analysis is planned when approximately 75% of the final PFS events have 
occurred for each PFS primary endpoint, using Lan-DeMets O’Brien-Fleming 
approximation spending function. 
• 
Median PFS in Arm C within both the PD-L1 ≥ 50% and ITT Analysis Sets is 
24.9 months. 
Table 1 below summarizes the statistical assumption and power in the sample size calculation in Arm A 
and Arm C; and the total sample size of the study would be 700. 
Table 1: Statistical Assumptions, Sample Size, and Power 
1-sided 
alpha 
Analysis 
Set 
HR  
(A vs C) 
mPFS in 
A 
mPFS in 
C 
Accrual 
Duration 
Sample 
size in 
A+C 
# Events 
at FA in 
A+C 
Power 
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0.025 
PD-L1 ≥ 
50% 
0.6 
41.5 
24.9 
41.3 
300 
141 
85.2% 
0.025 
ITT 
0.7 
35.6 
24.9 
41.3 
600 
288 
85.1% 
Abbreviation: A: Arm A; C: Arm C; FA: final analysis, mPFS: median Progression-free Survival. 
Sample size and power is calculated using EAST (Version 6.5) and R (Version 4.1.2). 
Interim Analyses 
There is 1 planned interim analysis for this study, using Lan-DeMets O’Brien-Fleming approximation 
spending function (Lan and DeMets 1983). 
The interim analysis of PFS primary analysis will be performed at a later time when the target number of 
events in either the PD-L1 ≥ 50% or in ITT Analysis Sets is reached, which is approximately 106 events 
in the PD-L1 ≥ 50% Analysis Set and 216 events in the ITT Analysis Set (75% of the target number of 
PFS events in each analysis set) in Arm A and Arm C, approximately 45 months after the first patient 
randomized. The final analysis of PFS will take place after approximately 141 and 288 PFS events have 
been observed in the 2 analysis sets, respectively, and approximately 56 months after the first patient is 
randomized. Event number and stopping boundaries in p-value for primary analyses of PFS are shown in 
Table 2. The boundaries will be updated according to the actual numbers of events in the interim and 
final analyses, using the above pre-specified alpha spending function. 
Table 2: 
Event Number and Testing Boundaries of Interim Analyses and Final Analysis 
Analysis 
Set 
Type of 
Analysis 
# Events 
p-value for 
Efficacy IA 
Approximate 
HR Threshold 
for Efficacy 
Probability of 
Crossing Efficacy 
Boundary Under 
Alternative 
Hypothesis 
PD-L1 
≥ 50% 
IA 
106 
0.0097 
0.635 
61.5% 
FA 
141 
0.0221 
0.713 
85.2% 
ITT 
IA 
216 
0.0097 
0.727 
61.1% 
FA 
288 
0.0221 
0.789 
85.1% 
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LIST OF ABBREVIATIONS AND TERMS 
Abbreviation 
Definition 
ADAs 
antidrug antibodies 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
BOR 
best overall response 
CD 
cluster of differentiation 
CK 
creatine kinase 
CK-MB 
creatine kinase cardiac muscle isoenzyme 
CR 
complete response 
cCRT 
concurrent chemoradiotherapy 
CT 
computed tomography 
ctDNA 
circulating tumor DNA 
DLT 
dose-limiting toxicity 
DOR 
duration of response 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture (system) 
EOT 
End-of-Treatment (Visit) 
EVs 
Extracellular vesicle  
FDG 
fluorine-18 [F-18] fluorodeoxyglucose 
GCP 
Good Clinical Practice 
HBcAb 
hepatitis B core antibody 
HBsAb 
hepatitis B surface antibody 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
ICF 
informed consent form 
IEC 
Independent Ethics Committee 
imAE 
immune-related adverse event 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat (Analysis Set) 
LA NSCLC 
locally advanced non-small cell lung cancer 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
MSI 
microsatellite instability 
NCI-CTCAE 
National Cancer Institute-Common Terminology Criteria for Adverse Events 
NK 
natural killer 
BGB-A1217 
Ociperlimab 
ORR 
overall response rate 
OS 
overall survival 
PBMC 
peripheral blood mononuclear cells 
PD 
progressive disease 
PD-1 
programmed cell death protein-1 
PD-L1 
programmed cell death protein-ligand 1 
PET 
positron-emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PR 
partial response 
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Abbreviation 
Definition 
PTV 
planning target volume 
PVR 
poliovirus receptor 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RT 
radiotherapy 
SAE 
serious adverse event 
SOC 
System Organ Class 
SpO2 
percutaneous arterial oxygen saturation 
T3 
Triiodothyronine 
T4 
Thyroxine 
TEAE 
treatment-emergent adverse event 
TC 
tumor cells 
TIGIT 
T-cell immunoglobulin and ITIM domain 
BGB-A317 
 tislelizumab 
TIL 
tumor-infiltrating lymphocyte 
TMB 
tumor mutation burden 
TTDM 
time to death or distant metastasis 
ULN 
upper limit of normal 
 
 
 
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1. 
INTRODUCTION 
1.1. 
Background Information 
1.1.1. 
Background Information on Non-Small Cell Lung Cancer 
Lung cancer is the most common cancer worldwide with approximately 2.3 million new 
diagnoses and 1.8 million deaths in 2020, which corresponds to the highest incidence among 
cancers and the highest cancer-related mortality. In 2020, an estimated 477,534 new cases of 
lung cancer were diagnosed in Europe, 253,537 in North America, and 1.3 million in Asia. 
Approximately 1.1 million deaths in Europe, 384,176 in North America, and 159,641 in Asia 
were related to lung cancer (World Health Organization 2020). In China in 2015, lung cancer 
was 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 (Chen et al 2016). Worldwide, lung cancer 
is one of the most common types of cancers and it is more common in men than women, 
representing 16.8% of all cancers in men and 8.8% of all cancers in women. 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 patients with lung cancer is relatively poor. However, the prognosis depends 
greatly on the stage at which the cancer is detected. Currently, lung cancer staging is performed 
worldwide according to the eighth edition of tumor, lymph node, and metastasis (TNM) 
Classification of Malignant Tumors (American Joint Committee on Cancer [AJCC] 2017). If 
lung cancer is diagnosed in its earliest stages, cure is possible through surgery or 
chemoradiotherapy. Unfortunately, cases of lung cancer are most often detected relatively late in 
the illness, which makes a cure less likely. About one-third of patients with NSCLC present with 
locally advanced (LA) Stage III disease, which includes patients with involvement of 
locoregional mediastinal lymph nodes or mediastinal organs, etc., with 5-year survival rates of 
36% for Stage IIIA, 26% for Stage IIIB, and 13% for Stage IIIC (American Cancer Society 
2018). Some patients with Stage IIIA disease can undergo resection and have improved survival 
compared with those with unresectable tumors. 
1.1.2. 
Current Treatment of Locally Advanced, Unresectable Non-Small Cell Lung 
Cancer 
1.1.2.1. 
Concurrent Chemoradiotherapy 
Concurrent chemoradiotherapy (cCRT) has been the backbone of previously untreated standard 
of care for patients with unresectable LA Stage III NSCLC (National Comprehensive Cancer 
Network [NCCN] 2021; European Society for Medical Oncology [ESMO] guidelines 2020). 
Combined modality treatment with chemotherapy and radiation was shown to be superior to 
radiotherapy (RT) alone (Rolland et al 2007). The positive outcomes for cCRT have been shown 
in multiple studies. A meta-analysis from the mid-1990s using updated data on individual 
patients from 52 randomized clinical trials (NSCLC Collaborative Group 1995) and a subsequent 
meta-analysis of platinum-based chemotherapies from 1764 patients (Aupérin et al 2006) 
demonstrated that adding sequential or concurrent chemotherapy to radiotherapy improved 
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survival in patients with LA NSCLC. When concurrent versus sequential chemoradiotherapy was 
compared directly in data for 1205 patients from 6 clinical trials, there was a significant benefit 
with cCRT on overall survival (OS) (HR 0.84; 95% confidence interval [CI]: 0.74, 0.95; 
p = 0.004), with an absolute benefit of 5.7% (from 18.1% to 23.8%) at 3 years and 4.5% (from 
10.6% to 15.1%) at 5 years. For progression-free survival (PFS), the HR was 0.90 (95% CI: 0.79, 
1.01; p = 0.07). Concurrent treatment decreased locoregional progression (HR 0.77, [95% CI: 
0.62, 0.95], p = 0.01), although distant progression was not different between concurrent 
treatment and sequential treatment (HR 1.04, [95% CI: 0.86, 1.25], p = 0.69). Concurrent 
chemoradiotherapy increased acute esophageal toxicity, but there was no significant difference 
regarding acute pulmonary toxicity (Aupérin et al 2010). 
Induction and consolidation chemotherapy have also been studied to improve outcomes for 
patients with unresectable Stage III NSCLC. Induction chemotherapy showed high incidence for 
neutropenia with no improvement in OS (Vokes et al 2007). Consolidation chemotherapy has 
also not been shown to have any impact on OS compared with cCRT alone (Tsujino et al 2013). 
Therefore, cCRT is considered a standard of care for patients with unresectable LA Stage III 
NSCLC. 
Multiple chemotherapy regimens have been used in combination with radiation for the treatment 
of Stage III NSCLC. Most regimens are combinations of cisplatin with either pemetrexed, 
etoposide, vinblastine, or vinorelbine. Few studies have been conducted comparing these 
chemotherapy regimens, and no chemotherapy regimen has been clearly demonstrated to be 
better than others. Of the chemotherapy doublets that have comparative evidence, cisplatin in 
combination with either pemetrexed or etoposide has been studied in Stage III NSCLC 
population. The PROCLAIM multinational trial (Senan et al 2016) endeavored to establish 
whether cisplatin plus pemetrexed is superior to cisplatin plus etoposide when given concurrently 
with standard RT at 60-66 Gray (Gy), followed by a consolidation phase. OS was not superior 
with cisplatin plus pemetrexed than with cisplatin plus etoposide (median OS, 26.8 months 
versus 25.0 months; p = 0.831). Both arms exhibited low incidences of Grade 3 or 4 pneumonitis 
(< 3%), with no significant differences between arms in treatment discontinuations due to drug-
related adverse events (AEs) or drug-related deaths. The PROCLAIM study therefore establishes 
that outcomes with cisplatin with either pemetrexed or etoposide when used in cCRT with 
conventional RT are similar. As an alternative to cisplatin in combination with pemetrexed 
doublet chemotherapy regimen, carboplatin is recommended by the NCCN guidelines as well 
(NCCN 2021). Carboplatin with paclitaxel given weekly during radiation is another cCRT option 
recommended by the NCCN guidelines (NCCN 2021). This regimen has been evaluated in 
several studies (Belani et al 2005; Vokes et al 2007; Yamamoto et al 2010; Bradley et al 2015) 
and is commonly used as the treatment for unresectable LA Stage III NSCLC in the US and 
other countries globally. Weekly carboplatin plus paclitaxel was used as the chemotherapy 
regimen in the RTOG 0617 study that evaluated standard versus high doses of radiation to be 
given concurrently with chemotherapy (Bradley et al 2015). A Phase 3 trial of concurrent 
thoracic radiation in unresectable Stage III NSCLC found that weekly carboplatin plus paclitaxel 
was superior to second-generation chemotherapy regimens such as mitomycin plus vindesine, 
weekly irinotecan plus carboplatin, or cisplatin, or carboplatin as a single agent with RT 
(Yamamoto et al 2010). Of note, in the Phase 3 PACIFIC study, which evaluated the 
anti-programmed cell death protein ligand-1 (anti-PD-L1) inhibitor durvalumab compared with 
placebo after cCRT, carboplatin with paclitaxel was the most common chemotherapy regimen 
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chosen by the investigator, administered to 33.9% of the patients in the intent-to-treat (ITT) 
population (Antonia et al 2017). Besides carboplatin plus paclitaxel, cisplatin plus docetaxel was 
also recommended by the Chinese Society of Clinical Oncology (CSCO) Guidelines (CSCO 
2021) and Japan Lung Cancer Society (JLCS) Guidelines (JLCS 2020). For patients > 70 years 
of age, the JLCS also recommended a single-agent carboplatin regimen (JLCS 2020). 
In an attempt to improve outcomes, higher doses of radiation have been studied in combination 
with chemotherapy. Approximately 60 Gy in 1.8- to 2-Gy fractions has been previously 
established as the standard conventional radiation dose in Stage III NSCLC in the RTOG 7301 
study (Bradley et al 2015). Subsequently, the RTOG 0617 study has shown that 74 Gy regimen 
showed no superiority to 60 Gy regimen in efficacy (Bradley et al 2015). In fact, the median OS 
was 28.7 months for 60 Gy cohort versus 20 months for 74 Gy cohort. Local relapse rates were 
also lower in the 60 Gy cohort. Thus, the accepted standard of care is approximately 60 Gy in 
2-Gy fractions (NCCN 2021; ESMO 2020). 
Of note, the aforementioned patients with Stage III NSCLC who were treated with cCRT 
regimens as standard of care include patients with epidermal growth factor receptor (EGFR) 
sensitizing mutations or anaplastic lymphoma kinase (ALK) gene translocations. (NCCN 2021; 
ESMO 2020). EGFR and ALK targeted agents are not utilized as upfront therapy for patients 
with Stage III NSCLC and are still being investigated in trials such as the Radiation Thoracic 
Oncology Group (RTOG) 1306 study (Berman and Simone 2016). 
1.1.2.2. 
Anti-PD-1/PD-L1 Therapy 
Anti-PD-1 therapy has emerged as an effective treatment for 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, and this checkpoint has been found to be 
activated in cancers, allowing tumors to evade the host immune system. 
1.1.2.2.1. PACIFIC Study 
In the LA NSCLC setting, the potential benefits of checkpoint blockade when given sequentially 
following completion of cCRT have been demonstrated in the PACIFIC trial (Antonia et al 2018; 
Gray et al 2020). This is a global Phase 3 trial of the anti-PD-L1 therapy, durvalumab, compared 
with placebo as consolidation therapy following 2 or more cycles of platinum-based 
chemotherapy administered concurrently with RT without progression in patients with 
unresectable Stage III NSCLC. Patients who were able to complete chemoradiotherapy and who 
remained progression free at the timepoint of completion of chemoradiotherapy were 
randomized within 1 to 42 days after completing at least 2 cycles of platinum-based 
chemotherapy (containing etoposide, vinblastine, vinorelbine, a taxane, or pemetrexed) 
administered concurrently with definitive RT of 54 to 66 Gy. The trial demonstrated that median 
PFS (mPFS) was significantly longer with durvalumab than that with placebo (mPFS, 
16.9 months versus 5.6 months; stratified HR for disease progression or death, 0.55 
[95% CI: 0.45, 0.68]) (Spigel et al 2022). Enrollment was not restricted to any threshold for the 
level of PD-L1 expression, and results showed that the PFS benefit was observed in both 
baseline PD-L1 expression subgroups (HR 0.44 [95% CI: 0.29, 0.67] for PD-L1 ≥ 25% and 0.64 
[95% CI: 0.48, 0.86] for PD-L1 < 25%). The safety profile of durvalumab in this population was 
consistent with that of other immunotherapies and with its known safety profile as monotherapy 
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in patients with more advanced disease (Stage IIIB or IV NSCLC) (Antonia et al 2018). 
Although the incidences of some adverse events of any cause, including pneumonitis or radiation 
pneumonitis, were increased with both durvalumab and placebo in this study, this was expected 
after definitive chemoradiotherapy. In addition, pneumonitis or radiation pneumonitis in patients 
who received durvalumab was mostly low grade, and the incidence of clinically important grade 
3 or 4 events was well balanced between groups (3.4% in the durvalumab group and 2.6% in the 
placebo group) and lower than that in other studies in the same disease context (Hanna et al 
2008; Gandara et al 2003). 
In February 2018, based on the results of the PACIFIC study, durvalumab was approved by the 
United States Food and Drug Administration (US FDA) for the treatment of patients with 
unresectable Stage III NSCLC whose cancer had not progressed after concurrent 
chemoradiotherapy (US FDA News Release 2018), followed by the approvals from 
Pharmaceuticals and Medical Devices Agency in Japan (PMDA) (AZ news 2018), the European 
Medicines Agency (EMA) (ESMO 2020), the National Medical Products Association (NMPA) 
of China (AZ news 2019), etc. However, the approval of EMA was restricted to baseline PD-L1 
≥ 1% population based on a post hoc subgroup analysis result that OS benefit varies from PD-L1 
expression (HR 0.53 [95% CI: 0.36, 0.77] for PD-L1 ≥ 1% and 1.36 [95% CI, 0.79 to 2.34] for 
PD-L1 < 1%). Durvalumab thus became the first immunotherapy approved to reduce the risk of 
disease progression in this setting and led to a change in the treatment for Stage III patients, with 
the recommendation as consolidation therapy after concurrent chemoradiotherapy (ESMO 2020, 
NCCN 2021). As of the data cutoff date of 11 Jan 2020, with the median follow-up duration of 
34.2 months, the median OS with durvalumab was 47.5 months versus 29.1 months with placebo 
(stratified HR 0.72 [95% CI: 0.59, 0.89]). The 12-, 24-, 36-, 48-, and 60-month OS rates with 
durvalumab and placebo were 83.1% versus 74.6%, 66.3% versus 55.3%, 56.7% versus 43.6%, 
49.6% versus 36.3%, and 42.9% versus 33.4%, respectively (Spigel et al 2022). 
With the improvement in PFS and OS, the PACIFIC study set a new benchmark of 
standard-of-care for LA Stage III NSCLC; however, there are still some caveats to this study. 
There is some uncertainty as to whether all patients enrolled in this study underwent appropriate 
evaluations for optimal staging, and whether this trial included patients with occult Stage IV 
disease (Copur et al 2018). 
In the post hoc subgroup analyses of the PACIFIC study, patients with EGFR-sensitizing 
mutations showed an inferior trend of PFS (HR 0.82 [95% CI: 0.39, 1.71]) and OS (HR 0.85 
[95% CI: 0.37, 1.97]) than those without EGFR-sensitizing mutations (PFS HR 0.52 
[95% CI: 0.41, 0.65]) and OS (HR 0.66 [95% CI: 0.52, 0.84]), although the number of enrolled 
patients with EGFR-sensitizing mutations was relatively small (29 in the durvalumab arm and 
14 in the placebo arm). Patients with nonsquamous histology seemed to benefit more in terms of  
PFS than those with squamous histology (HR 0.48 [95% CI: 0.37, 0.63] versus HR 0.71 [95% 
CI: 0.54, 0.94]), with the difference in the OS subgroup analysis HR 0.62 (95% CI: 0.47, 0.81) 
versus HR 0.82 (95% CI: 0.61, 1.09); the conclusion of benefit by subgroup of histology is to be 
further explored in a well pre-specified stratified study (Spigel et al 2022). 
1.1.2.2.2. GEMSTONE-301 Study 
Following PACIFIC, Phase 3 Study GEMSTONE-301 also provided evidence that the patients 
with unresectable stage III NSCLC who had not progressed from CRT could benefit from 
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consolidation anti-PD-L1 therapy, sugemalimab, versus placebo up to a treatment duration of 
24 months. As of 8 Mar 2021, with the median follow-up 14.3 (6.4 to 19.4) months and 13.7 (7.1 
to 18.4) months in the sugemalimab arm and placebo arm, respectively; mPFS was significantly 
longer with sugemalimab than that with placebo (9.0 months [95% CI: 8.1,14.1] vs 5.8 months 
[95% CI: 4.2, 6.6]; stratified HR was 0.64 [95% CI: 0.48, 0.85], p = 0.0026). OS data is not 
mature yet at the data cutoff date. Preliminary OS data showed that median OS was not reached 
(NR) (95% CI: NR, NR) in the sugemalimab arm versus 24.1 months (95% CI: 16.5, NR) in the 
placebo arm; stratified HR was 0.44 [95% CI: 0.27, 0.73], p = 0.0009). Different from PACIFIC 
Study, the GEMSTONE-301 Study included around one third of patients who received 
sequential CRT (sCRT) as well. The stratified subgroup analysis revealed the benefit trend for 
both cCRT and sCRT subgroups: for the cCRT subgroup, the mPFS of sugemalimab versus 
placebo was 10.5 versus 6.4 months (HR 0.66 [95% CI: 0.44, 0.99]); for the sCRT subgroup, the 
mPFS of sugemalimab versus placebo was 8.1 months versus 4.1 months (HR 0.59 [95% CI: 
0.39, 0.91]). In terms of safety profile, Grade 3 or 4 treatment-related adverse events occurred in 
22 (9%) of 255 patients in the sugemalimab arm versus 7 (6%) of 126 patients in the placebo 
arm; the most common being pneumonitis or immune-mediated pneumonitis (7 [3%] of 255 
patients in the sugemalimab arm vs 1 [< 1%] of 126 patients in the placebo arm). Treatment-
related serious adverse events occurred in 38 (15%) patients in the sugemalimab arm and 12 
(10%) in the placebo arm. Treatment-related deaths were reported in 4 (2%) of 255 patients 
(pneumonia in 2 patients, pneumonia with immune-mediated pneumonitis in 1 patient, and acute 
hepatic failure in 1 patient) in the sugemalimab arm, and none in the placebo arm (Zhou et al 
2022). The safety profile of sugemalimab in the GEMSTONE-301 Study was tolerable and 
consistent with the known safety profile of anti-PD-1/PD-L1 following CRT in this setting 
(Antonia et al 2018). 
1.1.2.3. 
Unmet Medical Needs 
Until recently, cCRT was the standard of care for patients with LA NSCLC with reported 5-year 
survival rates between 16% and 32%. In 2018, supported by the result of PACIFIC study 
(Antonia et al, 2017), durvalumab was approved by the US FDA (US FDA News Release 2018), 
PMDA (AZ news 2018),and China NMPA (AZ news 2019) for the treatment of patients with 
locally advanced, unresectable NSCLC whose disease did not progress after cCRT irrespective 
of PD-L1 expression. In Europe, durvalumab was approved by EMA for patients with locally 
advanced, unresectable NSCLC whose disease did not progress after cCRT with PD-L1 
expression on ≥ 1% of tumor cells (TC) (ESMO 2020). 
However, most patients still suffered from disease recurrence with an 18-month PFS rate of 
44.2%, and most patients still died with a 57% survival rate at 3 years in the PACIFIC study 
(Antonia et al, 2017). As such, there is still a high unmet medical need for this patient 
population. 
1.2. 
Compound 
1.2.1. 
Ociperlimab as a TIGIT Inhibitor 
Immune surveillance plays a critical role in cancer prevention. However, in situations where 
tumors develop resistance mechanisms to suppress the host immune system, tumors eventually 
grow out of control (Schreiber et al 2011; Swann and Smyth 2007). One such resistance 
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mechanism is the up-regulation of immune checkpoint receptors, such as programmed cell 
death-1 (PD-1) and T-cell immunoglobulin and ITIM domain (TIGIT) (Johnston et al 2014; 
Chauvin et al 2015; Pardoll 2012). 
Ociperlimab is a humanized immunoglobulin G (IgG) 1 monoclonal antibody binding to TIGIT 
under clinical development for the treatment of human malignancies. 
TIGIT (also known as VSIG9, VSTM3, or WUCAM) is a 26 kDa type I transmembrane 
glycoprotein and an immune checkpoint receptor, a member of the poliovirus receptor 
(PVR)/nectin family that plays an important role in promoting T-cell exhaustion in both chronic 
viral infections and tumor escape from immune surveillance (Yu et al 2009; Boles et al 2009; 
Stanietsky et al 2009; Levin et al 2011; Johnston et al 2014). TIGIT was initially discovered in a 
genomic search for genes specifically expressed in T cells that had a protein domain that 
consisted of inhibitory signaling motifs. The genes and cDNAs coding for TIGIT were cloned 
and characterized in mouse and human (Yu et al 2009). Mature human TIGIT contains 
223 amino acid residues (National Center for Biotechnology Information 2018). Its extracellular 
domain consists of amino acid residues 1 through 120, and the transmembrane domain and 
cytoplasmic C-terminal tail comprises residues 121 through 223. 
TIGIT-deficient mice (TIGIT-/-) showed increased susceptibility to an experimental autoimmune 
model (Joller et al 2014). TIGIT-overexpressing natural killer (NK) cells produced less 
interferon-gamma (IFN-γ) upon TIGIT/PVR ligation. In contrast, NK cells form TIGIT-deficient 
mice produced more IFN-γ in the presence of PVR-expressing target cells (Li et al 2014). 
Agonistic anti-TIGIT antibody could reduce the production of proinflammatory cytokines 
including IFN- γ and IL-17 by antigen-restimulated splenocytes and antigen-specific 
proliferation. Consistent with these observations, blockade of the TIGIT pathway in vivo by 
TIGIT-blocking antibody alone or in combination with an anti-PD-1 antibody reduced tumor 
growth in syngeneic mouse models (College of American Pathologist [CAP] guidelines 2018; 
Argast et al 2018; Dixon et al 2018). All these findings strongly suggest that TIGIT is a critical 
immune checkpoint receptor in the maintenance of immune tolerance. 
TIGIT is primarily expressed on immune cells, such as T cells, and NK cells (Manieri et al 
2017). When expressed on effector T cells (cluster of differentiation [CD] 4+ [CD4+] and CD8+), 
activation of TIGIT has been shown to reduce cytokine production and T-cell proliferation, all of 
which could be rescued by TIGIT-blocking antibodies or TIGIT expression knockdown (Joller et 
al 2014; Lozano et al 2012; Chauvin et al 2015). A similar phenomenon was also observed for 
NK cells (Stanietsky et al 2009; Zheng et al 2017). 
TIGIT is also expressed on FoxP3+ regulatory T (Treg) cells, especially in tumor tissues (Joller 
et al 2014; Kurtulus et al 2015). TIGIT-positive Treg cells demonstrated greater suppressive 
functions when compared with TIGIT-negative Tregs, with higher expression of effector 
molecules, such as IL-10, granzymes, and Fgl2 (Joller et al 2014). A high TIGIT/CD226 ratio in 
Tregs is associated with increased Treg frequencies in tumors and poor clinical outcomes upon 
immune checkpoint blockade (Fourcade et al 2018). Some studies have also shown that TIGIT 
suppresses immune responses mediated by dendritic cells by binding with PVR, especially in 
enhancement of IL-10 production and inhibition of IL-12 production (Yu et al 2009). 
As an immune “checkpoint” molecule, TIGIT initiates inhibitory signaling in immune cells when 
engaged by its ligands, PVR (CD155) and poliovirus receptor–related 2 (PVR-L2) (CD112, or 
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nectin-2). These ligands are primarily expressed on antigen-presenting cells and tumor cells 
(Casado et al 2009; Stanietsky et al 2009; Yu et al 2009; Levin et al 2011). The binding affinity 
of TIGIT to PVR (equilibrium dissociation constant [KD]: ~1 nM) is much higher than to 
PVR-L2 and whether the TIGIT: PVR-L2 interaction is functionally relevant in mediating 
inhibitory signals remains to be determined. The co-stimulatory receptor, CD226, binds to the 
same ligands with lower affinity (KD: ~100 nM) but delivers positive signals and enhances the 
cytotoxicity of T cells and NK cells (Bottino et al 2003; Stanietsky et al 2009). High affinity 
binding of TIGIT to PVR could compete off CD226-PVR interaction, thereby reducing the 
activation of T cells or NK cells (Stanietsky et al 2009). 
The cytoplasmic tail of TIGIT has an inhibitory ITIM and an immunoreceptor tail tyrosine 
(ITT)-like motif. In NK cells, TIGIT engagement induces the phosphorylation of tyrosine 
residues in its ITIM and ITT-like motifs through the Src kinases Fyn and Lck. The 
phosphorylation of TIGIT then leads to binding of Grb2 and β-arrestin 2 and the subsequent 
recruitment of SHIP-1 and SHP-2 to terminate PI3K and NK-κB signaling in the NK cells (Liu et 
al 2013; Stanietsky et al 2009). Engagement of agonistic TIGIT antibody induced T-cell receptor 
complex disruption (Stanietsky et al 2009). Additionally, interaction between TIGIT and PVR on 
dendritic cells could lead to phosphorylation of PVR and modulation of ERK activation in 
dendritic cells (Yu et al 2009). 
Upregulation of TIGIT expression in tumor-infiltrating lymphocytes (TILs) has been reported in 
many types of cancers, such as lung cancer (Tassi et al 2017), stomach cancer (He et al 2017), 
breast (Gandara et al 2018; Del Alcazar et al 2017), esophageal cancer (Xie et al 2016), brain 
cancer (Hung et al 2018), acute myeloid leukemia (Kong et al 2016), and melanoma (Mahnke 
and Enk 2016). Interestingly, TIGIT expression appears to be minimally expressed by peripheral 
effector cells while being significantly up-regulated by tumor localized effector cells, which 
strongly suggests that the tumor microenvironment utilizes TIGIT signaling to further 
suppress/evade immune-mediated tumor cytotoxicity (Johnston et al 2014). Further, upregulation 
of TIGIT signaling plays an important role in immune tolerance to cancer, similar to its function 
in the presence of chronic viral infections (Yin et al 2018; Chauvin et al 2015). Blockade of 
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). 
In mouse models, Fc with effector functions is critical for TIGIT antibody-mediated antitumor 
activity (College of American Pathologist (CAP) guidelines 2018; Argast et al 2018; Leroy et al 
2018). In CT26.WT mouse colon cancer model, anti-mouse TIGIT antibody of mIgG2a isotype 
(antibody-dependent cellular cytotoxicity enabling) demonstrated potent antitumor activity as 
monotherapy or in combination with anti-PD-1 antibody. In contrast, anti-TIGIT antibody with 
Fc devoid of effector functions did not show any of the antitumor efficacies in the same model, 
indicating that Fc-mediated effector functions are required for TIGIT antibody-mediated 
antitumor effects. Additionally, the observed efficacy was associated with an increased activity of 
effector T cells (CD8+ and CD4+) and also with Treg depletion within the tumor 
microenvironment. Argast and colleagues (College of American Pathologist (CAP) guidelines 
2018; Argast et al 2018) also observed that effector functions were critical for TIGIT 
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antibody-induced in vivo efficacy. Waight and colleagues (Waight et al 2018), reported the 
interaction of anti-TIGIT with FcγR on antigen-presenting cells enhanced antigen-specific T cell 
responses and antitumor activity. 
Taken as a whole, targeting TIGIT provides a potential mechanism to rescue immune cells 
(eg, T cells, NK cells, and dendritic cells) from the immunosuppressive tumor 
microenvironment, thereby inducing an efficient antitumor immune response. Blocking 
antibodies targeting the PD-1/PD-L1 pathway have shown remarkable results in the treatment of 
many different tumor types. However, based upon the rate of primary and secondary resistance 
to PD-1 blockade, it is apparent that additional immunoregulatory mechanism(s) underlie tumor 
immune escape. Indeed, research shows that the TIGIT pathway cooperates with PD-1 to 
maximize the suppression of effector TILs as well as to promote resistance to anti-PD-1 therapy. 
Therefore, TIGIT represents an ideal target with the potential to significantly improve and/or 
extend the therapeutic benefit of anti-PD-1 therapy to a greater number of patients. 
1.2.1.1. 
Nonclinical 
1.2.1.1.1. Pharmacology 
Ociperlimab binds to the extracellular domain of human TIGIT with high specificity and affinity 
(KD = 0.135 nM), as demonstrated by target-binding assays and surface plasmon resonance 
characterization. It competitively blocks TIGIT binding to PVR. In in vitro cell-based assays, 
ociperlimab “in a dose dependent manner”: “consistently and dose dependently enhances the 
functional activities of activated human peripheral blood mononuclear cells (PBMCs)”. 
Additionally, ociperlimab has shown antitumor activities 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 enhanced tumor growth inhibition compared with either 
therapy alone. 
Ociperlimab has the constant region of a wild-type human IgG1 to enable the Fc-mediated 
effector functions. Ociperlimab has demonstrated competent binding to complement 1q (C1q) 
and all FcγRs, including FcγRI, FcγRIIA, FcγRIIB, and FcγRIIIA, in in vitro binding assays, and 
induces antibody-dependent cellular cytotoxicity against TIGIT-overexpressing cell line, but no 
antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity against primary 
T cells in cell-based assays. 
Refer to the Ociperlimab Investigator’s Brochure for detailed information regarding 
pharmacology studies. 
1.2.1.1.2. 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 based on the homology sequence of TIGIT, although it demonstrates a relatively 
lower ociperlimab-binding affinity compared to human TIGIT (with EC50 756-fold weaker). 
Ociperlimab does not bind to mouse TIGIT due to the significant sequence divergence between 
human and mouse TIGIT; however, ociperlimab demonstrates a comparable binding affinity in 
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TIGIT receptor occupancy assays with CD3+ splenocytes from humanized TIGIT knock-in mice 
compared to CD3+ human PBMCs (with EC50 of 48.8 ng/mL versus 63.2 ng/mL, respectively). 
In addition, ociperlimab shows significant inhibition of GL261 tumor growth in humanized 
TIGIT knock-in mice at a dose of 0.4 mg/kg and above via weekly intraperitoneal dosing. 
The toxicity and safety profile of ociperlimab was characterized in a 4-week repeat dose 
toxicology study in humanized TIGIT knock-in mice and a 13-week repeat dose toxicology 
study in cynomolgus monkeys. These toxicity studies were conducted following Good 
Laboratory Practice regulations. Furthermore, ociperlimab was evaluated in a 4-week repeat dose 
study in humanized TIGIT knock-in mice with subcutaneous MC-38 tumors. The dose levels 
spanned from the intended human therapeutic doses to 10-fold higher in the 4-week mouse 
studies and 20-fold higher in the 13-week monkey study. 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. The tissue cross-reactivity was evaluated 
in the normal frozen tissues from humans. The cytokine release responses were also evaluated 
using fresh human PBMCs. 
No apparent toxicity was noted in humanized mice after repeated dosing of ociperlimab at either 
5 or 50 mg/kg weekly for 4 weeks, nor in monkeys following repeated dosing at 10, 30, or 100 
mg/kg once every 2 weeks for 13 weeks. The toxicokinetic profile was characterized in both the 
mouse and monkey studies and the systemic exposure appeared to be dose proportional with no 
gender difference in either study. A trend of accumulation was noted after repeated doses in 
mice, however, 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 in these studies. Immunogenicity with positive antidrug antibodies (ADAs) against 
ociperlimab was noted in several mice dosed at 5 and 50 mg/kg over the 4 weeks; however, with 
the exception of one animal with strong ADA response at 5 mg/kg dose, most of these animals 
showed weak ADA signal or were proved to have false positive results. In monkeys, positive 
ADAs against ociperlimab were observed in 6/10, 3/10, and 4/10 animals during the dosing 
period, and 3/4, 2/4, and 2/4 during the recovery period, at 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. 
The tissue cross reactivity of ociperlimab was evaluated in frozen normal human tissues using an 
immunohistochemistry method, with appropriate positive and negative controls. 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 non-activated PBMCs with ociperlimab when compared to human IgG. 
The results suggested that ociperlimab had potentially low risks of causing acute cytokine release 
syndrome. 
Overall, no apparent toxicity was noted in the monkey or transgenic mice toxicity studies. No 
unexpected tissue cross reactivity was found in human or monkey tissues. The toxicokinetic 
profile was well characterized with dose-proportional increases in systemic exposure without 
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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 50 mg/kg in the 4-week mouse study and 100 mg/kg in the 
13-week monkey toxicity study. The safety profile of ociperlimab is considered adequate to 
support first-in-human dosing. 
Refer to the Ociperlimab Investigator’s Brochure for detailed information regarding toxicology 
studies. 
1.2.1.2. 
Clinical Experience 
1.2.1.2.1. Clinical Experience From Other TIGIT Inhibitors 
To date, Phase 1 and 2 clinical studies have been initiated for several TIGIT antibodies. Initial 
clinical data include data released for OncoMed’s Etigilimab (Mettu et al 2022), Merck’s 
vibostolimab (Golan et al 2018; Niu et al 2020; Ahn et al 2020), Genentech/Roche’s tiragolumab 
(Cho et al 2021), and iTeos Therapeutics’ EOS-448 (Van den Mooter et al 2021). 
The combination of anti-PD-1/PD-L1 antibody and anti-TIGIT antibody is further being 
explored in NSCLC. The most compelling data currently available includes the study of 
tiragolumab (anti-TIGIT Ab) in combination with atezolizumab and the study of vibostolimab 
(anti-TIGIT Ab) monotherapy or combined with pembrolizumab. 
The CITYSCAPE study is randomized Phase 2 trial designed to assess preliminary efficacy 
between tiragolumab in combination with atezolizumab versus atezolizumab. It showed 
impressive improvement in both ORR and PFS in the ITT (tumor proportion score [TPS] ≥ 1%) 
population compared to atezolizumab alone, with an even greater magnitude of improvement 
seen in the PD-L1 TPS ≥ 50% subgroup. An analysis of the safety of tiragolumab plus 
atezolizumab showed the combination were well tolerated. The safety profile was similar to 
atezolizumab alone, and while immune-mediated adverse events (imAEs) were more frequent 
with tiragolumab plus atezolizumab, most imAEs were primarily Grade 1-2 (mostly IRR and 
rash) and were manageable. Based on these observed efficacy and safety results, 
Genentech/Roche is conducting an ongoing Phase 3 study (SKYSCRAPER-01) in first-line 
treatment for patients with NSCLC expressing PD-L1 TPS ≥ 50% (NCT04294810) (Rodriguez-
Abreu et al 2020; Cho et al 2021). 
The study of Vibostolimab (anti-TIGIT antibody) (NCT02964013) in combination with 
pembrolizumab enrolled patients with advanced metastatic NSCLC who were untreated or had 
experienced disease progression on prior therapies. This combination showed encouraging 
antitumor activity and tolerable safety. For patients who were untreated or previously treated 
with chemotherapy but naïve to anti-PD-1/PD-L1 therapy, the ORR rate was 24%, whereas 
limited activity was observed for vibostolimab alone and vibostolimab in combination with 
pembrolizumab (ORR 2% and 5% respectively) in patients with NSCLC whose disease had 
already progressed on prior anti-PD-1/PD-L1 therapy in (Niu et al 2020; Ahn et al 2020). 
Though it is acknowledged that this result should be interpreted with caution due to the small 
sample size, the result indicated that vibostolimab plus pembrolizumab are efficacious in anti-
PD-1/PD-L1 naïve NSCLC patients. 
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All the data above support further development of anti-TIGIT antibody in combination with 
existing therapeutic modalities. 
1.2.1.2.2. Preliminary Safety 
As of the data cutoff date of 28 July 2021, a total of 133 patients received ociperlimab treatment 
in Study AdvanTIG-105 and Study AdvanTIG-202. In Study AdvanTIG-105, 900 mg 
ociperlimab was administered as monotherapy in 9 patients in Cohort 1A (dose verification in 
China). A total of 76 patients have been enrolled and treated with ociperlimab at doses of 50, 
150, 450, 900, or 1800 mg in combination with tislelizumab 200 mg and have cleared the 
dose-limiting toxicity (DLT) period without DLTs in the Phase 1 dose-escalation part of the 
study. There were 25 patients from the Dose-Expansion Cohorts 1, 2, 4, 6, 7, and 9 were treated 
with ociperlimab in combination with tislelizumab 200 mg and chemotherapies.  In Study 
AdvanTIG-202, 23 patients have been treated with ociperlimab at a flat dose of 900 mg in 
combination with tislelizumab 200 mg in Cohort 1. Ociperlimab continues to appear to be safe 
and well-tolerated up to and including at the 900 mg dose level. 
As of the data cutoff date of 28 July 2021, of the 133 patients in the Safety Analysis Set, 
117 (88%) patients experienced ≥ 1 treatment-emergent adverse events (TEAEs) and 
77 (57.9%) patients experienced ≥ 1 TEAEs related to ociperlimab. TEAEs ≥ Grade 3 in severity 
were reported in 53 of 133 (39.8%) patients, and 8 (6.0%) patients experienced ≥ Grade 3 
TEAEs related to ociperlimab.  Serious TEAEs were reported in 47 (35.3%) patients, and 
7 (5.3%) of these were considered related to ociperlimab. TEAEs leading to ociperlimab 
discontinuation were reported in 9 (6.8%) patients. TEAEs leading to death were reported in 
6 (4.5%) patients, but none of these events were assessed as related to ociperlimab. No TEAEs 
were considered to be DLT events. 
Please refer to the Ociperlimab Investigator’s Brochure for detailed safety information. 
1.2.1.2.3. Clinical Pharmacology 
Preliminary pharmacokinetic (PK) data are available from a total of 51 patients treated with 
ociperlimab at the 50 mg, 150 mg, 450 mg, 900 mg, and 1800 mg dose levels in combination 
with tislelizumab 200 mg in the dose-escalation and dose-verification portions of Study 
AdvanTIG-105. Ociperlimab serum concentrations decreased in a biexponential manner after 
treatment administration. The mean elimination half-life ranged from 7.1 to 10.5 days. In Cycle 
1, ociperlimab exposures (area under the concentration-time curve [AUC] and maximum 
observed serum concentration [Cmax]) increased approximately dose-proportionally from the 
50 mg to the 1800 mg dose levels. 
As of 23 July 2021, peripheral TIGIT receptor occupancy data were available for 32 enrolled 
patients treated with ociperlimab at the 50 mg (n = 1), 150 mg (n = 3), 450 mg (n = 6), 900 mg 
(n = 16), and 1800 mg (n = 6) dose levels in Study BGB-900-105. Complete TIGIT receptor 
occupancy (100%) was observed on CD8, CD4, and Treg cells in peripheral blood at all the 
tested dose levels. 
Refer to the Ociperlimab Investigator’s Brochure for detailed information on ociperlimab clinical 
PK and pharmacodynamics 
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1.2.1.2.4. Efficacy 
The first-in-human Study AdvanTIG-105 evaluating the efficacy of ociperlimab in combination 
with tislelizumab in advanced solid tumors is still ongoing. Efficacy data from Study AdvanTIG-
105 (as of the data cutoff date of 21 February 2021) were presented at the 2021 meeting of the 
American Society of Clinical Oncology. A total of 26 evaluable patients received ociperlimab 
(dose range: 50 to 900 mg) in combination with tislelizumab 200 mg. One patient was treated 
with ociperlimab 50 mg, 3 with ociperlimab 150 mg, 6 with ociperlimab 450 mg, and 16 with 
ociperlimab 900 mg. Partial response (PR) was observed in 2 patients (1 receiving ociperlimab 
450 mg and 1 receiving ociperlimab 900 mg). Stable disease was observed in 9 patients 
(1 receiving ociperlimab 150 mg, 3 receiving ociperlimab 450 mg, and 5 receiving ociperlimab 
900 mg). The longest duration of stable disease was 54 weeks (a patient receiving ociperlimab 
150 mg). Three patients (2 receiving ociperlimab 450 mg and 1 receiving ociperlimab 900 mg) 
had a > 30% reduction in target lesions. More follow-up data will be updated in further updates 
to the Ociperlimab Investigator’s Brochure. 
1.2.2. 
Tislelizumab as a PD-1 Inhibitor 
1.2.2.1. 
Pharmacology 
Tislelizumab (also known as BGB-A317) is a humanized, IgG4-variant monoclonal antibody 
against PD-1 under clinical development for the treatment of several human malignancies. 
Tislelizumab acts by binding to the extracellular domain of human PD-1 with high specificity as 
well as high affinity (dissociation constant [KD] = 0.15 nM). It competitively blocks binding 
efforts by both PD-L1 and programmed cell death protein ligand-2 (PD-L2), thus inhibiting 
PD-1-mediated negative signaling in T cells. In in vitro cell-based assays, tislelizumab was 
observed to enhance the functional activity of human T cells and pre-activated primary PBMCs 
consistently and dose-dependently. Tislelizumab has also demonstrated in-vivo antitumor 
activity in several allogeneic xenograft models, in which PBMCs were co-injected with human 
cancer cells (A431 [epidermoid carcinoma]) or tumor fragments (BCCO-028 [colon cancer]) into 
immunocompromised mice. 
Tislelizumab is an IgG4-variant antibody to gamma fragment crystallizable region (Fc) receptors 
(FcγR) such as FcγRI and FcγRIIIA, and it has very low binding affinity to C1q, a subunit of 
complement 1. In vitro assays with tislelizumab suggest either low or no antibody-dependent 
cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or 
complement-dependent cytotoxicity (CDC) effects in humans (Labrijn et al 2009). 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 Investigator’s Brochure for additional details regarding 
nonclinical studies of tislelizumab. 
1.2.2.2. 
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, repeated-dose toxicology study in 
cynomolgus monkeys. Tissue cross-reactivity was evaluated in normal frozen tissues from both 
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humans and monkeys. The cytokine release assays were conducted using fresh human whole 
blood cells. The pivotal toxicology studies were conducted following Good Laboratory Practice 
(GLP) regulations. The single-dosing regimens spanned from the intended human doses to 
10-fold higher than the maximum of the intended human doses, and the repeated-dosing 
regimens spanned to 3-fold higher than the maximum of the intended human doses. 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 was well 
characterized, with 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 
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-301. 
Please refer to the Tislelizumab Investigator’s Brochure for more detailed information on the 
toxicology of tislelizumab. 
1.2.2.3. 
Clinical Pharmacology 
Based on pooled data from 2596 patients across 12 clinical studies, the PK of tislelizumab was 
best characterized using a 3-compartmental linear population PK model with linear clearance 
mechanisms. No time-varying clearance was observed in tislelizumab PK. The Cmax and AUC 
increased in a nearly dose-proportional manner from 0.5 mg/kg to 10 mg/kg. The terminal t1/2 
was estimated to be approximately 23.8 days, and the steady state is expected to be reached in 
12 weeks. 
Refer to the Tislelizumab Investigator’s Brochure for detailed information regarding clinical 
pharmacology studies. 
1.2.2.4. 
Prior Clinical Experience With Tislelizumab 
Refer to the Tislelizumab Investigator’s Brochure for more detailed information on tislelizumab 
safety and efficacy data when given as monotherapy or in combination with chemotherapy. 
1.2.2.4.1. Pooled Safety Assessment of Tislelizumab 
1.2.2.4.1.1. Pooled Safety Assessment of Monotherapy Studies 
As of 20 May 2021, 1992 patients with solid tumors had been treated with tislelizumab 
monotherapy in 7 clinical studies, and 158 patients treated in 3 hematologic malignancy studies. 
Solid tumor studies with tislelizumab monotherapy include the following: 
BGB-A317_Study_001 (Phase 1a/1b study in Advanced Solid Tumors), BGB-A317-102 (Phase 
1/2 study in advanced solid tumors), BGB-A317-204 (Phase 2 study in locally advanced or 
metastatic urothelial bladder cancer), BGB-A317-208 (Phase 2 study in previously treated 
unresectable hepatocellular carcinoma), BGB-A317-209 (Phase 2 study in previously-treated 
locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch 
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repair deficient [dMMR] solid tumors), BGB-A317-302 (Phase 3 study in advanced 
unresectable/metastatic esophageal squamous cell carcinoma), and BGB-A317-303 (Phase 3 
study in non-small cell lung cancer). 
Refer to the Tislelizumab Investigator’s Brochure for more detailed information on tislelizumab 
safety data when given as monotherapy or in combination with chemotherapy. 
Pooled Demographics and Baseline Characteristics 
As of 20 May 2021, a pooled monotherapy analysis was conducted to provide a comprehensive 
review of the tislelizumab safety profile. Patients included in this analysis (N = 1992) had a 
median age of 60.0 years with 72.1% of them being male. Median duration of treatment exposure 
was 4.1 months (range: 0.1 to 41.5 months) and median duration of study follow-up was 11.5 
months (range: 0.1 to 58.9 months). 
Treatment-Related Adverse Events 
Of the 1992 patients in the solid tumor group within the pooled monotherapy studies, 
1391 (69.8%) experienced ≥ 1 treatment-related TEAE. The most commonly occurring TEAEs 
(≥ 5% of patients) assessed as related to tislelizumab irrespective of grade were aspartate 
aminotransferase (AST) increased (250 patients, 12.6%), ALT increased (242 patients, 12.1%), 
hypothyroidism (197 patients, 9.9%), anaemia (186 patients, 9.3%), rash (159 patients, 8.0%), 
pruritus (142 patients, 7.1%), fatigue (138 patients, 6.9%), decreased appetite (115 patients, 
5.8%), blood bilirubin increased (111 patients, 5.6%), and diarrhoea (103 patients, 5.2%). 
Further, 269 of the 1992 patients (13.5%) experienced at least 1 ≥ Grade 3 TEAE assessed as 
related to tislelizumab. The most frequent ≥ Grade 3 TEAEs that occurred in ≥ 1% of the patients 
were AST increased (25 patients, 1.3%), and ALT increased and anaemia (20 patients, 1.0% 
each). 
Treatment-Emergent and Related Serious Adverse Events 
A total of 706 of the 1992 patients (35.4%) in the solid tumor group within the pooled 
monotherapy studies experienced ≥ 1 treatment-emergent serious adverse events (SAE). The 
most commonly occurring treatment-emergent SAEs (irrespective of relationship to study drug) 
were pneumonia (95 patients, 4.8%), pneumonitis (33 patients, 1.7%), dysphagia (23 patients, 
1.2%), and pleural effusion and pyrexia (20 patients, 1.0% each). 
A total of 209 of the 1992 patients (10.5%) experienced ≥ 1 tislelizumab-related 
treatment-emergent SAE. The most common treatment-emergent SAE deemed related to 
tislelizumab was pneumonitis (31 patients, 1.6%). All other tislelizumab-related 
treatment-emergent SAEs occurred in ≤ 1% of patients. 
Immune-Mediated Adverse Events 
Of the 1912 patients in the adjudicated solid tumor group within the pooled monotherapy studies, 
286 patients (15.0%) experienced ≥ 1 imAE of any grade. The most commonly occurring imAEs 
of any grade were hypothyroidism (115 patients, 6.0%), pneumonitis (41 patients, 2.1%), 
immune-mediated lung disease (14 patients, 0.7%), rash (13 patients, 0.7%), and ALT increased 
and hyperthyroidism (12 patients, 0.6% each). A total of 73 patients (3.8%) had ≥ 1 imAE that 
was ≥ Grade 3 in severity. The most commonly occurring imAEs that were ≥ Grade 3 in severity 
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were pneumonitis (15 patients, 0.8%) and interstitial lung disease (7 patients, 0.4%) 
(Tislelizumab Investigator’s Brochure). 
Infusion-Related Reactions 
Infusion-related reactions, including high-grade hypersensitivity reactions, following 
tislelizumab administration are common. 
Of the 1992 patients in the solid tumor group within the pooled monotherapy studies, 58 patients 
(2.9%) experienced ≥ 1 infusion-related reaction of any grade. The most commonly occurring 
infusion-related reactions of any grade were infusion-related reactions (28 patients, 1.4%); 
pyrexia (17 patients, 0.9%); rash (5 patients, 0.3%); and hypotension, nausea, and pruritus 
(3 patients, 0.2% each). There were 5 patients (0.3%) with ≥ Grade 3 infusion-related reactions. 
The most common ≥ Grade 3 infusion-related reaction was infusion-related reaction (2 patients, 
0.1%). All other ≥ Grade 3 infusion-related reactions occurred in 1 patient each. 
Fatal Adverse Events 
A total of 163 patients (8.2%) within the solid tumor studies had died within 30 days of the last 
dose of study treatment as of 20 May 2021. The causes of death for these patients were adverse 
events (54 patients, 2.7%), disease under study (52 patients, 2.6%), disease progression 
(50 patients, 2.5%), and other (7 patients, 0.4%). 
1.2.2.4.1.2. Pooled Safety Assessment of Combination Studies With Chemotherapy 
A pooled analysis of combination studies with tislelizumab and chemotherapy was conducted to 
provide a comprehensive safety assessment separately from other combination therapy studies. 
(Tislelizumab Investigator’s Brochure). As of 20 May 2021, a total of 544 patients were treated 
with tislelizumab in combination with chemotherapy in 4 studies, including BGB-A317-205 
(Phase 2 study in esophageal, gastric, or gastroesophageal junction carcinoma), BGB-A317-206 
(Phase 2 study in lung cancer), BGB-A317-304 (Phase 3 study in nonsquamous NSCLC), and 
BGB-A317-307 (Phase 3 study in squamous NSCLC). 
Of the 544 patients in the pooled chemotherapy combination studies, 543 (99.8%) experienced 
≥ 1 TEAE and 472 patients (86.8%) experienced ≥ 1 TEAE considered related to tislelizumab 
treatment. A total of 192 patients (35.3%) experienced at least one ≥ Grade 3 TEAE considered 
related to tislelizumab. SAEs were reported in 225 patients (41.4%) and 104 patients (19.1%) 
experienced a serious tislelizumab-related TEAE. A total of 24 patients (4.4%) experienced a 
TEAE leading to death. 
1.2.2.4.2. Efficacy Assessment of Tislelizumab 
As of 20 May 2021, efficacy data in patients with NSCLC are available from 6 of the ongoing 
monotherapy studies in solid tumors, BGB-A317_Study_001, Study BGB-A317-102, Study 
BGB-A317-203, Study BGB-A317-204, Study BGB-A317-207, and Study BGB-A317-208 
(Tislelizumab Investigator’s Brochure; Lu et al 2020; Wang J et al 2020). 
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1.2.2.4.2.1. Efficacy Assessment of Monotherapy Studies 
Study BGB-A317_Study_001 
Study BGB-A317_Study_001 is a 2-stage study consisting of a Phase 1a dose-escalation (0.5 to 
10 mg/kg) and dose-finding component with 3 parts (2 and 5 mg/kg given either once every 
2 weeks or Q3W, and a fixed dose of 200 mg given Q3W) to establish the maximum tolerated 
dose (MTD), if any, and a recommended Phase 2 dose (RP2D), which is followed by a Phase 1b 
component to investigate efficacy in select tumor types at the RP2D to further evaluate safety 
and tolerability of tislelizumab. Indication-specific cohorts included esophageal (EC), gastric 
(GC), hepatocellular (HCC), and non-small cell lung (NSCLC) cancer. Efficacy data from 
BGB-317_Study_001 were published in Desai et al 2020 (data cutoff May 2019). 
The patients with NSCLC (n = 49) enrolled to Study_001 were treated at the 2 or 5 mg/kg dose 
every 2 weeks and every 3 weeks dosing schedules (97% received the 5 mg/kg dose every 
3 weeks). Among these 49 patients with NSCLC, the ORR was 12.2% ([95% CI: 4.63%, 
24.77%], all PR), the disease control rate (DCR) (CR + PR + SD) was 59.2% (95% CI: 44.21%, 
73.0%), and the clinical benefit rate (CBR) (CR + PR + ≥ 24 weeks of SD) was 34.7% (95% CI: 
21.67%, 49.64%). The median time to initial response was 91.0 days (range: 62 to 189 days). As 
of the cutoff date of 26 August 2020, the median duration of response (DOR) for these patients 
was not reached; 6 of 49 patients with an objective response to tislelizumab had an ongoing 
response at the time of cutoff date. The median PFS was 4.2 months (95% CI: 2.1, 7.8 months). 
The median OS was 11.5 months (95% CI, 9.3 to 32.8 months). 
Study BGB-A317-102 
Study BGB-A317-102 is a non-randomized, Phase 1/2 study of tislelizumab monotherapy in 
Chinese patients with advanced solid tumors. Phase 1 includes a dose verification substudy and a 
substudy of PK evaluation of the products derived from 2 manufacturing processes and scales. 
Phase 2 evaluates the activity and safety of tislelizumab at its RP2D of 200 mg given Q3W in 
indication-specific expansion cohorts. Efficacy data from Study BGB-A317-102 were published 
in Shen et al 2020 (data cutoff 01 December 2018). 
Among the 56 patients with NSCLC enrolled to Study 102 and treated with tislelizumab 200 mg 
Q3W IV, the ORR (CR + PR) was 17.9% (95% CI, 8.9% to 30.4%, all PR), the DCR 
(CR + PR + SD) was 55.4% (95% CI, 41.5% to 68.7%), and the CBR (CR + PR + ≥ 24 weeks of 
SD) was 30.4% (95% CI, 18.8% to 44.1%). As of the cutoff date of 31 May 2020, median DOR 
for these patients was not reached; 10 of 56 patients with an objective response to tislelizumab 
had an ongoing response. The median PFS was 4.0 months (95% CI, 2.1 to 8.1 months). The 
estimated 6-month and 12-month PFS event-free rates were 40% (95% CI, 30% to 50%) and 
30% (95% CI, 20% to 40%), respectively. The median OS was not yet evaluable. The estimated 
6-month and 12-month OS event free rates were 70% (95% CI, 60% to 80%) and 60% (95% CI, 
40% to 70%), respectively. 
Study BGB-A317-303 
RATIONALE 303 is a Phase 3 randomized, open-label, multicenter global clinical trial to 
evaluate the efficacy and safety of tislelizumab compared with docetaxel in the second- or 
third-line setting in patients with LA or metastatic NSCLC whose disease has progressed on a 
prior platinum-based chemotherapy. 
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A total of 805 patients were randomized 2:1 to either the tislelizumab arm or the docetaxel arm 
in 10 countries. The study met its primary endpoint of OS in the ITT population and in patients 
with PD-L1 expression ≥ 25% population at interim analysis with a data cutoff date of 10 Aug 
2020. Compared with docetaxel, OS was significantly longer with tislelizumab (stratified HR 
0.64 [95% CI, 0.527 to 0.778]; p < 0.0001); median OS was 17.2 months and 11.9 months in 
tislelizumab and docetaxel arm, respectively. Benefit of OS in patients with PD-L1 expression 
≥ 25% receiving tislelizumab versus docetaxel was also observed (stratified HR 0.52 [95% CI, 
0.384 to 0.713]; p < 0.0001); median OS was 19.1 months and 11.9 months in tislelizumab and 
docetaxel arm, respectively. Among the secondary endpoints in ITT population, median PFS was 
reported as 4.1 months versus 2.6 months (HR 0.64, p < 0.0001); ORR was 21.9% versus 7.1%; 
DCR was 55.7% versus 42.2%; and DOR was 13.5 months versus 6.2 months (HR 0.31, 
p < 0.0001) for the tislelizumab and docetaxel arm, respectively (Zhou et al 2021). 
1.2.2.4.2.2. Efficacy Assessment of Combination Studies With Chemotherapy 
Study BGB-A317-206 
Study BGB-A317-206 is a multi-cohort, Phase 2 study of tislelizumab in combination with 
standard chemotherapy as first-line treatment in Chinese patients with LA or metastatic lung 
cancer. In the cohort of nonsquamous NSCLC, patients were treated with tislelizumab 200 mg 
plus pemetrexed-cisplatin or carboplatin (n = 16). In the cohort of squamous NSCLC, patients 
were treated with tislelizumab 200 mg plus paclitaxel-cisplatin or carboplatin (n = 15). In the 
cohort of squamous NSCLC, patients were treated with tislelizumab plus gemcitabine-cisplatin 
or carboplatin (n = 6). Across treatment arms, confirmed ORRs ranged from 43.8% to 80%. The 
median PFS time ranging from 7.0 months to not reached (NR). OS data is not yet mature for all 
cohorts until data cutoff of 30 June 2019 (Wang et al 2020). 
Study BGB-A317-304 
Study BGB-A317-304 is a Phase 3, 2-arm, randomized, multicenter study to compare the 
efficacy and safety of tislelizumab combined with cisplatin or carboplatin plus pemetrexed 
(Arm A) versus cisplatin or carboplatin plus pemetrexed (Arm B) as first-line treatment in 
334 patients with stage IIIB or IV nonsquamous NSCLC (confirmed EGFR wildtype and without 
ALK rearrangement). 
A total of 334 patients were randomized, and Study BGB-A317-304 met its primary endpoint of 
PFS at interim analysis with a data cutoff date of 23 January 2020. Compared with the 
chemotherapy-only arm, PFS as assessed by the IRC was significantly longer with tislelizumab 
in combination with chemotherapy (stratified HR = 0.645 [95% CI, 0.462 to 0.902]; p = 0.0044); 
median PFS by IRC was 9.7 months in Arm A and 7.6 months in Arm B. Similar median PFS 
results were observed for Arm A versus Arm B (HR = 0.561 [95% CI, 0.411 to 0.767]; 
p = 0.0001) when assessed by investigators. With more than 75% of the patients censored in both 
arms, median OS was not reached in either arm. Higher ORR by IRC (57.4% versus 36.9%) and 
DCR by IRC (89.2% versus 81.1%) were observed in the tislelizumab plus chemotherapy arm 
compared with chemotherapy alone. Among 128 responders with tislelizumab combination 
therapy, median DOR by IRC was 8.5 months (95% CI, 6.80 to 10.58 months); in the 41 patients 
who achieved a response with chemotherapy alone, median DOR by IRC was 6.0 months (95% 
CI, 4.99 months to not evaluable). At time of data cutoff, > 62% of patients were censored in 
each arm, suggesting DOR by IRC was not fully mature in either arm (Lu et al 2020). 
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Study BGB-A317-307 
Study BGB-A317-307 is a phase 3, 3-arm, open-label, randomized, multicenter study to compare 
the efficacy and safety of tislelizumab combined with carboplatin and either paclitaxel (Arm A) 
or nab-paclitaxel (Arm B) versus paclitaxel plus carboplatin alone (Arm C) as first-line treatment 
in 360 patients with stage IIIB or IV squamous NSCLC. 
A total of 360 patients were randomized, and Study BGB-A317-307 has been fully enrolled and 
met its primary endpoint of PFS at interim analysis with a data cutoff date of 06 December 2019. 
Median PFS was 7.6 months (95% CI, 6.0 to 9.8 months) and 7.6 months (95% CI, 5.8 to 
11.0 months) in Arms A and B, respectively, both of which were significantly longer than the 
median PFS in Arm C (5.5 months, [95% IC, 4.2 to 5.7]). With a median study follow-up time of 
8.6 months, median OS had not been reached. ORR was 73% (95% CI, 63.6% to 80.3%) and 
75% (95% CI, 66.0% to 82.3%) in Arms A and B, respectively, and higher compared with 
Arm C (50% [95% CI, 40.4% to 58.8%]). DCR was 88% (95% CI, 80.2% to 92.8%) and 91% 
(95% CI, 84.1% to 95.3%) in Arms A and B, respectively, and higher compared with Arm C 
(80% [95% CI, 71.9% to 86.9%]). Similarly, DOR was longer in both tislelizumab-containing 
arms compared with chemotherapy alone (8.2 months [95% CI, 5.0 to NE] for Arm A, 
8.6 months [95% CI, 6.3 months to NE] for Arm B and 4.2 months [95% CI, 2.8 to 4.9 months] 
for Arm C) (Wang J et al 2020). 
1.3. 
Study Rationale 
As described earlier, despite the wealth of evidence supporting TIGIT’s role in promoting tumor 
immune tolerance, the available clinical data of TIGIT blockade alone hasn’t shown an effective 
antitumor response, compared with the increased antitumor response signal observed with 
anti-TIGIT plus anti-PD-1/PD-L-1 combination (see Section 1.2.1). Therefore, the clinical 
development of ociperlimab focuses on rational combinations, such as with tislelizumab. Taking 
this into account, the study of the combination of ociperlimab and tislelizumab is designed to 
evaluate the effect of ociperlimab in combination with tislelizumab in maximizing the patient’s 
potential therapeutic benefit and to characterize the safety and efficacy of this combination. 
1.3.1. 
Rationale for the Dose Selection 
1.3.1.1. 
Rationale for the Selection of Ociperlimab Dose 
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-fold higher than 30 mg (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-fold higher than 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 
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each in the 450 mg, 900 mg, and 1800 mg cohorts. Ociperlimab exposure in all 3 patients with a 
partial response was consistent with that expected at the 900 mg dose level. The confirmed DCR 
observed in the 450 mg, 900 mg, and 1800 mg cohorts were 60%, 64.3% and 60%, respectively. 
Although the best overall response and DCR 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 lower than 450 mg 
1.3.1.2. 
Rationale for the Selection of Tislelizumab Dose 
The dose of 200 mg intravenously Q3W was selected based on safety, efficacy, and PK 
assessments in the first-in-human study BGB-A317_Study_001. A wide range of doses were 
investigated in this study, including 2 mg/kg and 5 mg/kg on schedules of once every 2 weeks 
(Q2W) and once every 3 weeks (Q3W). For the Q3W schedule, a fixed dose of 200 mg was also 
investigated, and it was ultimately selected for the following reasons: 
• All doses tested, including 200 mg once every 3 weeks, were tolerated. The MTD 
was not reached with doses up to 10 mg/kg once every 2 weeks. The observed serum 
concentration after 200 mg dosing was within the range seen with 2 mg/kg and 
5 mg/kg dosing. 
• Preliminary clinical activity was observed at this dose. 
• Exposure-response relationships were flat for ORR and safety endpoints across a 
variety of tumor types (data from BGB-A317_Study_001, Study BGB-A317-102, and 
Study BGB-A317-203). In addition, no clinically significant covariates were 
identified in population PK analysis. 
• Compared with doses based on patient weight, a fixed dose simplifies dose 
administration and reduces the chance of medical errors. 
Compared with a once every 2 weeks schedule, a once every 3 weeks schedule allows for more 
convenient integration with common chemotherapeutic regimens and increases patient 
convenience. 
1.3.2. 
Rationale for Combination of Ociperlimab and Tislelizumab in the Treatment of 
Non-Small Cell Lung Cancer 
Upregulation of TIGIT expression in TILs has been reported in NSCLC (Tassi et al 2017). 
Blockade of a 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). Preclinical studies have also indicated that platinum-
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based chemotherapy elicits tumor CD8+ T-cell infiltration and sensitizes tumors to immune 
checkpoint blockade therapy, which results in a durable control of cancer (Pfirschke et al 2016). 
The Cancer Genome Atlas (TCGA) dataset showed upregulation of TIGIT and PVR expression 
in tumor samples than in normal samples in both adenocarcinoma lung cancer and squamous cell 
lung cancer. The TCGA RNAseq dataset showed that patients with NSCLC with low expression 
of PVR have longer survival than those with high PVR expression (p = 0.0082). This is 
consistent with the important role of the TIGIT/PVR signaling pathway in the immune tolerance 
to cancer (Section 1.2.1). In addition, increased expression of TIGIT and PD-1 in human NSCLC 
suggests potential synergy of combination of an anti-TIGIT antibody and anti-PD-1 antibody can 
have a potential synergic effect (Solomon and Garrido-Laguna 2018). 
Clinically, treatment with anti-TIGIT antibody in combination with anti-PD-1/PD-L1 therapy 
has the potential to be more efficacious than anti-PD-1/PD-L1 in metastatic NSCLC without 
prior checkpoint inhibitor therapy. The combination of tiragolumab plus atezolizumab resulted in 
an ORR of 38.8%, PFS of 5.6 months and OS of 23.2 months ORR of 20.6%, PFS of 3.9 months 
and OS of 14.5 months with placebo plus atezolizumab in first-line Stage IV NSCLC patients 
with PD-L1 TPS ≥ 1% (Cho et al 2021). Similarly, the vibostolimab plus pembrolizumab 
combination resulted in an unconfirmed and confirmed ORR of 29% and 24%, respectively, in 
patients who were untreated or had been treated with at least 1 line of platinum-containing 
chemotherapy who had not previously received anti-PD-1/PD-L1 therapy. However, in patients 
with NSCLC who had experienced prior anti-PD-1/PD-L1 treatment, both the unconfirmed and 
confirmed ORR for vibostolimab plus pembrolizumab combination were 5%, and were not 
superior to the ORR with vibostolimabalone  (unconfirmed and confirmed ORR 7% and 2% 
respectively) (Niu et al 2020; Ahn et al 2020). 
The safety profiles of both the tiragolumab plus atezolizumab and vibostolimab plus 
pembrolizumab combinations were tolerable. The imAE rate with the tiragolumab plus 
atezolizumab combination was higher than that with placebo plus atezolizumab (76.1% versus 
47.1%), but most of the imAEs were manageable Grade 1 or 2 events of infusion-related 
reactions, including rash. the incidence rate of TRAE of any grade was slightly higher with the  
vibostolimab plus pembrolizumab combination than with vibostolimab monotherapy, (71% 
versus 59%); however, the incidence rate of ≥ Grade 3 TRAE was similar for the 2 arms (15% 
versus 13%), indicating that most of the TRAEs in the combination arm are Grade 1 or 2 (Cho et 
al 2021; Rodriguez-Abreu et al 2020; Niu et al 2020; Ahn2020). 
As mentioned in Section 1.2.1.2.2, Study AdvanTIG-105 showed the preliminary safety for 
ociperlimab plus tislelizumab was consistent with that of other anti-TIGIT plus anti-PD-1/PD-L1 
treatment, with no MTD reached and no DLT events occurred during the treatment period for 
each dose level. Ociperlimab plus tislelizumab appeared to be well-tolerated at all administered 
dose levels. Adding ociperlimab to tislelizumab will likely further enhance the overall clinical 
activity of the anti-PD-1/PD-L1 therapy and prevent progression/disease-related death in LA 
Stage III NSCLC in the front line. 
1.3.3. 
Rationale for Durvalumab as the Comparator 
The rationale for using durvalumab as the comparator is based on the PFS and OS benefit 
demonstrated in the PACIFIC study (Antonia et al 2018; Gray et al 2020; Faivre-Finn et al 
2020). The study reported that median PFS was significantly longer with durvalumab than with 
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placebo (median PFS 16.9 months versus 5.6 months, stratified HR for disease progression or 
death 0.55), with an acceptable safety profile in the durvalumab group (Antonia et al 2018). In 
February 2018, durvalumab was approved by the US FDA for the treatment of patients with 
unresectable Stage III NSCLC whose cancer had not progressed after chemoradiation (US FDA 
News Release 2018); this approval was also followed by approvals from the PMDA (AZ news 
2018), EMA (ESMO 2020), NMPA (AZ news 2019), etc. This immunotherapy thus became the 
first treatment approved to reduce the risk of NSCLC progression in this setting and led to a 
change in the treatment for patients with Stage III disease, with the recommendation that anti-
PD-L1 consolidation therapy be offered after cCRT (NCCN 2021). As of the data cutoff date of 
11 Jan 2020, with the median duration of follow-up of 34.2 months, the median OS with 
durvalumab was 47.5 months versus 29.1 months with placebo (stratified HR = 0.72 [95% CI, 
0.59 to 0.89]). The 12-, 24-, 36-, 48-, and 60-month OS rates with durvalumab and placebo were 
83.1% versus 74.6%, 66.3% versus 55.3%, 56.7% versus 43.6%, 49.6% versus 36.3%, and 
42.9% versus 33.4%, respectively (Spigel et al 2022). 
1.3.4. 
Biomarker Strategy Rationale 
Biomarker analyses including but not limited to the analyses of PD-L1 expression, TIGIT 
pathway molecules, gene expression profiling (GEP), circulating tumor DNA (ctDNA), tumor 
mutation burden (TMB), microsatellite instability (MSI), gene mutation profiles, extracellular 
vesicle (EVs) and TILs will be performed in the study treatment of ociperlimab plus tislelizumab 
and tislelizumab or durvalumab monotherapy, to explore the predictive, prognosis biomarkers 
and potential mechanisms of resistance. 
PD-L1 was expressed in TC and TILs in advanced NSCLC and its expression level showed 
correlation 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 immunohistochemistry (IHC) assays, 22C3 and SP263 pharmDx, were 
approved as the companion diagnostic (CDx) assay to identify NSCLC patients for treatment 
with KEYTRUDA (pembrolizumab) monotherapy (Herbst et al 2016). The PACIFIC study was 
not designed to evaluate durvalumab versus placebo based on archival tumor PD-L1 expression 
and 37% patients were not PD-L1 expression evaluable, but the results of the exploratory 
analyses support treatment benefit with durvalumab versus placebo in all subgroups including 
PD-L1 expression in terms of PFS, ORR etc. On the other hand, post-hoc analysis of PD-L1 
expression showed a larger PFS benefit in patients with PD-L1 ≥ 1% than in those with PD-L1 
< 1% (PFS HR, 0.47 vs 0.80). The OS benefit was mainly driven by the PD-L1 ≥ 1% subgroup 
(HR = 0.61, 95% CI ,0.44 to 0.85), while there was no treatment benefit in PD-L1 < 1% 
subgroup (HR = 1.15, 95% CI, 0.75 to1.75) (Spigel et al 2022). Based on this ad-hoc analysis 
from the PACIFIC study, PD-L1 IHC SP263 pharmDx assay also received CE-IVD certification 
in Europe to identify patients with Stage III NSCLC with PD-L1 ≥ 1% in TC for durvalumab 
maintenance therapy after CRT, which indicates PD-L1 expression is probably a predictive 
biomarker for anti-PD-1/PD-L-1 treatment in LA NSCLC. 
However, the predictive role of PD-L1 in identifying patients with LA NSCLC who could 
benefit from combination treatment with dual-immunotherapeutic agents for maintenance 
therapy after cCRT is still not well-explored. In the CITYSCAPE study, patients with NSCLC 
with PD-L1 ≥ 50% in TC derived significant benefit from atezolizumab (anti-PD-L1) plus 
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tiragolumab (anti-TIGIT) than patients with PD-L1 1-49% (PFS HR 0.29 versus 1.07, OS HR 
0.23 versus 1.16), suggesting that PD-L1 is a predictive biomarker for treatment co-targeting the 
PD-1 and TIGIT pathways (Cho et al 2021). In this study, patients with NSCLC with 
PD-L1 ≥ 50% in TC will be randomized to 3 different treatment arms and PD-L1 ≥ 50% was 
designed to be one of the stratification factors to balance the 3 treatment arms and to explore the 
association of PD-L1 expression with clinical efficacy. 
Neither the randomized Phase 3 Study PACIFIC nor GEMSTONE-301 has revealed the 
prevalence of patients with unresectable Stage III NSCLC whose tumors express PD-L1 ≥ 50% 
in the PD-L1 ≥ 1% population. In 2 retrospective analyses of unresectable Stage III NSCLC 
studies, the proportion of PD-L1 ≥ 50% population was reported to be 63% and 58% (IHC assay 
22C3), respectively (Desilets et al 2020; Kartolo ea al 2021). Referring to data in the first-line 
NSCLC treatment, the prevalence of PD-L1 ≥ 50% population was 43%, 52% (nonsquamous 
only), and 41% (squamous only) (IHC assay 22C3) in CITYSCAPE, KEYNOTE-189, and 
KEYNOTE-407, respectively (Cho et al 2021; Gadgeel et al 2020; Paz-Ares et al 2020); 
however, in another 2 first-line randomized controlled trials (RCT), Rationale-304 
(nonsquamous) and Rationale-307 (squamous), this prevalence was both reported to be 58%, and 
in the second or third line RCT (Rationale-303), this prevalence was reported to be 50% (IHC 
SP263) (Lu et al 2020; Wang et al 2020; Zhou et al 2021). Based on the data above, the 
enrollment of patients in this study with PD-L1, 1% to 49% will be stopped upon reaching 
around 50% to ensure that the prevalence of the enrolled population is close to the natural PD-L1 
expression. 
In addition to PD-L1 expression, TMB, MSI, abundance and location of TILs, and tumor and 
immune-related gene expression profile 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). In melanoma patients, high 
TIGIT/CD226 ratio on Treg cells correlated with poor clinical outcome upon treatment with 
anti-PD-1 or anti-PD-L1 antibodies. Additionally, a higher frequency of TIGIT+ T cells among 
PD-1+CD8+ T cells were associated with hyperprogressive disease during PD-1/PD-L1 
blockade, and these patients showed a lower survival rate (Kim et al 2019). These results 
suggested that signaling through TIGIT pathway in tumor tissues might contribute to resistance 
to current immune checkpoint inhibitors targeting PD-1 or PD-L1 (Fourcade et al 2018). 
Therefore, the expression of TIGIT pathway molecules including TIGIT, CD226, CD155, 
CD112, as well as PD-L1, ctDNA, TMB, MSI, TILs, EVs, and gene expression profile will be 
studied, and their relationship with clinical response to study treatment will be further assessed to 
explore potential predictive biomarkers. 
Besides biomarkers that have the potential to predict clinical efficacy, mechanisms of resistance 
to immunotherapeutics are also not well understood and need more exploration. Identification of 
somatic mutations or gene expression profiles that are associated with disease progression or 
acquired resistance to study treatment may increase the understanding of disease pathobiology 
and help in collecting biological evidence for combination strategies. 
1.4. 
Benefit-Risk Assessment 
Study AdvanTIG-301 compares the combination of tislelizumab plus anti-TIGIT monoclonal 
antibody ociperlimab versus durvalumab in patients with locally advanced, unresectable NSCLC 
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who have been treated with cCRT and whose disease has not progressed. As discussed above, 
there is extensive evidence supporting TIGIT’s role in regulating immune response as well as the 
interaction between the TIGIT and PD-1 pathways in promoting tumor immune escape (Section 
1.2.1, Section 1.3.2). Combined with the clinical efficacy that has been demonstrated for 
tislelizumab as PD-1 inhibitor (Section 1.2.2), the data strongly suggest that ociperlimab has the 
potential to improve and/or extend the therapeutic benefits of tislelizumab, especially in the anti-
PD-1/PD-L1 treatment-naïve settings. 
As discussed earlier (Section 1.2.1.1.2, Section 1.2.1.2, Section 1.3.1, and Section 1.3.2), based 
upon the mechanism(s) of action, nonclinical as well as 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. Although 
there is the risk of observing augmented safety signals as has been shown for other anti-PD-1 
based immuno-oncology combinations, a comprehensive algorithm derived from the European 
Society for Medical Oncology and American Society for Clinical Oncology, has been established 
to monitor, diagnose, as well as manage such immune-related toxicities (Specific Appendix 10). 
It is important to note that peripheral effector T cells typically do not express TIGIT, which 
contrasts with TILs stimulated by the antigens in 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). 
Blockade of the PD-1 pathway has demonstrated strong antitumor efficacy either alone or in 
combination with standard of care in multiple cancer indications. As discussed in Section 1.2.1.2 
and Section 1.2.2.4, PD-1 blockade by tislelizumab has been evaluated in more than 
1992 patients with a safety and efficacy profile similar to what has been reported for other 
anti-PD-(L)1 therapies. 
As shown specifically in Appendix 1, a comprehensive monitoring plan will be utilized to 
monitor patient safety. The subsequent safety data will be continuously analyzed by the 
sponsor’s study team and in consultation with investigator(s) as needed. Refer to Section 1.2.1.2, 
Section 1.2.2.4, and Section 8 for information regarding additional safeguards and considerations 
related to potential risk. 
In addition, available data from clinical trials of other anti-PD-1/PD-L1 antibodies, including 
tislelizumab, durvalumab, sugemalimab, and pembrolizumab, have demonstrated favorable 
benefit/risk ratio. Available data indicates that tislelizumab has a tolerable safety profile and very 
promising antitumor activity when administered in patients with advanced lung cancer. Also, 
studies PACIFIC, GEMSTONE-301, and LUN14-179 have released a consistent and favorable 
benefit/risk profile of anti-PD-1/PD-L1 single agent administered following concurrent 
chemoradiotherapy (Section 1.1.2.2; Durm et al 2020). When further adding another 
immunotherapy agent to consolidation therapy following cCRT based on anti-PD-1/PD-L1 
therapy, eg anti-CD73 and anti-NKG2A, the interim analysis of Study COAST indicated that no 
new safety signals identified in the arms of dual immunotherapy agents while promising efficacy 
data was observed (COAST 2021). 
In summary, there is strong scientific rationale that the combined blockade of the TIGIT pathway 
and PD-1/PD-L1 pathway following standard chemoradiotherapy may result in enhanced 
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antitumor activity and benefit more patients as compared with anti-PD-1/PD-L1 monotherapy 
without a major increase in the risk of immune-related toxicities. 
An Independent Data Monitoring Committee (IDMC) will be established to regularly monitor 
the safety of ociperlimab, tislelizumab, and durvalumab. 
1.5. 
Study Conduct 
This study will be conducted in compliance with the protocol approved by the Institutional 
Review Board (IRB) or Independent Ethics Committee (IEC) and in accordance with Good 
Clinical Practice (GCP) standards. 
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2. 
STUDY OBJECTIVES AND ENDPOINTS 
The study objectives and endpoints defined in this section apply to the patients enrolled since 
Protocol Amendment (PA) 2.0 implementation only, unless otherwise specified. The same rules 
apply to the following sections in this protocol. 
2.1. 
Study Objectives and Endpoints 
Table 3: 
Primary Objectives and Endpoints 
Objectives 
Endpoints 
Compare progression-free survival (PFS) as 
assessed by the Independent Review 
Committee (IRC) per Response Evaluation 
Criteria in Solid Tumors (RECIST) Version 
(v) 1.1 in ociperlimab plus tislelizumab 
(Arm A) versus Durvalumab (Arm C) among 
patients with locally advanced non-small cell 
lung cancer (LA NSCLC) whose disease has 
not progressed after concurrent 
chemoradiotherapy (cCRT) and with PD-L1 
≥ 50% 
PFS by the IRC, defined as the time from the 
date of randomization to the date of first 
documentation of disease progression 
assessed by the IRC per RECIST v1.1 or 
death, whichever occurs first 
Compare PFS as assessed by the IRC per 
RECIST v1.1 in ociperlimab plus tislelizumab 
(Arm A) versus Durvalumab (Arm C) among 
patients with LA NSCLC whose disease has 
not progressed after cCRT and with PD-L1 
≥ 1% 
Table 4: 
Secondary Objectives and Endpoints 
Objectives 
Endpoints 
Compare overall survival (OS) in Arm A 
versus Arm C among patients with PD-L1 
≥ 50% 
OS defined as the time from the date of 
randomization until the date of death due to 
any cause 
Compare OS in Arm A versus Arm C among 
patients with PD-L1 ≥ 1% 
Evaluate overall response rate (ORR) and 
duration of response (DOR) as assessed by 
both the IRC and investigators in Arm A 
ORR, defined as the proportion of patients 
who achieve a complete response (CR) or 
partial response (PR) assessed by both the 
IRC and investigators per RECIST v1.1 
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Objectives 
Endpoints 
versus Arm C among patients with PD-L1 
≥ 50% and ≥ 1% 
DOR, defined as the time from the first 
determination of a confirmed objective 
response assessed by both the IRC and 
investigators per RECIST v1.1 until the first 
documentation of disease progression or 
death, whichever occurs first 
Evaluate time to death or distant metastasis 
(TTDM) in Arm A versus Arm C among 
patients with PD-L1 ≥ 50% and ≥ 1% 
Time to death or distant metastasis (TTDM), 
defined as the time from the date of 
randomization until the first date of distant 
metastasis assessed by both the IRC and 
investigators, or death. Distant metastasis is 
defined as any new lesion that is outside of 
the radiation field per RECIST v1.1 or proven 
by biopsy. 
Compare PFS2 in Arm A versus Arm C 
among patients with PD-L1 ≥ 50% and ≥ 1% 
PFS2, defined as the time from randomization 
to the disease progression after next line of 
treatment, or death from any cause, whichever 
occurs first 
Evaluate safety and tolerability in 3 treatment 
arms among patients with PD-L1 ≥ 50% and 
≥ 1% 
Safety and tolerability, defined as AEs (using 
NCI-CTCAE v5.0), laboratory tests, vital 
signs, ECOG Performance Status, physical 
examinations, concomitant medications, and 
dose modifications 
Compare impact of treatments on patient 
health-related quality of life (HRQoL) in 
Arm A versus Arm C among patients with 
PD-L1 ≥ 50% and ≥ 1% 
HRQoL, measured via patient-reported 
outcomes (PROs) using EORTC QLQ-C30, 
EORTC QLQ-LC13, and EQ-5D-5L 
questionnaires 
Characterize the pharmacokinetics (PK) of 
ociperlimab and tislelizumab 
Serum concentrations of ociperlimab and 
tislelizumab at specified timepoints 
Assess host immunogenicity to ociperlimab 
and tislelizumab 
Immunogenic responses to ociperlimab and 
tislelizumab evaluated through detection of 
antidrug antibodies 
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Objectives 
Endpoints 
Evaluate the association of PD-L1 and TIGIT 
expression with clinical efficacy to 
ociperlimab plus tislelizumab or tislelizumab 
or durvalumab only 
PD-L1 and TIGIT expression in archival 
and/or fresh tumor tissues before study 
treatment or at disease 
progression/reoccurrence, and their 
association with clinical efficacy 
Table 5: 
Exploratory Objectives and Endpoints 
Objectives 
Endpoints 
Evaluate PFS, ORR, DOR by the IRC and 
investigators per RECIST v1.1 and OS, 
TTDM, PFS2 and HRQoL in Arm A versus 
Arm B among patients with PD-L1 ≥ 50% 
and ≥ 1% 
PFS, ORR, DOR, TTDM, by the IRC and 
investigators per RECIST v1.1; 
OS, PFS2, HRQoL 
Evaluate the potential association of 
exploratory biomarkers with response or 
resistance to ociperlimab plus tislelizumab or 
tislelizumab or durvalumab only, and with 
patient prognosis 
Status of exploratory biomarkers including 
but not limited to the expression of CD226, 
CD155, and CD112, gene expression 
profiling (GEP), circulating tumor DNA 
(ctDNA), TMB, MSI, gene mutation profiles, 
extracellular vesicle (EVs), and TILs in 
archival and/or fresh tumor tissues and blood 
before and after study treatment, and the 
association between these biomarkers and 
clinical efficacy, disease status, response, and 
resistance mechanisms 
Evaluate patient-reported global impression 
of severity (PGI-S) and patient-reported 
treatment side-effect burden (PRTSE) 
PGI-S and PRTSE 
Evaluate the efficacy in  patient who finished 
definitive cCRT treatment and received at 
least 1 consolidation treatment among patients 
enrolled under PA 1.0 
PFS by investigators 
2.2. 
Definition of Primary Estimand 
2.2.1. 
Primary Estimand 1 – PFS benefit in patients with LA NSCLC who have not 
progressed after cCRT and with PD-L1 ≥ 50% 
The primary scientific question of interest is: Does ociperlimab in combination with tislelizumab 
prolong time to death/progression (PFS) compared to durvalumab in patients with unresectable 
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LA NSCLC whose disease has not progressed after cCRT and with PD-L1 ≥ 50% (no 
subsequent anticancer therapy after assigned therapy). 
The primary estimand is described by the following attributes: 
1. Treatment of interest: 
The experimental treatment consists of ociperlimab 900 mg combined with tislelizumab 
200 mg Q3W for a maximum of 12 months. The standard of care treatment consists of 
durvalumab 10 mg/kg Q2W (or 1500 mg Q4W where the dosage has been approved by 
the local health authority) for a maximum of 12 months. 
2. Population: 
Patients with unresectable LA NSCLC whose disease has not progressed after cCRT and 
whose tumors express PD-L1 on ≥ 50% of TC. 
3. Primary variable: 
Progression-free survival (PFS), defined as the time from the date of randomization to the 
date of the first documented tumor progression assessed by Independent Review 
Committee IRC per RECIST v1.1, or death, whichever occurs first. 
4. Handling of intercurrent events: 
• Anticancer therapy, subsequent to assigned therapy, that is started before 
IRC-assessed PD: PFS will be censored at the last adequate disease assessment before 
the subsequent anticancer therapy (hypothetical strategy) 
• Discontinuation of treatment: tumor assessment and survival data collected after 
discontinuation of study treatment will be used for analysis (treatment policy 
strategy) 
• Death due to COVID-19: death due to COVID-19 will be considered as part of PFS 
events (composite strategy) 
• COVID-19 infection: any incidence of COVID-19 infection will be ignored 
(treatment policy strategy) 
5. Population-level summary: HR and its 95% CI for PFS comparing 
ociperlimab + tislelizumab versus durvalumab, estimated using a Cox regression model 
stratified by age (< 65 years versus ≥ 65 years), and histology (squamous versus 
nonsquamous). 
2.2.2. 
Primary Estimand 2 – PFS benefit in patients with LA NSCLC whose disease 
has not progressed after cCRT and with PD-L1 ≥ 1% 
The primary scientific question of interest is: Does ociperlimab in combination with tislelizumab 
prolong time to death/progression (PFS) compared to durvalumab in patients with unresectable 
LA NSCLC whose disease has progressed after cCRT and with PD-L1 ≥ 1% (no subsequent 
anticancer therapy after assigned therapy). 
The attributes of Primary Estimand 2 are the same as Primary Estimand 1, except that the 
population consists of patients with PD-L1 expression on ≥ 1%; and for HR calculation, the 
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stratification factors in Cox model include age (< 65 years versus ≥ 65 years), PD-L1 expression 
in TC (≥ 50% versus < 50%), and histology (squamous versus nonsquamous). 
2.3. 
Definition of Key Secondary Estimand 
2.3.1. 
Key Secondary Estimand 1 – OS benefit in patients with LA NSCLC whose 
disease has not progressed after cCRT and with PD-L1 ≥ 50% 
The scientific question of interest is: Does ociperlimab in combination with tislelizumab prolong 
time to death (OS) compared to durvalumab in patients with unresectable LA NSCLC whose 
disease has not progressed after cCRT and with PD-L1 expression on ≥ 50%, regardless of 
whether to receive subsequent anticancer therapy after assigned therapy. 
The key secondary estimand 1 is described by the following attributes: 
1. Treatment of interest is the same as those in the primary estimand. 
2. Population: 
Patients with unresectable LA NSCLC whose disease has not progressed after cCRT and 
with PD-L1 expression on ≥ 50% of TC. 
3. Primary variable: 
Overall survival defined as the time from the date of randomization to the date of death 
due to any cause. 
4. Handling of intercurrent events: 
• Anticancer therapy, subsequent to assigned therapy, started prior to death: any 
incidence will be ignored, ie, any death or patients’ data collected after the new 
anticancer therapy will be considered for analysis (treatment policy strategy) 
• Discontinuation of treatment: any death or patients’ data collected after the 
discontinuation of treatment will be considered for analysis (treatment policy 
strategy) 
• Any unforeseen intercurrent events: OS will take into account all deaths and any 
patients’ data after any unforeseen intercurrent events (treatment policy) 
5. Population-level summary: HR of OS and its 95% CI for OS comparing 
ociperlimab + tislelizumab versus durvalumab, estimated using a Cox regression model 
stratified by age (< 65 years versus ≥ 65 years), and histology (squamous versus 
nonsquamous). 
2.3.2. 
Key Secondary Estimand 2 – OS benefit in patients with LA NSCLC whose 
disease has not progressed after cCRT and with PD-L1 ≥ 1% 
The attributes of this estimand are the same as Key Secondary Estimand 1, except that the 
population consists of patients with PD-L1 expression on ≥ 1%, and for HR calculation, the 
stratification factors in Cox model include age (< 65 years versus ≥ 65 years), PD-L1 expression 
in TC (≥ 50% versus < 50%), and histology (squamous versus nonsquamous). 
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3. 
STUDY DESIGN 
3.1. 
Summary of Study Design 
This is an open-label, randomized, multicenter, Phase 3 study to compare the efficacy and safety 
of ociperlimab plus tislelizumab (Arm A) versus durvalumab (Arm C) in patients with 
unresectable, PD-L1 selected LA NSCLC whose disease has not progressed after cCRT. 
Patients who have diagnosed with histologically or cytologically confirmed, unresectable LA 
Stage III NSCLC with PD-L1 ≥ 1% of TC and whose disease has not progressed after definitive, 
platinum-based cCRT are eligible. Approximately 700 patients will be enrolled and randomized 
in a 3:1:3 ratio to Arm A, Arm B, or Arm C in this study. Randomization will be stratified by age 
(< 65 years versus ≥ 65 years), PD-L1 expression in TC (≥ 50% versus < 50%), and histology 
(squamous versus nonsquamous). 
The PD-L1 expression status will be closely monitored. For enrolled patients with PD-L1, 1% to 
49% of TC will be stopped as necessary through Interactive Response Technology (IRT) when 
the prevalence for this population reaches around 50%. This will ensure that the population 
reflects the natural PD-L1 expression prevalence. 
During the treatment period, in Arm A, patients will receive ociperlimab 900 mg combined with 
tislelizumab 200 mg Q3W. In Arm B, patients will receive tislelizumab 200 mg Q3W. In Arm C, 
patients will receive durvalumab 10 mg/kg Q2W (or 1500 mg Q4W where the dosage has been 
approved by a local health authority). Patients in all 3 arms will receive study treatment for a 
maximum of 12 months, or until PD per RECIST v1.1, unacceptable toxicity, death, or another 
discontinuation criterion is met, whichever occurs first. 
End-of-Treatment (EOT) Visit, Safety Follow-up Visit, and Survival Follow-up Visit will be 
conducted to monitor patient status and collect data beyond study treatment. 
Safety and efficacy will be monitored by an IDMC. There is 1 planned interim analysis in this 
study for superiority. Please refer to details in Section 10.2 and Section 9.8, respectively. 
The study conduct will be overseen by a Steering Committee (SC) composed of selected 
investigators. Please refer to details in Section 10.3. 
The study design schema is presented in Figure 3. 
Figure 3: 
Study Schema 
 
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Abbreviations: ALK, anaplastic lymphoma kinase; C1D1, Cycle 1 Day 1; cCRT, concurrent chemoradiotherapy; 
ECOG PS, Eastern Cooperative Oncology Group Performance Status; EGFR, epidermal growth factor receptor; 
NSCLC, non-small cell lung cancer; PD-L1, programmed cell death protein ligand-1; R, randomization; TC, tumor 
cells; TIGIT, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain. 
For all study procedures see Section 7 and Appendix 1. 
Note, the study was initially implemented with Protocol Amendment 1.0 (dated on 16 Apr 2021, 
PA 1.0). In the PA 1.0, patients with newly diagnosed, histologically confirmed, unresectable LA 
NSCLC and evaluable PD-L1 expression all comers were enrolled; cCRT was given within the 
study. In Protocol Amendment 2.0 (date 21 Apr 2022, PA 2.0), the enrollment of the target 
population has been revised into patients with unresectable LA NSCLC whose disease has not 
progressed after definitive, platinum-based cCRT with PD-L1 expression on ≥ 1% of TC as 
assessed by the central lab; cCRT was given outside of the study; the eligibility criteria have 
been updated to reflect the patient population change. The enrollment of PA 1.0 will be stopped 
before PA 2.0 implementation. Patients recruited into the study prior to PA 2.0 will not be 
included in the primary and secondary analysis but would be included in exploratory analysis 
defined by PA 2.0. 
For all patients randomized with PA 1.0 prior to PA 2.0 implementation (defined as the 
Concurrent Part of the study): 
Patients who are still on study treatment will be informed of the substantial change from PA 1.0 
to PA 2.0, the rationale for this change, and the following treatment options. Investigators will 
discuss the local available standard-of-care with the patients, and patients have the right to 
discontinue from the assigned study treatment and receive standard-of-care treatment outside of 
the study proposed by their physician. However, after discussion of benefit-risk of the study 
treatment with the treating physician, the patients who are still willing to continue the assigned 
study treatment will be offered the assigned treatment until PA 1.0 defined treatment 
discontinuation point. 
All patients (including those who chooses to stop assigned study treatment) are requested to 
continue in the study for follow-up visits unless the study discontinuation criterion is met. 
The care of the patients enrolled under PA 1.0, including but not limited to treatment, safety 
management and visits, will follow the details in Appendix 17, which are mostly consistent with 
those defined in PA 1.0, except for minor updates. 
3.2. 
Prescreening 
All patients will undergo prescreening for central evaluation of PD-L1 status up to 120 days 
before randomization. PD-L1 status will be determined centrally in either a previously obtained 
archival tumor tissue or fresh tissue obtained from a biopsy collected prior to the initiation of 
cCRT. A separate prescreening informed consent must be obtained. 
Archival tumor tissue must be collected for the purpose of PD-L1 evaluation and other 
exploratory biomarker analysis. If no archival samples are available, a fresh tumor biopsy prior 
to the first dose of CRT is mandatory (Section 7.8). 
EGFR, ALK, RET, and ROS1 mutational status, if known, will also be collected at this time. 
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Patients with nonsquamous NSCLC and unknown EGFR mutational status will be required to 
have a tissue-based EGFR test performed either locally or centrally, or endobronchial 
ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) based EGFR test performed 
locally during prescreening. Patients found to have EGFR sensitizing mutations will not be 
eligible. 
3.3. 
Screening Period 
Patients with PD-L1 ≥ 1% of TC and with no EGFR-sensitizing mutations or known ALK, RET, 
or ROS1 mutation will then proceed to screening. Screening evaluations will be performed 
within 28 days before randomization. Patients who agree to participate in this study will sign the 
informed consent form (ICF) before undergoing any screening procedure. 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. 
3.4. 
Treatment Period 
After completing all prescreening and screening activities, eligible patients will be randomized in 
a 3:1:3 ratio to 3 arms (Arm A, Arm B, and Arm C). Randomization will be stratified by age 
(< 65 years versus ≥ 65 years), PD-L1 expression in TC (≥ 50% versus < 50%), and histology 
(squamous versus nonsquamous). 
Patients will receive open-label treatments as follows: 
• Arm A: Ociperlimab 900 mg Q3W combined with tislelizumab 200 mg Q3W 
intravenously up to 12 months, or until PD per RECIST v1.1, unacceptable toxicity, 
death, or until another discontinuation criterion is met 
• Arm B: Tislelizumab 200 mg intravenously Q3W up to 12 months, or until PD per 
RECIST v1.1, unacceptable toxicity, death, or until another discontinuation criterion 
is met 
• Arm C: Durvalumab 10 mg/kg intravenously Q2W (or 1500 mg Q4W where the 
dosage has been approved by a local health authority) up to 12 months, or until PD 
per RECIST v1.1, unacceptable toxicity, death, or until another discontinuation 
criterion is met 
Radiological assessment of tumor-response status will be performed approximately every 
9 weeks (± 7 days) after randomization, for the first 54 weeks, and every 12 weeks (± 7 days) 
thereafter based on RECIST v1.1. Tumor response will be assessed by both the IRC and the 
investigator. Tumor assessments are required to be performed on schedule regardless of whether 
study treatment has been administered or held; that is, tumor assessments should not be adjusted 
for delays in cycles. Details are provided in Section 7.6. 
Administration of study treatment will continue up to 12 months, or until PD as assessed by the 
investigator per RECIST v1.1, unacceptable toxicity, or death, or until another discontinuation 
criterion is met, whichever occurs first. Once PD is assessed by the investigator, the IRC is 
required to complete central image review and convey the results to the investigator as soon as 
possible. If the investigator-assessed PD is NOT confirmed by the IRC, the medical monitor will 
discuss the findings with the investigator and the study treatment is recommended to continue as 
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long as it is considered to be in the best interest of the patient. In the situation where the 
investigator believes the patient must urgently begin subsequent systemic therapy without 
waiting for confirmation of PD by IRC, the investigator must contact the medical monitor to 
inform them of the plan to urgently discontinue study treatment. 
A patient who discontinues study treatment for reasons other than PD by the IRC (eg, toxicity, 
PD by the investigator, completion of the 12-month treatment) will continue to undergo tumor 
assessments following the original plan until the patient experiences PD per RECIST v1.1 
assessed by the IRC, withdraws consent, is lost to follow-up, dies, or until the study terminates, 
whichever occurs first. 
Study treatment beyond initial PD per RECIST v1.1 
If at the investigator’s discretion a patient could continue to benefit from the immunotherapy 
(ociperlimab and tislelizumab combination treatment in Arm A, tislelizumab in Arm B, or 
durvalumab in Arm C) after PD per RECIST v1.1 assessed by the IRC or investigator, the patient 
may continue their assigned treatment. The following criteria must be met in order to treat 
patients who may continue to benefit from study treatment after PD: 
• Absence of clinical symptoms and signs of PD (including clinically significant 
worsening of laboratory values) 
• Stable ECOG Performance Status (≤ 1) 
• Absence of rapid progression of disease or of progressive tumor at critical anatomical 
sites (eg, cord compression) that requires urgent alternative medical intervention 
• Investigators must obtain written informed consent for treatment beyond radiologic 
PD and inform patients that this practice is not considered standard in the treatment of 
cancer 
The decision to continue study treatment beyond initial PD per RECIST v1.1 assessed by the 
IRC or investigator must be agreed upon with the medical monitor and documented in the study 
records. 
Tumor assessment should continue as planned in patients receiving study treatment beyond 
initial PD per RECIST v1.1 criteria assessed by the IRC or investigator. Tumor assessment in 
such patients should continue until study treatment discontinuation. 
To determine the PK properties of ociperlimab and tislelizumab, and host immunogenic response 
to ociperlimab and tislelizumab, blood samples will be collected at various timepoints as outlined 
in Appendix 1. 
Blood sample must be collected at C1D1 (predose) for biomarker test. Optional blood samples 
will be collected at C3D1 (predose), C4D1 (predose), and at the EOT Visit after disease 
progression (Appendix 1). All these blood samples will be collected to explore association of 
blood-based biomarkers with response, resistance, and prognosis. Written informed consent is 
required before optional blood samples collection. 
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 
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be used for safety assessment. Safety assessments are further detailed in Section 7.5 and the 
Schedule of Assessments (Appendix 1). 
3.5. 
End of Treatment 
The End-of-Treatment (EOT) Visit is planned when the investigator determines that study 
treatment will no longer be used. 
The date of End of Treatment (EOT) is defined as the date the investigator determines that study 
treatment will no longer be used. Patients shall have an EOT Visit within 7 days after the date 
the investigator determines that study treatment will no longer be used, or before the initiation of 
a new anticancer treatment, whichever occurs first. For Arm A, patients shall have an EOT Visit 
only if both study drugs were discontinued. However, the EOT Visit may occur later than 7 days 
for specific circumstances, such as prolonged hospitalization. 
See Appendix 1 for assessments to be performed at the EOT. 
3.6. 
Safety Follow-up 
The Safety Follow-up Visit is planned when the investigator determines that study treatment will 
no longer be used. 
The date of Safety Follow-up Visit is defined as the date when safety assessments and 
procedures are performed after the last dose of study treatment for an individual patient. 
All patients that discontinue study treatment (both study drugs if in Arm A) will have a Safety 
Follow-up Visit approximately 30 days (± 7 days) after the last dose of study drug or before the 
initiation of new anticancer therapy, whichever occurs first. This visit will include the collection 
of data about AEs and serious adverse events (SAEs) that may have occurred after the patient 
discontinued the study drug. The investigator or his/her designee will continue to collect 
information on new anticancer therapy given after the last dose of study drug. In cases where the 
time window of EOT and Safety Follow-up visit overlap, these two visits can be combined. See 
Appendix 1 for assessments to be performed at the Safety Follow-up Visit. 
Additional Safety Follow up visits at 60, 90, and 120 days (this visit is only required for women 
of childbearing potential) after the last dose of study drug can be required (in clinic or over the 
phone, as needed based on assessments required). Patients will be contacted by telephone to 
assess imAEs and relevant concomitant medication use (ie, those associated with an imAE or 
any new anticancer therapy). These contacts should be made at 60 days (± 14 days) and 90 days 
(± 14 days) after the last dose of study treatment regardless of whether the patient starts a new 
anticancer therapy. For women of childbearing potential (see Appendix 5), an additional visit to 
perform a pregnancy test will occur at approximately 120 days (± 14 days) after the last dose of 
study treatment. If a patient reports a suspected imAE at a telephone follow-up contact, the 
investigator should arrange an unscheduled visit if further assessment is indicated. 
3.7. 
Survival Follow-up 
Patients will be followed for survival follow-up data after discontinuation of study treatment via 
telephone calls, patient medical records, and/or clinic visits approximately every 3 months 
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(± 14 days) after the 90-Day Safety Follow-up Visit or as directed by the sponsor until death, 
loss to follow-up, withdrawal of consent, or end of study by the sponsor. 
During the survival follow-up period subsequent anticancer therapy information including 
medication start date, end date, reason for treatment and date of progression after receiving the 
subsequent anticancer therapy will be collected. 
3.8. 
Discontinuation From the Study Treatment or From the Study 
3.8.1. 
Discontinuation From Study Treatment 
Patients have the right to withdraw from the study or 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 PD should 
be followed for assessments of antitumor activity (Section 7.6), safety (Section 7.5), and survival 
(Section 3.7), 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 from the study treatment for reasons that include, but are not limited to, 
the following: 
• Radiographic PD per RECIST v1.1 
• AE 
• Use of any concurrent antineoplastic therapy (ie, chemotherapy, hormonal therapy, 
immunotherapy, or standard or investigational agents [including herbal medicine and 
patent medicines] for the treatment of cancer) (Section 6.3). 
• Patient noncompliance 
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. 
Patients will discontinue from the study treatment for reasons following: 
• Patient’s decision to withdraw from study treatment 
• Any medical condition that the investigator determines may jeopardize the patient’s 
safety, if he or she were to continue the study treatment 
• Pregnancy. 
3.8.2. 
Patient Discontinuation From Study (End of Study for an Individual Patient) 
Patients will discontinue study for reasons which include, but are not limited to, the following: 
• Patient’s withdrawal of consent from study treatment and follow-up 
• Death 
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• Lost to follow-up 
• Patients have completed all study assessments 
3.9. 
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 
The sponsor will notify each investigator if a decision is made to terminate the study. Should this 
be necessary, patients who prematurely discontinued from treatment should be seen as soon as 
possible for an EOT 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 IRBs/IECs of the early termination of the study. 
At the end of study, patients who are still in the originally assigned treatment within 12 months 
after C1D1 and continue to benefit from the treatment at study termination in the opinion of the 
investigator, will be offered the option to continue treatment in a company-sponsored clinical 
trial until treatment duration reach 12 months after C1D1 or it 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 must meet all of the following inclusion criteria to be considered eligible for 
participation in this study: 
1. 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). 
2. Ability to provide written informed consent and to understand and agree to comply with 
the requirements of the study and the schedule of assessments. 
Note for sites in France: Patients who are unable to express their consent (adults 
protected by local law of Article L1121-8 Public Health Code) are not allowed to 
participate in the study. 
3. Patient has histologically or cytologically confirmed, locally advanced, unresectable 
Stage III NSCLC (AJCC Cancer Staging Manual 2017, derived from IASLC) prior to 
initiation of cCRT. 
Note: Tumors of mixed non-small cell histology will be categorized by the predominant 
cell type; if small cell elements are present, the patient is ineligible. 
4. Patients must have completed at least 2 cycles of platinum-based chemotherapy 
concurrent with radiotherapy. For patients who are recovering from toxicities associated 
with prior treatment, the first dose of study treatment may be delayed by up to 42 days 
from the end of the cCRT. It is recommended to screen the patients within 14 days after 
the completion of cCRT. 
a. The platinum-based chemotherapy regimen must contain cisplatin or carboplatin, and 
may contain one of the following agents: etoposide, vinblastine, vinorelbine, taxane 
(paclitaxel or docetaxel), or pemetrexed, according to the local standard-of-care 
regimens. If a patient was receiving a weekly chemotherapy regimen, platinum-based 
chemotherapy of at least 4 weeks should be completed. 
b. The last dose of chemotherapy must be administered no later than the last dose of 
radiotherapy. Consolidation chemotherapy is not allowed after radiotherapy; but 
induction chemotherapy no more than 2 cycles before cCRT is allowed. 
c. Where possible, chemotherapy regimens should be given according to National 
Comprehensive Cancer Network (NCCN) Guidelines, European Society for Medical 
Oncology (ESMO) Guidelines, Chinese Society of Clinical Oncology (CSCO) 
Guidelines, Japan Lung Cancer Society (JLCS) Guidelines, or other local guidelines 
if applicable. 
d. Patients must have received a total dose of radiation of 60 ± 10% Gy (54 to 66 Gy), 
as part of the CRT. 
e. The minimum technical standard for radiotherapy is 3D conformal radiotherapy 
(3D-CRT) with CT planning. Intensity modulated radiotherapy (IMRT) is 
recommended. 
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f. RT dose received by organs is recommended to be (the medical monitor needs to be 
consulted to confirm eligibility for the patients who received higher RT dose for the 
organs below): 
• 
Spinal cord: max dose ≤ 48 Gy 
• 
Lung: V20 ≤ 35%, mean dose ≤ 20 Gy 
• 
Esophagus: mean dose ≤ 34Gy 
• 
Heart: V50 ≤ 25%, mean dose ≤ 20 Gy 
5. Patients must have not experienced PD following definitive, platinum-based cCRT. 
6. Agree to provide archival tissue (formalin-fixed paraffin-embedded block containing 
tumor [preferred] or approximately 6 to 15 freshly cut unstained slides) or fresh biopsy 
obtained prior to cCRT (if archival tissue is not available) for prospective central 
evaluation of PD-L1 levels and retrospective analysis of other biomarkers. PD-L1 status 
will be assessed centrally in either a previously obtained archival tumor tissue or fresh 
tissue obtained from a biopsy collected prior to the first dose of cCRT via VENTANA 
PD-L1 (SP263) assay. Only patients with PD-L1 ≥ 1% of TC are eligible. 
7. ECOG Performance Status of 0 or 1. 
8. Patients must have adequate organ function as indicated by the following screening 
laboratory values obtained within 7 days before randomization: 
a. Patients must not have required blood transfusion or growth factor support ≤ 14 days 
before sample collection at screening for the following: 
i. 
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L 
ii. 
Platelets ≥ 75 x 109/L 
iii. 
Hemoglobin ≥ 90 g/L or ≥ 5.6 mmol /L (Note: Criteria must be met 
without a transfusion within 14 days of obtaining the sample) 
b. Serum creatinine ≤ 1.5 x upper limit of normal (ULN), or for patients whose serum 
creatinine > 1.5×ULN, estimated Glomerular Filtration Rate (GFR) by Chronic 
Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or Calculated 
creatinine clearance (CrCl) by Cockcroft-Gault (CG) equation ≥ 30 mL/min 
(Appendix 14). 
c. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN for patients 
with Gilbert syndrome). 
d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN. 
e. INR and aPPT ≤ 1.5 x ULN. This applies only to patients who are not receiving 
therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be 
on a stable dose. 
9. Female patients of childbearing potential must consent to use a highly effective method 
of birth control for the duration of the study, and for ≥ 120 days after the last dose of 
ociperlimab and tislelizumab in Arm A or tislelizumab in Arm B, or ≥ 90 days after the 
last dose of durvalumab, and have a negative urine or serum pregnancy test ≤ 7 days 
before the first dose of any of the study treatment. 
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10. Nonsterile male patients must consent to use a highly effective method of birth control 
for the duration of the study and for ≥ 120 days after the last dose of ociperlimab and 
tislelizumab in Arm A or tislelizumab in Arm B, or ≥ 90 days after the last dose of 
durvalumab 
a. A sterile male is defined as one for whom azoospermia has been previously 
demonstrated in a semen sample examination as definitive evidence of infertility. 
b. Male patients with known “low sperm counts” (consistent with “sub-fertility”) are not 
to be considered sterile for purposes of this study. 
4.2. 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from this study: 
1. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, TIGIT, or any other antibody 
or drugs specifically targeting T-cell co-stimulation or checkpoint pathways. 
2. Diagnosed with NSCLC that harbors an EGFR-sensitizing mutation, ALK gene 
translocation, ROS1 gene translocation or RET gene rearrangement. 
a. For nonsquamous and squamous NSCLC, patients with known EGFR mutation 
status, ALK translocation, ROS1 translocation, or RET rearrangement who are 
sensitive to available targeted inhibitor therapy are excluded (Note: If no targeted 
therapy approved by the local health authority is available for ROS1 or RET 
mutations, then these patients are eligible). 
b. For nonsquamous NSCLC, patients with unknown EGFR mutation status will be 
required to undergo a tissue-based EGFR test locally or at a central laboratory before 
randomization. An additional ≥ 6 slides are required if EGFR mutation status needs to 
be tested in a central laboratory. Patients with sensitive EGFR mutation status will be 
excluded. Patients with unknown ALK, ROS1, or RET status may be enrolled. 
c. Patients with squamous NSCLC and unknown EGFR, ALK, ROS1, or RET status will 
not be required to be tested before randomization. 
3. Distant metastasis identified by imaging assessment and/or other examinations after 
definitive, platinum-based cCRT. 
4. Patients who received chemotherapy and radiotherapy with ≤ 1 cycle overlap for LA 
NSCLC. 
5. Patients who received systemic anticancer treatment besides the specified cCRT. 
6. Any unresolved toxicity CTCAE > Grade 2 from the prior cCRT. Patients with 
irreversible toxicity that is not reasonably expected to be exacerbated by study treatment 
may be included (eg, hearing loss). 
7. Patients with any grade pneumonitis from prior cCRT. 
8. Active autoimmune diseases or history of autoimmune diseases that may relapse 
(Appendix 4). 
Note: 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). 
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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. 
9. Any active malignancy ≤ 2 years before the first dose of study treatment 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). 
10. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily 
of prednisone [in Japan, prednisolone] or equivalent) or other immunosuppressive 
medication ≤ 14 days before the first dose of study treatment. 
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 [in Japan, 
prednisolone] 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. 
11. 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 the first dose of study treatment. 
12. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent 
drainage (recurrence within 2 weeks of intervention). Note for sites in Germany: patients 
with malignant pleural or pericardial effusion or ascites are excluded regardless of 
whether it is uncontrollable or not. 
13. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled lung 
diseases including pulmonary fibrosis, acute lung diseases, etc. 
14. Infection (including tuberculosis infection, etc) requiring systemic antibacterial, 
antifungal, or antiviral therapy within 14 days before the first dose of study treatment. 
Note: Antiviral therapy is permitted for patients with chronic hepatitis B virus (HBV) or 
hepatitis C virus (HCV) infection. 
15. 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 (defined as patients with 
positive HBsAg but asymptomatic), 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 enrollment. 
16. 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 
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will be performed only for patients testing positive for HCV antibody. Patients receiving 
antivirals at screening should have been treated for > 2 weeks before enrollment. 
17. Known history of HIV infection. Note for sites in Germany and where required by Health 
Authority or local guidance: An HIV serology test (including antigen and/or antibodies) 
will be conducted at baseline for the patients with unknown HIV status and patients with 
positive HIV test will be excluded. 
18. Any major surgical procedure ≤ 28 days before the first dose of study treatment. Patients 
must have recovered adequately from the toxicity and/or complications from the 
intervention before the first dose of study treatment. 
19. Prior allogeneic stem cell transplantation or organ transplantation. 
20. 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 the first dose of study treatment. 
b. Pulmonary embolism ≤ 28 days before the first dose of study treatment. 
c. Any history of acute myocardial infarction ≤ 6 months before the first dose of 
study treatment. 
d. Any history of heart failure meeting New York Heart Association (NYHA) 
Classification (Appendix 6) III or IV ≤ 6 months before the first dose of study 
treatment. 
e. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before the 
first dose of study treatment. 
f. Any history of cerebrovascular accident ≤ 6 months before the first dose of study 
treatment. 
g. Uncontrolled hypertension that cannot be managed by standard anti-hypertension 
medications ≤ 28 days before the first dose of study treatment. 
For France only, specify: systolic pressure ≥ 140 mmHg or diastolic pressure 
≥ 90 mmHg on repeated measurements. 
h. Any episode of syncope or seizure ≤ 28 days before the first dose of study 
treatment. 
21. A history of severe hypersensitivity reactions to other monoclonal antibodies or history of 
hypersensitivity to the ingredients of tislelizumab or ociperlimab. 
22. Receipt of any immunotherapy (eg, interleukin, interferon, thymosin [not approved in 
Japan], etc) or any investigational therapies within 14 days or 5 half-lives (whichever is 
longer) before the first dose of study treatment. 
23. Administration of a live vaccine ≤ 28 days before the first dose of study treatment. 
Note: Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. 
Intranasal vaccines are live vaccines and are not allowed. For COVID-19 vaccines, 
non-live vaccines are allowed, including inactivated vaccines; live or live-attenuated 
vaccines ≤ 28 days before the first dose of stud treatment are not allowed. 
24. Underlying medical conditions (including laboratory abnormalities) or alcohol or drug 
abuse or dependence that will be unfavorable for the administration of study treatment, or 
affect the explanation of treatment toxicity or AEs, or result in insufficient or impaired 
compliance with study conduct. 
25. Patients who are pregnant or suspected of being pregnant, breastfeeding, or planning to 
get pregnant during the study. 
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Note for sites in Japan: women of breast-feeding that agree to stop breast-feeding prior to 
screening are allowed to enroll. They cannot breast-feed during the study and for at least 
120 days after the last dose of study drugs. 
26. Concurrent participation in another therapeutic clinical study. 
Note: Concurrent participation in observational or non-interventional 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. 
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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, USP Type I) containing a total of 300 mg antibody in 15 mL of buffered 
isotonic solution. 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 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 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 in the 
Pharmacy Manual. Refer to the Pharmacy Manual for details regarding intravenous 
administration, accountability, and disposal. Refer to the Tislelizumab Investigator’s Brochure 
for other details regarding tislelizumab. 
5.1.3. 
Durvalumab 
Durvalumab is a monoclonal antibody formulated for intravenous infusion in a single-dose vial, 
containing a total of 500 mg antibody in 10 mL (or 120 mg antibody in 2.4 mL, 50 mg/mL) clear 
to opalescent, colorless to slightly yellow solution. 
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. 
Please refer to the Pharmacy Manual for details regarding administration, accountability, and 
disposal. 
5.2. 
Dosage, Administration, and Compliance 
Planned dosage and dosing frequency for study treatment are presented in Table 6 and Table 7. 
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For all 3 arms, the first dose of the immunotherapy (ociperlimab and tislelizumab in Arm A, 
tislelizumab in Arm B, durvalumab in Arm C) is to be administered within 2 business days of 
randomization. C1D1 is defined as the day of the administration of the first dose of the 
immunotherapy. Immunotherapy will be given starting from C1D1 and continued for a duration 
of up to 12 months. 
In Arm A, ociperlimab and tislelizumab should be administered on the same day if feasible. If 
the first dose of ociperlimab and tislelizumab were not administered on the same day for reasons 
other specified, C1D1 is defined as the day of administration of the first dose of tislelizumab. For 
Arm B or Arm C, C1D1 is defined as the day of administration of the first dose of tislelizumab 
or durvalumab, respectively. 
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. Guidelines for dose modification or treatment discontinuation and for the 
management of imAE and infusion-related reactions are provided in detail in Section 8.7 and 
Appendix 12. 
Accurate records of all study treatment received, dispensed, returned, and disposed should be 
maintained in the site’s Drug Inventory Log. Refer to the Pharmacy Manual for details of study 
treatment management, drug preparation, storage, and administration. 
Table 6: 
Planned Dose, Frequency of Administration, and Route of Administration 
for Study Drugs 
Study drugs 
Dose 
Frequency of 
Administration 
Route of 
Administration 
Duration of 
Treatment 
Ociperlimab 
900 mg 
Day 1 of each cycle 
(21 days) 
Intravenous 
Refer to Section 3.4 
Tislelizumab 
200 mg 
Day 1 of each cycle 
(21 days) 
Intravenous 
Refer to Section 3.4 
Durvalumab 
10 mg/kg or 1500 mg a 
Day 1 of each cycle 
(14 days) or Day 1 of 
each cycle (28 days) 
Intravenous 
Refer to Section 3.4 
Abbreviation: AUC, area under the concentration-time curve; Q4W, every 4 weeks. 
a 1500 mg Q4W will be used where the dosage has been approved by a local health authority. 
Table 7: 
Administration of Ociperlimab and Tislelizumab and Monitoring Time 
Cycle 
Ociperlimab and tislelizumab combination in 
Arm A 
Tislelizumab in Arm B 
Cycle 1 
Day 1 
Tislelizumab infusion for ≥ 60 minutes followed 
by 
Ociperlimab infusion for ≥ 60 minutes 
Patient monitoring for ≥ 120 minutes 
Tislelizumab infusion for ≥ 60 minutes 
Patient monitoring for ≥ 60 minutes 
Cycle 2 
Day 1 
Tislelizumab infusion for ≥ 60 minutes followed 
by 
Tislelizumab infusion for ≥ 60 minutes 
Patient monitoring for ≥ 60 minutes 
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Ociperlimab infusion for ≥ 60 minutes 
Patient monitoring for ≥ 120 minutes 
Cycle 3 
Day 1 
onwards 
Tislelizumab infusion for ≥ 30 minutes followed 
by 
Ociperlimab infusion for ≥ 30 minutes 
Patient monitoring for ≥ 60 minutes 
Tislelizumab infusion for ≥ 30 minutes 
Patient monitoring for ≥ 30 minutes 
5.2.1. 
Ociperlimab and Tislelizumab Treatment Administration 
Patients will receive tislelizumab 200 mg on Day 1 of each 21-day cycle (ie, Q3W) followed by 
the administration of ociperlimab 900 mg for Arm A, or patients will receive tislelizumab 
200 mg on Day 1 of each 21-day cycle (ie, Q3W) for Arm B. 
Ociperlimab and tislelizumab for Arm A and tislelizumab for Arm B are administered by 
intravenous infusion through an intravenous line containing a sterile, nonpyrogenic, 
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. 
As specified in Table 7, the initial infusion (C1D1 and C2D1) will be delivered for ≥ 60 minutes 
for each study drug of the immunotherapy in Arm A and Arm B; if this is well tolerated, then the 
subsequent infusions from Cycle 3 onward may be administered for ≥ 30 minutes for each study 
drug of the immunotherapy in Arm A and Arm B, which is the shortest period permissible for 
infusion. 
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 
infusion speed is controlled through alternative means and consistent with approved institutional 
procedures. 
At the end of the infusion period, the line will be flushed with enough normal saline to make sure 
the complete doses of the immunotherapy are administered. 
As a routine precaution, after infusion of ociperlimab and tislelizumab in Arm A on C1D1 and 
C2D1, patients will be monitored for ≥ 2 hours in an area with resuscitation equipment and 
emergency agents; similarly, after infusion of tislelizumab in Arm B on C1D1 and C2D1, 
patients will be monitored for ≥ 1 hour. From Cycle 3 onward, at least a 60‑minute monitoring 
period is required in an area with resuscitation equipment and emergency agents for Arm A; and 
for Arm B, the monitoring period is at least 30 minutes. 
5.2.2. 
Durvalumab 
Durvalumab 10 mg/kg will be administered by intravenous infusion for ≥ 60 minutes every 
2 weeks (or 1500 mg Q4W where the dosage has been approved by a local health authority) for 
up to 12 months. For the patient whose body weight is < 30 kg, only the regimen of durvalumab 
10 mg/kg Q2W is applicable. 
Refer to the Pharmacy Manual and local prescribing information of durvaluamb for detailed 
instructions on drug preparation, storage, and administration. 
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5.2.3. 
Supportive Care 
Patients should receive full supportive care, including epoetin and other hematopoietic growth 
factors (eg, colony-stimulating factors), transfusions of blood and blood products, antibiotics, 
antiemetics, other applicable medications, as needed according to local standard of care 
guidelines or practices. 
All patients are strongly suggested to accept nutrition support if there is any indication including 
(but not limited to): medium-severe dysphagia; weight loss > 5% in 1 month; Body Mass Index 
(BMI) < 18.5 kg/m2; scored patient-generated subjective global assessment ≥ 4 score; and food 
intake is < 60% required for > 3 days. 
5.3. 
Incorrect Administration or Overdose 
Any overdose (defined as ≥ 600 mg of tislelizumab in a 24-hour period) or incorrect 
administration of any of the study drugs should be noted in the patient’s chart and on the 
appropriate eCRF. 
AEs associated with an incorrect administration or overdose of study treatment will be recorded 
on the AE eCRF. Any SAEs associated with an incorrect administration or overdose must be 
reported within 24 hours of awareness via the SAE reporting process as described in 
Section 8.6.2. Supportive care measures should be administered as appropriate. 
5.4. 
Investigational Medicinal Product Accountability 
The investigational medicinal products required for completion of this study (ociperlimab, 
tislelizumab, and durvalumab) will be provided by the sponsor. The investigational site will 
acknowledge receipt of investigational medicinal products. Any damaged shipments will be 
replaced. 
Accurate records of all investigational medicinal products received, dispensed, returned, and 
disposed should be recorded on the site’s Drug Inventory Log. Refer to the Pharmacy Manual for 
details of investigational medicinal product management. 
5.5. 
Dose Modification 
A dose interruption is an interruption of an infusion. A dose delay is a deviation from the 
prescribed dosing schedule (ie, the drug is withheld beyond the visit window). 
Every effort should be made to administer the study treatment according to the planned dose and 
schedule. In the event of significant toxicities, dosing may be delayed based on the guidelines 
provided below. Reasons for dose modifications or delays, the supportive measures taken, and 
the outcome will be documented in the patient's chart and recorded in the eCRF. Skipped doses 
due to reasons others than AE (eg, COVID-19 lockdown, warfare, etc) should be added at the 
back end to ensure the total duration of treatment in each arm is 12 months or corresponding 
cycles, ie, a maximum of 17 cycles in Arm A and B, 26 cycles for Q2W regimen and 13 cycles 
for Q4W regimen in Arm C. 
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 weight, 
laboratory findings) as appropriate. 
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5.5.1. 
Dose Interruption or Delay for Ociperlimab and Tislelizumab 
If a dose delay is required, both study drugs are to be delayed (ie, ociperlimab and tislelizumab 
must both be delayed and if applicable restarted at the same time in Arm A). Exceptions may be 
considered following consultation between the investigator and the medical monitor. 
If treatment is delayed due to TEAEs, treatment may resume only after the AEs have returned to 
baseline or ≤ Grade 1 severity except for alopecia or AEs that, in the opinion of the investigator, 
are not considered a safety risk to the patient. If a treatment delay is due to laboratory results 
worsening, eg, hematologic or biochemical parameters, the frequency of relevant blood tests 
should be increased as clinically indicated. 
In general, dose delays for reasons other than management of AEs are prohibited. A dose delay 
of ≤ 12 weeks is allowed under the following guidance and at the discretion of the investigator 
after consultation with the medical monitor or designee. 
In Arm A and B, if a dose is delayed for the immunotherapy (ociperlimab and tislelizumab in 
Arm A, tislelizumab in Arm B) for ≤ 10 days for a planned dosing cycle, the immunotherapy 
should be administered. If the delay is > 10 days, the patient should skip administration of the 
immunotherapy and the immunotherapy will be administered on Day 1 of the next planned cycle. 
If imAEs are persistent without any improvement for more than 12 weeks, permanent 
discontinuation of the study treatment should be considered. In Arm A, the treatment 
discontinuation in response to imAEs should be applied to both ociperlimab and tislelizumab 
because the causality of imAEs may not be distinguished from one study drug to the other. 
If the patient recovers from the treatment-related AE after 12 weeks, re-initiation of the study 
drugs is permitted only in patients who are deemed to be deriving clinical benefit per the opinion 
of the investigator following agreement between the investigator and the medical monitor. 
Management guidelines for imAEs and infusion-related reactions in patients treated with the 
immunotherapy are presented in Section 8.7, and Appendix 12. 
The tumor assessment schedule will not be altered even if the administration of the study drug is 
delayed. 
5.5.2. 
Dose Reductions for Ociperlimab and Tislelizumab 
There will be no dose reductions allowed for ociperlimab or tislelizumab in Arm A and Arm B. 
5.5.3. 
Dose Interruption, Delay or Modification for Durvalumab 
There will be no dose reductions allowed for durvalumab. Please refer to prescribing information 
Recommended Dosage Modifications (Appendix 15) approved by US FDA for specific 
information. Note, in countries/regions other than US, recommended dosage modifications of 
durvalumab prescribing information approved by local health authority may differ from that 
approved by US FDA. In these cases, please refer to the recommendations approved by local 
health authority. 
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6. 
PRIOR AND CONCOMITANT THERAPY 
6.1. 
Prior Therapy 
Patients should not have received prior therapies targeting PD-1, PD-L1, PD-L2, TIGIT, T-cell 
costimulation or checkpoint pathways; or immunotherapy (eg, interleukin, interferon, or 
thymosin) or investigational therapy ≤ 14 days or 5 half-lives (whichever is longer) before the 
first dose of study treatment; or systemic anticancer treatment besides the specified cCRT. 
6.2. 
Permitted Concomitant Medications/Procedures 
Unless noted otherwise, 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, hematopoietic growth factors, red blood cell/platelet 
transfusions) and in a patient’s interest are allowed. Opiates and other medication required for 
pain management of patients are allowed. 
All concomitant medication will be recorded on the eCRF including all prescription, 
over-the-counter, herbal supplements, and intravenous medications and fluids. 
Bisphosphonates are permitted during the study for a nonmalignant indication. Use of potentially 
hepatotoxic drugs in patients with impaired hepatic function is allowed but should be carefully 
monitored. 
Vaccines for COVID-19 are allowed except for any live vaccine (ie, live SARS-CoV-2 virus) 
that may be developed. Attenuated (vector) COVID-19 vaccines are inactivated vaccines and as 
such, are permitted. 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. The specific 
COVID-19 vaccine should be recorded instead of generic language, eg, mRNA-1273 vaccine 
(Moderna), BioNTech vaccine (Pfizer), etc. 
6.2.1. 
Systemic Corticosteroids 
Systemic corticosteroids administered for the control of imAEs must be tapered gradually (see 
Appendix 12) and must be administered at non-immunosuppressive doses (≤ 10 mg/day of 
prednisone [in Japan, prednisolone] or equivalent) before the next immunotherapy 
administration. The short-term use of steroids as prophylactic treatments (eg, patients with 
contrast allergies to diagnostic imaging contrast dyes) is permitted. 
6.2.2. 
Hepatitis B Treatment 
Patients with active hepatitis B, defined as HBV DNA ≥ 500 IU/mL at screening, must initiate 
antiviral treatment ≥ 2 weeks before the first dose of study treatment. The patients would not be 
eligible unless HBV DNA decreases to < 500 IU/mL. If the patients are treated and eligible, 
antiviral treatment must continue until 6 months after the last dose of study treatment. Patients 
should continue effective antiviral treatment during the study to decrease potential viral 
re-activation 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 
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(Terrault et al 2016, AASLD/IDSA HCV Guidance Panel 2015). 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 at screening) 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 enrollment and continue treatment during the study and for 6 months after study treatment 
discontinuation. 
6.2.3. 
Hepatitis C Treatment 
Patients with detectable HCV RNA who are receiving treatment at screening must meet the 
criterion of negative HCV RNA to be eligible. If the patients are treated and eligible, they will 
remain on continuous, effective antiviral therapy during the study. Investigators can consider 
treatment with antivirals following the international or local guidelines as appropriate. However, 
interferon-based therapy for HCV is not permitted on study. Patients who are given antiviral 
therapy must initiate treatment > 2 weeks before enrollment and continue treatment during the 
study and for 6 months after study treatment discontinuation. 
6.3. 
Prohibited Concomitant Medications/Procedures 
The following medications are prohibited during the study: 
• Any concurrent anticancer therapy (ie, chemotherapy, hormonal therapy, 
immunotherapy, or standard or investigational agents including herbal medicine and 
patent medicines for the treatment of cancer [Appendix 16]). 
• Live vaccines within 28 days before the first dose of study treatment and 60 days 
following the last dose of study treatment. 
• Herbal remedies with immune-stimulating properties or that are known to potentially 
interfere with liver or other major organ functions. 
Patients must notify the investigator of all herbal remedies and supplements used during the 
study. 
6.4. 
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 [in Japan, prednisolone] 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. 
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6.5. 
Potential Interactions Between the Study Drugs and Concomitant 
Medications 
Information regarding clinical drug interactions with ociperlimab is not available and no 
dedicated drug-drug interaction studies are planned. However, the potential for drug-drug 
interaction between the study drugs (ociperlimab and tislelizumab) and other drug products is 
very low because ociperlimab and tislelizumab are therapeutic monoclonal antibodies. Because 
ociperlimab and tislelizumab are expected to be degraded into amino acids and recycled into 
other proteins, they are unlikely to influence drug-metabolizing enzymes or transporters. 
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7. 
STUDY ASSESSMENT 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. 
Prescreening 
All patients will undergo prescreening for central evaluation of PD-L1 status before 
randomization. PD-L1 status will be determined centrally using either a previously obtained 
archival tumor tissue or fresh biopsy tissue sample collected prior to the first dose of cCRT. A 
separate prescreening informed consent must be obtained. 
Archival tumor tissue must be collected for the purpose of PD-L1 evaluation and other 
exploratory biomarker analysis. If no archival samples are available, a fresh tumor biopsy prior 
to the first dose of cCRT is mandatory (Section 7.8) 
EGFR, ALK, ROS1, and RET mutational status, if known, will also be collected at this time. 
Only for patients with nonsquamous NSCLC: If EGFR mutational status is unknown, patients 
with nonsquamous NSCLC will be required to have a tissue-based EGFR test performed either 
locally or centrally, or EBUS-TBNA based EGFR test locally, at prescreening. Patients found to 
have EGFR sensitizing mutations will not be eligible. 
The following tasks will be performed during the Prescreening Visit: 
• Obtain written informed consent (prescreening ICF) to obtain archival tissue or biopsy 
• Collect EGFR, ALK, ROS1 and RET mutational status if known; obtain consent to have 
EGFR mutational status determined if unknown (for patients with nonsquamous NSCLC 
only) 
• Prepare tumor samples and ship to the qualified central lab for analysis as specified in the 
lab manual 
7.2. 
Screening Period 
Screening evaluations will be performed ≤ 28 days before randomization. A patient who agrees 
to participate in this study will sign the ICF before undergoing any screening assessment. The 
screening period begins on the first day that a screening assessment 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 informed consent has been 
obtained 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. Patients who 
are suspected or known to have concurrent serious respiratory illness or exhibit significant 
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respiratory symptoms unrelated to underlying cancer should take a pulmonary function test (refer 
to Appendix 1 for details) based upon the treatment physician’s judgement. For the description 
of other assessments that are conducted during screening as well as throughout the study, refer to 
Safety Assessments (Section 7.5), Tumor and Response Evaluations (Section 7.6), PK and ADA 
Assessments (Section 7.7) and Biomarkers (Section 7.8) sections. 
Rescreening under limited conditions may be allowed after consultation with the sponsor 
(eg, when a patient’s laboratory result narrowly misses a laboratory criterion and it is correctable 
and not due to rapidly deteriorating condition or PD). Rescreening is allowed only once. 
Rescreened patients must provide new informed consent, as described in Section 7.2.1. A new 
patient number will be assigned as described in Section 7.2.2. 
7.2.1. 
Informed Consent and Prescreening and Screening Log 
Voluntary, written informed consent for participation in the study must be obtained before 
performing any study-specific procedures at Prescreening Visit and Screening Visit. The ICFs 
for prescreened and enrolled patients and for patients who are screened but not enrolled will be 
maintained at the study site. 
All prescreening and screening evaluations must be completed and reviewed to confirm that 
patients meet all eligibility criteria before randomization. The investigator will maintain a 
prescreening and screening log to record details of all patients screened and to confirm eligibility 
or record reasons for screening failure, as applicable. 
7.2.2. 
Patient Numbering 
After obtaining informed consent, study site personnel will access the Interactive Response 
Technology (IRT) system to assign a unique patient number to a potential study participant. 
7.2.3. 
Demographic Data and Medical History 
Demographic data will include age or year of birth, sex, and self-reported race/ethnicity. 
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  and 
tobacco (ie, former or current or never). Prior or concomitant medications include 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. 
7.2.4. 
Females of Childbearing Potential and Contraception 
Childbearing potential is defined as being physiologically capable of becoming pregnant, ie, 
fertile, following menarche and until becoming post-menopausal unless permanently sterile. 
Refer to Appendix 5 for contraception guidelines and definitions of “women of childbearing 
potential” and “no childbearing potential.” 
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7.2.5. 
Pulmonary Function Tests 
All patients should take a pulmonary function test (refer to Appendix 1 for details) at screening 
to assist in the determination of eligibility for the study. 
Pulmonary function testing includes assessment of spirometry and oxygenation. The assessment 
of oxygenation should include at least pulse oximetry (percutaneous arterial oxygen saturation, 
SpO2) at rest and with exercise; an assessment of diffusion capacity is optional. Respective test 
results should be submitted to the sponsor. 
The medical monitor needs to be consulted to confirm eligibility if test results indicate 
significantly impaired pulmonary function, eg, resting pulse oximetry < 90% on room air and 
further desaturation upon exercise, absolute forced expiratory volume (FEV1) value < 1L, FEV1 
of age and sex adjusted predicted performance levels < 50%, diffusing capacity of the lungs for 
carbon monoxide (DLCO) (if performed) < 40% of age and sex adjusted predicted performance 
levels (Pellegrino et al 2005). 
Tests may be repeated as clinically indicated while on study. 
Notes for sites in Japan: at each subsequent visits before dosing, an assessment of oxygenation is 
to be performed including at least SpO2 at rest and with exercise according to Appendix 1, an 
assessment of diffusion capacity is optional; a spirometry test may be repeated as clinically 
indicated. 
7.2.6. 
HIV Serology Test 
Note for Germany and where required by Health Authority or local guidance: An HIV serology 
test (including antigen and/or antibodies) will be conducted at baseline for the patients with 
unknown HIV status. 
7.2.7. 
COVID-19 Test 
A COVID-19 test may be conducted according to local practice. 
7.3. 
Enrollment 
7.3.1. 
Confirmation of Eligibility 
The investigator is responsible for ensuring that each patient meets the eligibility criteria for this 
study. All results from the screening procedures and relevant medical history must be available 
before eligibility can be determined. No eligibility waivers will be granted. 
The sponsor’s medical monitor will support the investigator and/or site staff by answering any 
queries or questions relating to protocol eligibility criteria to confirm eligibility. 
7.3.2. 
Randomization 
Site personnel will access the IRT system to randomize the patient and assign study treatment by 
permuted block stratified randomization. Study treatment must commence within 2 business days 
after randomization/treatment assignment. 
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7.4. 
Study Drug Dispensation 
All study drugs will be dispensed and administered as described in Section 5.2. 
7.5. 
Safety Assessment 
7.5.1. 
Vital Signs 
Vital signs will include measurements of body temperature (˚C), pulse rate, and blood pressure 
(systolic and diastolic). Pulse rate and blood pressure will be measured while the patient is in a 
seated position after resting for 10 minutes. 
The patient’s vital signs are required to be recorded within 60 minutes before, during, and within 
30 minutes after completion of infusion of study treatment (ociperlimab and tislelizumab in Arm 
A, tislelizumab in Arm B, and durvalumab in Arm C). For subsequent infusions, vital signs will 
be collected within 60 minutes before infusion and, if clinically indicated, during and within 
30 minutes after the completion of infusion. 
Weight is required to be measured once on the scheduled assessment day and before study 
treatment if there is any. Height measurements are only required at screening. 
Note for sites in Germany: when both ociperlimab and tislelizumab are administered, vital signs 
are required to be measured at 3 timepoints (within 60 minutes before, during, and within 
30 minutes after the completion of infusion) throughout all treatment periods. When tislelizumab 
alone or durvalumab is administered, the 3-timepoint vital signs are required for the first 
infusion, and vital signs within 60 minutes before infusion are required at subsequent infusions. 
Details of vital signs are specified in Appendix 1. 
7.5.2. 
Physical Examinations 
During the Screening Visit, a complete physical examination will be conducted, including 
evaluations of 1) head, eyes, ears, nose, and 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 eCRF with appropriate disease/condition terms. 
Patients should be solicited at every visit for any vision changes (eg, blurred/distorted vision, 
blind spots, change in color vision, photophobia, tenderness/pain, and eyelid swelling) and 
should be referred to an ophthalmologist if further evaluation is needed. 
At subsequent visits (and as clinically indicated), limited, symptom-directed physical 
examinations will be performed. New or worsened clinically significant abnormalities will be 
recorded as AEs on the eCRF. Refer to Section 8.3 regarding AE definitions and reporting and 
follow-up requirements. 
Note for sites in Japan: Bilateral lung auscultation will be performed at screening and subsequent 
visits as described in Appendix 1. 
7.5.3. 
Eastern Cooperative Oncology Group Performance Status 
ECOG Performance Status (Appendix 3) will be assessed during the study. 
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7.5.4. 
Laboratory Safety Tests 
Local and/or central laboratory assessments of clinical chemistry, hematology, coagulation, and 
urinalysis will be conducted as outlined in Appendix 2 per the timepoints shown in Appendix 1. 
If hematology and serum chemistry at screening are not performed within 7 days before the planed 
C1D1, these tests should be repeated and reviewed before randomization. If a coagulation test 
was performed and reviewed during screening, it is not mandated to repeat before C1D1 unless 
the investigator deems it necessary. Hematology, serum chemistry (including liver function 
tests), creatine kinase (CK) and creatine kinase cardiac muscle isoenzyme (CK-MB) as specified 
in Appendix 2 should be performed weekly for the first 9 weeks for Arm A and B (equal to 
3 cycles), first 8 weeks for Arm C (equal to 4 cycles for Q2W regimen, 2 cycles for Q4W 
regimen), at the beginning of each subsequent cycle, and the EOT Visit (Appendix 1). After 
Cycle 1, these laboratory tests are to be performed and reviewed within 48 hours before study 
treatment administration. Urinalysis is to be conducted during the treatment period only if 
clinically warranted. 
Local laboratory assessments will include the following: 
• Hematology (complete blood count [CBC], including hemoglobin, hematocrit, white 
blood cell [WBC] count [neutrophils and lymphocyte], and platelet count) 
• Serum chemistry (glucose, blood urea nitrogen [BUN] or urea, creatinine, sodium, 
potassium, magnesium, chloride, calcium, phosphorus, direct bilirubin, total bilirubin, 
ALT, AST, alkaline phosphatase, lactate dehydrogenase [LDH], total protein, 
albumin) 
• Coagulation test (international normalized ratio, prothrombin time, and activated 
partial thromboplastin time) 
• Urine or serum pregnancy test (for women of childbearing potential, including 
premenopausal women who have had a tubal ligation) 
• Urinalysis (complete [including, but not limited to specific gravity, pH, glucose, 
protein, ketones] and/or microscopic at screening and if clinically indicated) 
• Thyroid function testing (thyroid stimulating hormone [TSH], free T3 or total T3, free 
T4 or total T4). 
Details about sample collection and shipment will be provided in a separate instruction manual. 
Investigators should use results from the same local laboratories for assessing eligibility, safety 
monitoring, and dosing decision for each patient. 
7.5.4.1. 
Cardiac Enzyme Monitoring 
Although immune-mediated myocarditis is a rare complication of immune checkpoint inhibitors, 
serum CK and CK-MB are monitored in all tislelizumab studies to protect study patients and to 
quantify the risk of muscle inflammation (see Appendix 1 for the blood collection schedule and 
Appendix 12 for guidelines for management of suspected immune-mediated myocarditis, 
respectively). Serum troponins may be substituted per local guideline if used consistently 
through the study. 
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Serum CK and CK-MB testing will be implemented for all patients at screening, at scheduled 
visits during the treatment periods, and at the EOT Visits. In the event that CK-MB fractionation 
is not available, serum troponins (troponin I and/or T) measurements will be performed instead 
per local guidelines if used consistently throughout the study. 
7.5.5. 
Electrocardiograms 
The ECG recordings will be obtained during screening, and as clinically indicated during the 
treatment period, and at the EOT Visit (Appendix 1). 
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 patient should rest in semi-recumbent supine position for ≥ 10 minutes in the absence of 
environmental distractions that may induce changes in heart rate (eg, television, radio, 
conversation, etc) before each ECG collection. 
7.5.6. 
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. 
7.5.7. 
Hepatitis B and C Testing 
Testing will be performed by a central laboratory and/or the local laboratory at screening (and as 
clinically indicated) and will include HBV/HCV serology (HBsAg, hepatitis B surface antibody 
[HBsAb], hepatitis B core antibody [HBcAb], and HCV antibody). In the case of positive 
HBsAg result or positive HCV antibody result, these tests will be followed by viral load 
assessment (HBV DNA or HCV RNA) at screening. 
For patients who have detectable HBV DNA or HCV RNA at screening or upon repeated testing, 
the respective viral load test will be performed every 12 weeks. A detailed schedule is provided 
in Appendix 1. 
7.6. 
Tumor and Response Evaluations 
Tumor imaging will be performed ≤ 28 days before randomization. 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. During the study, tumor imaging will be performed approximately every 
9 weeks (± 7 days) from randomization for the first 54 weeks, and every 12 weeks (± 7 days) 
thereafter, based on RECIST v1.1. If a tumor assessment is missed or conducted outside of the 
specified assessment window, all subsequent scans should be conducted according to the planned 
schedule. Tumor assessments must be performed on schedule regardless of whether study 
treatment has been administered or held; that is, tumor assessments should not be adjusted for 
delays in cycles. 
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Screening assessments must include: 
• CT scans (with oral/intravenous contrast, unless contraindicated) of the chest, 
abdomen, and pelvis; brain imaging by MRI or CT with contrast; and bone scan. 
Note: If PET/CT is performed at screening, bone scan is not required at screening. 
• PET/CT or bone scan should be performed for the whole body, or as sufficient to rule 
out distant metastases (eg, from skull base to knees). 
• If the CT scan portion of PET/CT is with contrast and is of sufficiently high quality, a 
separate CT scan at screening for the chest, abdomen, and pelvis can be skipped. 
• MRI (or CT scan if MRI is contraindicated or not readily available) with contrast of 
the head is required at screening. 
• If the patient’s disease stage was confirmed as Stage III NSCLC (AJCC 2017) based 
on PET/CT or bone scan and brain imaging via MRI or CT with contrast performed 
before cCRT, these tests are not required to repeat at screening. 
If the CT scan portion of FDG-PET/CT is not qualified enough as specified above, screening 
assessment must include CT scans (with oral/intravenous contrast, unless contraindicated) of the 
chest, abdomen, and pelvis. At each subsequent assessment, at least CT scans (with 
oral/intravenous contrast, unless contraindicated) of the chest and abdomen, are included. If 
contraindication exists, other modalities can be allowed after consultation with the medical 
monitor (eg, MRI, CT without contrast). 
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 must be used throughout the study (eg, the same contrast 
protocol for CT scans). 
• If a patient is known to have a contraindication to CT contrast media or develops a 
contraindication during the study, a noncontrast CT of the chest plus a 
contrast-enhanced MRI (if possible) of abdomen ± pelvis should be performed. 
• If a CT scan for tumor assessment is performed on a PET/CT scanner, the CT 
acquisition must be consistent with the standards of a diagnostic CT scan. 
• MRI (or CT scan if MRI is contraindicated or not readily available) of the head or 
bone scan or PET/CT is performed if clinically indicated at the discretion of 
investigator before the discontinuation of tumor assessment. 
• At the investigator’s discretion, other methods of assessment of target lesion and 
non-target lesions per RECIST v1.1 may be used. 
Response will be assessed by the IRC and by the investigator using RECIST v1.1 (see 
Appendix 13). The same evaluator should perform assessments, if possible, to ensure internal 
consistency across visits. 
Administration of study treatment will continue for up to 12 months, or until PD as assessed by 
the investigator per RECIST v1.1, unacceptable toxicity, death; or another discontinuation 
criterion is met. Once PD is assessed by the investigator, the IRC is required to complete central 
image review and convey the results to the investigator as soon as possible. If the investigator-
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assessed PD is NOT confirmed by the IRC, the medical monitor will discuss the findings with 
the investigator and the study treatment is recommended to continue as long as this is considered 
to be in the best interest of the patient. In the situation where the investigator believes the patient 
must urgently begin subsequent systemic therapy without waiting for confirmation of PD by 
IRC, the investigator must contact the medical monitor to inform them of the plan to urgently 
discontinue study treatment. 
A patient who discontinues study treatment for reasons other than disease progression assessed 
by the IRC (eg, toxicity, PD by the investigator, completion of the 12-month treatment) will 
continue to undergo tumor assessments following the original plan until the patient experiences 
PD per RECIST v1.1 by the IRC, withdraws consent, is lost to follow-up, dies, or until the study 
terminates, whichever occurs first. 
Study treatment beyond initial PD per RECIST 1.1 
If at the investigator’s discretion a patient could continue to benefit from ociperlimab and 
tislelizumab combination treatment or tislelizumab or durvalumab after PD per RECIST v1.1 
assessed by the IRC or investigator, the patient may continue their assigned treatment. The 
following criteria must be met in order to treat patients who may continue to benefit from study 
treatment after PD: 
• Absence of clinical symptoms and signs of PD (including clinically significantly 
worsening of laboratory values) 
• Stable ECOG Performance Status ≤ 1 
• Absence of rapid progression of disease or of progressive tumor at critical anatomical 
sites (eg, cord compression) that requires urgent alternative medical intervention 
• Investigators must obtain written informed consent for treatment beyond radiologic 
PD and inform patients that this practice is not considered standard in the treatment of 
cancer. 
The decision to continue study treatment beyond initial PD per RECIST v1.1 assessed by the 
IRC or investigator must be agreed upon with the medical monitor and documented in the study 
records. 
Tumor assessment should continue as planned in patients receiving study treatment beyond 
initial PD per RECIST v1.1 assessed by the IRC or investigator. Tumor assessment in such 
patients should continue until study treatment discontinuation. 
Second Progression 
Following the first progression assessed by IRC, patients will be assessed every 12 weeks 
(± 7 days) for a second progression (using the patient’s status at the first progression as reference 
for assessment of second progression). A patient’s second progression status is defined according 
to local standard clinical practice and may involve any of: objective radiological, symptomatic 
progression or death. Measurements per RECIST v1.1 will not be collected for assessment of 
PFS2. The date of PFS2 assessment and investigator’s opinion of progression status (progressed 
or non-progressed) at each assessment will be recorded in the eCRF. 
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7.7. 
Pharmacokinetic and Antidrug Antibody Testing 
Checkpoint inhibitors may elicit an immune response. Patients with signs of any potential 
immune response will be closely monitored. Validated screening and confirmatory assays will be 
employed to detect ADA at multiple timepoints throughout the study. In addition, blood samples 
will be collected for characterization of ociperlimab and tislelizumab PK at the timepoints 
specified in the Schedule of Assessments (Appendix 1). 
PK and ADA assays of ociperlimab and tislelizumab will be managed through a central 
laboratory. Serum samples will be assayed for ociperlimab and tislelizumab concentrations using 
validated immunoassays. 
• ADA assays: serum samples will be tested for the presence of ADAs to ociperlimab 
and tislelizumab using validated immunoassays. 
• PK assays: serum samples will be assayed for ociperlimab and tislelizumab serum 
concentrations using validated immunoassays. 
Refer to the laboratory manual for instructions regarding sample collection, handling, labeling, 
storage, and shipping of laboratory samples. 
7.8. 
Biomarker 
Shipping, storage, and handling of blood samples as well as archival tumor and/or fresh tumor 
tissues for the assessment of biomarkers will be handled by a central laboratory. Refer to the 
laboratory manual for details of sample handling and the Schedule of Assessments (Appendix 1) 
for timepoints. 
Tissue-based biomarkers, including but not limited to the expression of TIGIT, CD226, CD155, 
CD112, and PD-L1, GEP, TMB, MSI, gene mutation profiles, and TILs at baseline and at 
disease progression/reoccurrence will be tested. (Note: For the sites in mainland China, tissues 
will be obtained to test the expression of TIGIT, CD226, CD155, CD112, and PD-L1, GEP, 
TMB, MSI, gene mutation profiles, and TILs at baseline and at disease 
progression/reoccurrence). 
Patients are required to provide tumor tissues (archival tumor tissues collected before cCRT 
[FFPE blocks containing tumor [preferred] or approximately 15 [≥ 6] freshly cut unstained FFPE 
slides]). If archival tumor tissues are not available, a fresh tumor biopsy is required prior to the 
first dose of cCRT. Acceptable fresh biopsy samples include core needle biopsies for deep tumor 
tissue or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or 
mucosal lesions. 
If clinically feasible, it is highly recommended to obtain a tumor biopsy at the time of disease 
progression to explore the immune- or tumor-related biomarkers and biological changes that 
might drive disease progression or acquired resistance to ociperlimab and tislelizumab. Blood 
samples must be collected at C1D1 (predose) for a blood-based biomarker test. Optional blood 
will be collected at C3D1 (predose), C4D1 (predose), and at the EOT Visit after the disease 
progression (Appendix 1). All these blood samples will be collected to explore the association of 
blood-based biomarkers with response, resistance, and prognosis. (Note: Blood-based 
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biomarkers, including ctDNA, TMB, MSI, EVs and gene mutational profiles, will be explored in 
the blood samples which will be collected in the sites in China mainland). 
Written informed consent is required for any of the fresh tumor biopsies and blood sample 
collection. Tumor tissue should be of good quality in terms of total and viable tumor content. 
Fine needle aspiration, brushing, cell pellets from pleural effusion, and lavage samples are not 
acceptable. 
7.9. 
Health-Related Quality of Life 
Patients will be asked to complete 5 PROs, that include the EORTC QLQ-C30 (Appendix 7), 
EORTC QLQ-LC13 (Appendix 8), EQ-5D-5L questionnaires (Appendix 9), PGI-S 
(Appendix 10), and PRTSE (Appendix 11) before any clinical activities are performed during 
on-study clinic visits according to the schedule in Appendix 1. The questionnaires will be 
provided in the patient’s preferred language. 
7.10. 
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 any study treatment is given 
unless otherwise noted. Laboratory results must be reviewed before dosing. 
If the timing of a protocol-mandated study visit coincides with a holiday, weekend, or other 
events, the visit should be scheduled for the nearest feasible date (the visit window is provided in 
Appendix 1), with subsequent visits conducted according to the planned schedule every 3 weeks 
(Arm A and Arm B) or every 2 or 4 weeks (Arm C) from C1D1. 
7.11. 
Unscheduled Visits 
Unscheduled visits may be performed at any time at the patient’s or the investigator’s request 
and may include vital signs/physical examination; ECOG Performance Status; AE review; 
concomitant medications and procedures review; radiographic assessments; disease-related 
constitutional symptoms; and 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 PD, 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 Treatment 
8.1.1. 
Risks Associated With Ociperlimab and Tislelizumab 
Ociperlimab and tislelizumab are investigational agents that are currently in clinical 
development. Limited safety data are available in patients and the full safety profile has not been 
characterized. 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 8.7.3. 
Ociperlimab-mediated TIGIT inhibition may increase the risk of imAEs. However, no apparent 
immunotoxicity, or toxicity in general, has been observed in animal models treated with 
ociperlimab. Furthermore, in the absence of activation, peripheral effector T cells do not 
typically express TIGIT, thereby minimizing any potential negative additive affect as it relates to 
peripheral immune tolerance. 
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 workup procedures for suspected imAEs are provided in 
Appendix 12. 
8.1.2. 
Risks Associated With Durvalumab 
Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that binds to 
PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80. The PD-L1/PD-1 pathway is 
involved in peripheral tolerance; therefore, such therapy may increase the risk of imAEs similar 
to PD-L1/PD-1 class drugs, specifically the induction or enhancement of autoimmune 
conditions. The risks are immune-mediated pneumonitis, hepatitis, colitis, endocrinopathies, 
nephritis, dermatologic reactions; and other immune-mediated adverse reactions (incidence of 
less than 1%) such as aseptic meningitis, hemolytic anemia, immune thrombocytopenic purpura, 
myocarditis, myositis, and ocular inflammatory toxicity, including uveitis and keratitis. Besides 
immune-related side effects, and infusion-related reactions are common. Overall infection is also 
very common. 
Refer to the durvalumab prescribing information for details. 
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 
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nonclinical/clinical data from other TIGIT and PD-L1/PD-1 inhibitors, were considered. 
Specifically, patients 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 first dose 
of the study treatment are excluded from the study. Refer to 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, 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 8), physical examinations, laboratory measurements 
(hematology, clinical chemistry, etc), 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 autoimmune conditions or infection. 
At the start of each cycle, study treatment(s) will be provided only after clinical laboratory 
results have been reviewed. Administration of study treatment will be performed in a setting 
where emergency medical equipment and staff who are trained to respond to medical 
emergencies are available (for additional information, see Section 5.2). 
Serum samples will be drawn for determination of ADAs to ociperlimab and tislelizumab in all 
randomized patients. 
Investigators are instructed to report all AEs (includes 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 8.7. 
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 study 
treatment, whether considered related to study treatment or not. 
Examples of AEs include: 
• Worsening of a chronic or intermittent pre-existing condition, including an increase in 
severity, frequency, duration, and/or has an association with a significantly worse 
outcome 
• New conditions detected or diagnosed after study treatment administration even 
though the condition might 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 
treatment 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 before 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 NCI-CTCAE v5.0. 
Toxicities that are not specified in 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 
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-
care, activities of daily living 
• 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 treatment and the 
occurrence of each AE or SAE using best clinical judgement. Alternative causes, such as natural 
history of the underlying diseases, concomitant therapy, and other risk factors, and the temporal 
relationship of the AE or SAE to the study treatment will be considered and investigated. The 
investigator should consult the Tislelizumab Investigator’s Brochure, Ociperlimab Investigator’s 
Brochure, durvalumab prescribing information in the determination of his/her assessment. 
There may be situations when an SAE has occurred, and the investigator has minimal 
information to include in the initial report to the sponsor. However, it is very important that the 
investigator always assesses causality for every SAE before transmission of the SAE report to 
the sponsor because the causality assessment is 1 of the criteria used when determining 
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regulatory reporting requirements. The investigator may change his/her opinion of causality 
considering follow-up information, amending the SAE report accordingly. 
The causality of each AE should be assessed and classified by the investigator as “related” or 
“not related.” An AE is considered related if there is “a reasonable possibility” that the AE may 
have been caused by the study treatment (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 treatment 
• Biological plausibility 
An AE should be considered “related” to study treatment if any of the following are met; 
otherwise, the event should be assessed as “not related”: 
• There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out 
• There is evidence to suggest a causal relationship, and the influence of other factors is 
unlikely 
• There is some evidence to suggest a causal relationship (eg, the AE occurred within a 
reasonable time after administration of the study treatment[s]). 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 screen failure patients) 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, 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 that 
worsen significantly during the study. The definition of clinically significant is based on the 
judgement 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 AE 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 AE 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 was 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 SAEs: 
• Hospitalization for elective treatment of a pre-existing 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 study drug’s reference safety information [RSI]) and 
meets the definition of an serious adverse drug reaction (SADR), the specificity or severity of 
which is not consistent with those noted in Tislelizumab Investigator’s Brochure, Ociperlimab 
Investigator’s Brochure, durvalumab prescribing information. 
8.6. 
Timing, Frequency, and Method of Capturing Adverse Events and 
Serious Adverse Events 
8.6.1. 
Adverse Event Reporting Period 
After the main ICF has been signed, during the screening period, only SAEs should be collected 
and reported to the sponsor. 
After initiation of study treatment, all AEs and SAEs, regardless of relationship to study 
treatment, will be reported until either 30 days after last dose of study treatment or 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, tislelizumab, or durvalumab, 
regardless of whether the patient starts a new anticancer therapy. All SAEs considered related to 
the study treatment(s) 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 8. For the follow-up period 
for AEs, see Section 8.3.4. For the definition of treatment-emergent adverse events (TEAEs), see 
Section 9.3.2. 
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Table 8:  
Guidance for Duration of Recording New or Worsening Adverse Events in 3 
Arms 
Event Type 
Record new or worsening events that occur during this period 
Begin 
End 
SAEsa 
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 
treatment 
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 
treatment 
Up to 90 days after last dose (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 treatment(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 9. 
Table 9: 
Time Frames and Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee 
 
Time frame for 
sending initial 
report 
Documentation 
method 
Time frame for 
sending 
follow-up 
report 
Documentation 
method 
Reporting 
method 
All SAEs 
Within 24 hours 
after first 
knowledge of 
the AE 
SAE report 
As expeditiously 
as possible 
SAE report 
Email or fax 
SAE form or 
pregnancy form 
Abbreviations: AE, adverse event; SAE, serious adverse event. 
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, he/she is to report the 
information to the sponsor within 24 hours, as outlined above in Section 8.6.2.1. The SAE report 
will always be completed as thoroughly as possible, including all available details of the event, 
and forwarded to the sponsor or designee within the designated time frames. 
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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 promptly 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 drug 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, tislelizumab, and durvalumab 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 
PD, which is expected in this study population and 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 not usually considered an AE. If the only information available is death 
and the cause of death is unknown, then the death is reported as an event (eg, “death,” “death of 
unknown cause,” or “death unexplained”). 
8.6.6. 
Pregnancies 
If a female patient or the female partner of a male patient becomes pregnant while the patient is 
receiving study treatment or within 120 days after the last dose of ociperlimab and tislelizumab 
in Arm A or tislelizumab in Arm B, or within 90 days after the last dose of durvalumab in 
Arm C, a pregnancy report form must 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 always be reported as an 
SAE. Similarly, any congenital anomaly/birth defect in a child born to a patient exposed to the 
study treatment 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 reference safety information documents: 
• Tislelizumab Investigator’s Brochure 
• Ociperlimab Investigator’s Brochure 
• Durvalumab prescribing information 
8.6.8. 
Assessing and Recording Immune-Mediated Adverse Events 
Since treatment with anti-PD-1 or immune checkpoint inhibitors can cause autoimmune 
disorders, AEs considered by the investigator to be immune-mediated (see Section 8.7.3) should 
be classified as imAEs and identified as such on the eCRF AE page until Day 90 after treatment 
discontinuation. 
Investigators should consult the guidance on diagnostic evaluation and management of imAEs, 
which are commonly seen with immune checkpoint inhibitors, in Appendix 12. 
An extensive list of potential imAEs appears in Section 8.7.3, Table 11. 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 12. 
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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 each as a separate AE in eCRF and 
identified as an infusion-related reaction. Refer to the eCRF completion guidelines for details. 
8.7. 
Management of Adverse Events of Special Interest 
As a routine precaution, after infusion of ociperlimab and tislelizumab in Arm A on Day 1 of 
Cycle 1 and Cycle 2, patients must be monitored for at least 2 hours afterwards in an area with 
resuscitation equipment and emergency agents; similarly, after infusion of tislelizumab in Arm B 
on C1D1 and C2D1, patients will be monitored for ≥ 1 hour. From Cycle 3 onward, at least a 
60-minute monitoring period is required in an area with resuscitation equipment and emergency 
agents for Arm A, and for Arm B, the monitoring period is at least 30 minutes. 
The management for infusion-related reactions, severe hypersensitivity reactions, and imAEs 
according to the NCI-CTCAE criteria are outlined in the following subsections. 
8.7.1. 
Infusion-Related Reactions 
Patients should be closely monitored for infusion-related reactions. Immediate access to an 
Intensive Care Unit or equivalent environment and appropriate medical therapy (including 
epinephrine, corticosteroids, intravenous antihistamines, bronchodilators, and oxygen) must be 
available to treat infusion-related reactions. 
Treatment modification for symptoms of infusion-related reactions due to study drugs is 
provided in Table 10. 
Table 10: 
Treatment Modification for Symptoms of Infusion-Related Reactions Due to 
Study Drugs 
NCI-CTCAE grade 
Treatment modification for Ociperlimab and 
Tislelizumab 
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. 
Grade 2 - moderate 
Therapy or infusion interruption indicated but 
responds promptly to symptomatic treatment 
(eg, antihistamines, nonsteroidal anti-inflammatory 
drugs, narcotics, intravenous fluids); prophylactic 
medications indicated for ≤ 24 hours. 
Stop infusion. Infusion may be resumed at 50% of 
previous rate once infusion-related reactions has resolved 
or decreased to Grade 1 in severity. Any worsening is 
closely monitored. Proper medical management should be 
instituted as described in the text following this table. 
Grade 3 – severe 
Prolonged (eg, not rapidly responsive to 
symptomatic medication and/or brief interruption 
of infusion); recurrence of symptoms following 
Immediately stop the infusion. Proper medical 
management should be instituted as described in the text 
following this table. 
The patient should be withdrawn from the study treatment. 
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NCI-CTCAE grade 
Treatment modification for Ociperlimab and 
Tislelizumab 
initial improvement; hospitalization indicated for 
clinical sequelae. 
Grade 4 – life-threatening 
Life-threatening consequences; urgent intervention 
indicated. 
Immediately stop the infusion. Proper medical 
management should be instituted as described in the text 
following this table. 
The patient should be withdrawn from the study treatment. 
Hospitalization is recommended. 
Abbreviations: NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events. 
In Arm A and Arm B, once the ociperlimab or tislelizumab infusion rate has been decreased by 
50% or suspended due to an infusion-related reaction, it must remain decreased for all 
subsequent infusions. If the patient has a second infusion-related reaction (≥ Grade 2) on the 
slower infusion rate, the infusion should be discontinued, and the patient should be withdrawn 
from ociperlimab and tislelizumab 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 
acetaminophen and/or 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, the patient should receive oral 
pre-medication with an antihistamine (eg, diphenhydramine or equivalent) and an antipyretic 
(eg, paracetamol or equivalent), and the patient 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 antihistamine, antipyretic, glucocorticoids, epinephrine, bronchodilators, and 
oxygen. 
8.7.2. 
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 (United Kingdom) 
(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 stopped 
immediately, and the patient discontinued from the study. 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 are 
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 patients will be administered epinephrine injection and dexamethasone infusion if 
hypersensitivity reaction is observed, and then the patient should be placed on monitor 
immediately and an Intensive Care Unit 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, 500 mg naproxen sodium) may be 
administered 2 hours before and 8 hours after the start of each dose of study treatment. 
Alternative treatments for fever (ie, paracetamol) may be administered to the patient at the 
discretion of the investigator. 
8.7.3. 
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, PD, or other neoplastic causes) with appropriate diagnostic 
tests that may include but are not limited to serologic, immunologic, and histologic (biopsy) data. 
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, the imAE indicator on the eCRF AE page should be checked. 
A list of potential imAEs is shown below in Table 11. All conditions similar to those listed 
should be evaluated in patients receiving ociperlimab and tislelizumab in Arm A, tislelizumab in 
Arm B to determine whether they are immune-mediated. 
Recommendation for diagnostic evaluation and management of imAEs is based on ESMO and 
American Society of Clinical Oncology guidelines (Haanen et al 2017; Brahmer et al 2018) and 
common immune-mediated toxicities are detailed in Appendix 12. For any AEs not included in 
Appendix 12, refer to the American Society of Clinical Oncology Clinical Practice Guideline 
(Brahmer et al 2018) for further guidance on diagnostic evaluation and management of 
immune-mediated toxicities. 
Table 11: 
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 
Eye 
episcleritis; conjunctivitis; iritis/uveitis 
Musculoskeletal 
arthritis; arthralgia; myalgia; myasthenic syndrome/myasthenia gravis; myositis 
Blood 
anemia; leukopenia; thrombocytopenia 
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Body system affected 
Events 
Renal 
interstitial nephritis; glomerulonephritis; acute renal failure 
Cardiac 
pericarditis; myocarditis; heart failure 
Neurologic 
encephalitis; meningitis; meningoradiculitis; meningoencephalitis; Guillain-Barre 
syndrome; neuropathy 
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase. 
Recommendations for managing imAEs are detailed in Appendix 12. 
If a toxicity does not resolve to ≤ Grade 1 within 12 weeks, study treatment should be 
discontinued after consultation with the sponsor. Patients who experience a recurrence of any 
event at the same or higher severity grade with rechallenge should permanently discontinue 
treatment. 
8.7.4. 
Adverse Events of Special Interest of Durvalumab 
Infusion-related reaction, infection, and imAEs are of special interest with durvalumab. Please 
refer to durvalumab prescribing information which has been approved by local health authority. 
Appendix 15 provides recommended dosage modifications from the durvalumab prescribing 
information approved by the US FDA for reference. 
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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). 
All the analyses defined in this section apply to the patients enrolled within the updated PA 2.0 
only, unless otherwise specified. 
9.1. 
Statistical Analysis 
The following descriptive statistics will be used to summarize the trial data on the basis of their 
nature unless otherwise specified: 
• Continuous variables: number of nonmissing observations (N), mean, standard 
deviation, median, minimum, and maximum 
• Categorical variables: frequencies and percentages 
• Time-to-event variables: number of nonmissing observations (N), median, minimum 
and maximum. Kaplan-Meier event rates may also be provided if applicable for 
specific time to event variables 
There are a maximum of 2 PFS analyses for the primary efficacy endpoints. Any additional data 
for ongoing participants following the final analysis will be further summarized in a final study 
report. 
9.1.1. 
Randomization Methods 
As discussed in Section 7.3.2, patients will be randomized using the IRT system for this study by 
permuted block stratified randomization with stratification factors of age (< 65 years versus 
≥ 65 years), PD-L1 expression on TC (≥ 50% versus < 50% ), and histology (squamous versus 
nonsquamous). The PD-L1 expression status will be closely monitored. Enrollment of patients 
with expression of PD-L1 1% to 49% of TC will be stopped as necessary through the IRT system 
upon reaching around 50% to ensure the population are close to the natural PD-L1 expression 
prevalence. 
9.1.2. 
Analysis Sets 
The Intent-to-treat (ITT) Analysis Set includes all randomized patients. Patients will be analyzed 
according to their treatment assigned at randomization. This will be one of the primary analysis 
sets for demography and efficacy analyses. 
The PD-L1 ≥ 50% Analysis Set is a subset of the ITT Analysis Set including patients with ≥ 50% 
of TCs with membrane positivity for PD-L1 at any intensity above background staining using 
VENTANA PD-L1 (SP263) assay. Patients will be analyzed according to their treatment 
assigned at randomization. This will be the other primary analysis set for demography and 
efficacy analyses. 
The Safety Analysis Set includes all randomized patients who received ≥ 1 dose of study 
treatment. This will be the primary analysis set for all safety analyses. 
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PD-L1 ≥ 50% Safety Analysis Set is a subset of the Safety Analysis Set including patients whose 
PD-L1 ≥ 50%. This will be the analysis set for the safety analyses in patients with PD-L1 ≥ 50%. 
The PK Analysis Set includes all patients who received any dose of any component of study 
treatment per the protocol, for whom any quantifiable postdose PK data are available. 
The Immunogenicity Analysis Set includes all patients who received any dose of any component 
of study treatment for whom both baseline ADA result and at least 1 postbaseline ADA result are 
available. 
9.1.3. 
Patient Disposition 
The number of patients randomized, treated, and discontinued from the study treatment and/or 
study and those with critical protocol deviations will be counted. The primary reason for study 
treatment 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) as of 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 will be summarized using descriptive statistics in 
the ITT Analysis Set. Continuous variables include age, weight, vital signs, time since initial 
cancer diagnosis, etc. Categorical variables include sex, ECOG Performance Status, 
region/country, race, etc. 
9.1.5. 
Prior and Concomitant Medications 
Medications will be coded using the World Health Organization Drug Dictionary drug codes and 
further coded to the appropriate Anatomical Therapeutic Chemical code indicating therapeutic 
classification. Prior medications will be defined as medications that stopped before the day of 
first dose of study treatment. Concomitant medications will be defined as medications that 
1) started before the first dose of study treatment and were continuing at the time of the first dose 
of study treatment, or 2) started on or after the date of the first dose of study treatment up to 
30 days after last dose of study treatment. 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 study 
treatment regardless of whether or not the patient starts a new anticancer therapy. Prior and 
concomitant medications will be summarized and listed by drug and drug class. 
9.2. 
Efficacy Analyses 
The familywise type I error will be strongly controlled at 1-sided level of 0.025. PFS analysis in 
Arms A and C will be carried out in the PD-L1 ≥ 50% Analysis Set first. A formal statistical test 
of PFS in the ITT Analysis Set will be performed only if the PFS analysis in the PD-L1 ≥ 50% 
Analysis Set is statistically significant favoring ociperlimab + tislelizumab. If the null hypothesis 
for PFS between Arm A and Arm C in the ITT Analysis Set is rejected, the secondary endpoint 
OS in PD-L1 ≥ 50% and ITT Analysis Sets between Arm A and Arm C will be tested 
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sequentially. There is one interim analysis planned at around 75% information fraction of PFS 
events in each analysis set across Arm A and C. 
See Figure 4 for the fixed-sequence testing strategy diagram of the study. 
Figure 4: 
Fixed-Sequence Testing Strategy for Primary and Key Secondary Endpoints 
 
 
Abbreviations: PFS, progression-free survival; OS, overall survival. 
9.2.1. 
Primary Efficacy Analysis 
9.2.1.1. 
Primary Estimand 
Primary estimand is defined in Section 2.2. 
9.2.1.2. 
Primary Analysis for Primary Estimand 
PFS by IRC comparison between Arm A and Arm C in PD-L1 ≥ 50% and ITT Analysis 
Set: 
The null hypothesis to be tested: HR (A vs C) ≥ 1 
against the alternative: HR (A vs C) < 1 
The null hypothesis will be tested using a log-rank test, stratified by stratification factors at 
randomization (age, PD-L1 expression [in ITT Analysis Set only] and histology), in the 
PD-L1 ≥ 50% and ITT analysis sets sequentially, as described above. 
PFS distribution will be estimated using the Kaplan-Meier method in the PD-L1 ≥ 50% and ITT 
Analysis Set. 
The median PFS and the cumulative probability of PFS at every 3 months including PFS-6m and 
PFS-12m if estimable, will be calculated for each treatment arm and presented with 2-sided 95% 
CIs. 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 PFS including the 
treatment arm as a factor and stratification factors at randomization (age, PD-L1 expression [in 
ITT only] and histology) as strata. From this model, the HR of PFS will be estimated and 
presented with a 2-sided 95% CI. 
9.2.1.3. 
Handling of Missing Values Not Related to Intercurrent Event 
PFS will be censored at the last adequate tumor assessment for the following: 
• patients without disease progression or death as of the clinical cutoff date 
1 
 
 
 
1 
1 
Primary 
Primary 
Secondary 
 
Secondary 
𝐻1 PFS in PD-L1 ≥ 50% 
analysis set 
(Arm A vs. C) 
α = 2.5% 
 
𝐻2 PFS in ITT 
(Arm A vs. C) 
α = 0 
 
𝐻3 OS in PD-L1 ≥ 50% 
analysis set 
(Arm A vs. C) 
α = 0 
 
𝐻4 OS in PD-L1 ITT 
(Arm A vs. C) 
α = 0 
 
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• patients who, as of the clinical cutoff date, have withdrawn consent for the study or 
are lost to follow-up 
• patients with a PFS event (PD or death) after ≥ 2 missing or non-adequate tumor 
assessments 
PFS will be censored at the date of randomization if no baseline or any post-baseline tumor 
assessments and without death ≤ 19 weeks after randomization. 
The above text follows the PFS censoring rule specified in Tables C1 and C2 of Appendix C of 
the FDA “Guidance for industry clinical trial endpoints for the approval of non-small cell lung 
cancer drugs and biologics (2015)” (US FDA 2015). 
9.2.1.4. 
Sensitivity Analyses/Supplementary for Primary Endpoint/Estimand 
Sensitivity analyses (eg, unstratified Cox model or PFS per investigator assessment) and 
supplementary analyses (eg, ignoring subsequent anticancer therapy when driving PFS) may be 
considered and will be detailed in the SAP. 
9.2.2. 
Efficacy Analysis for Key Secondary Estimand 
9.2.2.1. 
Definition of Key Secondary Estimand 
Key secondary estimand in terms of OS is defined in Section 2.3. 
9.2.2.2. 
Primary Analysis for Key Secondary Estimand 
OS comparison between Arm A and Arm C in PD-L1 ≥ 50% and ITT Analysis Sets: 
The null hypothesis to be tested: HR (A vs C) ≥ 1 
against the alternative: HR (A vs C) < 1 
The null hypothesis will be tested using a log-rank test, stratified by stratification factors at 
randomization (age, PD-L1 expression [in ITT only] and histology). OS test in PD-L1 ≥ 50% 
and ITT analysis set will be conducted sequentially at 1-sided significance level of 0.025, after 
both null hypotheses of PFS are rejected. 
OS distribution will be estimated using the Kaplan-Meier method in the PD-L1 ≥ 50% and ITT 
Analysis Sets. 
The median OS and the cumulative probability of OS at every 6 months including OS-6m and 
OS-12m if estimable, will be calculated for each treatment arm and presented with 2-sided 95% 
CIs. 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 the treatment arm as a factor and stratification factors at randomization (age, PD-L1 
expression [in ITT only] and histology) as strata. From this model, the HR of OS will be 
estimated and presented with a 2-sided 95% CI. 
For patients who are alive by the clinical cutoff date, OS will be censored at the last known alive 
date. Detailed derivation and imputation rule of last known alive date will be defined in the SAP. 
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9.2.2.3. 
Sensitivity Analyses/Supplementary for Key Secondary Endpoint/Estimand 
Sensitivity analyses (eg, unstratified Cox model) and supplementary analyses (eg, Max-Combo) 
may be considered and will be detailed in the SAP. 
9.2.3. 
Other Secondary Efficacy Analysis 
Overall Response Rate (ORR) 
ORR by both the IRC and the investigator per RECIST v1.1 in both PD-L1 ≥ 50% and ITT 
Analysis Set will be summarized, between Arm A versus Arm C. Two-sided 95% CI of ORR 
will be calculated using the Clopper-Pearson method in the ITT analysis set. The odds ratio for 
ORR between treatment arms will be calculated using the Cochran-Mantel-Haenszel (CMH) 
method adjusting for stratification factors at randomization (age, PD-L1 expression [in ITT only] 
and histology), and its two-sided 95% CIs will be calculated. Mantel-Haenszel common risk 
difference in ORR will be estimated, with its 95% confidence interval constructed by a normal 
approximation and Sato’s variance estimator. The proportion for each of the response categories 
including CR will be presented by treatment arm. 
Duration of Response (DOR) 
DOR will be analyzed among the responders in PD-L1 ≥ 50% and ITT Analysis Set based on 
assessment by the IRC and the investigator, between Arm A versus Arm C. All the censoring 
rules for PFS primary analysis would be applied to DOR as well. 
The Median and other quantiles of DOR and the cumulative probability of DOR at every 
3 months if estimable, will be calculated for each treatment arm and presented with 2-sided 95% 
CIs. 
Time to Death or Distant Metastasis (TTDM) 
TTDM by both the IRC and the investigator per RECIST v1.1 in PD-L1 ≥ 50% and ITT Analysis 
Set between Arm A versus Arm C will be analyzed. The detailed censor rule will be defined in 
the SAP. 
Progression-free survival after next line of treatment (PFS2) 
PFS2 in PD-L1 ≥ 50% and ITT Analysis Set, between Arm A versus Arm C, will be analyzed 
similarly as the primary analysis of the primary estimand. The detailed censor rule will be 
defined in the SAP. 
Health-Related Quality of Life (HRQoL) 
HRQoL will be analyzed and compared between Arm A versus Arm C in the PD-L1 ≥ 50% and 
ITT Analysis Sets via the postbaseline scores of EORTC QLQ-C30’s Global Health Status/QoL 
(GHS), functional scales and symptom scores and symptoms single item scores, EORTC 
QLQ-LC13’s index score and symptoms scales and single item scores, and EQ-5D-5L 
descriptive scale scores as well as the Visual Analogue Scale (VAS) scores. Observed values and 
changes from baseline will be summarized using descriptive statistics. Compliance rates 
(adjusted completion rates) will be reported for all the three questionnaires at each PRO data 
collection timepoint. 
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A mixed model repeated measure (MMRM) will be performed to evaluate and compare changes 
from baseline between Arm A and Arm C at the prespecified key visits Week 25 and 43, in the 
PD-L1 ≥ 50% and ITT Analysis Sets. The prespecified PRO endpoints of GHS used will be 
physical function, fatigue domains of QLQ-C30, dyspnea, coughing, hemoptysis and pain in 
chest, pain in arms and shoulders, and peripheral neuropathy domains of QLQ-LC13. The key 
clinical cycles are clinically justified as they both fall after the first and second scheduled tumor 
assessments. 
Time to deterioration in the PRO endpoints will be estimated using Kaplan-Meier method 
between Arm A versus Arm B in the PD-L1 ≥ 50% and ITT Analysis Sets. Deterioration 
thresholds will be based the (Osoba et al 1998) definition and will be derived from the 
published 10-point EORTC threshold. Other sensitivity analysis would explore a secondary 
deterioration threshold using an anchor-based meaningful within-patient change (MWPC) 
framework as needed. 
PD-L1 and TIGIT expression 
PD-L1 and TIGIT expression will be evaluated before, after study treatment, or at disease 
progression/reoccurrence, and their association with clinical efficacy will be assessed when 
appropriate and data allow. 
9.2.4. 
Exploratory Efficacy Analyses 
Analyses of PFS, ORR, DOR, TTDM assessed by IRC and investigator per RECIST v1.1, OS, 
PFS2, and HRQoL in the PD-L1 ≥ 50% and ITT Analysis Sets, will also be conducted between 
Arm A versus Arm B. The comparisons are descriptive only and aim to evaluate the contribution 
of Ociperlimab as a component of the study. 
Potential predictive markers, including but not limited to CD226, CD155, CD112, GEP, ctDNA, 
TMB, MSI, gene mutation profiles, EVs and TILs may be assessed when appropriate. 
Compliance rates and scores of the PGI-S and PRTSE will be analyzed descriptively. 
9.2.5. 
Subgroup Analyses 
Subgroup analysis of PFS and OS will be descriptively conducted to assess the consistency of 
treatment effect across various subgroups. Details will be provided in the SAP. 
9.3. 
Safety Analyses 
Safety will be assessed by monitoring and recording of all AEs graded by NCI-CTCAE v5.0. 
Laboratory values (eg, hematology, clinical chemistry, urinalysis), vital signs, ECGs, and 
physical examinations will also be used to assess safety profile. Descriptive statistics will be 
used to analyze all safety data in the SAS. 
9.3.1. 
Extent of Exposure 
Extent of exposure to each study drug will be summarized descriptively as the number of cycles 
received (number and percentage of patients), duration of exposure, cumulative total dose 
received per patient (mg), dose intensity, and relative dose intensity. 
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The number (percentage) of patients with dose interruption, dose delay, and drug discontinuation 
because of AEs will be summarized for each study treatment. Reasons for above dose 
modifications and discontinuation will be summarized as well. 
Patient data listings will be provided for all dosing. 
9.3.2. 
Adverse Events 
The AE verbatim descriptions (investigator’s description from the eCRF) will be classified into 
standardized medical terminology using the Medical Dictionary for Regulatory Activities 
(MedDRA). AEs will be coded to MedDRA (Version 24 or higher) lowest level term closest to 
the verbatim term, Preferred Term (PT), and primary System Organ Class (SOC). 
A TEAE is defined as an AE that had an onset date or a worsening in severity from baseline 
(pretreatment) on or after the first dose of study treatment up to 30 days following study 
treatment discontinuation or initiation of the first new systemic anticancer therapy after the last 
study treatment, whichever occurs first. Only those AEs that were treatment-emergent will be 
included in TEAE 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 treatment and up to 90 days from the last dose of study treatment, 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 TEAE. All imAEs will be reported 
separately. All AEs, treatment-emergent or otherwise, will be presented in patient data listings. 
COVID-19 related AEs will be summarized separately. 
The incidence of TEAEs will be reported as the number (percentage) of patients with TEAEs by 
SOC and PT. A patient will be counted only once by the highest severity grade per NCI-CTCAE 
v5.0 or higher within an SOC and PT, even if the patient experienced > 1 TEAE within a specific 
SOC and PT. 
The number (percentage) of patients with TEAEs will also be summarized by relationship to the 
study treatment. Treatment-related AEs include those events considered by the investigator to be 
related to study treatment or with missing assessment of the causal relationship. 
SAEs, deaths, ≥ Grade 3 TEAEs, imAEs, treatment-related TEAEs, and TEAEs that led to 
treatment discontinuation, dose interruption, or dose delay will be summarized. 
9.3.3. 
Laboratory Analyses 
Clinical laboratory (eg, hematology, clinical chemistry, coagulation, and urinalysis) 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 included in the clinical study report for this protocol. 
Descriptive summary statistics (eg, n, mean, standard deviation, median, minimum, and 
maximum for continuous variables; 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 change. 
Laboratory parameters that are graded in NCI-CTCAE v5.0 or higher will be summarized by 
NCI-CTCAE grade. In the summary of laboratory parameters by NCI-CTCAE grade, parameters 
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with NCI-CTCAE grading in both high and low directions (eg, calcium, glucose, magnesium, 
potassium, and sodium) will be summarized separately. 
9.3.4. 
Vital Signs 
Descriptive statistics for vital sign parameters (systolic and diastolic blood pressure, pulse rate, 
temperature, and weight) and changes from baseline will be presented by visit. Vital signs will 
be listed by patient and visit. 
9.4. 
Pharmacokinetic Analyses 
Pharmacokinetic samples will be collected in this study as outlined 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, including population PK analyses and exposure-response (efficacy or 
safety endpoints) analyses may be conducted as appropriate and the results of such analyses may 
be reported separately from the CSR. 
9.5. 
Immunogenicity Analyses 
Samples to assess anti-ociperlimab and anti-tislelizumab antibodies will be collected only in 
patients who receive study drugs and at sites that are able to adequately perform sampling, 
handling, and processing as outlined in the laboratory manual. 
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. 
9.6. 
Other Exploratory Analyses 
Summary statistics will be provided for exploratory biomarkers including but not limited to 
expression of CD226, CD155, CD112, GEP, ctDNA, TMB, MSI, gene mutation profiles, EVs, 
and TILs in tumor tissues and/or peripheral blood when appropriate and data allow. 
An exploratory analysis of the potential correlation of these tumor tissue or blood-based 
biomarkers with response, resistance, and prognosis will be performed to understand disease 
pathobiology and explore potential predictive biomarkers when appropriate and data allow. 
Summary of descriptive analysis will be provided for PGI-S and PRTSE in Arm A versus 
Arm C, among patients with PD-L1 ≥ 50% and ≥ 1%. 
Patients randomized under PA 1.0 (Concurrent Part) 
Analyses of PFS, ORR, DOR assessed by investigator per RECIST v1.1, OS, TTDM and 
HRQoL among randomized patients in Concurrent Part. The comparisons across 3 arms are 
descriptive only. In addition, for patients finish definitive cCRT treatment and receive at least 1 
consolidation treatment, their PFS assessed by the investigator, will be analyzed separately. 
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Safety profile will be assessed among randomized patients who received at least one dose of 
study treatment in the Concurrent Part. 
The cutoff for primary analyses of the Concurrent Part will be approximately 14 months after 
last patient randomized. 
9.7. 
Sample Size Consideration 
The sample size calculation is based on the number of events regarding primary efficacy 
analyses of PFS between Arm A and Arm C for both comparisons in the PD-L1 ≥ 50% and ITT 
Analysis Sets. Exponential distribution is assumed for PFS. To demonstrate efficacy with regards 
to PFS, the estimates of the number of events required are based on the following assumptions: 
1. The randomization ratio for Arm A versus Arm B versus Arm C is 3:1:3. 
2. A steady-state enrollment rate of 20 patients per month and an enrollment ramp-up 
duration of 12 months. 
3. PFS evaluation dropout rate of 5% per 12 months. 
4. The prevalence of PD-L1 ≥ 50% among ITT is approximately 50%. Enrollment of 
patients with PD-L1 < 50% might be stopped, if necessary, to ensure that the percentage 
of PD-L1 ≥ 50% is no less than 50% of the ITT analysis set. 
5. Sequential testing procedure is implemented to control overall alpha at 2.5% one-sided. 
PFS analysis between Arm A versus Arm C in the PD-L1 ≥ 50% analysis set will be 
performed first, and PFS analysis between Arm A versus Arm C in the ITT analysis set 
will be carried out only if the PFS analysis in the PD-L1 ≥ 50% analysis set is statistically 
significant favoring Arm A. 
6. One interim analysis is planned when approximately 75% of final PFS events have 
occurred for each PFS primary endpoint, using Lan-DeMets O’Brien-Fleming 
approximation spending function. 
7. Median PFS in Arm C within both PD-L1 ≥ 50% and ITT analysis set is 24.9 months. 
Table 12 below summarizes the statistical assumption and power in the sample size calculation 
in Arm A and C; and the total sample size of the study would be 700. 
Table 12: Statistical assumptions, sample size and power 
1-sided 
Alpha 
Analysis 
Set 
HR  
(A vs C) 
mPFS 
in A 
mPFS 
in C 
Accrual 
Duration 
Sample 
Size in 
A+C 
# Events 
at FA in 
A+C 
Power 
0.025 
PD-L1 
≥ 50% 
0.6 
41.5 
24.9 
41.3 
300 
141 
85.2% 
0.025 
ITT 
0.7 
35.6 
24.9 
41.3 
600 
288 
85.1% 
Abbreviation: A: Arm A; C: Arm C; FA: final analysis; vs, versus 
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Sample size and power is calculated by EAST (Version 6.5) and R (Version 4.1.2). Details of 
interim analysis will be presented in Section 9.8. 
9.8. 
Interim Analysis 
There is 1 planned interim analysis for this study, using Lan-DeMets O’Brien-Fleming 
approximation spending function (Lan and DeMets 1983). 
The interim analysis of PFS primary analysis will be performed at a later time when the target 
number of events in either the PD-L1 ≥ 50% or ITT Analysis Sets is reached, which is 
approximately 106 events in the PD-L1 ≥ 50% analysis set and 216 events in the ITT analysis set 
(75% of the target number of PFS events in each analysis set) among Arms A and C, 
approximately 45 months after first patient randomized. The final analysis of PFS will take place 
after approximately 141 and 288 PFS events have been observed in the 2 analysis sets, 
respectively, and approximately 56 months after the first patient is randomized. Event number 
and testing boundaries in p-value for primary analyses of PFS are shown in Table 13. The 
boundaries will be updated according to the actual numbers of events in the interim and final 
analyses, using the above prespecified alpha spending function. 
Table 13: 
Event number, and Testing Boundaries of Interim Analyses and Final 
Analysis 
Analysis Set 
Type of 
Analysis 
# Events 
p-value for Efficacy 
IA 
Approximate 
HR Threshold 
for Efficacy 
Prob of Crossing 
Efficacy 
Boundary Under 
Alternative 
Hypothesis 
PD-L1 ≥ 50% 
IA 
106 
0.0097 
0.635 
61.5% 
FA 
141 
0.0221 
0.713 
85.2% 
ITT 
IA 
216 
0.0097 
0.727 
61.1% 
FA 
288 
0.0221 
0.789 
85.1% 
 
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10. 
STUDY COMMITTEES 
10.1. 
Independent Review Committee 
An Independent Review Committee (IRC) will be established to perform an independent review 
of all radiological images for the efficacy analysis and to determine all instances of response and 
disease progression based on RECIST v1.1 criteria, in addition to the local investigator review of 
radiographs. The results from the investigator’s review of radiographic images will be used to 
determine whether patients should be enrolled or should continue study treatment. The tumor 
assessment by the IRC will be used for the reporting of the study results. 
All decisions made during the performance of the study will be based on the local investigator’s 
assessment of radiographic images, clinical status, and relevant examination of the patients. Sites 
will submit specific radiographic image files to the centralized data review facility during the 
study at an ongoing basis or at the sponsor’s request. Detailed rules and guidelines for 
radiographic imaging and tumor assessments by the IRC are outlined separately in the Imaging 
Manual and the IRC Charter. 
10.2. 
Independent Data Monitoring Committee 
Safety monitoring and efficacy review will be performed by an IDMC. The first safety 
monitoring and review will occur after approximately 42 patients (≥ 18 patients each for Arm A 
and C, ≥ 6 patients for Arm B) have been randomized and treated for ≥ 30 days from C1D1 or no 
later than 6 months after first patient enrolled. The subsequent safety monitoring and review will 
be conducted as determined by the IDMC, or approximately every 6 months thereafter. The 
IDMC may recommend study modification including early termination of the study due to safety 
concerns, or for evidence of compelling efficacy at the pre-planned interim analyses. Enrollment 
may continue during these IDMC safety reviews. The function and membership of the IDMC 
will be described in the IDMC charter. 
In addition to the planned IDMC review(s), ad hoc reviews may take place based on new 
information. 
Following IDMC review and discussion, the sponsor will make all final decisions regarding any 
change in study conduct. More details could be found in the IDMC charter. 
10.3. 
Steering Committee 
The study conduct will be overseen by a steering committee composed of selected clinicians. 
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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 GCP guidelines, the study monitor 
must have direct access to the investigator’s source documentation to verify the data recorded in 
the eCRFs for consistency. 
The 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 monitor should have access to any patient records needed to 
verify the entries on the eCRFs. The investigator agrees to cooperate with the 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 to representatives of a regulatory agency or the 
sponsor access to records, facilities, and personnel 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 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 drugs. This includes acknowledgment of receipt of each shipment of 
study drugs (quantity and condition), patient drug dispensation records, and returned or 
destroyed study drugs. 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 the sponsor 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 
for disposal, arrangements will be made between the site and the sponsor or its representative for 
destruction or return of unused study drug supplies. 
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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 International Council for Harmonisation E6 guideline for GCP and the 
principles of the Declaration of Helsinki or the laws and regulations of the country in which the 
research is conducted, whichever affords the greater protection to the individual. The study will 
also comply with the requirements of the International Council for Harmonisation 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 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 IRB/IEC 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 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 before 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 re-consented 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 principal 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 principal 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 principal investigator and site must ensure that any personal and medical 
information transmitted to the 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 principal investigator and site may provide certain of this personal or 
medical information to the sponsor or its representatives. Such personal or medical information 
may not be provided as part of the protocol (eg, as part of the eCRF, or on samples or reports 
submitted to the central lab). 
Investigator and site personnel 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 the sponsor for sharing and transferal of personal and medical information. 
In the event of a breach of the confidentiality of a patient’s personal or medical information, the 
principal investigator, site personnel, 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. 
Data 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 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 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 is 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 investigator or designee must sign the completed 
casebooks to attest to their accuracy, authenticity, and completeness. 
Data contained in the eCRFs are the sole property of sponsor and should not be made available 
in any form to third parties without written permission from sponsor, except for authorized 
representatives of 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 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 course of the study, a study monitor 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 giving due consideration 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, PT, and primary SOC. 
Concomitant medications will be coded using the World Health Organization Drug Dictionary 
(WHODrug). Medical history will be coded using MedDRA. 
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14.2. 
Data Integrity and In-house Blinding 
Due to the open-label design of the study, access to the patient-level clinical data in the EDC 
system will be assigned to predefined study personnel only. 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 share such outputs from the EDC 
system with other functions/persons who do not have access to the EDC. In addition, the central 
imaging vendor will perform the central imaging review without knowledge of treatment arm 
assignment. More details of data integrity and in-house blinding will be provided and described 
in the Data Integrity Protection Plan (DIPP). 
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 
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 but not be limited to 
documents such as 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, and screening and enrollment log, 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 assure 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 or 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. 
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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 
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 the IRB/IEC. 
14.4. 
Protocol Deviations 
The investigator is responsible for ensuring 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 the sponsor. 
The investigator is to document and explain any deviations from the approved protocol. The 
investigator must promptly report any important 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 International Council for 
Harmonisation Guideline for Structure and Content of Clinical Study Reports (ICH E3). 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. For 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 or stricter local 
criteria (International Committee of Medical Journal Editors 2020). 
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 sponsors 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 process of 
reviewing manuscripts and presentations that are based on the data from this study is detailed in 
the investigator’s clinical study agreement. Each investigator agrees that, in accordance with the 
terms of 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/provide of all study data to the sponsor 
• Resolution and closure of all data queries 
• Accountability, reconciliation, and arrangements for unused study drugs 
• 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 reasons. 
Potential reasons for suspension or discontinuation include but 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 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 and 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 all unused study drugs in accordance with the applicable 
sponsor procedures for the study. 
Financial compensation to 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, expertise, 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 protocol, is executed between the sponsor and the study center that 
contract’s ownership provisions shall apply rather than this protocol. 
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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 
protocol is executed, that contract’s provisions shall apply rather than this protocol. 
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15. 
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APPENDICES 
 
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APPENDIX 1. SCHEDULE OF ASSESSMENTS 
Assessment 
Pre-screening a Screening 
b 
Treatment Cycles 
End-of-
Treatment 
Visit c  
 Safety 
Follow-Up d 
Tumor 
assessment/Survi
val Follow-up e 
Cycles 1 to 3  
(Arm A and B: every 
21 days; Arm C every 
14 or 28 f days) 
≥ Cycle 4 and up to 12 
months 
(Arm A and B: every 
21 days; Arm C every 
14 or 28 f days)  
Days (Window) 
-120 to the 
initiation of 
screening 
-28 to -1 1 (+2 or 
±3) g 8 (±3) 15 (±3) 
1 (±3) 
0 to 7 days 
30 (±7), 60, 90,
and 120 (±14) 
days after last 
dose 
Every 12 weeks 
(±7 or 14 days) 
Prescreening informed consent a 
X 
- 
- 
- 
- 
- 
- 
- 
- 
Informed consent b 
- 
X 
- 
- 
- 
- 
- 
- 
- 
Inclusion/exclusion criteria 
- 
X 
- 
- 
- 
- 
- 
- 
- 
Randomization h 
- 
X 
- 
- 
- 
- 
- 
- 
- 
Demographics/medical history 
/prior medications or proceduresi 
- 
X 
- 
- 
- 
- 
- 
- 
- 
Concomitant medication 
/procedures evaluation 
- 
Continuous from ≤ 28 days before randomization until 30 days after the last dose of 
study treatment 
- 
AE evaluation j 
- 
Continuous from informed consent until 30 days after the last dose of study treatment for AEs; 90 days 
after the last dose of ociperlimab or tislelizumab or durvalumab for imAEs. All SAEs considered related to 
the study treatment that are brought to the attention of the Investigator should be reported regardless of 
time since the last dose of treatment. 
Physical examination k 
- 
X 
X 
- 
- 
X 
X 
- 
- 
Vital signs/height and weight l 
- 
X 
X 
- 
- 
X 
X 
- 
- 
ECOG PS 
- 
X 
X 
- 
- 
X 
X 
- 
- 
Pulmonary function Test m 
- 
X 
Clinically indicated; Notes for sites in Japan: SpO2 at each subsequent visits before dosing 
12-lead electrocardiogram 
- 
X 
Only if clinically indicated 
X 
- 
- 
Hematology Laboratory n 
- 
X 
X 
X 
X 
X 
X 
- 
- 
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Assessment 
Pre-screening a Screening 
b 
Treatment Cycles 
End-of-
Treatment 
Visit c  
 Safety 
Follow-Up d 
Tumor 
assessment/Survi
val Follow-up e 
Cycles 1 to 3  
(Arm A and B: every 
21 days; Arm C every 
14 or 28 f days) 
≥ Cycle 4 and up to 12 
months 
(Arm A and B: every 
21 days; Arm C every 
14 or 28 f days)  
Days (Window) 
-120 to the 
initiation of 
screening 
-28 to -1 1 (+2 or 
±3) g 8 (±3) 15 (±3) 
1 (±3) 
0 to 7 days 
30 (±7), 60, 90,
and 120 (±14) 
days after last 
dose 
Every 12 weeks 
(±7 or 14 days) 
Chemistry laboratory n 
- 
X 
X 
X 
X 
X 
X 
- 
- 
CK and CK-MB n 
- 
X 
X 
X 
X 
X 
X 
- 
- 
Coagulation laboratory n 
- 
X 
X 
- 
- 
X 
X 
- 
- 
Thyroid function (o)o 
- 
X 
Cycle 3 or each cycleo 
Every 2 cycles or each 
cycleo 
X 
- 
- 
HBV/HCV/HIV testp 
- 
X 
As clinically indicated 
- 
- 
Urinalysis n 
- 
X 
As clinically indicated 
- 
- 
β-hCG pregnancy testq 
- 
X 
X 
- 
- 
X 
X 
X  
- 
Tumor assessment CT/MRI 
- 
X 
Tumor imaging will be performed approximately every 9 weeks (± 7 days) from randomization, 
for the first 54 weeks, and every 12 weeks (± 7 days) thereafter based on RECIST v1.1. 
Following the first progression assessed by IRC, patients will be assessed every 12 weeks (± 7 
days) for a second progression (using the patient’s status at the first progression as reference for 
assessment of second progression). 
FDG-PET/CT or bone scan; and 
brain MRI with contrast or head 
CT scan with contrastr 
- 
X 
Only if clinically indicated 
QLQ-C30, QLQ-LC13, EQ-5D-
5Ls 
- 
- 
Cycle 1 and every 6 weeks thereafter 
X 
- 
- 
PGI-Ss 
- 
- 
X 
- 
- 
At Week 25 and Week 
43 
- 
- 
- 
PRTSEs 
- 
- 
Week 7, Week 25, and Week 43 
- 
- 
- 
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Assessment 
Pre-screening a Screening 
b 
Treatment Cycles 
End-of-
Treatment 
Visit c  
 Safety 
Follow-Up d 
Tumor 
assessment/Survi
val Follow-up e 
Cycles 1 to 3  
(Arm A and B: every 
21 days; Arm C every 
14 or 28 f days) 
≥ Cycle 4 and up to 12 
months 
(Arm A and B: every 
21 days; Arm C every 
14 or 28 f days)  
Days (Window) 
-120 to the 
initiation of 
screening 
-28 to -1 1 (+2 or 
±3) g 8 (±3) 15 (±3) 
1 (±3) 
0 to 7 days 
30 (±7), 60, 90,
and 120 (±14) 
days after last 
dose 
Every 12 weeks 
(±7 or 14 days) 
Pharmacokineticst 
- 
- 
Xt 
- 
- 
Cycle 5, 9, 17 
X 
- 
- 
Anti-ociperlimab and anti-
tislelizumab blood samplesu 
- 
- 
Xu 
- 
- 
Cycle 5, 9, 17 
X 
- 
- 
Archived tumorv 
X 
- 
- 
- 
- 
- 
- 
- 
- 
Fresh tumor biopsyv 
X (if needed) 
- 
- 
- 
- 
- 
X (optional) - 
- 
Biomarkers: whole bloodw 
- 
- 
Xw 
- 
- 
X (optional) 
X (optional) - 
- 
EGFR/ALK/ROS1/RET testing 
on tumor tissue (if status not 
available)x 
X 
- 
Tislelizumab ± Ociperlimab or 
durvalumab administration 
- 
- 
X 
- 
- 
X 
- 
- 
- 
Survival status 
- 
- 
- 
- 
- 
- 
- 
X 
X 
Subsequent therapy since IP 
discontinuation 
- 
- 
- 
- 
- 
- 
- 
X 
X 
Abbreviations: ADA, antidrug antibody; AE, adverse event; ALK, anaplastic lymphoma kinase; β-hCG, beta human chorionic gonadotropin; C, Cycle ; cCRT, 
concurrent chemoradiotherapy; CD, cluster of differentiation; CK, creatine kinase; CK-MB, creatine kinase cardiac muscle isoenzyme; CT, computed 
tomography; D, day; DLCO, diffusing capacity of the lungs for carbon monoxide; ECOG PS, Eastern Cooperative Oncology Group Performance Status; 
EGFR, epidermal growth factor receptor; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer-Quality of Life C30 questionnaire; 
EOT, End of Treatment; EQ-5D-5L, European Quality of Life-5 Dimensions health state classifier to 5 Levels; FDG-PET, fluorodeoxyglucose - positron 
emission tomography; FEV, forced expiratory volume; FFPE, formalin-fixed paraffin-embedded; GEP, gene expression profiling; HBcAb, hepatitis B core 
antibody; HBsAb, hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; imAE, immune-mediated 
adverse event; IEC, Independent Ethics Committee; IP, investigational product; IRB, Institutional Review Board; IRC, Independent Review Committee; IRT, 
integrated response technology; LC13, Lung Cancer Module of EORTC QLQ-C30; MRI, magnetic resonance imaging; NCI, National Cancer Institute; 
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NSCLC, non-small cell lung cancer; PD, progressive disease; PD-L1, programmed cell death protein-ligand 1; PK, pharmacokinetics; PRO, patient-reported 
outcomes; PGI-S, patient reported global impression of severity; RECIST v1.1, Response Evaluation Criteria in Solid Tumors Version 1.1; SAE, serious 
adverse event; TIL, tumor-infiltrating lymphocyte; TMB, tumor mutational burden. 
a All patients will undergo prescreening for central evaluation of PD-L1 status up to 120 days before randomization. PD-L1 status will be determined centrally 
using either a previously obtained archival tumor tissue or fresh biopsy tissue sample collected prior to the initiation of cCRT. A separate prescreening 
informed consent must be obtained. 
b Written informed consent is required before performing any study-specific tests or procedures at Screening Visit. Screening evaluations must be completed 
within 28 days of randomization. Results of standard of care tests or examinations performed before obtaining informed consent and within 28 days before 
randomization may be used for screening assessments rather than repeating such tests. 
c The date of End-of-Treatment (EOT) is defined as the date investigator determines that study treatment will no longer be used. For Arm A, patients shall have 
an EOT Visit only if both study drugs were discontinued. Patients shall have an EOT Visit within 7 days after the date investigator determines that study 
treatment will no longer be used, or before the initiation of a new anticancer treatment, whichever occurs first. However, the EOT Visit may occur later than 
7 for specific circumstances, such as prolonged hospitalization. If routine laboratory tests (eg, hematology, serum chemistry, CK and CK-MB, coagulation, etc) 
are completed within 7 days before the EOT Visit, these tests need not be repeated. Tumor assessment is not specially required at the EOT Visit. Patients who 
discontinue study treatment before disease progression confirmed by the IRC will need to undergo tumor assessments as outlined in Section 7.6, in some cases 
the time window of tumor assessment might overlap with EOT and/or Safety Follow-up visit. In the cases the time window of EOT and Safety Follow-up visit 
overlapped, these two visits can be combined. 
d The Safety Follow-up Visit could be completed at the site or by telephone. Note for sites in Germany: a 120-Day Safety Follow-up Visit for pregnancy test will 
be implemented at the site or by telephone. 
e Patients whose disease has not progressed at the end of the 12-month study treatment period will continue to perform tumor imaging every 12 weeks (± 7 days) 
until progressive disease per RECIST v1.1. Following the first progression assessed by IRC, patients will be assessed every 12 weeks (± 7 days) for a second 
progression (using the patient’s status at the first progression as reference for assessment of second progression). A patient’s second progression status is 
defined according to local standard clinical practice and may involve any of: objective radiological, symptomatic progression or death. Measurements per 
RECIST v1.1 will not be collected for assessment of PFS2.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 90-Day Safety Follow-up Visit until death, loss to follow-up, withdrawal of consent, or end of 
study by sponsor. All patients will be followed for survival and subsequent anticancer therapy information unless a patient requests to be withdrawn from 
follow-up. Schedule of Survival Follow-up Visit can be modulated to combine with tumor assessment of PFS or PFS2 for operational convenience while 
keeping the follow-up visits interval as approximately every 12 weeks 
f Durvalumab regimen:10 mg/kg Q2W (or 1500 mg Q4W where the dosage has been approved by a local health authority). For the patient whose body weight is 
< 30 kg, only the regimen of durvalumab 10 mg/kg Q2W is applicable. Refer to local prescribing information of durvaluamb for detailed instructions. 
g Patients should have Cycle 1 Day 1 (C1D1) dosing initiated within 2 business days of randomization. For C2D1 and C3D1, patients should receive study drugs 
with ± 3 days. 
h Patients will be randomized into either Arm A or Arm B or Arm C via IRT. 
i Includes age or year of birth, sex, and self-reported race/ethnicity; 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. Refer to Section 7.2.3 for additional information. 
j The AEs and laboratory abnormalities will be graded per NCI-CTCAE v5.0. All AEs will also be evaluated for seriousness. After the main informed consent 
form has been signed, during the screening period, only SAEs should be recorded. After initiation of study treatment, all AEs and SAEs, regardless of 
relationship to study treatment, will be reported until either 30 days after last dose of study treatment or initiation of new anticancer therapy, whichever occurs 
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first. Immune-mediated AEs (serious or nonserious) should be reported until 90 days after the last dose of ociperlimab, tislelizumab, or durvalumab regardless 
of whether or not the patient starts a new anticancer therapy. All SAEs considered related to the study treatment that are brought to the attention of the 
Investigator should be reported regardless of time since the last dose of treatment. 
k At the Screening Visit, a complete examination will be conducted, including evaluations of 1) head, eyes, ears, nose and throat; 2) cardiovascular; 3) 
dermatological; 4) musculoskeletal; 5) respiratory; 6) gastrointestinal; and 7) neurological systems. At subsequent visits (and as clinically indicated), limited, 
symptom-directed physical examinations will be performed. For patients enrolled in Japan, bilateral lung auscultation will be performed at screening and 
subsequent visits. 
l Vital signs collected on study include body temperature (˚C), pulse rate, and blood pressure (systolic and diastolic). Pulse rate and blood pressure should be 
collected while the patient is in a seated position after resting for 10 minutes. The patient’s vital signs are required to be recorded within 60 minutes before, 
during, and within 30 minutes after the completion of infusion of study treatment (ociperlimab and tislelizumab in Arm A, tislelizumab in Arm B, and 
durvalumab in Arm C). For subsequent infusions, vital signs will be collected within 60 minutes before infusion and, if clinically indicated, during and within 
30 minutes after the completion of infusion. Weight is required to be measured once on the scheduled assessment day and before study treatment if there is any. 
Height measurements are only required at screening. Note for sites in Germany: when both ociperlimab and tislelizumab are administered, vital signs are 
required to be measured at 3 timepoints (within 60 minutes before, during, and within 30 minutes after the completion of infusion) throughout all treatment 
periods. When tislelizumab alone or durvalumab is administered, the 3 timepoint vital signs are required for the first infusion, and vital signs within 60 minutes 
before infusion are required at subsequent infusions. 
m Pulmonary function testing includes assessment of spirometry and oxygenation. The assessment of oxygenation should include at least pulse oximetry 
(percutaneous arterial oxygen saturation, SpO2) at rest and with exercise; an assessment of diffusion capacity is optional. Respective test results should 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, absolute FEV1 value < 1L, FEV1 of age and sex adjusted predicted performance levels < 50%, DLCO (if performed) < 40% 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. Notes for sites in Japan: at each subsequent visits before dosing, an assessment of oxygenation is to be performed 
including at least SpO2 at rest and with exercise, an assessment of diffusion capacity is optional; a spirometry test may be repeated as clinically indicated. 
n Local and/or central laboratory assessments on serum chemistry, hematology, CK and CK-MB, coagulation, and urinalysis will be conducted, of which certain 
elements will be collected as specified in Appendix 2. If hematology and serum chemistry at screening are not performed within 7 days before the planed 
C1D1, these tests should be repeated and reviewed before randomization. If the coagulation test has been performed and reviewed during screening, it is not 
mandatory to repeat this test before C1D1 unless the investigator deems necessary. Hematology, serum chemistry (including liver function tests), CK and CK-
MB as specified in Appendix 2 should be performed weekly for the first 9 weeks for Arm A and B (equal to 3 cycles) and first 8 weeks for Arm C (equal to 4 
cycles for Q2W regimen, 2 cycles for Q4W regimen), at the beginning of each subsequent cycle, and the EOT Visit. After Cycle 1, these laboratory tests are to 
be performed and reviewed within 48 hours before study drug administration. Urinalysis is to be conducted during the treatment period only if clinically 
warranted. Refer to Section 7.5.4 and Section 8.3.5 for additional information regarding clinical assessment and management of clinical laboratory 
abnormalities. 
o Analysis of free T3 or total T3, free T4 or total T4, and thyroid stimulating hormone will be performed by a central laboratory or the local study site laboratory. 
Thyroid function tests will be performed at screening, every 2 cycles for Arm A and Arm B (ie, Cycles 3, 5, 7, etc.), every 2 cycles for durvalumab-Q2W (ie, 
Cycles 3, 5, 7, etc.) and every cycle for durvalumab-Q4W, and at the EOT Visit. 
p Testing will be performed by a central laboratory and/or the local laboratory at screening (and as clinically indicated) and will include HBV/HCV serology 
(HBsAg, hepatitis B surface antibody [HBsAb], hepatitis B core antibody [HBcAb], and HCV antibody). In the case of positive HBsAg result or positive HCV 
antibody result, these tests will be followed by viral load assessment (HBV DNA or HCV RNA) at screening. After screening, HBV/HCV serology (HBsAg, 
HBsAb, HBcAb, and HCV antibody) and viral load assessment (HBV DNA and HCV RNA) may be performed if clinically indicated; for patients who have 
detectable HBV DNA or HCV RNA at screening or upon repeated testing, respective viral load testing will be performed every 12 weeks. Note for sites in 
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Germany and where required by the Health Authority or local guidelines: An HIV serology test (including antigen and/or antibodies) will be conducted at 
baseline for the patients with unknown HIV status, and patients with positive HIV test will be excluded. 
q 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 first dose of study treatment. Urine pregnancy tests will be performed at each cycle before dosing, at EOT, and at each Safety 
Follow-up Visit., Note for sites in Germany: a 120-Day Safety Follow-up Visit for pregnancy test will be implemented at the site or by telephone. A serum 
pregnancy test must be performed if the urine pregnancy test is positive or equivocal. 
r If PET/CT is performed at screening, bone scan is not required at screening. PET/ CT or bone scan should be performed for the whole body, or sufficient to 
rule out distant metastases (eg, from skull base to knees). MRI (or CT scan if MRI is contraindicated or not readily available) with contrast of the head is 
required at screening. If the patient’s disease stage was confirmed as Stage III NSCLC (AJCC 2017) based on PET/CT or bone scan and brain imaging via MRI 
or CT with contrast performed before cCRT, these tests are not required to repeat at screening. 
s Patients will be asked to complete three PROs, that include the EORTC QLQ-C30, EORTC QLQ-LC13, and EQ-5D-5L questionnaires before any clinical 
activities are performed, or any health-related discussion with the health care providers, during on-study clinic visits at C1D1 and every 6 weeks thereafter for 
up to 12 months and/or EOT, whichever comes first. Patients also are asked to complete 2 questionnaires that include PGI-S at C1D1, Day1 of Week 25, and 
Day1 of Week 43 (all arms), and PRTSE at Day 1 of Week 7, Week 25, and Week 43 (all Arms). For patients in Arm C who receive Q4W regimen, if the 
questionnaires visit falls into the interval of two dosing visits, it could be re-scheduled to combine with the neariest next dosing cycle visit. 
t Only for patients randomized to Arm A and Arm B: Procedures for collection of ociperlimab and tislelizumab PK and ADA samples are described in the 
laboratory manual. Predose (within 60 minutes before starting infusion) PK samples are required to be collected at Day 1 of Cycles 1, 2, 5, 9, 17, and at the 
EOT Visit for both ociperlimab and tislelizumab. Postdose (within 30 minutes after completing infusion) PK samples for both ociperlimab and tislelizumab are 
required to be collected on Day 1 of Cycles 1 and 5. Should a patient present with any ≥ Grade 3 imAE, an additional blood PK sample may be taken to 
determine the serum concentration of ociperlimab or tislelizumab. These tests are required when it is allowed by local regulations/IRBs/IECs. 
u All immunogenicity (ADAs) blood samples (serum) will be collected predose (within 60 minutes before dose) on dosing days Day 1 of Cycles 1, 2, 5, 9, 17, 
and the EOT Visit for both ociperlimab and tislelizumab in Arm A or tislelizumab in Arm B. All samples should be drawn at the same time as blood collection 
for predose PK analysis. These tests are required when it is allowed by local regulations/IRBs/IECs. 
v Tissue-based biomarkers (including but not limited to PD-L1, TIGIT, CD226, CD155, CD112, GEP, TMB, MSI, gene mutation profiles, and TILs) will be 
assessed on baseline and/or at disease progression/reoccurrence. Archival tumor tissues (FFPE block [preferred] or approximately 15 [at least 6] freshly cut 
unstained FFPE slides) or a tumor biopsy at baseline are required to be collected prior to cCRT during prescreening. For patients with readily accessible tumor 
lesions and who consent to the biopsies, a fresh biopsy will be collected prior to cCRT. Optional biopsies will also be taken at the EOT Visit after disease 
progression. (Note: For the sites in mainland China, tissues will be obtained to test the expression of PD-L1, TIGIT, CD226, CD155, CD112, GEP, TMB, MSI, 
gene mutation profiles, and TILs at baseline, and at disease progression/reoccurrence). 
w  Blood sample must be collected at C1D1 (predose) for blood based biomarker test. Optional blood will be collected at C3D1 (predose), C4D1 (predose) and at 
the EOT Visit after the disease progression. Collected blood samples will be used to explore association of blood-based biomarkers with response, resistance, 
and prognosis. Written informed consent is required before optional blood samples collection. (Note: Blood-based biomarkers, including ctDNA, TMB, MSI, 
gene mutational profiles, and extracellular vesicle (EVs), will be explored in the blood samples which will be collected in the sites in mainland China). 
x For patients with nonsquamous NSCLC histology with unknown EGFR mutation status, tissue-based test results are mandatory at screening; patients with 
unknown ALK, ROS1 and RET status may be enrolled. Patients with squamous NSCLC and unknown EGFR, ALK, ROS1, or RET status will not be required 
to be tested at screening. EGFR mutation status may be assessed locally or at a central laboratory. An additional ≥ 6 slides are required if EGFR mutation status 
needs to be tested in the central lab. 
 
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APPENDIX 2. CLINICAL LABORATORY ASSESSMENTS 
Serum Chemistry 
Hematology 
Coagulation 
Urinalysis 
(screening and as 
clinically 
indicated) 
Thyroid Function 
Alkaline phosphatase 
Hemoglobin 
Prothrombin time a 
pH 
Thyroid 
stimulating 
hormone 
Alanine 
aminotransferase 
Hematocrit 
Partial 
thromboplastin time 
or activated partial 
thromboplastin time 
Specific gravity 
Free T3 or Total T3 
Aspartate 
aminotransferase 
White blood cell 
count 
International 
normalized ratio 
Glucose 
Free T4 or total T4 
Albumin 
Neutrophil 
count 
 
Protein 
 
Total bilirubin 
Lymphocyte 
count 
 
Ketones 
 
Direct bilirubin 
Platelet count 
 
Blood 
 
Blood urea nitrogen 
or urea 
 
 
24-hour protein b 
 
Potassium 
 
 
 
 
Sodium 
 
 
 
 
Calcium c 
 
 
 
 
Creatinine 
 
 
 
 
Glucose 
 
 
 
 
Lactate 
dehydrogenase 
 
 
 
 
Total protein 
 
 
 
 
Magnesium 
 
 
 
 
Phosphorus 
 
 
 
 
Chloride 
 
 
 
 
Creatine 
kinase/ 
CK-MB d 
 
 
 
 
Abbreviations: CK-MB, creatine kinase cardiac muscle isoenzyme. 
 a For sites in France, prothombine rate (%) will be measured. Other coagulation assessment maybe performed per 
local guidance. 
 b On routine urinalysis, if urine protein is ≥ 2+ by dipstick then 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. 
 c Calcium values will be corrected for patients with hypoalbuminemia. 
d Cardiac enzyme testing is to monitor potential event of immune-related myocarditis. CK/CK-MB can be tested 
separately or in combination with other serum chemistry assessments. In the event that CK-MB fractionation is not 
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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. 
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APPENDIX 3. EASTERN COOPERATIVE ONCOLOGY GROUP 
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 housework, 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. 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. 
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 myasthenia 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-Koyanagi-Harada disease 
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APPENDIX 5. CONTRACEPTION GUIDELINES AND DEFINITIONS 
OF “WOMEN OF CHILDBEARING POTENTIAL,” “NO 
CHILDBEARING POTENTIAL” 
Contraception Guidelines 
The Clinical Trials Facilitation Group’s recommendations related to contraception and 
pregnancy testing in clinical trials include the use of highly effective forms of birth control 
(Clinical Trials Facilitation Group 2020). These methods include the following: 
• Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with the inhibition of ovulation (oral, intravaginal, or transdermal) 
• Progestogen-only hormonal contraception associated with the inhibition of ovulation: 
− oral 
− injectable 
− implantable  
• Intrauterine device 
• Intrauterine hormone-releasing system 
• Bilateral tubal occlusion 
• Vasectomized male partner, provided that the vasectomized partner is the sole sexual 
partner of the woman of childbearing potential study participant and that the 
vasectomized partner has received medical assessment of surgical success 
• Sexual abstinence (defined as refraining from heterosexual intercourse during the 
entire period of exposure associated with the study treatment). 
NOTE: Total sexual abstinence should only be used as a contraceptive method if it is in 
line with the patient’s usual and preferred lifestyle. 
Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods), 
declaration of abstinence for the duration of exposure to study drugs, 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 
combined with another acceptable method 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 post-menopausal 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: 
− ≥ 55 years of age with no spontaneous menses for ≥ 12 months OR 
− < 55 years of age with no spontaneous menses for ≥ 12 months AND with a 
postmenopausal follicle-stimulating hormone concentration (FSH) > 30 mIU/mL 
and all alternative medial causes for the lack of spontaneous menses for 
≥ 12 months have been ruled out, such as polycystic ovarian syndromes, 
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 Group 2020). 
 
The followings are approved or permitted in Japan: 
• 
Intrauterine devices (IUD, all types) or intrauterine hormone releasing systems (IUS) 
• 
Orally combined (estrogen- and progestogen-containing) hormonal contraception 
associated with the inhibition of ovulation 
   Other contraceptions are also accepted: 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner 
• 
Sexual abstinence (defined as refraining from heterosexual intercourse during the entire 
period of risk associated with the study treatment)* 
(*: Sexual abstinence may be used as a contraceptive method only if it is in line with 
the patients’ usual and preferred lifestyle.) 
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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, MA: Little, Brown and Co.; 1964:p 114. 
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APPENDIX 7. EUROPEAN ORGANISATION FOR RESEARCH AND 
TREATMENT OF CANCER QUALITY OF LIFE CANCER 
QUESTIONNAIRE QLQ-C30 
 
 
 
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APPENDIX 8. EUROPEAN ORGANISATION FOR RESEARCH AND 
TREATMENT OF CANCER QUALITY OF LIFE QUESTIONNAIRE 
LUNG CANCER QLQ-LC13 
 
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APPENDIX 9. THE 5-LEVEL VERSION OF EUROPEAN QUALITY OF 
LIFE 5-DIMENSIONAL QUESTIONNAIRE 
 
 
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APPENDIX 10. PATIENT GLOBAL IMPRESSION OF SEVERITY (PGI-S) 
 
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Appendix 11. 
PATIENT REPORTED TREATMENT-RELATD 
SIDE-EFFECT BURDEN (PRTSE) 
 
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Appendix 12. 
Immune-Mediated Adverse Event Evaluation and 
Management 
The recommendations below for the diagnosis and management of any imAE are intended as 
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, PD, 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 drugs and the AE? 
• How did the patient respond to withdrawal of study drugs? 
• Did the event recur when study drugs was/were reintroduced? 
• Was there a clinical response to corticosteroids? 
• Is the event an autoimmune endocrinopathy? 
• Is PD 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 electronic case report form should be checked. 
Recommended diagnostic tests in the management of possible immune-mediated adverse events 
Immune-mediated toxicity 
Diagnostic evaluation guideline 
Thyroid disorders 
Scheduled and repeat 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.  
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. 
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Recommended diagnostic tests in the management of possible immune-mediated adverse events 
Immune-mediated toxicity 
Diagnostic evaluation guideline 
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 3-4; every 2-3 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 nephrology for further management 
assistance.  
Dermatology 
Consider other causes by conducting a physical examination; consider 
dermatology referral for skin biopsy. 
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 I and consider a muscle biopsy. 
Myocarditis 
Perform ECG, echocardiogram, troponin I, and refer to a cardiologist. 
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; ANA, antinuclear antibody; AST, aspartate 
aminotransferase; CK, creatine kinase; 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; 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, 
with patients is required 
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• 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 medical monitor 
• For some Grade 3 toxicities that resolve quickly, rechallenge with study drugs may be 
considered if there is evidence of a clinical response to study treatment after 
consultation with the 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 
Autoimmune 
toxicity 
Grade 
Treatment guidelines (subject to 
clinical judgement) 
Study drug 
management 
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 
treatment 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 co-
morbidities, 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. 
Hypophysitis 
1-2 
Mild 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. Taper corticosteroids 
over at least 1 month. 
Continue study 
treatment. 
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Autoimmune 
toxicity 
Grade 
Treatment guidelines (subject to 
clinical judgement) 
Study drug 
management 
3-4 
Moderate-severe 
symptoms 
Refer patient to an endocrinologist 
for assessment and treatment. 
Initiate pulse IV 
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 
endocrinology advice. Maintain 
hormone replacement according to 
endocrinology advice. 
Hold study treatment 
for patients with 
headache/visual 
disturbance due to 
pituitary inflammation 
until 
resolved/improved to 
Grade 2 or less. 
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 
study treatment until 
appearance improves 
and cause is 
determined. 
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 study treatment 
(Note for sites in 
Japan: However, in 
the case that 
symptoms are 
controlled on 
prednisolone ≤ 10 
mg/day, treatment can 
be continued.) 
Retreatment is 
acceptable if 
symptoms resolve 
completely or are 
controlled on 
prednisolone 
≤ 10 mg/day. 
Discontinue study 
treatment if symptoms 
persist with 
corticosteroid 
treatment. 
(Note for sites in 
Japan: If the event 
recurs upon 
reintroduction of 
study treatment, the 
patient should 
discontinue the 
treatment.) 
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Autoimmune 
toxicity 
Grade 
Treatment guidelines (subject to 
clinical judgement) 
Study drug 
management 
3-4 
Severe or life-threatening 
symptoms 
Breathless at rest 
Admit to a hospital and initiate 
treatment with IV 
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 study 
treatment. 
Neurological 
toxicity 
1 
Mild symptoms 
– 
Continue study 
treatment. 
2 
Moderate symptoms 
Treat with oral prednisolone 0.5-
1 mg/kg/day. Taper over at least 
4 weeks. Obtain neurology 
consultation. 
Hold study treatment; 
resume when 
resolved/improved to 
Grade 0-1. 
3-4 
Severe/life-threatening 
Initiate treatment with oral 
prednisolone or IV 
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 study 
treatment. 
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 
(non-enteric coated). 
Do not wait for any diagnostic tests 
to start treatment. Taper steroids 
over 2-4 weeks, consider 
endoscopy if symptoms are 
recurring. 
Hold study treatment; 
resume 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 IV 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. 
Hold study treatment; 
retreatment may be 
considered when 
resolved/improved to 
baseline grade and 
after discussion with 
the study medical 
monitor. 
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Autoimmune 
toxicity 
Grade 
Treatment guidelines (subject to 
clinical judgement) 
Study drug 
management 
4 
Life-threatening 
symptoms 
If no improvement in 72 hours or 
symptoms worsen, consider 
infliximab 5 mg/kg; if no 
perforation, sepsis, TB, hepatitis, 
NYHA Grade III/IV CHF or other 
immunosuppressive treatment: 
MMF or tacrolimus. 
Consult gastroenterologist to 
conduct 
colonoscopy/sigmoidoscopy. 
Discontinue study 
treatment. 
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Autoimmune 
toxicity 
Grade 
Treatment guidelines (subject to 
clinical judgement) 
Study drug 
management 
Skin reactions 
1 
Skin rash, with or without 
symptoms, < 10% BSA 
Avoid skin irritants and sun 
exposure; topical emollients 
recommended. 
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. 
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: IV 
methylprednisolone 0.5-
1 mg/kg/day; convert to oral 
prednisolone and taper over at least 
4 weeks. 
Hold study treatment. 
Re-treat when AE is 
resolved or improved 
to mild rash (Grade 1-
2) after discussion 
with the study 
medical monitor. 
4 
Skin sloughing > 30% 
BSA with associated 
symptoms (eg, erythema, 
purpura, epidermal 
detachment) 
Initiate IV 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 study 
treatment. 
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 study treatment 
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 study treatment; 
treatment may be 
resumed when 
resolved/improved to 
baseline grade and 
prednisolone tapered 
to ≤ 10 mg. 
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Autoimmune 
toxicity 
Grade 
Treatment guidelines (subject to 
clinical judgement) 
Study drug 
management 
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 
IV (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. 
4 
ALT or AST > 20 x ULN 
Initiate IV methylprednisolone 
2 mg/kg/day. Convert to oral 
prednisolone and taper over at least 
6 weeks.  
Discontinue study 
treatment. 
Worsening LFTs despite steroids: 
If on oral prednisolone, change to pulsed IV methylprednisolone 
If on IV, add MMF 500-1000 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. 
2 
Creatinine > 1.5 x -3X 
baseline or > 1.5 x -3X 
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 > 3X-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 IV 
(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. 
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Autoimmune 
toxicity 
Grade 
Treatment guidelines (subject to 
clinical judgement) 
Study drug 
management 
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. 
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 study treatment 
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. 
Ocular toxicity 
1 
Asymptomatic eye 
exam/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 
treatment 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 study treatment 
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 IV (methyl)prednisolone 
2 mg/kg/day. Convert to oral 
prednisolone and taper over at least 
4 weeks. 
Discontinue study 
treatment. 
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 IV 
(methyl)prednisolone 1-
2 mg/kg/day. Convert to oral 
prednisolone when amylase/lipase 
Hold study treatment; 
reintroduce only after 
discussion with the 
study medical 
monitor. 
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Autoimmune 
toxicity 
Grade 
Treatment guidelines (subject to 
clinical judgement) 
Study drug 
management 
improved to Grade 2, and taper 
over at least 4 weeks. 
 
4 
Acute abdominal pain, 
surgical emergency 
Admit to hospital for emergency 
management and appropriate 
referral.  
Discontinue study 
treatment. 
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 
worsens, hold study 
treatment 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 study treatment 
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. 
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 IV 
(methyl)prednisolone 1-
2 mg/kg/day. Convert to oral 
prednisolone when symptoms 
improved to Grade 2 and taper over 
at least 4 weeks. 
Hold study treatment 
until improved to 
Grade 0-1. 
4 
Life-threatening 
complications or 
dehydration 
Admit to hospital for emergency 
care. Consider IV corticosteroids if 
not contraindicated by infection. 
Discontinue study 
treatment. 
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 study treatment 
until improved to 
Grade 0-1. 
3-4 
Severe weakness, 
limiting self-care 
Admit to hospital and initiate oral 
prednisolone 1 mg/kg. Consider 
bolus IV (methyl)prednisolone and 
1-2 mg/kg/day maintenance for 
Hold study treatment 
until improved to 
Grade 0-1. 
Discontinue if any 
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Autoimmune 
toxicity 
Grade 
Treatment guidelines (subject to 
clinical judgement) 
Study drug 
management 
severe activity restriction or 
dysphagia. If symptoms do not 
improve add immunosuppressant 
therapy. Taper oral steroids over at 
least 4 weeks. 
evidence of 
myocardial 
involvement. 
Myocarditis 
< 2 
Asymptomatic but 
significantly increased 
CK-MB or increased 
troponin OR clinically 
significant 
intraventricular 
conduction delay 
Admit to hospital and refer to a 
cardiologist. 
Transfer all patients with 
moderate/severe cardiac symptoms 
or any increase in cardiac serum 
markers to the coronary care unit. 
Initiate oral prednisolone or IV 
(methyl)prednisolone at 1-
2 mg/kg/day. 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. 
Hold study treatment 
until completely 
resolved or 
myocarditis has been 
ruled out. 
2 
Symptoms on mild-
moderate exertion 
Discontinue study 
treatment unless 
cardiac involvement 
has been excluded and 
symptoms have 
completely resolved. 
3 
Severe symptoms with 
mild exertion 
4 
Life-threatening 
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; CK, creatine kinase; CK-MB, creatine kinase cardiac muscle isoenzyme; CHF, congestive heart 
failure; INR, international normalized ratio; IV, intravenous; LFT, liver function test; MMF, mycophenolate mofetil; 
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. 
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Appendix 13. 
Response Evaluation Criteria in Solid Tumors (RECIST) 
Guidelines, Version 1.1 
The text below was obtained from the following reference: 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 (Version 1.1). 
Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are 
used in the RECIST criteria. 
Note: Lesions are either measurable or non-measurable 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) scan (irrespective of scanner type) and 
magnetic resonance imaging (MRI) (no less than double the slice thickness and a 
minimum of 10 mm). 
• 10 mm caliper measurement by clinical examination (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 or MRI scan (CT/MRI scan slice 
thickness recommended to be ≥ 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 to < 15 mm 
with conventional techniques or < 10 mm using spiral CT scan), are considered non-measurable 
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 non-measurable. 
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. 
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• 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. 
• Blastic bone lesions are non-measurable. 
Cystic lesions: 
• Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) 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 
non-cystic lesions are present in the same patient, these are preferred for selection as 
target lesions. 
Lesions with prior local treatment: 
• Tumor lesions situated in a previously irradiated area, or in an area subjected to other 
loco-regional therapy, are usually not considered measurable unless there has been 
demonstrated progression in the lesion. 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 organ, 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 or MRI 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 × 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 non-target lesions. Nodes that have a short axis < 10 mm are 
considered non-pathological 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 
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sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease. 
Non-target Lesions 
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
non-target lesions and should also be recorded at baseline. Measurements are not required, and 
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 non-target 
lesions involving the same organ as a single item on the case record form (eg, “multiple enlarged 
pelvic lymph node” 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 accessible by clinical examination. 
Clinical lesions: Clinical lesions will only be considered measurable when they are superficial 
and P10 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 is preferred over chest x-ray, particularly when progression is 
an important endpoint, because 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. 
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• 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 CR or surgical resection is an endpoint. 
• 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 CA-125 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 
CA-125 progression criteria which are to be integrated with objective tumor 
assessment for use in first-line 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 (SD) to differentiate between response (or SD) and progressive disease 
(PD). 
RESPONSE CRITERIA 
Evaluation of Target Lesions 
• Complete response (CR): Disappearance of all target lesions. Any pathological lymph 
nodes (whether target or non-target) 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. 
• 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 1 or more 
new lesions is also considered progression). 
• Stable disease: 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 recorded in a separate section where, to 
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qualify for CR, each 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 non-nodal) 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 non-reproducible, 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 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 Non-target Lesions 
While some non-target lesions may actually be measurable, they need not be measured and 
instead should be assessed only qualitatively at the timepoints specified in the protocol. 
• CR: Disappearance of all non-target lesions and normalization of tumor marker level. 
All lymph nodes must be non-pathological in size (< 10 mm short axis). 
• PD: Unequivocal progression (as detailed below) of existing non-target lesions. 
(Note: the appearance of 1 or more new lesions is also considered progression.) 
• Non-CR/Non-PD: Persistence of 1 or more non-target lesion(s) and/or maintenance of 
tumor marker level above the normal limits. 
• When the patient also has measurable disease: In this setting, to achieve “unequivocal 
progression” on the basis of the non-target disease, there must be an overall level of 
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substantial worsening in non-target disease such that, even in presence of SD or PR in 
target disease, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy. A modest “increase” in the size of 1 or more non-target 
lesions is usually not sufficient to qualify for unequivocal progression status. The 
designation of overall progression solely on the basis of change in non-target disease 
in the face of SD or PR of target disease will therefore be extremely rare. 
• When the patient has only non-measurable 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 
non-measurable disease burden. Because worsening in non-target disease cannot be 
easily quantified (by definition: if all lesions are truly non-measurable) 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 non-measurable 
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 non-measurable 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 PD; 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 pre-existing 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 PD. An example of this is the patient who has 
visceral disease at baseline and while on trial 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. 
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While fluorine-18 [F-18] fluorodeoxyglucose (FDG)-PET response assessments need additional 
study, it is sometimes reasonable to incorporate the use of FDG-PET scanning to complement 
CT scanning 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 FDG-PET at baseline, with a positive FDG-PET at follow-up, is a sign of 
PD based on a new lesion. 
• No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDG-
PET at follow-up corresponds to a new site of disease confirmed by CT, this is PD. If 
the positive FDG-PET 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 
FDG-PET scan). If the positive FDG-PET at follow-up corresponds to a pre-existing 
site of disease on CT that is not progressing on the basis of the anatomic images, this 
is not PD. 
Evaluation of Best Overall Response 
The BOR is the best response recorded from the start of the study treatment until the end of 
treatment considering 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 BOR assignment will depend on the findings of both target and non-
target 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 BOR 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 timepoints (for example, a patient who has 
SD at first assessment, PR at second assessment, and PD on last assessment has a BOR 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 timepoint 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. 
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Target lesions 
Non-target 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 
Stable disease 
Non-PD or not all 
evaluated 
No 
Stable disease 
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. 
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” on the eCRF. 
In trials where confirmation of response is required, repeated ‘NE’ timepoint 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 timepoint 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 PD 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. 
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. 
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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 at 
the next scheduled assessment, progression is confirmed, the date of progression should be the 
earlier date when progression was suspected. 
CONFIRMATORY 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 SD 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 PD is objectively 
documented (taking as reference for PD 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 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). 
The clinical relevance of the duration of SD varies in different studies and diseases If the 
proportion of patients achieving SD 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 SD. 
Note: The duration of response (DOR) and SD as well as the progression-free survival (PFS) 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 consider many 
parameters including disease types and stages, treatment periodicity, and standard practice. 
However, these limitations of the precision of the measured endpoint should be considered if 
comparisons between trials are to be made. 
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APPENDIX 14. CHRONIC KIDNEY DISEASE EPIDEMIOLOGY 
COLLABORATION (CKD-EPI) AND COCKCROFT-GAULT (CG) 
EQUATION 
CKD-EPI Equation 
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 x min (Scr /κ, 1)α x max(Scr /κ, 1)-1.209 x 0.993Age x 1.018 [if female] x 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. 
Note, the unit of the value generated by the website above is mL/min/1.73 m2, this is 
standardized to a body surface area (BSA) value of 1.73 m2, will not be appropriate in patients 
with BSAs different than the standard (1.73 m2). To individualize GFR for drug dosing, need to 
convert mL/min/1.73 m2 to mL/min via multiplying the standardized GFR by the individual’s 
BSA calculated using an appropriate formula and divide by 1.73 (US FDA 2020). 
BSA formulas deemed as appropriate (US FDA 2020) 
Du Bois formula (Dubios D et al 1916):  BSA = 0.007184 × W0.425 × H0.725 
Mosteller formula (Mosteller 1987):  BSA = 0.016667 × W0.5 × H0.5 
The online calculator for BSA can be found here: 
https://www.calculator.net/body-surface-area-calculator.html 
 
 
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Cockcroft-Gault Equation 
For Serum Creatinine Concentration (SCr) in mg/dL a 
CrCl for males (mL/min)  =    
     (140−age)(weightb)      
(72)(SCr)
 
CrCl for females (mL/min)  =    
(0.85)(140−age)(weightb)
(72)(SCr)
 
For Serum Creatinine Concentration (SCr) in µmol/L a 
CrCl for males (mL/min)  =    
     (140−age)(weightb)      
(0.81)(SCr)
 
CrCl for females (mL/min) =    
(0.85)(140−age)(weightb)
(0.81)(SCr)
 
a Age in years and weight in kilograms. 
b Recommend using ideal body weight if the patient’s BMI > 30 kg/m2 in calculation of estimated CrCl. 
c Ideal body weight (IBW) formula (Devine 1974): 
IBW for males (kg) = 49.9 kg + 0.89 kg/cm × (height − 152.4 cm) 
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APPENDIX 15. RECOMMENDED DOSAGE MODIFICATIONS FOR 
ADVERSE REACTIONS OF DURVALUMAB 
This table is cited from durvalumab prescribing information approved by US FDA (date, 
version). Note, in countries/regions other than US, some recommended dosage modifications of 
durvalumab prescribing information approved by local health authority may differ from that 
approved by US FDA. In such cases, please refer to the recommendations approved by the local 
health authority.
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Source: durvalumab prescribing information approved by US FDA. Note: in countries/regions other than US, some 
recommended dosage modifications of durvalumab prescribing information approved by the local health authority 
may differ from that approved by US FDA. In such cases, please refer to the recommendations approved by the local 
health authority. 
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APPENDIX 16. 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.  
Ginsenoside-Rg3 capsule 
CIDAN Capsule 
Yangzheng Xiaoji Jiaonang 
Huaer Keli 
Huazheng Huisheng Koufuye 
Haishengsu injection 
Juzentaihoto 
Xiaoaiping Wan/Pian/Jiao Nang/Ke Li 
Cinobufacini/Huachansu injection 
Xiaoaiping Zhusheye 
Cinobufacini/Huachansu Pian/Capsules 
Niuhuang Xingxiao pill 
Boerning capsule 
Polyporus polysaccharide injection 
Norcantharidin Pian 
Hedyotis Dissusa wild injection 
Shendan Sanjie Jiaonang 
Zi Long jin pian 
Shengqi Fuzheng Zhusheye 
Ganfule Jiaonang / GFL tablet 
Shen Lian Jiao Nang/Ke Li 
Zhongjiefeng tablet 
Ma Te Ling injection 
Weifuchun pill 
Hui Sheng Kou Fu Ye 
Ai Di Zhu She Ye 
Fufang Banmao Jiaonang 
Qizhen Jiaonang 
Fufang Hongdoushan Jiaonang 
Zedoary turmeric oil injection 
Fufang Kushen Zhusheye 
Kanglixin Jiaonang 
Tian Xian capsule 
Jinpu capsule 
Qining injection 
Jinlong Capsules 
Weimaining Jiao Nang 
Lentinan 
Anerxin/Ginseng polysaccharide injection 
Yadanzi/Brucea javanica Youru Zhusheye 
Ankangxin Jiaonang 
Yadanziyou Ruan jiao nang/Kou Fu Ru Ye 
Antike capsule 
Shelian Jiaonang 
Yanshu injection 
Bozhi Glycopeptide Injection 
Ping Xiao Pian/Jiao Nang 
Delisheng Injection 
Kanglixin Jiaonang 
Elemene Injection 
Kang’ai Zhusheye 
Sodium Cantharidinate Injection 
Kanglaite Injection 
Xianchan tablet 
Kanglaite Soft Capsules 
Xihuang Wan 
 
 
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APPENDIX 17. PATIENT CARE AND STUDY CONDUCT FOR 
PATIENTS ENROLLED WITH PA 1.0 
1. 
STUDY DESIGN OF PA 1.0 
1.1. 
Summary of Study Design 
This is an open-label, randomized, multicenter study to compare the efficacy and safety of 
ociperlimab (BGB-A1217) plus tislelizumab plus cCRT followed by ociperlimab plus 
tislelizumab (Arm A) or tislelizumab plus cCRT followed by tislelizumab (Arm B) versus cCRT 
followed by durvalumab (Arm C) in previously untreated, unresectable LA NSCLC. 
Newly diagnosed Stage III patients with histologically confirmed, locally advanced, and 
unresectable NSCLC are eligible. Patients are enrolled and randomized in a 1:1:1 ratio to Arm A, 
Arm B, or Arm C in this study. Randomization will be stratified by age (< 65 years versus 
≥ 65 years), PD-L1 expression in TC (≥ 1% versus < 1%), and histology (squamous versus 
nonsquamous). 
During the treatment period, in Arm A, patients will receive 2 cycles of ociperlimab 900 mg 
Q3W combined with tislelizumab 200 mg Q3W with cCRT (cCRT phase), and receive 
ociperlimab combined with tislelizumab Q3W for a maximum of 12 months after the completion 
of cCRT phase. In Arm B, patients will receive 2 cycles of tislelizumab 200 mg Q3W combined 
with cCRT (cCRT phase), and receive tislelizumab 200 mg Q3W for a maximum of 12 months 
after the completion of cCRT phase. In Arm C, patients will undergo 2 cycles of cCRT (cCRT 
phase), and receive durvalumab 10 mg/kg Q2W (or 1500 mg Q4W where the dosage has been 
approved by a local health authority) for a maximum of 12 months after the completion of cCRT 
phase. All 3 arms will receive study drugs until a maximum of 12 months after the completion of 
cCRT phase, PD per RECIST v1.1, unacceptable toxicity, death, or another discontinuation 
criterion is met, whichever occurs first. 
During the cCRT phase, the choice of chemotherapy regimen to be used as part of study 
treatment will be at the investigator’s discretion as specified in Section 2.2.3 of Appendix 17. For 
the 3 arms, RT should start concurrently with chemotherapy in the beginning of Cycle 1, in the 
best case, on Cycle 1 Day 1 (C1D1). If local technical or logistical circumstances do not allow 
the start of RT on C1D1, RT is strongly recommended to start within 3 days after C1D1, but no 
later than 7 days after C1D1. For Arm A and Arm B, immunotherapy (ociperlimab plus 
tislelizumab for Arm A, tislelizumab for Arm B) will be given starting from C1D1 during the 
cCRT phase, and continued until up to 12 months after the completion of cCRT phase, or PD per 
RECIST v1.1, unacceptable toxicity, death, or another discontinuation criterion is met, 
whichever occurs first. For Arm C, durvalumab will be commenced within 42 days after the 
cCRT phase until up to 12 months after the completion of cCRT phase, or PD per RECIST v1.1, 
unacceptable toxicity, death, or another discontinuation criterion is met, whichever occurs first. 
End-of-Treatment (EOT) Visit, Safety Follow-up Visit, and Survival Follow-up Visit will be 
conducted to monitor the patient’s status and collect data beyond study treatment.
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Table 14: 
Schedule of Assessment for PA 1.0 
Assessment 
Screeninga 
Treatment Cycles 
End-of-
Treatment 
Visit b 
Safety 
Follow-up 
Visit c 
Tumor 
Assessment 
/Survival 
Follow-up d 
Cycles 1 to 2 during 
cCRT Phase 
(Cisplatin and 
Etopside: every 28 
days; Chemotherapy 
other than cisplatin 
and etopside: every 21 
days) 
≥ Cycle 3 and up to 12 
months 
(ociperlimab and 
tislelizumab or 
tislelizumab: every 21 
days; 
Durvalumab: every 14 
or 28e days) 
Days (Window) 
-28 to -1 
1 (+2 
or ±3)f 8 (±3) 15 (±3) 
1 (±3)g 
0 to 7 days 
30 (±7), 60 
and 90 (±14) 
days after last 
dose 
Every 12 
weeks (±7 or 
14 days) 
STUDY ENTRY AND GENERAL ASSESSMENTS 
Informed consent a 
X 
- 
- 
- 
- 
- 
- 
- 
Inclusion/exclusion criteria 
X 
- 
- 
- 
- 
- 
- 
- 
Randomizationh 
X 
- 
- 
- 
- 
- 
- 
- 
Demographics/medical history/prior 
medications or proceduresi 
X 
- 
- 
- 
- 
- 
- 
- 
Concomitant medication/procedures 
evaluationi 
Continuous from ≤ 28 days before randomization until 30 days after the last dose of study 
treatment 
- 
EGFR/ALK testing on tumor tissue (if 
status not available)j 
X 
- 
- 
- 
- 
- 
- 
- 
Confirmation of mediastinal nodal 
involvement, if applicable 
X 
 
- 
- 
- 
- 
- 
- 
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Assessment 
Screeninga 
Treatment Cycles 
End-of-
Treatment 
Visit b 
Safety 
Follow-up 
Visit c 
Tumor 
Assessment 
/Survival 
Follow-up d 
Cycles 1 to 2 during 
cCRT Phase 
(Cisplatin and 
Etopside: every 28 
days; Chemotherapy 
other than cisplatin 
and etopside: every 21 
days) 
≥ Cycle 3 and up to 12 
months 
(ociperlimab and 
tislelizumab or 
tislelizumab: every 21 
days; 
Durvalumab: every 14 
or 28e days) 
Days (Window) 
-28 to -1 
1 (+2 
or ±3)f 8 (±3) 15 (±3) 
1 (±3)g 
0 to 7 days 
30 (±7), 60 
and 90 (±14) 
days after last 
dose 
Every 12 
weeks (±7 or 
14 days) 
SAFETY ASSESSMENTS 
AE evaluationk 
Continuous from informed consent until 30 days after the last dose of study treatment for AEs; 90 days after the 
last dose of ociperlimab or tislelizumab or durvalumab for imAEs. 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. 
Physical examinationl 
X 
X 
X 
X 
X 
X 
- 
- 
Vital signs/height and weightm 
X 
X 
X 
X 
X 
X 
- 
- 
ECOG PS 
X 
X 
X 
X 
X 
X 
- 
- 
Body surface area calculation 
- 
X 
Xn 
Xn 
- 
- 
- 
- 
Pulmonary function Testo 
X 
Only if clinically indicated 
12-lead electrocardiogram 
X 
Only if clinically indicated 
X 
- 
- 
Hematology laboratoryp 
X 
X 
X 
X 
X 
X 
- 
- 
Chemistry laboratoryp 
X 
X 
X 
X 
X 
X 
- 
- 
CK and CK-MBp 
X 
X 
X 
X 
X 
X 
- 
- 
Coagulation laboratoryp 
X 
X 
- 
- 
X 
X 
- 
- 
Thyroid functionq 
X 
Every 2 cycles or each cycleq 
X 
- 
- 
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Assessment 
Screeninga 
Treatment Cycles 
End-of-
Treatment 
Visit b 
Safety 
Follow-up 
Visit c 
Tumor 
Assessment 
/Survival 
Follow-up d 
Cycles 1 to 2 during 
cCRT Phase 
(Cisplatin and 
Etopside: every 28 
days; Chemotherapy 
other than cisplatin 
and etopside: every 21 
days) 
≥ Cycle 3 and up to 12 
months 
(ociperlimab and 
tislelizumab or 
tislelizumab: every 21 
days; 
Durvalumab: every 14 
or 28e days) 
Days (Window) 
-28 to -1 
1 (+2 
or ±3)f 8 (±3) 15 (±3) 
1 (±3)g 
0 to 7 days 
30 (±7), 60 
and 90 (±14) 
days after last 
dose 
Every 12 
weeks (±7 or 
14 days) 
HBV/HCV testr  
X 
As clinically indicated  
- 
- 
Urinalysisp  
X 
As clinically indicated 
- 
- 
β-hCG pregnancy tests 
X 
X 
- 
- 
X 
X 
X 
- 
EFFICACY ASSESSMENTS 
Tumor assessment CT/MRI 
X 
Tumor imaging will be performed approximately every 9 weeks (± 7 days) from randomization, for 
the first 54 weeks, and every 12 weeks (± 7 days) thereafter based on RECIST v1.1. The first tumor 
assessment after randomization (the 9-week tumor assessment) is allowed to be performed within 42 
days after cCRT, and should take place before the initiation of immunotherapy after the cCRT phase.
Following the first progression assessed by the investigator, patients will be assessed every 12 weeks
(± 7 days) for a second progression (using the patient’s status at the first progression as reference for 
assessment of second progression). 
FDG-PET/CT and Brain MRI with contrast
or head CT scan with contrast 
X 
Only if clinically indicated 
QLQ-C30, QLQ-LC13, EQ-5D-5Lt 
- 
Cycle 1 and every 6 weeks thereafter 
X 
- 
- 
PGI-St 
- 
X 
- 
- 
At Week 25 and Week 
43 
- 
- 
- 
PRTSEt 
- 
Week 7, Week 25, and Week 43 
- 
- 
- 
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Assessment 
Screeninga 
Treatment Cycles 
End-of-
Treatment 
Visit b 
Safety 
Follow-up 
Visit c 
Tumor 
Assessment 
/Survival 
Follow-up d 
Cycles 1 to 2 during 
cCRT Phase 
(Cisplatin and 
Etopside: every 28 
days; Chemotherapy 
other than cisplatin 
and etopside: every 21 
days) 
≥ Cycle 3 and up to 12 
months 
(ociperlimab and 
tislelizumab or 
tislelizumab: every 21 
days; 
Durvalumab: every 14 
or 28e days) 
Days (Window) 
-28 to -1 
1 (+2 
or ±3)f 8 (±3) 15 (±3) 
1 (±3)g 
0 to 7 days 
30 (±7), 60 
and 90 (±14) 
days after last 
dose 
Every 12 
weeks (±7 or 
14 days) 
PHARMACOKINETIC ASSESSEMENTS 
Pharmacokineticsu 
- 
Xu 
- 
- 
Cycle 5, 9, 17 
X 
- 
- 
Anti-ociperlimab and anti-tislelizumab 
blood samplesv 
- 
Xv 
- 
- 
Cycle 5, 9, 17 
X 
- 
- 
BIOMARKER ASSESSMENTS 
Archived tumorw 
X 
- 
- 
- 
- 
- 
- 
- 
Fresh tumor biopsyw 
X (if needed)
 
 
 
 
X 
(optional) 
w 
 
 
Biomarkers: whole bloodx 
- 
X 
(optio
nal) 
- 
- 
X (optional) 
X 
(optional) 
 
 
TREATMENT 
Arm A or B: Tislelizumab ± Ociperlimab 
administration 
- 
X 
- 
- 
X 
- 
- 
- 
Arm C: durvalumab administration 
- 
- 
- 
- 
X 
- 
- 
- 
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Assessment 
Screeninga 
Treatment Cycles 
End-of-
Treatment 
Visit b 
Safety 
Follow-up 
Visit c 
Tumor 
Assessment 
/Survival 
Follow-up d 
Cycles 1 to 2 during 
cCRT Phase 
(Cisplatin and 
Etopside: every 28 
days; Chemotherapy 
other than cisplatin 
and etopside: every 21 
days) 
≥ Cycle 3 and up to 12 
months 
(ociperlimab and 
tislelizumab or 
tislelizumab: every 21 
days; 
Durvalumab: every 14 
or 28e days) 
Days (Window) 
-28 to -1 
1 (+2 
or ±3)f 8 (±3) 15 (±3) 
1 (±3)g 
0 to 7 days 
30 (±7), 60 
and 90 (±14) 
days after last 
dose 
Every 12 
weeks (±7 or 
14 days) 
Radiotherapy administrationy 
- 
60 Gy in 30 fractions 
(2 Gy per day/5 days per 
week) 
- 
- 
- 
- 
Cisplatin Plus Etoposide 
Etoposide administrationz 
- 
X (D1-
D5) 
- 
- 
- 
- 
- 
- 
Cisplatin administrationaa 
- 
X 
X 
- 
- 
- 
- 
- 
Carboplatin Plus paclitaxel 
Appropriate chemotherapy pre-medications
administrationbb 
- 
X 
X 
X 
- 
- 
- 
- 
Paclitaxel administrationcc 
- 
X 
X 
X 
- 
- 
- 
- 
Carboplatin administrationdd 
- 
X 
X 
X 
- 
- 
- 
- 
Cisplatin Plus Pemetrexed 
Appropriate chemotherapy pre-medications
administrationee 
- 
X 
- 
- 
- 
- 
- 
- 
Pemetrexed administrationff 
- 
X 
- 
- 
- 
- 
- 
- 
Cisplatin administrationgg 
- 
X 
- 
- 
- 
- 
- 
- 
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Assessment 
Screeninga 
Treatment Cycles 
End-of-
Treatment 
Visit b 
Safety 
Follow-up 
Visit c 
Tumor 
Assessment 
/Survival 
Follow-up d 
Cycles 1 to 2 during 
cCRT Phase 
(Cisplatin and 
Etopside: every 28 
days; Chemotherapy 
other than cisplatin 
and etopside: every 21 
days) 
≥ Cycle 3 and up to 12 
months 
(ociperlimab and 
tislelizumab or 
tislelizumab: every 21 
days; 
Durvalumab: every 14 
or 28e days) 
Days (Window) 
-28 to -1 
1 (+2 
or ±3)f 8 (±3) 15 (±3) 
1 (±3)g 
0 to 7 days 
30 (±7), 60 
and 90 (±14) 
days after last 
dose 
Every 12 
weeks (±7 or 
14 days) 
Carboplatin Plus Pemetrexed 
Appropriate chemotherapy pre-medications
administrationhh 
- 
X 
- 
- 
- 
- 
- 
- 
Pemetrexed administrationii 
- 
X 
- 
- 
- 
- 
- 
- 
Carboplatin administrationjj 
- 
X 
- 
- 
- 
- 
- 
- 
FOLLOW-UP 
Survival status 
- 
- 
- 
- 
- 
- 
X 
X 
Subsequent therapy since IP 
discontinuation 
- 
- 
- 
- 
- 
- 
X 
X 
Abbreviations: ADA, antidrug antibody; AE, adverse event; ALK, anaplastic lymphoma kinase; β-hCG, beta human chorionic gonadotropin; C, Cycle ; cCRT, 
concurrent chemoradiotherapy; CD, cluster of differentiation; CK, creatine kinase; CK-MB, creatine kinase cardiac muscle isoenzyme; CR, complete response; 
CT, computed tomography; D, day; DLCO, diffusing capacity of the lungs for carbon monoxide; ECOG PS, Eastern Cooperative Oncology Group Performance 
Status; EGFR, epidermal growth factor receptor; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer-Quality of Life C30 
questionnaire; EOT, End of Treatment; EQ-5D-5L, European Quality of Life-5 Dimensions health state classifier to 5 Levels; FDG-PET, fluorodeoxyglucose - 
positron emission tomography; FEV, forced expiratory volume; FFPE, formalin-fixed paraffin-embedded; GEP, gene expression profiling; HBcAb, hepatitis B 
core antibody; HBsAb, hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; imAE, immune-
mediated adverse event; INR, international normalized ratio; IEC, Independent Ethics Committee; IP, investigational product; IRB, Institutional Review Board; 
IRT, integrated response technology; LC13, Lung Cancer Module of EORTC QLQ-C30; MRI, magnetic resonance imaging; NCI, National Cancer Institute; 
NSCLC, non-small cell lung cancer; PD, progressive disease; PD-L1, programmed cell death protein-ligand 1; PK, pharmacokinetics; PGI-S, patient reported 
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global impression of severity; PRO-CTCAE, Patient-Reported Outcome Version of Common Terminology Criteria of Adverse Events; PT, prothrombin time; 
SAE, serious adverse event; TIL, tumor-infiltrating lymphocyte; TMB, tumor mutational burden. 
a Written informed consent is required before performing any study-specific tests or procedures. Screening evaluations must be completed within 28 days of 
randomization. Results of standard of care tests or examinations performed before obtaining informed consent and within 28 days before randomization may be 
used for screening assessments rather than repeating such tests. 
 b EOT is defined as the date investigator determines that study treatment will no longer be used. For Arm A, patients shall have an EOT visit only if both study 
drugs were discontinued. Patients shall have an EOT visit within 7 days after the date investigator determines that study treatment will no longer be used, or 
before the initiation of a new anticancer treatment, whichever occurs first. However, the EOT visit may occur later than 7 days for specific circumstances, such 
as prolonged hospitalization. If routine laboratory tests (eg, hematology, serum chemistry, CK and CK-MB, coagulation, etc.) are completed within 7 days 
before the EOT, these tests need not be repeated. Tumor assessment is not specially required at the EOT. Patients who discontinue study treatment before 
disease progression assessed by the investigator will need to undergo tumor assessments as outlined in Section 4.5 of Appendix 17; in some cases the time 
window of tumor assessment might overlap with EOT and/or Safety Follow-up visit. In the cases the time window of EOT and Safety Follow-up visit 
overlapped, these two visits can be combined. 
 c The Safety Follow-up Visit 60-Day and 90-Day Follow-up Visit could be completed at the site or by telephone. 
 d Patients whose disease has not progressed at the end of the 12-month study treatment period will continue to perform tumor imaging every 12 weeks (± 7 days) 
until progressive disease per RECIST v1.1. Following the first progression assessed by the investigator, patients will be assessed every 12 weeks (± 7 days) for 
a second progression (using the patient’s status at the first progression as reference for assessment of second progression). A patient’s second progression status 
is defined according to local standard clinical practice and may involve any of: objective radiological, symptomatic progression or death. Measurements per 
RECIST v1.1 will not be collected for assessment of PFS2. Survival follow-up information will be collected via telephone calls, patient medical records, and/or 
clinic visits approximately every 3 months after the Safety Follow-up Visit until death, loss to follow-up, withdrawal of consent, or end of study by sponsor. All 
patients will be followed for survival and subsequent anticancer therapy information unless a patient requests to be withdrawn from follow-up. Schedule of 
Survival Follow-up Visit can be modulated to combine with tumor assessment of PFS or PFS2 for operational convenience while keeping the follow-up visits 
interval as approximately every 12 weeks. 
e Durvalumab regimen:10 mg/kg Q2W (or 1500 mg Q4W where the dosage has been approved by a local health authority). For the patient whose body weight is 
< 30 kg, only the regimen of durvalumab 10 mg/kg Q2W is applicable. Refer to local prescribing information of durvaluamb for detailed instructions. 
f Patients should have Cycle 1 Day 1 (C1D1) dosing initiated within 2 business days of randomization. For C2D1 and C3D1, patients should receive study drugs 
with ± 3 days. 
g Cycle 3 Day 1 dosing may be delayed in order to ensure that cCRT is completed before Cycle 3 Day 1 dosing. 
h Patients will be randomized into either Arm A or Arm B or Arm C via IRT. 
i Includes age or year of birth, sex, and self-reported race/ethnicity; 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. Refer to Section 4.1.3 of Appendix 17 for additional information. 
j For patients with nonsquamous NSCLC histology with unknown EGFR mutation status, tissue-based test results are mandatory at screening; patients with 
unknown ALK status may be enrolled. Patients with squamous NSCLC and unknown EGFR mutation or ALK status will not be required to be tested at 
screening. EGFR mutation status may be assessed locally or at a central laboratory. An additional ≥ 6 slides are required if EGFR mutation status needs to be 
tested in a central lab. 
k The AEs and laboratory abnormalities will be graded per NCI-CTCAE v5.0. All AEs will also be evaluated for seriousness. After the informed consent form 
has been signed, but before the first administration of study treatment, only SAEs should be recorded. After initiation of study treatment, all AEs and SAEs, 
regardless of relationship to study treatment, will be reported until either 30 days after last dose of study treatment (including chemoradiotherapy) (s) or 
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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, tislelizumab, or durvalumab 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. 
l At the Screening Visit, a complete examination will be conducted, including evaluations of 1) head, eyes, ears, nose, and throat; 2) cardiovascular; 3) 
dermatological; 4) musculoskeletal; 5) respiratory; 6) gastrointestinal; and 7) neurological systems. For any abnormality at subsequent visits (and as clinically 
indicated), limited, symptom-directed physical examinations will be performed. 
m Vital signs collected on study include body temperature (˚C), pulse rate, and blood pressure (systolic and diastolic). Pulse rate and blood pressure should be 
collected while the patient is in a seated position after resting for 10 minutes. The patient’s vital signs are required to be recorded within 60 minutes before, 
during, and within 30 minutes after the completion of infusion of study treatment (ociperlimab and tislelizumab in Arm A, tislelizumab in Arm B, and 
durvalumab in Arm C). For subsequent infusions, vital signs will be collected within 60 minutes before infusion and, if clinically indicated, during and within 
30 minutes after the completion of infusion. Weight is required to be measured once on the scheduled assessment day and before study treatment if there is any. 
Height measurements are only required at screening. 
n Day 8 and Day 15 body surface area calculation only applies for patients who plan to receive chemotherapy on Day 8 and/or Day 15. 
o Pulmonary function testing includes assessment of spirometry and oxygenation. The assessment of oxygenation should include at least pulse oximetry 
(percutaneous arterial oxygen saturation, SpO2) at rest and with exercise; an assessment of diffusion capacity is optional. Respective test results should 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, absolute FEV1 value < 1L, FEV1 of age and sex adjusted predicted performance levels < 50%, DLCO (if performed) < 40% 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. 
p Local and/or central laboratory assessments on serum chemistry, hematology, CK and CK-MB, coagulation, and urinalysis will be conducted, of which certain 
elements will be collected as specified in Appendix 2. If hematology and serum chemistry at screening are not performed within 7 days of the planed C1D1, 
these tests should be repeated and reviewed before randomization. If the coagulation test has been performed and reviewed during screening, it is not 
mandatory to repeat this test before C1D1 unless investigator deems necessary. Hematology, serum chemistry (including liver function tests), CK and CK-MB 
as specified in Appendix 2 should be performed weekly during cCRT phase, at the beginning of each subsequent cycle after cCRT, and the EOT Visit. After 
Cycle 1, these laboratory tests are to be performed and reviewed within 48 hours before study drug administration. Urinalysis is to be conducted during the 
treatment period only if clinically warranted. Refer to Section 4.4.4 and Section 5.3.5 of Appendix 17 for additional information regarding clinical assessment 
and management of clinical laboratory abnormalities.  
q Analysis of free T3 or total T3, free T4 or total T4, and thyroid stimulating hormone will be performed by a central laboratory or the local study site laboratory. 
Thyroid function tests will be performed at Screening, from C3D1 onwards, every 2 cycles for Arm A and Arm B (ie, Cycles 3, 5, 7, etc.), every 2 cycles for 
durvalumab-Q2W (ie, Cycles 3, 5, 7, etc.) and every cycle for durvalumab-Q4W, and at the EOT Visit. 
r Testing will be performed by a central laboratory and/or the local laboratory at screening and will include at screening HBV/HCV serology (HBsAg, HBsAb, 
HBcAb, and HCV antibody). In the case of positive HBsAg result or positive HCV antibody result, these tests will be followed by viral load assessment (HBV 
DNA or HCV RNA) at screening. After screening, HBV/HCV serology (HBsAg, HBsAb, HBcAb, and HCV antibody) and viral load assessment (HBV DNA 
and HCV RNA) may be performed if clinically indicated; for patients who have detectable HBV DNA or HCV RNA at screening or upon repeat testing, 
respective viral load testing will be performed every 12 weeks. 
s 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 first dose of study treatment. Urine pregnancy tests will be performed at each cycle before dosing, at EOT, and at each Safety 
Follow-up Visit. A serum pregnancy test must be performed if the urine pregnancy test is positive or equivocal. 
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t Patients will be asked to complete three PROs, that include the EORTC QLQ-C30, EORTC QLQ-LC13, and EQ-5D-5L questionnaires before any clinical 
activities are performed, or any health-related discussion with the health care providers, during on-study clinic visits at C1D1, and every 6 weeks thereafter for 
up to 12 months and/or EOT, whichever comes first. Patients also are asked to complete 2 questionnaires that include PGI-S at C1D1, Day1 of Week 25, and 
Day1 of Week 43 (all arms), and PRTSE at Day 1 of Week 7, Week 25, and Week 43 (all Arms). For patients in Arm C who receive Q4W regimen, if the 
questionnaires visit falls into the interval of two dosing visits, it could be re-scheduled to combine with the nearest next dosing cycle visit. 
u Only for patients randomized to Arm A and Arm B: Procedures for collection of ociperlimab and tislelizumab PK and ADA samples are described in the 
Laboratory Manual. Predose (within 60 minutes before starting infusion) PK samples are required to be collected at Day 1 of Cycles 1, 2, 5, 9, 17, and at the 
EOT Visit for both ociperlimab and tislelizumab. Postdose (within 30 minutes after completing infusion) PK samples for both ociperlimab and tislelizumab are 
required to be collected on Day 1 of Cycles 1 and 5. Should a patient present with any ≥ Grade 3 imAE, an additional blood PK sample may be taken to 
determine the serum concentration of ociperlimab or tislelizumab. These tests are required when it is allowed by local regulations/IRBs/IECs. 
v All immunogenicity (ADAs) blood samples (serum) will be collected predose (within 60 minutes before dose) on dosing days Day 1 of Cycles 1, 2, 5, 9, 17, 
and the EOT Visit for both ociperlimab and tislelizumab in Arm A or tislelizumab in Arm B. All samples should be drawn at the same time as blood collection 
for predose PK analysis. These tests are required when it is allowed by local regulations/IRBs/IECs. 
w Tissue-based biomarkers (including but not limited to PD-L1, TIGIT, CD226, CD155, CD112, GEP, TMB, gene mutations, MSI, and TILs) will be assessed on 
baseline and biopsy tissue at disease progression. Archival tumor tissues (FFPE block [preferred] or approximately 15 [at least 6] freshly cut unstained FFPE 
slides) with an associated pathology report or a tumor biopsy at baseline are required to be collected. For patients with readily accessible tumor lesions and who 
consent to the biopsies, a fresh biopsy is highly recommended at baseline. Optional biopsies will also be taken at the time of disease progression. (Note: For the 
sites in China mainland, tissues will be obtained to test the expression of PD-L1, TIGIT, CD226, CD155, CD112, GEP, TMB, gene mutations, MSI, and TILs 
at baseline, and at disease progression/reoccurrence). 
x Optional blood samples will be taken at C1D1 (predose), C3D1 (predose), C4D1 (predose), and at the EOT Visit after the disease progression to explore 
association of blood-based biomarkers with response, resistance and prognosis. (Note: Blood-based biomarkers, including ctDNA, TMB, MSI, EVs and gene 
mutational profiles, will be explored in the blood samples which will be collected in the sites in China mainland). 
y The schedule of radiotherapy and chemotherapy administrations is detailed in the specific section. Once commenced, radiotherapy should be given for 5 
consecutive days weekly. Radiotherapy commences on Day 1 of chemotherapy, with a ± 3 days administrative window allowed after C1D1. 
 
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1.2. 
Screening Period 
Screening evaluations will be performed within 28 days before randomization. Patients who 
agree to participate in this study will sign the informed consent form (ICF) before undergoing 
any screening procedure. 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. 
Archival tumor tissue must be collected for the purpose of biomarker analysis. If no archival 
samples are available, a fresh tumor biopsy at baseline is mandatory. 
1.3. 
Treatment Period 
After completing all screening activities, eligible patients will be randomized in a 1:1:1 ratio to 
3 arms (Arm A, Arm B, and Arm C). Randomization will be stratified by age (< 65 years versus 
≥ 65 years), PD-L1 expression in TC (≥ 1% versus < 1%), and histology (squamous versus 
nonsquamous). 
Patients will receive open-label treatments as follows: 
• Arm A: Two cycles of ociperlimab 900 mg Q3W combined with tislelizumab 200 mg 
Q3W intravenously with cCRT, followed by ociperlimab 900 mg Q3W combined with 
tislelizumab 200 mg Q3W intravenously up to 12 months after the completion of cCRT 
phase or PD per RECIST v1.1, unacceptable toxicity, or death, or until another 
discontinuation criterion is met 
• Arm B: Two cycles of tislelizumab 200 mg intravenously Q3W combined with cCRT, 
followed by tislelizumab 200 mg intravenously Q3W up to 12 months after the 
completion of cCRT phase 
• Arm C: Two cycles of cCRT, followed by durvalumab 10 mg/kg intravenously Q2W (or 
1500 mg Q4W where the dosage has been approved by a local health authority) up to 
12 months after the completion of cCRT phase or PD per RECIST v1.1, unacceptable 
toxicity, or death, or until another discontinuation criterion is met 
Radiological assessment of tumor-response status will be performed approximately every 
9 weeks (± 7 days) from randomization, for the first 54 weeks, and every 12 weeks (± 7 days) 
thereafter based on RECIST v1.1. The first tumor assessment after randomization (the 9-week 
tumor assessment) is allowed to be performed within 42 days after the cCRT phase, and should 
take place before the initiation of immunotherapy (ociperlimab and tislelizumab in Arm A, 
tislelizumab in Arm B, durvalumab in Arm C) after the cCRT phase. Tumor response will be 
assessed by the investigator. Tumor assessments are required to be performed on schedule 
regardless of whether study treatment has been administered or held; that is, tumor assessments 
should not be adjusted for delays in cycles, except for the first 9-week tumor assessment. 
Tumor response will be assessed by the investigator. 
Administration of study treatment will continue up to 12 months following the completion of 
cCRT, or until PD as assessed by the investigator per RECIST v1.1, unacceptable toxicity, or 
death, or until another discontinuation criterion is met. 
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A patient who discontinues study treatment for reasons other than disease progression (eg, 
toxicity, completion of the 12-month treatment) will continue to undergo tumor assessments 
following the original plan until the patient experiences PD per RECIST v1.1 assessed by the 
investigator, withdraws consent, is lost to follow-up, or death, or until the study terminates, 
whichever occurs first. 
Study treatment beyond initial PD per RECIST 1.1 
If at the investigator’s discretion a patient could continue to benefit from the immunotherapy 
(ociperlimab and tislelizumab combination treatment in Arm A, tislelizumab in Arm B, or 
durvalumab in Arm C) after PD per RECIST v1.1, the patient may continue their assigned 
treatment. The following criteria must be met in order to treat patients who may continue to 
benefit from study drugs after PD:  
• Absence of clinical symptoms and signs of disease progression (including clinically 
significant worsening of laboratory values) 
• Stable ECOG Performance Status (≤ 1) 
• Absence of rapid progression of disease or of progressive tumor at critical anatomical 
sites (eg, cord compression) that requires urgent alternative medical intervention 
• Investigators must obtain written informed consent for treatment beyond radiologic 
PD and inform patients that this practice is not considered standard in the treatment 
of cancer 
The decision to continue study drug(s) beyond initial PD per RECIST v1.1 must be agreed upon 
with the medical monitor and documented in the study records. 
Tumor assessment should continue as planned in patients receiving study drug(s) beyond initial 
PD per RECIST v1.1 criteria. Tumor assessment in such patients should continue until study 
treatment discontinuation. 
To determine the PK properties of ociperlimab and tislelizumab, and host immunogenic response 
to ociperlimab and tislelizumab, blood samples will be collected at various timepoints as outlined 
in Table 14. 
Optional blood samples will be collected at C1D1 (predose), C3D1 (predose), C4D1 (predose), 
and at the EOT Visit after the disease progression (Table 14). All these blood samples will be 
collected to explore association of blood-based biomarkers with response, resistance and 
prognosis. (Note: Blood-based biomarkers, including ctDNA, TMB, MSI, EVs and gene 
mutational profiles, will be explored in the blood samples which will be collected in the sites in 
China mainland). 
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 4.4 of 
Appendix 17 and the Schedule of Assessments (Table 14) 
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1.4. 
End of Treatment 
The End-of-Treatment (EOT) Visit is planned when the investigator determines that study 
treatment will no longer be used. 
The date of End-of-Treatment (EOT) is defined as the date investigator determines that study 
treatment will no longer be used. Patients shall have an EOT Visit within 7 days after the date 
investigator determines that study treatment will no longer be used, or before the initiation of a 
new anticancer treatment, whichever occurs first. For Arm A, patients shall have an EOT Visit 
only if both study drugs were discontinued. However, the EOT Visit may occur later than 7 days 
for specific circumstances, such as prolonged hospitalization. 
See Table 14 for assessments to be performed at the EOT. 
1.5. 
Safety Follow-up 
The Safety Follow-up Visit is planned when the investigator determines that study treatment will 
no longer be used. 
The date of Safety Follow-up Visit is defined as the date when safety assessments and 
procedures are performed after the last dose of study treatment for an individual patient. 
All patients that discontinue study treatment (both study drugs if in Arm A) will have a Safety 
Follow-up Visit approximately 30 days (± 7 days) after the last dose of study drug or before the 
initiation of new anticancer therapy, whichever occurs first. This visit will include the collection 
of data about AEs and serious adverse events (SAEs) that may have occurred after the patient 
discontinued the study drug. The investigator or his/her designee will continue to collect 
information on new anticancer therapy given after the last dose of study drug. In the cases the 
time window of EOT and Safety Follow-up visit overlapped, these two visits can be combined. 
See Table 14 for assessments to be performed at the Safety Follow-up Visit. 
Additional Safety Follow up visits at 60 and 90 days after the last dose of study drug can be 
required (in clinic or over the phone, as needed based on assessments required). Patients will be 
contacted by telephone to assess imAEs and relevant concomitant medication use (ie, those 
associated with an imAE or any new anticancer therapy). These contacts should be made at 
60 days (± 14 days) and 90 days (± 14 days) after the last dose of study treatment regardless of 
whether the patient starts a new anticancer therapy. If a patient reports a suspected imAE at a 
telephone follow-up contact, the investigator should arrange an unscheduled visit if further 
assessment is indicated. 
1.6. 
Survival Follow-up 
Patients will be followed for survival follow-up data after discontinuation of study treatment via 
telephone calls, patient medical records, and/or clinic visits approximately every 3 months 
(± 14 days) after the 90-Day Safety Follow-up Visit or as directed by the sponsor until death, 
loss to follow-up, withdrawal of consent, or end of study by the sponsor. 
During the survival follow-up period subsequent anticancer therapy information including 
medication start date, end date, reason for treatment, and date of progression after receiving the 
subsequent anticancer therapy will be collected. 
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1.7. 
Discontinuation From the Study Treatment or From the Study 
1.7.1. 
Discontinuation From Study Treatment 
Patients have the right to withdraw from the study or 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 4.5 of 
Appendix 17), safety (Section 4.4 of Appendix 17), and survival (Section 1.6 of Appendix 17), 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 from the study treatment for reasons that include, but are not limited to, 
the following: 
• Radiographic disease progression per RECIST v1.1 
• AE 
• Use of any concurrent antineoplastic therapy (ie, chemotherapy, hormonal therapy, 
immunotherapy, or standard or investigational agents [including herbal medicine and 
patent medicines] for the treatment of cancer) (Section 3.3 of Appendix 17). 
• Patient noncompliance 
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. 
Patients will discontinue from the study treatment for reasons following: 
• Patient’s decision to withdraw from study treatment 
• Any medical condition that the investigator determines may jeopardize the patient’s 
safety, if he or she were to continue the study treatment 
• Pregnancy. 
1.7.2. Patient Discontinuation From Study (End of Study for an Individual Patient)  
Patients will discontinue study for reasons which include, but are not limited to, the following:  
• Patients withdrawal of consent 
• Death 
• Lost to follow-up 
• Patients have completed all study assessments 
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1.8. 
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 
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 
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 IRBs/IECs of the early termination of the study. 
At the end of study, patients who are still in the originally assigned treatment within 12 months 
after the cCRT phase and continue to benefit from the treatment at study termination in the 
opinion of the investigator, will be offered the option to continue treatment in a 
company-sponsored clinical trial until treatment duration reach 12 months after the cCRT phase 
or it 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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2. 
STUDY TREATMENT 
2.1. 
Formulation, Packaging, and Handling 
2.1.1. 
Ociperlimab 
Ociperlimab is a monoclonal antibody formulated for intravenous infusion in a single-use vial 
(20 mL glass vial, USP Type I) containing a total of 300 mg antibody in 15 mL of buffered 
isotonic solution. 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 Investigator’s Brochure for other details regarding 
ociperlimab. 
2.1.2. 
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 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 Tislelizumab Investigator’s Brochure for other details regarding 
tislelizumab. 
2.1.3. 
Durvalumab 
Durvalumab is a monoclonal antibody formulated for intravenous infusion in a single-dose vial, 
containing a total of 500 mg antibody in 10 mL (or 120 mg antibody in 2.4 mL, 50 mg/mL) clear 
to opalescent, colorless to slightly yellow solution. 
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. 
Please refer to the Pharmacy Manual for details regarding administration, accountability, and 
disposal. 
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2.1.4. 
Chemotherapy 
Management (ie, handling, storage, administration, and disposal) of cisplatin, carboplatin, 
etoposide, paclitaxel, pemetrexed will be in accordance with the relevant local guidelines and/or 
prescribing information/summary of product characteristics. 
For further details, see the manufacturer’s prescribing information for the respective 
chemotherapeutic agents. 
2.2. 
Dosage, Administration, and Compliance 
Planned dosage and dosing frequency for study drugs are presented in Table 15 and Table 16. 
For Arm A and Arm B, the first dose of the immunotherapy (ociperlimab and tislelizumab in 
Arm A, tislelizumab in Arm B) is to be administered within 2 business days of randomization. 
C1D1 is defined as the day of the administration of the first dose of the immunotherapy. 
Immunotherapy will be given starting from C1D1 in the cCRT phase and continued for a 
duration up to 12 months after the cCRT phase. 
For Arm A and Arm B, during the cCRT phase, immunotherapy administration should be given 
followed by chemotherapy. In Arm A, ociperlimab and tislelizumab should be administered on 
the same day if feasible, in case the logistical circumstances do not allow for all of the 
intravenous study drug (including ociperlimab, tislelizumab, and platinum-based doublet 
chemotherapy) administration on the same day, then chemotherapy should start as soon as 
possible within the following 3 days. If the first doses of ociperlimab and tislelizumab were not 
administered on the same day for reasons other specified, C1D1 is defined as the day of 
administration of the first dose of tislelizumab. 
For Arm C, C1D1 is defined as the day of administration of the first dose of chemotherapy 
and/or radiation. 
The choice of the chemotherapy regimen will be made at the investigator’s discretion, but the 
platinum and pemetrexed regimen is only available for patients with nonsquamous histology. 
For all 3 arms, during the cCRT phase, for all patients, RT commences with chemotherapy in the 
beginning of Cycle 1, in the best case, on C1D1. If local technical or logistical circumstances do 
not allow the start of RT on C1D1, RT is strongly recommended to start within 3 days after 
C1D1, but no later than 7 days after C1D1. On the day of treatment, chemotherapy should 
generally be delivered before RT. It is recommended that RT should follow within 30 to 
60 minutes after the completion of chemotherapy or post-cisplatin hydration when administrative 
circumstance allows, such as when both chemotherapy and RT are administered at the same 
center/location. However, in other situations, logistical considerations may result in RT being 
delivered before the administration of chemotherapy or post-cisplatin hydration, eg, when the RT 
and chemotherapy are delivered at 2 separate centers/locations. It is allowed if RT and/or 
chemotherapy do not start on C1D1 for administrative reasons, and the start of administration of 
RT and/or chemotherapy is still within the 3-day window after C1D1. In this case, the full 
planned dose of RT and chemotherapy should be administered unless other specified. 
For the 3 arms, in the event that RT is delayed to allow recovery from toxicities, the 
administration of immunotherapy (ociperlimab and tislelizumab in Arm A, tislelizumab in 
Arm B, and durvalumab in Arm C) after cCRT (starting from Cycle 3 Day 1) will not begin until 
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completion of the full course of RT. Efforts should be made to administer Cycle 3 Day 1 
immunotherapy within 14 days after the cCRT phase; if this cannot be managed, Cycle 3 Day 1 
immunotherapy should be given no later than 42 days after the cCRT phase. 
All patients will be monitored continuously for AEs. Treatment modifications (eg, dose delay, 
reduction, interruption or discontinuation) will be based on specific laboratory and AE criteria, 
as described in Section 2.5 of Appendix 17. Guidelines for dose modification or treatment 
discontinuation and for the management of imAE and infusion-related reactions are provided in 
detail in Section 5.7 of Appendix 17 and Appendix 12. 
Accurate records of all study treatment received, dispensed, returned, and disposed should be 
maintained in the site’s Drug Inventory Log. Refer to the Pharmacy Manual for details of study 
drug management, drug preparation, storage, and administration. 
Table 15: 
Planned Dose, Frequency of Administration, and Route of Administration 
for Study Drugs 
Study drugs 
Dose 
Frequency of 
Administration 
Route of 
Administration 
Duration of 
Treatment 
Ociperlimab 
900 mg 
Day 1 of each cycle 
(21 days) 
Intravenous 
Refer to 
Section 1.3  
Tislelizumab 
200 mg 
Day 1 of each cycle 
(21 days) 
Intravenous 
Refer to 
Section 1.3 
Durvalumab 
10 mg/kg or 1500 mg a 
Day 1 of each cycle 
(14 days) or Day 1 
of each cycle (28 
days) 
Intravenous 
Refer to 
Section 1.3 
Cisplatin Plus 
Etoposide 
Etoposide 
50 mg/m2 
Day 1 to Day 5 of 
each cycle 
Intravenous 
2 cycles (each 
cycle 28 days) 
Cisplatin 
50 mg/m2 
Day 1 and Day 8 of 
each cycle 
Intravenous 
2 cycles (each 
cycle 28 days) 
Carboplatin 
Plus 
Paclitaxel 
Paclitaxel 
40-50 mg/m2 
Weekly for 6 weeks 
Intravenous 
6 weeks 
Carboplatin 
AUC 2 
Weekly for 6 weeks 
Intravenous 
6 weeks 
Cisplatin Plus 
Pemetrexed 
Pemetrexed 
500 mg/m2 
Day 1 of each cycle 
Intravenous 
2 cycles (each 
cycle 21 days) 
Cisplatin 
75 mg/m2 
Day 1 of each cycle 
Intravenous 
2 cycles (each 
cycle 21 days) 
Carboplatin 
Plus 
Pemetrexed 
Pemetrexed 
500 mg/m2 
Day 1 of each cycle 
Intravenous 
2 cycles (each 
cycle 21 days) 
Carboplatin 
AUC 5 
Day 1 of each cycle 
Intravenous 
2 cycles (each 
cycle 21 days) 
Abbreviation: AUC, area under the concentration-time curve; Q4W, every 4 weeks. 
a 1500 mg Q4W will be used where the dosage has been approved by a local health authority. 
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Table 16: 
Administration of Ociperlimab and Tislelizumab and Monitoring Time 
Cycle 
Ociperlimab and Tislelizumab combination 
in Arm A 
Tislelizumab in Arm B 
Cycle 1 
Day 1 
Tislelizumab infusion for ≥ 60 minutes 
followed by 
Ociperlimab infusion for ≥ 60 minutes 
Patient monitoring for ≥ 120 minutes 
Tislelizumab infusion for ≥ 60 minutes 
Patient monitoring for ≥ 60 minutes 
Cycle 2 
Day 1 
Tislelizumab infusion for ≥ 60 minutes 
followed by 
Ociperlimab infusion for ≥ 60 minutes 
Patient monitoring for ≥ 120 minutes 
Tislelizumab infusion for ≥ 60 minutes 
Patient monitoring for ≥ 60 minutes 
Cycle 3 
Day 1 
onwards 
Tislelizumab infusion for ≥ 30 minutes 
followed by 
Ociperlimab infusion for ≥ 30 minutes 
Patient monitoring for ≥ 60 minutes 
Tislelizumab infusion for ≥ 30 minutes 
Patient monitoring for ≥ 30 minutes 
2.2.1. Ociperlimab and Tislelizumab 
Patients will receive tislelizumab 200 mg on Day 1 of each 21-day cycle (ie, Q3W) followed by 
the administration of ociperlimab 900 mg for Arm A, or patients will receive tislelizumab 200 
mg on Day 1 of each 21-day cycle (ie, Q3W) for Arm B. 
Ociperlimab and tislelizumab for Arm A and tislelizumab for Arm B are administered by 
intravenous infusion through an intravenous line containing a sterile, nonpyrogenic, 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. 
As specified in Table 16, the initial infusion (C1D1 and C2D1) will be delivered for 
≥ 60 minutes for each study drug of the immunotherapy in Arm A and Arm B; if this is well 
tolerated, then the subsequent infusions from Cycle 3 onward may be administered for 
≥ 30 minutes for each study drug of the immunotherapy in Arm A and Arm B, which is the 
shortest period permissible for infusion. 
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 
infusion speed is controlled through alternative means and consistent with approved institutional 
procedures. 
At the end of the infusion period, the line will be flushed with enough normal saline to make sure 
the complete doses of the immunotherapy are administered. 
As a routine precaution, after infusion of ociperlimab and tislelizumab in Arm A on Day 1 of 
Cycle 1 and Cycle 2, patients will be monitored for ≥ 2 hours in an area with resuscitation 
equipment and emergency agents; similarly, after infusion of tislelizumab in Arm B on C1D1 
and C2D1, patients will be monitored for ≥ 1 hour. From Cycle 3 onward, at least a 60‑minute 
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monitoring period is required in an area with resuscitation equipment and emergency agents for 
Arm A, and for Arm B, the monitoring period is at least 30 minutes. 
2.2.2. 
Durvalumab 
Durvalumab 10 mg/kg will be administered by intravenous infusion for ≥ 60 minutes every 
2 weeks (or 1500 mg Q4W where the dosage has been approved by a local health authority) up 
to 12 months after the cCRT phase. For the patient whose body weight is < 30 kg, only the 
regimen of durvalumab 10 mg/kg Q2W is applicable. 
Refer to the pharmacy manual and local prescribing information of durvaluamb for detailed 
instructions on drug preparation, storage, and administration. 
2.2.3. 
Chemotherapy 
2.2.3.1. 
Cisplatin Plus Etoposide 
Cisplatin 50 mg/m2 will be administered on Days 1 and 8, and etoposide 50 mg/m2 will be 
administered from Day 1 to Day 5 every 28 days for 2 cycles by intravenous infusion. 
For cisplatin, all patients should receive adequate hydration (including pretreatment hydration) 
and diuretics. Urinary output > 2000 mL should be maintained in the following 24 hours of the 
infusion. 
For etoposide, extravasation of infusion should be avoided. 
Additional pre-medications should be administered as per standard practice. 
2.2.3.2. 
Carboplatin Plus Paclitaxel 
Carboplatin AUC 2 weekly (by Calvert Equation and Cockcroft-Gault Equation, Appendix 14, 
and Table 17) and paclitaxel 40 to 50 mg/m² weekly (as per standard of care and treatment 
guidelines) will be administrated for 6 weeks by intravenous infusion. 
Once the initial dose of carboplatin is calculated it does not need to be recalculated for 
subsequent cycles unless the patient is experiencing toxicity and requires dose modification to a 
lower dose of carboplatin (Percy Ivy et al 2020). 
For paclitaxel, all patients should be pre-medicated with oral or injectable steroids according to 
the manufacturer’s prescribing information and/or standard practice. Due to their 
immunomodulatory effects, pre-medication with steroids should be limited when clinically 
feasible. Additionally, in the event of chemotherapeutic agent-related skin rash, topical steroid 
use is recommended as front-line treatment when clinically feasible. 
Needles or intravenous administration sets containing aluminum parts that may come in contact 
with carboplatin infusion should not be used for the preparation and administration of the drug. 
Aluminum can react with carboplatin causing precipitate formation and loss of potency. 
Additional pre-medications such as diphenhydramine, and H2 antagonists should be 
administered as per local standard practice. 
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2.2.3.3. 
Cisplatin Plus Pemetrexed 
Cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 will be administered on Day 1 every 21 days for 
2 cycles by intravenous infusion. 
For cisplatin, all patients should receive adequate hydration (including pretreatment hydration) 
and diuretics. Urinary output > 2000 mL should be maintained in the following 24 hours of the 
infusion. 
For pemetrexed, all patients should receive the appropriate supplementation of vitamin B12 and 
folic acid according to the manufacturer’s prescribing information and/or local standard practice. 
In addition, all patients should receive the appropriate corticosteroid pre-medications as per the 
local standard practice. Due to their immunomodulatory effects, pre-medication with steroids 
should be limited when clinically feasible. Additionally, in the event of chemotherapeutic 
agent-related skin rash, topical steroid use is recommended as front-line treatment when 
clinically feasible. 
Additional pre-medications should be administered as per standard practice. 
2.2.3.4. 
Carboplatin Plus Pemetrexed 
Carboplatin AUC 5 (by Calvert Equation and Cockcroft-Gault Equation, Appendix 14, and 
Table 17) and pemetrexed 500 mg/m2 will be administered on Day 1 every 21 days for 2 cycles 
by intravenous infusion. 
Once the initial dose of carboplatin is calculated it does not need to be recalculated for 
subsequent cycles unless the patient is experiencing toxicity and requires dose modification to a 
lower dose of carboplatin (Percy Ivy et al 2020). For patients who have ≥ 10% weight change 
from baseline or who experience CTCAE ≥ grade 2 renal toxicity (serum creatinine 
> 1.5 x ULN) recommend recalculating of the carboplatin dose for subsequent cycles. In patients 
who require carboplatin dose modification, if the creatinine at the time of dose modification is 
lower than the baseline creatinine that was used, recommend using the prior (higher) creatinine 
value to base dose modification on (Roisin O and Paul S 2012). Please refer to local prescribing 
information and local practice if any conflict with the recommendation above. 
For pemetrexed, all patients should receive the appropriate supplementation of vitamin B12 and 
folic acid according to the manufacturer’s prescribing information and/or local standard practice. 
In addition, all patients should receive the appropriate corticosteroid pre-medications as per the 
local standard practice. Due to their immunomodulatory effects, pre-medication with steroids 
should be limited when clinically feasible. Additionally, in the event of chemotherapeutic 
agent-related skin rash, topical steroid use is recommended as front-line treatment when 
clinically feasible. 
Needles or intravenous administration sets containing aluminum parts that may come in contact 
with carboplatin infusion should not be used for the preparation and administration of the drug. 
Aluminum can react with carboplatin causing precipitate formation and loss of potency. 
Additional pre-medications should be administered as per standard practice. 
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Table 17: 
Carboplatin Dose Calculation 
Calvert Formula For 
Carboplatin Dose 
Calculation (Calvert 
AH et al 1989) 
Carboplatin Dose (mg) = Target area under the curve (AUC 
mg/mL/min) x (GFR* + 25) 
*GFR estimated by calculated creatinine clearance (CrCl) using 
Cockcroft-Gault Equation as Appendix 14. 
Other Consideration for carboplatin dose calculation 
Note, the recommendations below are cited from NCCN Chemotherapy Templates (NCCN 
2020), please refer to local guidance if any conflict. 
Maximum Dose 
Calculation 
The FDA has recommended that physicians consider capping the 
dose of carboplatin for desired exposure (AUC) to avoid potential 
toxicity due to overdosing. The maximum dose is based on a GFR 
estimate that is capped at 125 mL/min for patients with normal renal 
function. 
For a target AUC = 5, the maximum dose is 5 x 150 = 750 mg 
For a target AUC = 2, the maximum dose is 2 x 150 = 300 mg 
Overweight or obese 
patients (BMI ≥ 25 
kg/m2) 
Consider using an adjusted body weight: 
Adjusted body weight (kg) = ideal body weight (IBW) + 0.4 x 
(total body weight [TBW] – IBW) 
Equation of ideal body weight (Devine 1974): 
Male: IBW [kg] = 49.9 kg + 0.89 kg/cm × (height − 152.4 cm) 
Female: IBW [kg] = 45.4 kg + 0.89 kg/cm × (height − 152.4 cm) 
Patients with 
abnormally low serum 
creatinine (Cr) 
Including but not limited to elderly patients: consider using a 
minimum Cr of 0.7 mg/dL to avoid overestimation of GFR. 
2.2.4. Radiation Therapy 
The required administration sequence of immunotherapy, chemotherapy, and radiotherapy is 
specified in Section 2.2 of Appendix 17. Before the patient is dosed with any study treatment, the 
sequence of administration should be pre-planned per protocol, taking the administrative 
situation into consideration. 
Before inclusion of any patient on this study, the radiation oncologist will evaluate the thoracic 
CT scan or MRI to ensure that the treatment volumes are unlikely to significantly exceed the 
specified normal tissue constraints and that it is feasible to administer the radiotherapy dose at 
60 Gy for a patient. A patient will be excluded if the patient’s radiation treatment plans are likely 
to encompass a volume of whole lung receiving ≥ 20 Gy in total (V20) of more than 35% of lung 
volume. 
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All patients will receive radiotherapy using either a standardized 3-dimensional conformal 
radiotherapy technique, or intensity modulated radiotherapy (IMRT) on a linear accelerator 
delivering a beam energy of ≥ 6 MV. The total dose of radiotherapy will be 60 Gy, administered 
in 30 once-daily fractions of 2 Gy and 5 fractions per week for 6 weeks. 
Weekly clinical assessments are required during the cCRT phase. While 60 Gy in 30 fractions is 
the target dose of radiation, concern about patient tolerance discovered during treatment planning 
or delivery, for example, a V20 exceeding that recommended in the protocol, may dictate that a 
lower dose be administered. Definitive RT will be considered as receiving a minimum of 56 Gy 
to the planning target volume (PTV). 
Every effort should be made to continue the radiotherapy during the concurrent phase in a not 
delayed manner. Should a patient develop severe esophagitis necessitating dose delay of 
chemotherapy, the radiotherapy may continue, provided that the investigator believes that 
supportive care will enable the patient to complete this part of the therapy without excess risk. 
Further details on the radiotherapy process are available in the radiotherapy manual. 
2.2.4.1. 
Radiation Dose Specifications 
Patients will receive treatment 5 days per week, in once-daily fractions, 2 Gy per fraction, to a 
target dose of 60 Gy in 30 fractions. Normalization of the treatment plan will cover 95% of the 
PTV with the prescription dose. The minimum PTV dose should ideally not fall below 93% of 
the prescription dose. No field reductions will be permitted and the entire PTV must be treated 
daily. 
All radiation doses will be calculated with inhomogeneity corrections that take into account the 
density differences within the irradiated volume (that is, air in the lung and bone). All radiation 
doses will be calculated using a model-based, or more complex, algorithm (AAA, 
superposition/convolution, Monte Carlo, or Grid-based Boltzmann solver); no 
measurement-based, correction-based, or pencil beam algorithms are allowed on this trial. For a 
complete list of acceptable algorithms, see irochouston.mdanderson.org. If the algorithm allows 
a choice of reporting dose to medium or dose to water, dose to medium should be used. 
2.2.4.2. 
Variations of Dose Prescription 
The variations in dose prescription are described here, and summarized in Table 18 below 
(Senan et al 2016, NCCN 2021). 
No deviation: ≥ 99% of the PTV receives at least 93% of the prescribed dose, and no volume 
≥ 1 cm3 within the PTV receives > 110% of the prescribed dose, and no more than a contiguous 
volume of 1 cm3 outside the PTV receives a maximum of 110% of the prescribed dose, and the 
percent volume of both lungs (excluding PTV) receiving a dose of 5 Gy or higher (V5) is ≤ 65%. 
Minor deviation: Deviations of this magnitude are not desirable but are acceptable. Between 
< 99% but ≥ 95% of the PTV receives at least 93% of the prescribed dose, or a contiguous 
volume of > 1 cm3 within the PTV receives > 110% but ≤ 115% of the prescribed dose, or a 
contiguous volume of >1cm3 outside the PTV receives > 110% but ≤ 115% of the prescribed 
dose, or V5 is > 65% but ≤ 80%. 
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Major deviation: Doses in this region are not acceptable. Less than 95% of the PTV is covered 
by 93% of the prescribed dose, or a contiguous volume of > 1 cm3 within the PTV receives 
> 115% of the prescribed dose, or a contiguous volume of > 1 cm3 outside the PTV receives > 
115% of the prescribed dose, or V5 > 80%. 
Table 18: 
Summary of Dose Prescription Variations 
 
Per Protocol 
Variation Acceptable 
Variation 
Unacceptable 
PTV volume 
coverage 
≥ 99% of PTV receives 
at least 93% of prescribed 
dose 
≥ 95% but < 99% of 
PTV receives at least 
93% of prescribed dose 
< 95% of PTV 
receives 93% of 
prescribed dose 
Excessive 
dose within 
PTV 
No contiguous volume 
> 1 cm3 within the 
PTV receives > 110% 
of prescribed dose 
> 1 cm3 contiguous 
volume within PTV 
receives > 110% but 
≤ 115% of prescribed 
dose 
> 1 cm3 contiguous 
volume within PTV 
receives > 115% of 
prescribed dose 
Excessive 
dose outside 
PTV 
No contiguous volume 
> 1 cm3 outside PTV 
receives > 110% of 
prescribed dose 
> 1 cm3 contiguous 
volume outside PTV 
receives > 110% but 
≤ 115% of prescribed 
dose 
> 1 cm3 contiguous 
volume outside PTV 
receives > 115% of 
prescribed dose 
Spinal Cord 
D0.03cc ≤ 46 Gy 
46 Gy < D0.03cc ≤ 48 Gy 
D0.03cc > 48 Gy 
Excessive 
Lung V5/V20 
/mean dose 
V5 ≤ 65% 
V20 ≤ 35% 
Mean dose ≤ 20 Gy 
V5 > 65% but ≤ 80% 
 
V5 > 80% 
V20 > 35% 
Mean dose > 20Gy 
Heart 
V50 ≤ 25% 
Mean dose ≤ 20 Gy 
25% < V50 ≤ 33% 
20 Gy < Mean dose 
≤25Gy 
V50 > 33% 
Mean dose > 25 Gy 
Esophagus 
Mean dose ≤ 34 Gy 
34 Gy < Mean dose ≤ 40 
Gy 
Mean dose > 40 Gy 
Brachial 
Plexus 
D0.03cc ≤ 64 Gy 
64 Gy < D0.03cc ≤ 66 Gy 
D0.03cc > 66 Gy 
Abbreviations: PTV, planning target volume; V =volume. 
2.2.4.3. 
Simulation, Immobilization, and Treatment Imaging 
Each patient will be positioned in an institutional-specific immobilization device in the treatment 
position on a flat table. All planning CT scans should be performed in the treatment position 
using the same immobilization device for setup as is used at the linear accelerator. Optimal 
immobilization is critical for this protocol in order to ensure reproducibility of the daily setup. A 
4-dimensional computed tomography (4DCT) is recommended to be performed during 
simulation to assess tumor motion. The whole thorax (cricoid to L2) should be covered using 
< 5 mm slices in order to generate dose-volume histograms to be calculated of the lungs, spinal 
cord, heart, and esophagus. A treatment planning FDG-PET/CT scan (or FDG-PET alone) with 
the patient in the treatment position can be used for treatment planning. Where a PET/CT is 
obtained in the treatment position, the CT from this study may be used as the planning CT scan. 
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The Gross Tumor Volume (GTV), Clinical Tumor Volume (CTV), Internal Target Volume 
(ITV), and Planned Target Volume (PTV) will be defined on all appropriate slices (see 
definitions in Section 2.2.4.4 of Appendix 17). Intravenous contrast during the planning CT is 
optional, provided that a recent diagnostic chest CT was done with contrast to delineate the 
major blood vessels. If not, intravenous contrast can be administered during the planning CT, if 
this is considered necessary in the view of the radiation oncologist. If contrast is used, the 
densities can be overridden, or the contrast scan could be registered to a noncontrast scan for 
planning purposes. 
Acceptable methods of accounting for tumor motion include design of the PTV to cover the 
excursion of the lung primary cancer and nodes during breathing such as an ITV approach, 
breath-holds (eg, Eleckta ABC device), or respiratory gating (for example, Varian RPM system). 
During patient treatment, at least weekly image guided radiation therapy (IGRT) using 
orthogonal X-ray, cone beam CT, CT on rails, or MR guidance must be used for all patients, 
regardless of radiation techniques. Image guidance that allows for 3D shifts is the minimum 
requirement for this trial. Most advanced imaging techniques can be utilized as long as they also 
allow for 3D shifts. The setup margin in this trial is tied to the use of image guidance. 
Registering anatomy using soft tissue will be most effective for localization. Other soft tissues in 
the lung such as the carina can help for mediastinal alignment. Fiducial markers can be used for 
localization as needed. Any linear shifts seen that are ≥2 mm should be applied prior to 
treatment. 
2.2.4.4. 
Radiation Treatment Planning 
Three-Dimensional Conformal Radiotherapy (3DCRT) 
The PTV is to be treated with any combination of coplanar or noncoplanar 3D conformal fields 
shaped to deliver the specified dose while restricting the dose to the normal tissues. The 
treatment plan used for each patient will be based on an analysis of the volumetric dose, 
including dose-volume histogram analyses of the PTV and critical normal structures. Each field 
is to be treated daily. 
Intensity Modulated Radiation Therapy 
The use of IMRT is preferred over 3DCRT, provided that the institution has been using this 
technique for treating lung cancer for at least 6 months before study activations, as IMRT results 
in a greater proportion of out-of-target lung receiving radiation outside the PTV. Regardless of 
technique, it is recommended to maintain the total lung V5 level at 65% or less.  
Detailed Specification 
Target volumes: the definitions of volumes will be in accordance with the ICRU 50 (1999) for 
3DCRT and ICRU 83 (2010) for IMRT. 
GTV: The primary tumor and clinically positive lymph nodes seen on the planning CT (≥ 1 cm 
short axis diameter) or pre-treatment PET scan (SUV > 3) will constitute the GTV. This 
volume(s) may be disjointed. In the event of a collapsed lobe or lung segment, the use of PET to 
distinguish tumor from fluid/atelectasis is encouraged. 
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CTV: The CTV is defined to be the GTV plus a 0.5 cm margin as appropriate to account for 
microscopic tumor extension. The CTV should be adjusted to not expand into other organs such 
as esophagus, heart, major blood vessels, or bone unless clinically indicated. To follow 
anatomical boundary and clinical discretion when appropriate, the CTV margin may be irregular 
and not exactly be GTV plus a 0.5 cm margin. If an ITV approach is used, then the ITV plus 
0.5 cm margin forms the CTV. 
PTV: The PTV will be equal to the CTV plus 0.5 cm setup margin in all directions. When a 
4DCT scan is performed, a patient-specific internal target volume (ITV) may be directly derived 
from planning and appropriate margins added in order to derive a CTV and PTV, respectively. 
These determinations must be documented but are left to the discretion of the treatment radiation 
oncologist. This PTV will be used to define the treated volume. 
ITV: The ITV is defined as the CTV plus an internal margin to account for target/organ motion. 
The final PTV is defined to be the ITV plus a setup margin to account for patient positioning 
uncertainty and machine tolerance. 
2.2.4.5. 
Radiation Treatment Documentation 
Regardless of treatment technique, dose volume histograms will be generated for PTV, both 
lungs, lungs minus PTV, spinal cord, esophagus, heart, and (if near the treatment field) the 
brachial plexus. The following dose values should be recorded: 
• Prescription point dose 
• Minimum, maximum (D0.03cc), and mean dose in PTV 
• Maximum dose (D0.03cc) to spinal cord 
• V20 and V5 to the lung 
2.2.4.6. 
Organs at Risk 
Contouring of normal tissues and organs for radiotherapy planning will be in accordance with 
published guidelines (Kong et al 2011). See the RT manual for more information. Normal tissue 
constraints shall be prioritized in the following order for treatment planning: 
1 = spinal cord, 2 = lungs, 3 = heart, 4 = esophagus, and 5 = brachial plexus 
Spinal cord: The spinal canal will be contoured and taken to represent the spinal cord. The 
maximum cord dose will be limited to 46 Gy, but patients who receive up to 48 Gy in order to 
ensure adequate tumor dose will be considered to have as a minor deviation. Patients who 
receive more than 48 Gy to the cord will be counted as a major deviation. 
Lungs: The dose-volume constraint to the lungs is the second highest priority and must be met, 
except if it conflicts with spinal cord dose constraints. The volume of both lungs (total lung 
volume minus PTV) that receive more than 20 Gy (V20) should not exceed 35%. Mean lung 
dose should not exceed 20 Gy. V5 should not exceed 65%. 
Heart: The heart will be contoured on all slices; detailed guidance for contouring is per Feng et 
al 2011. The cranial border will include the infundibulum of the right ventricle and the apex of 
both atria, and it will exclude the great vessels as much as possible. The caudal border is defined 
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as the lowest part of the left ventricle that is distinguishable from the liver. The recommended 
dose limits are 50 Gy < 25%; mean dose ≤ 20 Gy of the heart. 
Esophagus: Esophagitis is an expected side effect of concurrent therapy and has a relationship to 
higher doses of radiation encompassing the entire esophageal circumference. The outer wall of 
the esophagus will be contoured completely throughout the length of esophagus that is 
encompassed by a dose of radiation ≥ 46 Gy. Mean esophageal dose should be limited to 
≤ 34 Gy, a dose up to ≤ 40 Gy will be considered a variation acceptable. 
Brachial Plexus: For tumors in close proximity to the brachial plexus, the plexus should be 
contoured to ensure that the maximal point dose to this structure is kept under 64 Gy. 
Radiation toxicities will be assessed according to NCI-CTCAE v5.0 criteria and reported per 
Section 5.3. Note that radiation toxicities can arise more than 90 days after the completion of RT. 
2.2.4.7. 
Quality Assurance and Compliance with Protocol-defined Radiation 
Prescription (Quality Control) 
A formal radiotherapy quality assurance (QA) program will be a mandatory component of this 
study. Eligible radiotherapy facilities will complete a facility questionnaire in order to ensure that 
they are equipped to deliver radiation to the required quality. Prior to the randomization of the 
first subject, sites will need to have undergone a “benchmarking” process where a 3-dimensional 
CT scan of an anonymized clinical case with stage III NSCLC will be electronically transmitted 
to participating sites by the QA program, and the local radiation oncologists from the sites will 
be required to contour target volumes and organs-at-risk volumes, in accordance with the quality 
assurance criteria specified for thoracic radiation therapy as defined in the approved RT QA 
program. This process will serve to ensure protocol-compliant contouring and radiotherapy 
planning. The radiotherapy plans will be reviewed by physicists and a radiation oncologist at the 
QA program, who will provide appropriate feedback to sites participating in this benchmarking. 
See the radiotherapy manual for additional information. 
Credentialing: 
Table 19: 
Credentialing Procedure 
Steps 
Procedures/ 
Requirements 
Information Link 
Step 1 
Facility & 
Motion 
Management 
Questionnaire 
The MD Anderson Dosimetry Lab electronic facility questionnaire 
(FQ), should be completed or updated with the most recent 
information about your institution. To access your site’s FQ, email 
mdadl@mdanderson.org to receive your FQ link.  Submit 
electronically a completed Motion Management Questionnaire 
located http://rpc.mdanderson.org/mdadl/home.htm 
Step 2* 
Independent 
Output 
Verification 
All sites delivering radiation therapy for patients enrolled in this 
study must have independent output verification. 
Step 3* 
Benchmark 
Sites need to download the DICOM CT benchmark case from the 
BeiGene website located 
http://rpc.mdanderson.org/mdadl/home.htm. There is also a 
document which includes the clinical details of the benchmark case. 
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This benchmark must be contoured and planned according to the 
AdvanTIG-301 protocol (see section 5.2.4 of the protocol) 
See the RT Manual for further credentialing information. 
Pre-treatment Subject Dosimetry Review: 
A pre-treatment subject dosimetry review of a treatment plan will be conducted for at least 1 case 
per center. The first patient’s treatment plan shall be submitted, at a minimum, 5 days prior to 
start of radiotherapy. Feedback on the treatment plan will be received by the center before 
radiotherapy commences. The objective of the review is to gain additional assurance that 
subjects treated at the site will conform to the protocol radiation requirements. Additional QA 
dosimetry reviews may be done subsequently in a sample of cases during the course of the study. 
Subjects may have their radiation field altered based on information obtained from these QA 
reviews. This should be sufficient to ensure adherence to the radiation prescription defined in the 
protocol. 
Post-treatment Subject Dosimetry Review: 
All subjects treated by radiation in the study will submit their data to the RT QA team to perform 
a retrospective radiation dosimetry review. This review will evaluate, for each case, adherence to 
the protocol radiation prescription. This will be a confirmation of the treatment delivered, and an 
overall assessment of compliance with protocol stipulations regarding radiation treatment. In 
case there is any deviation from the protocol, this information will be conveyed to the institution. 
2.2.5. Supportive Care 
Patients should receive full supportive care, including epoetin and other hematopoietic growth 
factors (eg, colony-stimulating factors), transfusions of blood and blood products, antibiotics, 
antiemetics, other applicable medications, as needed according to local standard of care 
guidelines or practices. 
All patients are strongly suggested to accept nutrition support if there is any indication including 
(but not limited to): medium-severe dysphagia; weight loss > 5% in 1 month; BMI < 18.5 kg/m2; 
scored patient-generated subjective global assessment ≥ 4 score; and food intake is < 60% 
required for > 3 days. 
2.3. 
Incorrect Administration or Overdose 
Any incorrect administration of ociperlimab or overdose of 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 incorrect administration or overdose of study drugs will be recorded on 
the AE eCRF. Any SAEs associated with an incorrect administration or overdose must be 
reported within 24 hours of awareness via the SAE reporting process as described in 
Section 5.6.2 of Appendix 17. Supportive care measures should be administered as appropriate. 
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2.4. 
Investigational Medicinal Product Accountability 
The investigational medicinal products required for completion of this study (ociperlimab, 
tislelizumab, and durvalumab) will be provided by the sponsor. The investigational site will 
acknowledge receipt of investigational medicinal products. Any damaged shipments will be 
replaced. 
Accurate records of all investigational medicinal products received, dispensed, returned, and 
disposed should be recorded on the site’s Drug Inventory Log. Refer to the Pharmacy Manual for 
details of investigational medicinal product management. 
2.5. 
Dose Delay or Modification 
A dose interruption is an interruption of an infusion. A dose delay is a deviation from the 
prescribed dosing schedule (ie, the drug is withheld beyond the visit window). 
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 provided below. Reasons for dose modifications or delays, the supportive 
measures taken, and the outcome will be documented in the patient's chart and recorded in the 
eCRF. Skipped doses due to reasons others than AE (eg, COVID-19 lockdown, warfare, etc) 
should be added at the back end to ensure the total duration of treatment after cCRT in each arm 
is 12 months or corresponding cycles, ie, a maximum of 17 cycles in Arm A and B, 26 cycles for 
Q2W regimen, and 13 cycles for Q4W regimen in Arm C. 
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 weight, 
laboratory findings) as appropriate. 
2.5.1. Dose Interruption or Delay for Ociperlimab and Tislelizumab 
If a dose delay is required, both study drugs are to be delayed (ie, ociperlimab and tislelizumab 
must both be delayed and if applicable restarted at the same time in Arm A). Exceptions may be 
considered following consultation between the investigator and the medical monitor. 
If treatment is delayed due to TEAEs, treatment may resume only after the AEs have returned to 
baseline or ≤ Grade 1 severity except for alopecia or AEs that, in the opinion of the investigator, 
are not considered a safety risk to the patient. If a treatment delay is due to laboratory results 
worsening, eg, hematologic or biochemical parameters, the frequency of relevant blood tests 
should be increased as clinically indicated. 
In general, dose delays for reasons other than management of AEs are prohibited. A dose delay 
of ≤ 12 weeks is allowed under the following guidance and at the discretion of the investigator 
after consultation with the medical monitor or designee. 
In Arm A and B, if a dose is delayed for the immunotherapy (ociperlimab and tislelizumab in 
Arm A, tislelizumab in Arm B) for ≤ 10 days for a planned dosing cycle (eg, Cycle 4 Day 1), the 
immunotherapy should be administered. If the delay is > 10 days, the patient should skip 
administration of the immunotherapy. The immunotherapy will be administered on Day 1 of the 
next planned cycle (eg, Cycle 5 Day 1). This 10-day dose delay time window does not apply to 
Cycle 3 Day 1. 
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If immune-mediated AEs are persistent without any improvement for more than 12 weeks, 
permanent discontinuation of the study drugs should be considered. In Arm A, the treatment 
discontinuation in response to imAEs should be applied to both ociperlimab and tislelizumab 
because the causality of imAEs may not be distinguished from one study drug to the other. 
If the patient recovers from the treatment-related AE after 12 weeks, re-initiation of the study 
drugs is permitted only in patients who are deemed to be deriving clinical benefit per the opinion 
of the investigator following agreement between the investigator and the medical monitor. 
Management guidelines for imAEs and infusion-related reactions in patients treated with the 
immunotherapy are presented in Section 5.7 of Appendix 17, and Appendix 12, respectively. 
The tumor assessment schedule will not be altered even if the administration of the study drug is 
delayed, except for the first 9-week tumor assessment. 
2.5.2. Dose Reductions for Ociperlimab and Tislelizumab 
There will be no dose reductions allowed for ociperlimab or tislelizumab in Arm A and Arm B. 
2.5.3. Dose Interruption, Delay or Modification for Durvalumab 
There will be no dose reductions allowed for durvalumab. Please refer to prescribing information 
Table 2 Recommended Dosage Modifications (Appendix 15) approved by US FDA for specific 
information. Note, in countries/regions other than US, some recommended dosage modifications 
of durvalumab prescribing information approved by the local health authority may differ from 
that approved by US FDA. In such cases, please refer to the recommendations approved by the 
local health authority (Appendix 15). 
2.5.4. Dose Delay or Modification for Radiotherapy 
Investigators will be advised to suspend the use of chemotherapy given with radiation if they 
believe that continuing chemotherapy administration will compromise delivery of full-dose 
radiation in a not delayed manner. 
Ideally, radiation therapy should be completed within 42 days. Treatment completion within 
49 days will be considered an acceptable deviation. 
Reversible or permanent alopecia, bone marrow toxicity, esophagitis and skin pigmentation are 
expected side effects of RT. Radiation-induced myocarditis and spinal cord injury rarely occur at 
doses lower than 50 Gy. Radiographic evidence of radiation-induced changes and subsequent 
fibrosis of the lung may occur within lung volumes receiving ≥ 20 Gy. It is essential to spare as 
much normal lung as possible in order to avoid symptomatic lung injury. 
• In case of radiation dose delay due to machine breakdown or public holidays or any 
dose delay of RT up to 7 days, radiation should be completed to the prescribed doses. 
Total number of fractions and elapsed days should be carefully reported. The reasons for 
delays should be carefully reported in cases where the RT treatment takes longer than 
49 days. 
• During the cCRT phase, esophagitis is managed according to Table 23 in regard to RT. 
During this cCRT period, in case of Grade 3 esophagitis related to chemotherapies or 
ociperlimab or tislelizumab, chemotherapies and/or ociperlimab in combination with 
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tislelizumab in Arm A, chemotherapies and/or tislelizumab in Arm B, chemotherapies 
in Arm C should be held if the investigator believes that continued use will jeopardize 
the delivery of full-dose RT, and radiation is to be continued. Resume the treatment with 
chemotherapies and/or ociperlimab in combination with tislelizumab in Arm A, or 
chemotherapies and/or tislelizumab in Arm B, or chemotherapies in Arm C is permitted 
if there is resolution of the esophagitis to ≤ Grade 2. 
• If Grade 4 esophagitis related to RT, chemotherapies, ociperlimab, or tislelizumab 
occurs; RT, chemotherapies, and/or ociperlimab in combination with tislelizumab in 
Arm A, or RT, chemotherapies and/or tislelizumab in Arm B, or chemotherapies in 
Arm C should be held until resolution of the esophagitis to ≤ Grade 2. 
• During the cCRT phase, in case of Grade 3 or Grade 4 radiation pneumonitis/lung 
infiltrates related to RT, the recommendation is to hold RT, chemotherapies and 
ociperlimab in combination with tislelizumab in Arm A; or RT, chemotherapies and 
tislelizumab in Arm B; or RT and chemotherapies in Arm C. Resume the treatment  
with RT, chemotherapies and ociperlimab in combination with tislelizumab in Arm A; 
or RT, chemotherapies and tislelizumab in Arm B; or RT and chemotherapies in Arm C 
is acceptable if symptoms resolve to ≤ Grade 1 or are controlled on prednisolone 
≤ 10 mg/day (or equivalent corticosteroids). Discontinue study treatment if symptoms 
persist with corticosteroid treatment. 
Radiation toxicities will be assessed according to NCI-CTCAE v5.0 criteria and reported per 
Section 5.3 of Appendix 17. Note that radiation toxicities can arise more than 90 days after the 
completion of RT. 
Esophagitis 
The first symptoms of acute esophagitis usually start in the second or third week of RT, 
commonly at the dose of 18.0 to 21.0 Gy of standard fractionated RT (Wei et al 2006) and 
include a sensation of difficult swallowing (dysphagia). This may progress to painful swallowing 
of food and saliva (odynophagia) and later to constant pain not necessarily related to swallowing. 
In severe cases, patients may not be able to swallow at all and may require intravenous 
hydration, feeding through a gastric tube and, in rare cases, parenteral nutrition. 
Symptomatic esophagitis is common with combined modality therapy (Werner-Wasik 2005) and 
it does not constitute a reason to delay radiotherapy or chemotherapy, provided oral intake is 
sufficient to maintain hydration. Symptoms of acute esophagitis may persist for 1 to 3 weeks 
after completion of RT. If CTCAE Grade 4 esophagitis occurs and treatment is delayed, every 
effort should be made to limit the radiation dose delay to 3 treatment days or less. Patients 
requiring hospitalization, placement of a feeding tube in the stomach, or intravenous feedings 
because of esophagitis may have their treatment dose delayed in order to allow for healing of the 
esophageal mucosa. 
Table 23 summarizes the dose modifications of the chemotherapy regimens in cases of Grade 3 
or 4 esophagitis. 
Table 20 lists esophagitis grading and clinical states according to NCI-CTCAE v5.0. 
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Table 20: 
CTCAE Scale: Acute Esophagitis Related to Radiation 
Grade 
Clinical State 
1 
Asymptomatic; clinical or diagnostic observations only; intervention not indicated 
2 
Symptomatic; altered eating/swallowing; oral supplements indicated 
3 
Severely altered eating/swallowing; tube feeding, TPN, or hospitalization indicated 
4 
Life-threatening consequences; urgent operative intervention indicated 
5 
Death 
Abbreviations: CTCAE, Common Terminology Criteria for Adverse Events; TPN, total parenteral nutrition. 
Acute esophageal toxicity should be managed with diet and medications, alone or in various 
combinations (Table 21 and Table 22), or comparable regimen, and intervention should be 
initiated at the first signs or symptoms of esophageal toxicity. 
Table 21: 
Dietary and Nutritional Support Recommendations for Acute Radiation 
Esophagitis 
Supportive Measure 
Recommendation 
Dietary modification 
• 
Consider dietician referral 
• 
Avoid potentially irritant foods (tobacco, alcohol, coffee, 
and spicy foods) 
• 
Soft, bland diet 
• 
Small, frequent meals 
Nutritional support 
• 
Liquid meal replacements/supplements 
• 
Intravenous hydration 
• 
Electrolyte correction 
• 
For prolonged symptoms, enteral feeding or total 
parenteral nutrition may be required, although former is 
preferred 
• 
Antiemetics may be beneficial 
Modified from Baker and Fairchild 2016. 
Table 22: 
Recommendations for Medication Management of Radiation Esophagitis 
Treatment 
Option 
Management of Esophagitis 
1 
Ketoconazole 200 mg PO QD 
2 
Fluconazole 100 mg PO QD until the completion of radiation 
3 
Mixture of: viscous lidocaine 60 mL + Mylanta (or generic equivalent 
antacid) 30 mL + sucralfate (1 gm/mL) 10 mL. Take 15 to 30 mL PO q3 to 4h PRN 
4 
Ranitidine 150 mg PO BID (or other histamine-2 [H2] receptor blocker or a proton pump 
inhibitor such as omeprazole) until completion of radiation 
5 
Grade 4 esophagitis: hold CRT until Grade 2 or less 
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Abbreviations: BID, twice daily; CRT, chemoradiotherapy; h, hour; PO, oral; PRN, when necessary; q, every; 
QD, every day. 
2.5.5. Dose Modifications for Chemotherapy Treatment 
Dose modifications for chemotherapy should be performed per applicable local prescribing 
information and per local practice according to the investigator’s clinical judgment. 
Recommended dose modifications for key chemotherapy toxicities are outlined in Table 23. If 
chemotherapy-related toxicities warrant a dosing delay, chemotherapy administration may restart 
as soon as is feasible. Chemotherapy may be delayed up to 3 weeks to allow sufficient time for 
recovery. Upon recovery, chemotherapy is recommended to be administered according to the 
dose as Table 23. Suggest to complete all chemotherapy before the last dose of radiotherapy. 
These serve as guidelines and do not replace investigator judgment and applicable local label 
recommendations if more stringent. 
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). Chemotherapy doses are not required to modify for any body weight change of 
˂ 10%. Calculating the chemotherapy doses by actual body weight is acceptable. 
Reduction of one chemotherapy agent and not the other agent is appropriate if, in the opinion of 
the investigator, the toxicity is clearly related to one of the treatments. If, in the opinion of the 
investigator, the toxicity is related to the combination of both chemotherapy agents, both drugs 
should be reduced according to recommended dose modifications. 
Study drug-related toxicities must be resolved to baseline, or Grade 1 (whichever is more severe) 
before administering the next dose, except for alopecia, ≤ Grade 2 fatigue or neuropathy. A 
maximum of 2 dose reductions for each chemotherapeutic agent are permitted except for 
carboplatin plus paclitaxel regimen. Once the dose has been decreased, it should remain reduced 
for all subsequent administrations or further reduced if necessary. There will be no dose 
escalations in this study. If additional reductions are required, that chemotherapeutic agent must 
be discontinued. 
If chemotherapy-related toxicities warrant a dosing delay, chemotherapy administration may 
restart as soon as it is feasible. 
If the patient develops an allergic reaction to the chemotherapy, the investigator may change the 
chemotherapeutic agent to one of the other agents allowed per protocol. Only one change in 
chemotherapeutic agent is allowed. 
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: 
− 
Nephrotoxicity is common with cisplatin. Encourage oral hydration. Avoid nephrotoxic 
drugs such as aminoglycoside antibiotics. 
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− 
Patients should not be given cisplatin or carboplatin if their estimated GFR by CKD-EPI 
equation or calculated creatinine clearance by Cockcroft-Gault Equation (Appendix 14) is 
< 60 mL/min or < 45 mL/min, respectively. 
− 
Pemetrexed should not be administered to patients whose estimated GFR by CKD-EPI 
equation or calculated creatinine clearance is by Cockcroft-Gault Equation (Appendix 14) 
< 45 mL/min. 
− 
Patients will be allowed to switch from cisplatin to carboplatin in pemetrexed-included 
regimen if patients become ineligible for cisplatin due to toxicity related to cisplatin if 
they have completed at least one cycle of cisplatin treatment. Reasons for platinum 
switch should be documented in source documents and eCRF. 
• 
Ototoxicity and sensory neural damage should be assessed before each cycle. Cisplatin is 
contraindicated in patients with a pre-existing hearing deficit. 
For toxicities not listed above, dose modifications are permitted per local standards. 
Table 23: 
Dose Modification of 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 
(Apply to cisplatin plus etoposide, cisplatin plus pemetrexed, and carboplatin plus 
pemetrexed regimens) 
Adverse event 
Treatment 
Febrile neutropenia; documented 
infection 
1) 
The first episode of febrile neutropenia or documented infection 
will result in antibiotic treatment and reduction by 25% of both drugs 
doses. 
2) 
If there is a second episode despite dose reduction, the patient 
must receive prophylactic antibiotics during the subsequent cycle. 
3) 
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 25% 
Thrombocyt
openia 
Grade 1 
Chemotherapy delay until recovered to normal; restart with the full dose 
Grade 2 or Grade 3 
without bleeding 
Chemotherapy delay until recovered to normal; dose reduction of all 
further doses by 25% 
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Grade 4 
Chemotherapy delay until recovered to normal; dose reduction of all 
further doses by 50%  
Grade 3 associated 
with clinically 
significant bleeding 
Chemotherapy delay until recovered to normal; dose reduction of all 
further doses by 50% 
Recurrence of Grade 3 or 4 after 2 
dose reductions (with either 
neutropenia or thrombocytopenia) 
Discontinue chemotherapy 
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 
provided triggers for dose modifications are recommendations only.  
(Apply to carboplatin plus paclitaxel regimen) 
Doses that are missed during the weekly schedule concurrent with radiation will not be made up 
but will be documented. 
Adverse Event 
Treatment 
Febrile neutropenia; documented infection 
Chemotherapy delay until recovered to ≤ Grade 1(ANC 
≥ 1.5 x 10^9/L) 
Neutropenia 
Grade 3 or 4 
Chemotherapy delay until recovered to ≤ Grade 1(ANC 
≥ 1.5 x 10^9/L) 
Thrombocytopenia 
≥ Grade 2 to 4 
Chemotherapy delay until recovered to ≤ Grade 1 (platelets 
< LLN -75000/mm3) 
≥ Grade 3 associated 
with clinically 
significant bleeding 
Discontinue chemotherapy 
Recommended Dose Modifications for Nonhematologic 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.  
In general, for nonhematologic toxicities greater than or equal to Grade 3, chemotherapy should 
be delayed until resolution to less than or equal to the patient’s baseline value before resuming 
treatment at a reduced dose. However, exceptions may be made for Grade 3 neurotoxicity or 
esophagitis. In the case of neurotoxicity, the investigator and patient may decide to continue 
treatment at a reduced dose, with no delay required, as neurotoxicity may not resolve to baseline 
values. Adjustments for esophagitis are recommended to follow dose modifications as described 
in the table below. 
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Chemotherapy Dose Modificationsa for Non-Hematological Toxicities 
Toxicity 
Grade 
Treatment  
Renal toxicity 
≥ Grade 1 
Delay chemotherapy until recovered to Grade 0 or baseline, change cisplatin 
to carboplatin, if possible; dose reduction by 25% for other drug; if it recurs, 
discontinue chemotherapy 
Ototoxicity  
Grade 2 
Dose reduction of all further doses of cisplatin by 25% 
Grade 3-4 
Delay chemotherapy until recovered to ≤ Grade 2, change cisplatin to 
carboplatin 
Sensory 
neuropathy b, c 
Grade 2 
Dose reduction for all further doses of cisplatin by 25% 
For carboplatin plus paclitaxel regimen, delay paclitaxel until ≤ Grade 1 
while continue carboplatin 
Grade 3 
Discontinue cisplatin, change cisplatin to carboplatin; Dose reduction by 
25% for etoposide 
For carboplatin plus paclitaxel regimen, discontinue paclitaxel while 
continuing carboplatin 
Grade 4 
Discontinue cisplatin, carboplatin, paclitaxel, and etoposide 
Hepatic toxicity 
(transaminase 
elevation) 
Grade 3 or 4 
Dose reduction by 25% for cisplatin and etoposide 
Diarrhea 
Grade 4 
Discontinue chemotherapy 
Oral mucositis 
or stomatitis 
≥ Grade 3 
Dose reduction for further doses of etoposide by 25% 
Dose reduction for further doses of pemetrexed by 50% 
For carboplatin plus paclitaxel regimen, discontinue chemotherapy for Grade 
4 
Esophagitis d, e 
≥ Grade 3 
For carboplatin plus paclitaxel regimen, hold chemotherapy until ≤ Grade 2 
For cisplatin plus etoposide regimen, delay chemotherapy at the discretion of 
investigator for Grade 3; delay chemotherapy for Grade 4 
Other 
organ 
toxicity 
Grade 2 
Delay chemotherapy until ≤ Grade 1 or baseline f. 
Grade 3-4 
Delay chemotherapy until recovered to ≤ Grade 1 or baselinee, dose 
reduction of all further dose by 25% 
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 
provided triggers for dose modifications are recommendations only. 
b Delay until resolution of toxicity to baseline value is not required for Grade 3 neurotoxicity. 
c At the discretion of the physician, patients experiencing Grade 3 neurologic toxicity as a transient ischemic attack 
that has completely resolved may not require dose reduction or discontinuation. 
d Grade 3 esophagitis will occur in a significant number of patients toward the end of radiation therapy. For patients 
who experience this event earlier in the course of their treatment than anticipated, the advice would be to hold 
chemotherapy and assess at weekly intervals. If symptoms do not progress at the time of assessment, chemotherapy 
can be resumed for carboplatin plus paclitaxel; chemotherapy can be resumed at 75% of previous dose for both 
drugs. 
e Grade 4 esophagitis results in holding chemotherapy until toxicity resolves to ≤ Grade 2, and then chemotherapy 
may be resumed for carboplatin plus paclitaxel; chemotherapy can be resumed at 75% of previous dose for both 
drugs. 
f Skin reactions, paronychia, alopecia, fatigue, and nausea/vomiting which may have resolved to Grade 2 or 
baseline. 
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2.5.6. Criteria for Discontinuing Chemotherapy Regimens 
Except where specified above, both chemotherapy drugs in the platinum-based doublet regimen 
should be discontinued for any of the following: 
• Any Grade 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: 
- 
AST or ALT > 5 x ULN for > 2 weeks 
- 
AST or ALT > 10 x ULN or 
- 
Total bilirubin > 5 x ULN or 
- 
Concurrent AST or ALT > 3 x ULN and total bilirubin > 2 x ULN 
• Any drug-related AE that recurs after 2 prior dose reductions 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. 
• If any toxicity does not resolve within 21 days, that component will be discontinued. 
For toxicities not listed above, the investigator would determine whether chemotherapy regimen 
should be discontinued per clinical judgment, patient’s well-being, and local standards. 
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3. 
PRIOR AND CONCOMITANT THERAPY 
3.1. 
Prior Therapy 
The exclusion criteria specify that patients should not have received prior therapies targeting 
PD-1, PD-L1, PD-L2, TIGIT, T-cell costimulation or checkpoint pathways; any prior therapy for 
lung cancer, including but not limited to chemotherapy, radiotherapy, targeted therapy, biologic 
therapy, or immunotherapy; any prior radiotherapy to the thorax, including radiotherapy to the 
esophagus, mediastinum, or for breast cancer; or immunotherapy (eg, interleukin, interferon, or 
thymosin) or investigational therapy ≤ 14 days or 5 half-lives (whichever is longer) before the 
first dose of study treatment. 
3.2. 
Permitted Concomitant Medications/Procedures 
Unless noted otherwise, 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, hematopoietic growth factors, red blood cell/platelet 
transfusions) and in a patient’s interest are allowed. Opiates and other medication required for 
pain management of patients are allowed. 
All concomitant medication will be recorded on the eCRF including all prescription, 
over-the-counter, herbal supplements, and intravenous medications and fluids. 
Bisphosphonates are permitted during the study for a nonmalignant indication. Use of potentially 
hepatotoxic drugs in patients with impaired hepatic function is allowed but should be carefully 
monitored. 
Vaccines for COVID-19 are allowed except for any live vaccine (ie, live SARS-CoV-2 virus) 
that may be developed. Attenuated (vector) COVID-19 vaccines are inactivated vaccines and as 
such, are permitted. 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. The specific 
COVID-19 vaccine should be recorded instead of generic language, eg, mRNA-1273 vaccine 
(Moderna), BioNTech vaccine (Pfizer), etc. 
3.2.1. Systemic Corticosteroids 
Systemic corticosteroids administered for the control of imAEs must be tapered gradually (see 
Appendix 12) and must be administered at non-immunosuppressive doses (≤ 10 mg/day of 
prednisone [in Japan, prednisolone] or equivalent) before the next immunotherapy (ociperlimab 
and tislelizumab in Arm A, tislelizumab in Arm B, or durvalumab in Arm C) administration. The 
short-term use of steroids as prophylactic treatments (eg, patients with contrast allergies to 
diagnostic imaging contrast dyes) is permitted. 
3.2.2. Hepatitis B Treatment 
Patients with active hepatitis B, defined as HBV DNA ≥ 500 IU/mL at screening, must initiate 
antiviral treatment 2 weeks before the first dose of study treatment. The patients would not be 
eligible unless HBV DNA decreases to < 500 IU/mL. If the patients are treated and eligible, 
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antiviral treatment must 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 
re-activation 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 at screening) 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 enrollment and continue treatment during the study and for 6 months after study treatment 
discontinuation. 
3.2.3. Hepatitis C Treatment 
Patients with detectable HCV RNA who are receiving treatment at screening must meet the 
criterion of negative HCV RNA to be eligible. If the patients are treated and eligible, they will 
remain on continuous, effective antiviral therapy during the study. Investigators can consider 
treatment with antivirals following the international or local guidelines as appropriate. However, 
interferon-based therapy for HCV is not permitted on study. Patients who are given antiviral 
therapy must initiate treatment > 2 weeks before enrollment and continue treatment during the 
study and for 6 months after study treatment discontinuation. 
3.3. 
Prohibited Concomitant Medications/Procedures 
The following medications are prohibited during the study: 
• Any concurrent anticancer therapy (ie, chemotherapy, hormonal therapy, 
immunotherapy, or standard or investigational agents including herbal medicine and 
patent medicines for the treatment of cancer [Appendix 16]). 
• Live vaccines within 28 days before the first dose of study drugs and 60 days following 
the last dose of study drugs. 
• Herbal remedies with immune-stimulating properties or that are known to potentially 
interfere with liver or other major organ functions. 
• Patients must notify the investigator of all herbal remedies and supplements used during 
the study. 
3.4. 
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 [in Japan, prednisolone] 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. 
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• Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) (aspirin, ibuprofen etc.) at least 
5 days before and 2 days after pemetrexed chemotherapy treatment period. 
3.5. 
Potential Interactions Between the Study Drugs and Concomitant 
Medications 
Information regarding clinical drug interactions with ociperlimab is not available and no 
dedicated drug-drug interaction studies are planned. However, the potential for drug-drug 
interaction between the study drugs (ociperlimab and tislelizumab) and other drug products is 
very low because ociperlimab and tislelizumab are therapeutic monoclonal antibodies. Because 
ociperlimab and tislelizumab are expected to be degraded into amino acids and recycled into 
other proteins, they unlikely influence drug-metabolizing enzymes or transporters. 
Caution should be exercised when administering 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 (Flockhart 2007; US FDA Development and 
Drug Interactions) are co-administered with paclitaxel, the toxicities may be exacerbated, and the 
investigator should closely monitor for them. Please refer to the prescribing information of 
paclitaxel for more information. 
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 nephrotoxic 
drugs or drugs that are tubularly secreted. Please refer to the prescribing information of 
pemetrexed for more information. 
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4. 
STUDY ASSESSMENT AND PROCEDURES 
A table of scheduled study assessments for PA 1.0 is provided in Table 14. 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. 
4.1. 
Screening Period 
Screening evaluations will be performed ≤ 28 days before randomization. A patient who agrees 
to participate in this study will sign the ICF before undergoing any screening assessment. The 
screening period begins on the first day that a screening assessment 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 informed consent has been 
obtained 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. Patients who 
are suspected or known to have concurrent serious respiratory illness or exhibit significant 
respiratory symptoms unrelated to underlying cancer should take a pulmonary function test (refer 
to Section 4.1.5 of Appendix 17 for details) based upon the treatment physician’s judgement. For 
the description of other assessments that are conducted during screening as well as throughout 
the study, refer to Safety Assessments (Section 4.4 of Appendix 17), Tumor and Response 
Evaluations (Section 4.5 of Appendix 17), PK and ADA Assessments (Section 4.6 of 
Appendix 17) and Biomarkers (Section 4.7 of Appendix 17) sections. 
Rescreening under limited conditions may be allowed after consultation with the sponsor 
(eg, when a patient’s laboratory result narrowly misses a laboratory criterion and it is correctable 
and not due to rapidly deteriorating condition or PD). Rescreening is allowed only once. 
4.1.1. Informed Consent and Screening Log 
Voluntary, written informed consent for participation in the study must be obtained before 
performing any study-specific procedures. The ICFs 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. 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. 
4.1.2. Patient Numbering 
After obtaining informed consent, study site personnel will access the Interactive Response 
Technology (IRT) system to assign a unique patient number to a potential study participant. 
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4.1.3. Demographic Data and Medical History 
Demographic data will include age or year of birth, sex, and self-reported race/ethnicity. 
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 
consumption and tobacco (ie, former or current or never).; Prior or concomitant medications 
include 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. 
4.1.4. Females of Childbearing Potential and Contraception 
Childbearing potential is defined as being physiologically capable of becoming pregnant, ie, 
fertile, following menarche and until becoming post-menopausal unless permanently sterile. 
Refer to Appendix 5 for contraception guidelines and definitions of “women of childbearing 
potential” and “no childbearing potential.” 
4.1.5. Pulmonary Function Tests 
All patients should take a pulmonary function test (refer to Table 14 for details) at screening to 
assist in the determination of eligibility for the study. 
Pulmonary function testing includes assessment of spirometry and oxygenation. The assessment 
of oxygenation should include at least pulse oximetry (percutaneous arterial oxygen saturation, 
SpO2) at rest and with exercise; an assessment of diffusion capacity is optional. Respective test 
results should be submitted to the sponsor. 
The medical monitor needs to be consulted to confirm eligibility if test results indicate 
significantly impaired pulmonary function, eg, resting pulse oximetry < 90% on room air and 
further desaturation upon exercise, absolute forced expiratory volume (FEV1) value < 1L, FEV1 
of age and sex adjusted predicted performance levels < 50%, diffusing capacity of the lungs for 
carbon monoxide (DLCO) (if performed) < 40% of age and sex adjusted predicted performance 
levels (Pellegrino et al 2005). 
Test may be repeated as clinically indicated while on study. 
4.1.6. COVID-19 Test 
A COVID-19 test may be conducted according to local practice. 
4.2. 
Enrollment 
4.2.1. Confirmation of Eligibility 
The investigator is responsible for ensuring that each patient meets the eligibility criteria for this 
study. All results from the screening procedures and relevant medical history must be available 
before eligibility can be determined. No eligibility waivers will be granted. 
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The sponsor’s medical monitor will support the investigator and/or site staff by answering any 
queries or questions relating to protocol eligibility criteria to confirm eligibility. 
4.2.2. Randomization 
Site personnel will access the IRT system to randomize the patient and assign study drugs by 
permuted block stratified randomization. Study treatment must commence within 2 business days 
after randomization/treatment assignment. 
4.3. 
Study Drug Dispensation 
All study drugs will be dispensed and administered as described in Section 2.2 of Appendix 17. 
4.4. 
Safety Assessment 
4.4.1. Vital Signs 
Vital signs will include measurements of body temperature (˚C), pulse rate, and blood pressure 
(systolic and diastolic). Pulse rate and blood pressure will be measured while the patient is in a 
seated position after resting for 10 minutes. 
The patient’s vital signs are required to be recorded within 60 minutes before, during, and within 
30 minutes after completion of infusion of study treatment (ociperlimab and tislelizumab in Arm 
A, tislelizumab in Arm B, and durvalumab in Arm C). For subsequent infusions, vital signs will 
be collected within 60 minutes before infusion and, if clinically indicated, during and within 
30 minutes after the completion of infusion. 
Weight is required to be measured once on the scheduled assessment day and before study 
treatment if there is any. Height measurements are only required at screening. 
4.4.2. Physical Examinations 
During the Screening Visit, a complete physical examination will be conducted, including 
evaluations of 1) head, eyes, ears, nose, and 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 eCRF with appropriate disease/condition terms. 
Patients should be solicited at every visit for any vision changes (eg, blurred/distorted vision, 
blind spots, change in color vision, photophobia, tenderness/pain and, eyelid swelling) and 
should be referred to an ophthalmologist if further evaluation is needed. 
At subsequent visits (and as clinically indicated), limited, symptom-directed physical 
examinations will be performed. New or worsened clinically significant abnormalities will be 
recorded as AEs on the eCRF. Refer to Section 5.3 of Appendix 17 regarding AE definitions and 
reporting and follow-up requirements. 
4.4.3. Eastern Cooperative Oncology Group Performance Status 
ECOG Performance Status (Table 14) will be assessed during the study. 
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4.4.4. Laboratory Safety Tests 
Local and/or central laboratory assessments of clinical chemistry, hematology, coagulation, and 
urinalysis will be conducted as outlined in Appendix 2 per the timepoints shown in Table 14. 
If hematology and serum chemistry at screening are not performed within 7 days before the planed 
C1D1, these tests should be repeated and reviewed before randomization. If a coagulation test 
was performed and reviewed during screening, it is not mandated to repeat before C1D1 unless 
investigator deems necessary. Hematology, serum chemistry (including liver function tests), 
creatine kinase (CK) and creatine kinase cardiac muscle isoenzyme (CK-MB) as specified in 
Appendix 2 should be performed weekly during cCRT, at the beginning of each subsequent 
cycle after cCRT, and the EOT Visit (Table 14). After Cycle 1, these laboratory tests are to be 
performed and reviewed within 48 hours before study treatment administration. Urinalysis is to 
be conducted during the treatment period only if clinically warranted. 
Local laboratory assessments will include the following: 
• Hematology (CBC, including hemoglobin, hematocrit, white blood cell [WBC] count 
[neutrophils and lymphocyte], and platelet count) 
• Serum chemistry (glucose, blood urea nitrogen [BUN] or urea, creatinine, sodium, 
potassium, magnesium, chloride, calcium, phosphorus, direct bilirubin, total bilirubin, 
ALT, AST, alkaline phosphatase, lactate dehydrogenase (LDH), total protein, albumin) 
• Coagulation test (international normalized ratio, prothrombin time, and activated partial 
thromboplastin time) 
• Urine or serum pregnancy test (for women of childbearing potential, including 
premenopausal women who have had a tubal ligation) 
• Urinalysis (complete [including, but not limited to specific gravity, pH, glucose, protein, 
ketones] and/or microscopic at screening and if clinically indicated) 
• Thyroid function testing (thyroid stimulating hormone [TSH], free T3 or total T3, free 
T4 or total T4). 
Details about sample collection and shipment will be provided in a separate instruction manual. 
Investigators should use results from the same local laboratories for assessing eligibility, safety 
monitoring, and dosing decision for each patient. 
4.4.4.1. 
Cardiac Enzyme Monitoring 
Although immune-mediated myocarditis is a rare complication of immune checkpoint inhibitors, 
serum creatine kinase (CK) and creatine kinase cardiac muscle isoenzyme (CK-MB) are 
monitored in all tislelizumab studies to protect study patients and to quantify the risk of muscle 
inflammation (see Table 14 for the blood collection schedule and Appendix 12 for guidelines for 
management of suspected immune-mediated myocarditis, respectively). Serum troponins may be 
substituted per local guideline if used consistently through the study. 
Serum CK and CK-MB testing will be implemented for all patients at screening, at scheduled 
visits during the treatment periods, and at the EOT. In the event that CK-MB fractionation is not 
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available, serum troponins (troponin I and/or T) measurements will be performed instead per 
local guidelines if used consistently throughout the study.  
4.4.5. Electrocardiograms 
The ECG recordings will be obtained during screening, and as clinically indicated during the 
treatment period, at the EOT Visit (Table 14). 
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 patient should rest in semi-recumbent supine position for ≥ 10 minutes in the absence of 
environmental distractions that may induce changes in heart rate (eg, television, radio, 
conversation, etc) before each ECG collection. 
4.4.6. 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 5.6 of Appendix 17. 
4.4.7. Hepatitis B and C Testing 
Testing will be performed by a central laboratory and/or the local laboratory at screening (and as 
clinically indicated) and will include HBV/HCV serology (HBsAg, hepatitis B surface antibody 
[HBsAb], hepatitis B core antibody [HBcAb], and HCV antibody). In the case of positive 
HBsAg result or positive HCV antibody result, these tests will be followed by viral load 
assessment (HBV DNA or HCV RNA) at screening. 
For patients who have detectable HBV DNA or HCV RNA at screening or upon repeat testing, 
the respective viral load test will be performed every 12 weeks. A detailed schedule is provided 
in Table 14. 
4.5. 
Tumor and Response Evaluations 
Tumor imaging will be performed ≤ 28 days before randomization. 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. During the study, tumor imaging will be performed approximately every 
9 weeks (± 7 days) from randomization for the first 54 weeks, and every 12 weeks (± 7 days) 
thereafter, based on RECIST v1.1. The first tumor assessment after randomization (the 9-week 
tumor assessment) is allowed to be performed within 42 days after cCRT and should take place 
before the initiation of immunotherapy after the cCRT phase. If a tumor assessment is missed or 
conducted outside of the specified assessment window, all subsequent scans should be conducted 
according to the planned schedule. 
Tumor assessments must be performed on schedule regardless of whether study treatment has 
been administered or held; that is, tumor assessments should not be adjusted for delays in cycles, 
except for the first 9-week tumor assessment. 
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Screening assessments must include: 
• FDG-PET/CT performed for the whole body, or sufficient to rule out distant 
metastases (eg, from skull base to knees). 
• If the CT scan portion is with contrast and is of sufficiently high quality, a separate 
CT scan at screening for the chest, abdomen, and pelvis can be skipped. 
• MRI (or CT scan if MRI is contraindicated or not readily available) with contrast of 
the head is required at screening. 
• While centers are encouraged to obtain tissue confirmation of lymph node metastases 
in N2 or N3 disease, the tumor board/multidisciplinary team in individual cases may 
dispense with this procedure (AJCC Cancer Staging Manual 2017). 
If the CT scan portion of FDG-PET/CT is not qualified enough as specified above, screening 
assessment must include CT scans (with oral/intravenous contrast, unless contraindicated) of the 
chest, abdomen, and pelvis; each subsequent assessment should include at least CT scans (with 
oral/intravenous contrast, unless contraindicated) of the chest and abdomen. If contraindication 
exists, other modalities can be allowed after consultation with the medical monitor (eg, MRI, CT 
without contrast). 
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 must be used throughout the study (eg, the same contrast 
protocol for CT scans). 
• If a patient is known to have a contraindication to CT contrast media or develops a 
contraindication during the study, a noncontrast CT of the chest plus a 
contrast-enhanced MRI (if possible) of abdomen and pelvis should be performed. 
• If a CT scan for tumor assessment is performed on a PET/CT scanner, the CT 
acquisition must be consistent with the standards of a diagnostic CT scan. 
• MRI (or CT scan if MRI is contraindicated or not readily available) of the head or bone 
scan is performed if clinically indicated at the discretion of investigator before the 
discontinuation of tumor assessment. 
• At the investigator’s discretion, other methods of assessment of target lesion and non-
target lesions per RECIST v1.1 may be used. 
Response will be assessed by the investigator using RECIST v1.1 (see Appendix 13). The same 
evaluator should perform assessments, if possible, to ensure internal consistency across visits. 
Administration of study treatment will continue until 12 months following the completion of 
cCRT; PD as assessed by the investigator per RECIST v1.1, unacceptable toxicity, death; or 
another discontinuation criterion is met. 
A patient who discontinues study treatment for reasons other than disease progression (eg, 
toxicity, completion of the 12-month treatment) will continue to undergo tumor assessments 
following the original plan until the patient experiences PD per RECIST v1.1, withdraws 
consent, is lost to follow-up, death, or until the study terminates, whichever occurs first. 
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Study treatment beyond initial PD per RECIST 1.1 
If at the investigator’s discretion a patient could continue to benefit from ociperlimab and 
tislelizumab combination treatment or tislelizumab or durvalumab after PD per RECIST v1.1, 
the patient may continue their assigned treatment. The following criteria must be met in order to 
treat patients who may continue to benefit from study drugs after PD:  
• Absence of clinical symptoms and signs of PD (including clinically significantly 
worsening of laboratory values) 
• Stable ECOG Performance Status ≤ 1 
• Absence of rapid progression of disease or of progressive tumor at critical anatomical 
sites (eg, cord compression) that requires urgent alternative medical intervention 
• Investigators must obtain written informed consent for treatment beyond radiologic PD 
and inform patients that this practice is not considered standard in the treatment of 
cancer. 
The decision to continue study drugs beyond initial PD per RECIST v1.1 must be agreed upon 
with the medical monitor and documented in the study records. 
Tumor assessment should continue as planned in patients receiving study drug(s) beyond initial 
PD per RECIST v1.1. Tumor assessment in such patients should continue until study treatment 
discontinuation. 
Second Progression 
Following the first progression assessed by the investigator, patients will be assessed every 12 
weeks (± 7 days) for a second progression (using the patient’s status at the first progression as 
reference for assessment of second progression). A patient’s second progression status is defined 
according to local standard clinical practice and may involve any of: objective radiological, 
symptomatic progression or death. Measurements per RECIST v1.1 will not be collected for 
assessment of PFS2. The date of PFS2 assessment and investigator’s opinion of progression 
status (progressed or non-progressed) at each assessment will be recorded in the eCRF. 
4.6. 
Pharmacokinetic and Antidrug Antibody Testing 
Checkpoint inhibitors may elicit an immune response. Patients with signs of any potential 
immune response will be closely monitored. Validated screening and confirmatory assays will be 
employed to detect ADA at multiple timepoints throughout the study. In addition, blood samples 
will be collected for characterization of ociperlimab and tislelizumab PK at the timepoints 
specified in the Schedule of Assessments (Table 14). 
PK and ADA assays of ociperlimab and tislelizumab will be managed through a central 
laboratory. Serum samples will be assayed for ociperlimab and tislelizumab concentrations using 
validated immunoassays. 
• ADA assays: serum samples will be tested for the presence of ADAs to ociperlimab and 
tislelizumab using validated immunoassays. 
• PK assays: serum samples will be assayed for ociperlimab and tislelizumab serum 
concentrations using validated immunoassays. 
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Refer to the laboratory manual for instructions regarding sample collection, handling, labeling, 
storage, and shipping of laboratory samples. 
4.7. 
Biomarker 
Shipping, storage, and handling of blood samples as well as archival tumor and/or fresh tumor 
tissues for the assessment of biomarkers will be handled by a central laboratory. Refer to the 
laboratory manual for details of sample handling and the Schedule of Assessments (Table 14) for 
timepoints. 
Tissue-based biomarkers, including but not limited to the expression of TIGIT, CD226, CD155, 
CD112, and PD-L1, GEP, TMB, gene mutations and microsatellite instability (MSI), and TILs at 
baseline, and at disease progression/reoccurrence will be tested. (Note: For the sites in China 
mainland, tissues will be obtained to test 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). 
Patients are required to provide tumor tissues (archival tumor tissues [FFPE blocks or 
approximately 15 [≥ 6] freshly cut unstained FFPE slides] or fresh biopsies). If archival tumor 
tissues are not available, a fresh tumor biopsy is required at baseline. Acceptable fresh biopsy 
samples include core needle biopsies for deep tumor tissue or excisional, incisional, punch, or 
forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. 
If clinically feasible, it is highly recommended to obtain a tumor biopsy at the time of disease 
progression to explore the immune- or tumor-related biomarkers and biological changes that 
might drive disease progression or acquired resistance to ociperlimab and tislelizumab or 
durvalumab. Blood sample must be collected at C1D1 (predose) for biomarker test. Optional 
blood samples will be collected at C3D1 (predose), at C4D1 (predose), and at the EOT Visit after 
the disease progression (Table 14). All these blood samples will be collected to explore the 
association of blood-based biomarkers with response, resistance and prognosis. (Note: Blood-
based biomarkers, including TMB, MSI, ctDNA, EVs and gene mutational profiles, will be 
explored in the blood samples which will be collected in the sites in China mainland). 
Written informed consent is required for any of the fresh tumor biopsies and blood sample 
collection. Tumor tissue should be of good quality in terms of total and viable tumor content. 
Fine needle aspiration, brushing, cell pellets from pleural effusion, and lavage samples are not 
acceptable. 
4.8. 
Health-Related Quality of Life 
Patients will be asked to complete 5 PROs, that include the EORTC QLQ-C30 (Appendix 7), 
EORTC QLQ-LC13 (Appendix 8), EQ-5D-5L questionnaires (Appendix 9), PGI-S 
(Appendix 10), and PRTSE (Appendix 11) before any clinical activities are performed during 
on-study clinic visits according to the schedule in Table 14. The questionnaires will be provided 
in the patient’s preferred language. 
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4.9. 
Visit Windows 
All visits must occur within ± 3 days from the scheduled date, unless otherwise noted (see 
Table 14). 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 any study treatment is given 
unless otherwise noted. Laboratory results must be reviewed before dosing. 
If the timing of a protocol-mandated study visit coincides with a holiday, weekend, or other 
events, the visit should be scheduled for the nearest feasible date (the visit window is provided in 
Table 14), with subsequent visits conducted according to the planned schedule every 3 weeks 
(Arm A and Arm B) or every 2 or 4 weeks (Arm C) from C3D1. For visit schedule of Cycle 1 
and Cycle 2, refer to Table 14. 
4.10. 
Unscheduled Visits 
Unscheduled visits may be performed at any time at the patient’s or the investigator’s request 
and may include vital signs/physical examination; ECOG Performance Status; AE review; 
concomitant medications and procedures review; radiographic assessments; disease-related 
constitutional symptoms; and 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 PD, 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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5. 
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. 
5.1. 
Risks Associated With Study Treatment 
5.1.1. Risks Associated With Ociperlimab and Tislelizumab 
Ociperlimab and tislelizumab are investigational agents that are currently in clinical 
development. Limited safety data are available in patients and the full safety profile has not been 
characterized. 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 5.7.3 of Appendix 17. 
Ociperlimab-mediated TIGIT inhibition may increase the risk of imAEs. However, no apparent 
immunotoxicity, or toxicity in general, has been observed in animal models treated with 
ociperlimab. Furthermore, in the absence of activation, peripheral effector T cells do not 
typically express TIGIT, thereby minimizing any potential negative additive affect as it relates to 
peripheral immune tolerance. 
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 workup procedures for suspected imAEs are provided in 
Appendix 12. 
5.1.2. Risks Associated With Durvalumab 
Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that binds to 
PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80. The PD-L1/PD-1 pathway is 
involved in peripheral tolerance; therefore, such therapy may increase the risk of imAEs similar 
to PD-L1/PD-1 class drugs, specifically the induction or enhancement of autoimmune 
conditions. The risks are immune-mediated pneumonitis, hepatitis, colitis, endocrinopathies, 
nephritis, dermatologic reactions; and other immune-mediated adverse reactions (incidence of 
less than 1%) such as aseptic meningitis, hemolytic anemia, immune thrombocytopenic purpura, 
myocarditis, myositis, and ocular inflammatory toxicity, including uveitis and keratitis. Besides 
immune-related side effects, and infusion-related reactions are common. Overall infection is also 
very common. 
Refer to the durvalumab prescribing information for details. 
5.1.3. Risks Associated With Concurrent Chemotherapy 
Please refer to Table 24 for the reported toxicity for the respective chemotherapeutic agents. The 
investigator should refer to the package insert for a complete list of potential side effects. 
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Table 24: 
The summary of the commonly and specific reported toxicity of the 
chemotherapeutic agents 
Agents 
Common toxicity 
Specific toxicity 
Cisplatin 
Leukopenia, 
thrombocytopenia and 
anemia; infectious 
complications; 
nausea/vomiting and other 
GI toxicity; hepatic 
impairment; fatigue; 
anorexia; constipation 
Nephrotoxicity; ototoxicity; peripheral neuropathies 
Carboplatin 
Ototoxicity and peripheral neuropathies 
Pemetrexed 
Nephrotoxicity; skin rash 
Paclitaxel 
Hypersensitivity reaction; neuropathies; myalgia; arthralgia; 
cardiovascular 
Etoposide 
Hypersensitivity reactions; ocular; respiratory; skin; 
neurologic 
5.1.4. Risks Associated With Radiotherapy 
AEs related to RT include nausea/vomiting, diarrhea, weight loss, fatigue, hematology toxicity, 
skin erythema, subcutaneous fibrosis, esophagitis, esophageal stricture, esophageal fistula, 
carditis, myelitis, acute radiation pneumonitis, and late pulmonary fibrosis. 
5.2. 
General Plan to Manage Safety Concerns 
5.2.1. Safety Monitoring Plan 
Safety will be evaluated in this study through the monitoring of all AEs, 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 25), physical examinations, laboratory measurements 
(hematology, clinical chemistry, etc), and other assessments including those listed in Table 14. In 
addition, patients will be closely monitored for the development of any signs or symptoms of 
autoimmune conditions or infection. 
At the start of each cycle, study treatment(s) will be provided only after clinical laboratory 
results have been reviewed. Administration of study treatment will be performed in a setting 
where emergency medical equipment and staff who are trained to respond to medical 
emergencies are available (for additional information, see Section 2.2 of Appendix 17). 
Serum samples will be drawn for determination of ADAs to ociperlimab and tislelizumab in all 
randomized patients. 
Investigators are instructed to report all AEs (includes 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 5.7 of Appendix 17. 
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5.3. 
Adverse Events 
5.3.1. 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 study 
treatment, whether considered related to study treatment or not. 
Examples of AEs include: 
• Worsening of a chronic or intermittent pre-existing condition, including an increase in 
severity, frequency, duration, and/or has an association with a significantly worse 
outcome 
• New conditions detected or diagnosed after study treatment administration even though 
the condition might have been present before the start of the study 
• Signs, symptoms, or the clinical sequelae of a suspected interaction 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment 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 before submission to the sponsor. 
5.3.2. 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 NCI-CTCAE v5.0. 
Toxicities that are not specified in 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 
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care, 
activities of daily living 
• 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 
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definitions. Seriousness serves as the guide for defining regulatory reporting obligations from the 
sponsor to applicable regulatory authorities as described in Section 5.6.2 of Appendix 17. 
5.3.3. Assessment of Causality 
The investigator is obligated to assess the relationship between the study treatment and the 
occurrence of each AE or SAE using best clinical judgement. Alternative causes, such as natural 
history of the underlying diseases, concomitant therapy, and other risk factors, and the temporal 
relationship of the AE or SAE to the study treatment will be considered and investigated. The 
investigator should consult the Tislelizumab Investigator’s Brochure, Ociperlimab Investigator’s 
Brochure, durvalumab prescribing information, chemotherapy prescribing information, and 
radiation manual in the determination of his/her assessment. 
There may be situations when an SAE has occurred, and the investigator has minimal 
information to include in the initial report to the sponsor. However, it is very important that the 
investigator always assesses causality for every SAE before transmission of the SAE report to 
the sponsor because the causality assessment is 1 of the criteria used when determining 
regulatory reporting requirements. The investigator may change his/her opinion of causality 
considering follow-up information, amending the SAE report accordingly. 
The causality of each AE should be assessed and classified by the investigator as “related” or 
“not related.” An AE is considered related if there is “a reasonable possibility” that the AE may 
have been caused by the study treatment (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 treatment  
• Biological plausibility 
An AE should be considered “related” to study treatment if any of the following are met; 
otherwise, the event should be assessed as “not related”: 
• There is clear evidence to suggest a causal relationship, and other possible contributing 
factors can be ruled out 
• There is evidence to suggest a causal relationship, and the influence of other factors is 
unlikely 
• There is some evidence to suggest a causal relationship (eg, the AE occurred within a 
reasonable time after administration of the study treatment[s]). However, the influence 
of other factors may have contributed to the AE (eg, the patient’s clinical condition or 
other concomitant AEs). 
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5.3.4. 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 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. 
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 5.6.2 of Appendix 17. 
5.3.5. Laboratory Test Abnormalities 
Abnormal laboratory findings (eg, clinical chemistry, 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 that 
worsen significantly during the study. The definition of clinically significant is based on the 
judgement 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 AE 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 AE eCRF, unless the etiology changes. The initial severity of 
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the event should be recorded, and the severity or seriousness should be updated any time the 
event worsens. 
5.4. 
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 was 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. 
• 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 SAEs: 
• Hospitalization for elective treatment of a pre-existing 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 
5.5. 
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 study drug’s reference safety information [RSI]) and 
meets the definition of an serious adverse drug reaction (SADR), the specificity or severity of 
which is not consistent with those noted in Tislelizumab Investigator’s Brochure, Ociperlimab 
Investigator’s Brochure, durvalumab prescribing information, chemotherapy prescribing 
information, and radiation manual. 
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5.6. 
Timing, Frequency, and Method of Capturing Adverse Events and 
Serious Adverse Events 
5.6.1. Adverse Event Reporting Period 
After the ICF has been signed, but before study treatment, only SAEs should be reported to the 
sponsor. 
After initiation of study treatment, all AEs and SAEs, regardless of relationship to study 
treatment, will be reported until either 30 days after last dose of study treatment (including 
chemoradiotherapy) or 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, tislelizumab, or durvalumab, regardless of whether the patient starts a new 
anticancer therapy. All SAEs considered related to the study treatment(s) 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 25. For the follow-up period 
for AEs, see Section 5.3.4 of Appendix 17. For the definition of treatment-emergent adverse 
events (TEAEs), see Section 9.3.2. 
Table 25:  
Guidance for Duration of Recording New or Worsening Adverse Events in 3 
Arms 
Event Type 
Record new or worsening events that occur during this period 
Begin 
End 
SAEsa 
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 5.6.4 of Appendix 17) 
All nonserious AEs, except 
those due to PD 
First dose of study 
treatment 
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 
treatment 
Up to 90 days after last dose (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 treatment(s) that are brought to the attention of the investigator should be 
reported regardless of time since the last dose of treatment. 
5.6.2. Reporting Serious Adverse Events 
5.6.2.1. 
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 26. 
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Table 26: 
Time Frames and Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee 
 
Time frame for 
sending initial 
report 
Documentation 
method 
Time frame for 
sending 
follow-up 
report 
Documentation 
method 
Reporting 
method 
All SAEs 
Within 24 hours 
after first 
knowledge of 
the AE 
SAE report 
As expeditiously 
as possible 
SAE report 
Email or fax 
SAE form or 
pregnancy form 
Abbreviations: AE, adverse event; SAE, serious adverse event. 
5.6.2.2. 
Completion and Transmission of the Serious Adverse Event Report 
Once an investigator becomes aware that an SAE has occurred in a patient, he/she is to report the 
information to the sponsor within 24 hours, as outlined above in Section 5.6.2.1 of Appendix 17. 
The SAE report will always be completed as thoroughly as possible, including 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 5.3.3 of Appendix 17. 
The sponsor will provide contact information for SAE receipt. 
5.6.2.3. 
Regulatory Reporting Requirements for Serious Adverse Events 
The investigator will promptly report all SAEs to the sponsor in accordance with the procedures 
detailed in Section 5.6.2.1 of Appendix 17. The sponsor has a legal responsibility to notify, as 
appropriate, both the local regulatory authority and other regulatory agencies about the safety of 
a drug 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 5.5 of Appendix 17) will be submitted to all applicable 
regulatory authorities and investigators for ociperlimab, tislelizumab, and durvalumab 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. 
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5.6.3. 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? 
5.6.4. Disease Progression 
PD, which is expected in this study population and 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 5.6.2 of Appendix 17). 
5.6.5. Deaths 
Death is an outcome and not usually considered an AE. If the only information available is death 
and the cause of death is unknown, then the death is reported as an event (eg, “death,” “death of 
unknown cause,” or “death unexplained”). 
5.6.6. Pregnancies 
If a female patient or the partner of a male patient becomes pregnant while receiving study 
treatment or within 120 days after the last dose of ociperlimab and tislelizumab in Arm A or 
tislelizumab in Arm B, or within 3 months after the last dose of durvalumab, or within 180 days 
after the last dose of chemotherapy or radiotherapy (14 months or 11 months after the last dose 
of cisplatin for female or male patients, respectively), a pregnancy report form must be 
completed and expeditiously submitted to the sponsor to facilitate outcome followup. 
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 always be reported as an 
SAE. Similarly, any congenital anomaly/birth defect in a child born to a patient exposed to the 
study treatment should be recorded and reported as an SAE. 
5.6.7. 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. 
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To determine the reporting requirements for individual SAEs, the sponsor will assess the 
expectedness of the SAEs using the following reference safety information documents: 
• Tislelizumab Investigator’s Brochure 
•  Ociperlimab Investigator’s Brochure 
• Durvalumab prescribing information 
• Cisplatin prescribing information 
• Carboplatin prescribing information 
• Pemetrexed prescribing information 
• Paclitaxel prescribing information 
• Etoposide prescribing information 
5.6.8. Assessing and Recording Immune-Mediated Adverse Events 
Since treatment with anti-PD-1 or immune checkpoint inhibitors can cause autoimmune 
disorders, AEs considered by the investigator to be immune-mediated (see Section 5.7.3 of 
Appendix 17) should be classified as imAEs and identified as such on the eCRF AE page until 
Day 90 after treatment discontinuation. 
Investigators should consult the guidance on diagnostic evaluation and management of imAEs, 
which are commonly seen with immune checkpoint inhibitors, in Appendix 12. 
An extensive list of potential imAEs appears in Table 28. 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 12. 
5.6.9. 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 each as a separate AE in eCRF and 
identified as an infusion-related reaction. Refer to the eCRF completion guidelines for details. 
5.7. 
Management of Adverse Events of Special Interest 
As a routine precaution, after infusion of ociperlimab and tislelizumab in Arm A on Day 1 of 
Cycle 1 and Cycle 2, patients must be monitored for at least 2 hours afterwards in an area with 
resuscitation equipment and emergency agents; similarly, after infusion of tislelizumab in Arm B 
on C1D1 and C2D1, patients will be monitored for ≥ 1 hour. From Cycle 3 onward, at least a 
60-minute monitoring period is required in an area with resuscitation equipment and emergency 
agents for Arm A, and for Arm B, the monitoring period is at least 30 minutes. 
The management for infusion-related reactions, severe hypersensitivity reactions, and imAEs 
according to the NCI-CTCAE criteria are outlined in the following subsections. 
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5.7.1. Infusion-Related Reactions 
Patients should be closely monitored for infusion-related reactions. Immediate access to an 
Intensive Care Unit or equivalent environment and appropriate medical therapy (including 
epinephrine, corticosteroids, intravenous antihistamines, bronchodilators, and oxygen) must be 
available to treat infusion-related reactions. 
Treatment modification for symptoms of infusion-related reactions due to study drugs is 
provided in Table 27. 
Table 27: 
Treatment Modification for Symptoms of Infusion-Related Reactions Due to 
Study Drugs 
NCI-CTCAE grade 
Treatment modification for Ociperlimab and 
Tislelizumab 
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.  
Grade 2 - moderate 
Therapy or infusion interruption indicated but 
responds promptly to symptomatic treatment 
(eg, antihistamines, nonsteroidal anti-inflammatory 
drugs, narcotics, intravenous fluids); prophylactic 
medications indicated for ≤ 24 hours. 
Stop infusion. Infusion may be resumed at 50% of 
previous rate once infusion-related reactions has resolved 
or decreased to Grade 1 in severity. Any worsening is 
closely monitored. Proper medical management should be 
instituted as described in the text following this table.  
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 in the text 
following this table. 
The patient should be withdrawn from the study treatment. 
Grade 4 – life-threatening 
Life-threatening consequences; urgent intervention 
indicated. 
Immediately stop the infusion. Proper medical 
management should be instituted as described in the text 
following this table. 
The patient should be withdrawn from the study treatment. 
Hospitalization is recommended. 
Abbreviations: NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events. 
In Arm A and Arm B, once the ociperlimab or tislelizumab infusion rate has been decreased by 
50% or suspended due to an infusion-related reaction, it must remain decreased for all 
subsequent infusions. If the patient has a second infusion-related reaction (≥ Grade 2) on the 
slower infusion rate, the infusion should be discontinued, and the patient should be withdrawn 
from ociperlimab and tislelizumab 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 
acetaminophen and/or 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, the patient should receive oral 
pre-medication with an antihistamine (eg, diphenhydramine or equivalent) and an antipyretic 
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(eg, paracetamol or equivalent), and the patient 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 antihistamine, antipyretic, glucocorticoids, epinephrine, bronchodilators, and 
oxygen. 
5.7.2. 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 (United Kingdom) 
(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 stopped 
immediately, and the patient discontinued from the study. 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 are 
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. 
The patients will be administered epinephrine injection and dexamethasone infusion if 
hypersensitivity reaction is observed, and then the patient should be placed on monitor 
immediately and an Intensive Care Unit 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, 500 mg naproxen sodium) may be 
administered 2 hours before and 8 hours after the start of each dose of study drug infusion. 
Alternative treatments for fever (ie, paracetamol) may be administered to the patient at the 
discretion of the investigator. 
5.7.3. 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, PD, or other neoplastic causes) with appropriate diagnostic 
tests that may include but are not limited to serologic, immunologic, and histologic (biopsy) data. 
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, the imAE indicator on the eCRF AE page should be checked. 
A list of potential imAEs is shown below in Table 28. All conditions similar to those listed 
should be evaluated in patients receiving ociperlimab and tislelizumab in Arm A, tislelizumab in 
Arm B to determine whether they are immune-mediated. 
Recommendation for diagnostic evaluation and management of imAEs is based on ESMO and 
American Society of Clinical Oncology guidelines (Haanen et al 2017; Brahmer et al 2018) and 
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common immune-mediated toxicities are detailed in Appendix 12. For any AEs not included in 
Appendix 12, refer to the American Society of Clinical Oncology Clinical Practice Guideline 
(Brahmer et al 2018) for further guidance on diagnostic evaluation and management of 
immune-mediated toxicities. 
Table 28: 
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 
Eye 
episcleritis; conjunctivitis; iritis/uveitis 
Musculoskeletal 
arthritis; arthralgia; myalgia; 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-Barre 
syndrome; neuropathy 
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase. 
Recommendations for managing imAEs are detailed in Appendix 12. 
If a toxicity does not resolve to ≤ Grade 1 within 12 weeks, study drugs should be discontinued 
after consultation with the sponsor. Patients who experience a recurrence of any event at the 
same or higher severity grade with rechallenge should permanently discontinue treatment. 
5.7.4. Adverse Events of Special Interest of Durvalumab 
Infusion-related reaction, infection, and imAEs are of special interest with durvalumab. Please 
refer to durvalumab prescribing information which has been approved by local health authority. 
Appendix 15 provides Table 2 Recommended Dosage Modifications in the durvalumab 
prescribing information approved by the US FDA for reference. 
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STATISTICAL ANALYSIS PLAN 
 
 
Study Protocol Number: 
BGB-A317-A1217-301  
Study Protocol Title: 
A Phase 3, Randomized, Open-Label Study to Compare 
Ociperlimab (BGB-A1217) Plus Tislelizumab (BGB-A317) 
Versus Durvalumab in Patients With Locally Advanced, 
Unresectable, PD-L1-Selected Non-Small Cell Lung Cancer 
Whose Disease Has Not Progressed After Concurrent 
Chemoradiotherapy 
Date: 
07Nov2023 
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SIGNATURE PAGE 
 
 
Author: 
 
 
 
Approval 
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TABLE OF CONTENTS 
1. .................. INTRODUCTION ........................................................................................................8 
1.1. .............. Study Overview ............................................................................................................8 
2. .................. STUDY OBJECTIVES ................................................................................................9 
2.1. .............. Primary Objective .........................................................................................................9 
2.2. .............. Secondary Objective .....................................................................................................9 
2.3. .............. Exploratory Objective ...................................................................................................9 
3. .................. STUDY ENDPOINTS ................................................................................................10 
3.1. .............. Primary Endpoint(s) ....................................................................................................10 
3.2. .............. Secondary Endpoints ..................................................................................................10 
3.3. .............. Exploratory Endpoints ................................................................................................10 
4. .................. SAMPLE SIZE CONSIDERATIONS .......................................................................10 
5. .................. DEFINITION OF PRIMARY ESTIMANDS ............................................................12 
6. .................. STATISTICAL METHODS .......................................................................................12 
6.1. .............. Analysis Sets ...............................................................................................................12 
6.2. .............. Data Analysis General Considerations .......................................................................12 
6.2.1. ........... Definitions and Computations ....................................................................................13 
6.2.2. ........... Conventions ................................................................................................................13 
6.2.3. ........... Handling of Missing Data ...........................................................................................14 
6.2.4. ........... Multiplicity Adjustment..............................................................................................14 
6.2.5. ........... Data Integrity ..............................................................................................................14 
6.3. .............. Subject Characteristics ................................................................................................14 
6.3.1. ........... Subject Disposition .....................................................................................................14 
6.3.2. ........... Protocol Deviations ....................................................................................................14 
6.3.3. ........... Demographic and Other Baseline Characteristics ......................................................14 
6.3.4. ........... Disease History ...........................................................................................................15 
6.3.5. ........... Prior Anticancer Drug Therapies and Surgeries .........................................................15 
6.3.6. ........... Prior and Concomitant Medications ...........................................................................15 
6.3.7. ........... Medical History ..........................................................................................................15 
6.4. .............. Efficacy Analysis ........................................................................................................15 
6.5. .............. Safety Analyses ..........................................................................................................20 
6.5.1. ........... Extent of Exposure .....................................................................................................20 
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6.5.2. ........... Adverse Events ...........................................................................................................23 
6.5.3. ........... Radiotherapy Quality Assurance ................................................................................27 
6.5.4. ........... Laboratory Values ......................................................................................................29 
6.5.5. ........... Vital Signs ..................................................................................................................29 
6.5.6. ........... Physical Examination .................................................................................................30 
6.5.7. ........... Eastern Cooperative Oncology Group (ECOG) .........................................................30 
6.6. .............. Pharmacokinetic Analyses ..........................................................................................30 
6.6.1. ........... Reporting of Pharmacokinetic Concentrations for Descriptive Statistics ..................30 
7. .................. IMMUNOGENICITY ANALYSES ..........................................................................30 
8. .................. CHANGES IN THE PLANNED ANALYSIS ...........................................................31 
9. .................. REFERENCES ...........................................................................................................32 
APPENDIX A. IMPUTATION OF MISSING OR PARTIALLY MISSING DATES ..............33 
APPENDIX B. CENSORING RULES FOR PRIMARY ANALYSIS OF PFS PER 
RECIST VERSION 1.1 ..............................................................................................36 
APPENDIX C. RULES FOR IDENTIFYING MISSING TUMOR ASSESSMENTS ..............37 
LIST OF TABLES 
Table 1 Scoring of QLQ-C30 version 3.0 ......................................................................................18 
Table 2 Scoring of QLQ-LC13 ......................................................................................................19 
Table 3 Example Formula to Calculate ADI and Planned Dose Intensity of 
Chemotherapy by Cycle .............................................................................................22 
Table 4 Clinical Laboratory Assessments ......................................................................................29 
Table 5 Censoring Rules for Primary and Sensitivity Analysis of PFS ........................................36 
Table 6 An example of scheduled tumor assessments with time window .....................................37 
LIST OF FIGURES 
Figure 1 Study Schema of PA 2.0 ....................................................................................................8 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Abbreviation 
Term 
3D-CRT 
3D conformal radiation 
ADAs 
antidrug antibodies 
AE 
adverse event 
ALK 
anaplastic lymphoma kinase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
AUC 
area under the concentration-time curve 
BOR 
best overall response 
BLA 
biologics license application 
CmDn 
cycle m day n 
CBR 
clinical benefit rate 
CI 
confidence interval 
CK 
creatine kinase 
CK-MB 
creatine kinase cardiac muscle isoenzyme 
CR 
complete response 
CRR 
complete response rate 
cCRT 
concurrent chemoradiotherapy 
CT 
computed tomography 
DCR 
disease control rate 
DOR 
duration of response 
DVA 
dose volume analysis 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture (system) 
EGFR 
epidermal growth factor receptor 
eGFR 
estimated glomerular filtration rate 
EORTC 
European Organisation for Research and Treatment of Cancer  
EQ-5D-5L 
EuroQol 5 dimension 5 level 
EOT 
End-of-Treatment (Visit) 
EVs 
extracellular vesicle  
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GTV 
gross tumor volume 
HR 
hazard ratio 
HRQoL 
health-related quality of life 
IDMC 
independent data monitoring committee 
imAE 
immune-related adverse event 
IMRT 
intensity modulated radiotherapy 
IRC 
Independent Review Committee 
ITT 
Intent-to-Treat (Analysis Set) 
ITIM 
immunoreceptor tyrosine-based inhibitory motif 
ITV 
internal target volume 
IV 
intravenously 
LA NSCLC 
locally advanced non-small cell lung cancer 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI-CTCAE 
National Cancer Institute-Common Terminology Criteria for Adverse Events 
NSCLC 
non-small cell lung cancer 
BGB-A1217 
ociperlimab 
OAR 
organs at risk 
ORR 
overall response rate 
OS 
overall survival 
PA 
protocol amendment 
PD 
progressive disease 
PD-L1 
programmed cell death protein-ligand 1 
PGI-S 
patient reported global impression of severity  
PFS 
progression-free survival 
PK 
pharmacokinetics 
PR 
partial response 
PRTSE 
patient reported treatment side-effect burden 
PT 
preferred term 
PTV 
planning target volume 
PVR 
poliovirus receptor 
Q1 
25th percentile 
Q3 
75th percentile 
QLQ-C30 
quality of life questionnaire core 30 
QLQ-LC13 
quality of life questionnaire-lung cancer 13 
QnW 
every n weeks 
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ORR 
objective response rate 
OS 
overall survival 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RT 
radiotherapy 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS 
safety analysis set 
SC 
steering committee 
SD 
standard deviation 
SOC 
System Organ Class 
T3 
Triiodothyronine 
T4 
Thyroxine 
TEAE 
treatment-emergent adverse event 
TC 
tumor cells 
TIGIT 
T-cell immunoglobulin and ITIM domain 
BGB-A317 
tislelizumab 
TIL 
tumor-infiltrating lymphocyte 
TMB 
tumor mutation burden 
TNM 
tumor nodes metastasis 
TTDM 
time to death or distant metastasis 
WHO DD 
World Health Organization Drug Dictionary 
VAS 
visual analogue scale 
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1. 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to describe the procedures and the statistical 
methods that will be used to analyze and report results, under abbreviated clinical study report 
(CSR) setting, for AdvanTIG-301 protocol amendment (PA) version 2.0: A Phase 3, Randomized, 
Open-Label Study to Compare Ociperlimab (BGB-A1217) Plus Tislelizumab (BGB-A317) 
Versus Durvalumab in Patients With Locally Advanced, Unresectable, programmed cell death 
protein-ligand 1 (PD-L1) Selected Non-Small Cell Lung Cancer (NSCLC) Whose Disease Has 
Not Progressed After Concurrent Chemoradiotherapy (cCRT). 
The study was initially implemented with Protocol Amendment 1.0 (PA 1.0, dated on 16 Apr 
2021). In the PA 1.0, patients with newly diagnosed, histologically confirmed, unresectable locally 
advanced NSCLC and evaluable PD-L1 expression all comers were enrolled; cCRT was given 
within the study. There were 63 patients who were randomized under the PA 1.0, from29 Jun 2021 
to 26 Apr 2022. No patient was randomized under the PA 2.0. The concurrent part (patients 
randomized under PA 1.0) was integrated into PA 2.0 and managed mainly per Appendix 17 of 
PA 2.0 after PA 2.0 became effective.  
Given the study was early terminated with no patients enrolled under PA 2.0 and only 63 patients 
randomized under the concurrent part (patients randomized under PA 1.0), the objectives of PA 
2.0 are exploratory and have been modified in this SAP by selecting the applicable objectives in 
PA 2.0 and PA 1.0. 
1.1. 
Study Overview 
The PA2.0 is an open-label, randomized, multicenter, Phase 3 study to compare the efficacy and 
safety of anti T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) 
domains (anti TIGIT) monoclonal antibody ociperlimab plus tislelizumab versus durvalumab in 
patients with unresectable locally advanced (LA) NSCLC whose disease has not progressed after 
definitive, platinum based cCRT and with PD L1 expression on ≥ 1% of tumor cells (TC) as 
assessed by the central lab using the VENTANA PD-L1 (SP263) assay. 
Randomization will be stratified by age (< 65 years versus ≥ 65 years), PD-L1 expression on TC 
(≥ 50% versus < 50%), and histology (squamous versus nonsquamous). The ITT and PD L1 ≥ 50% 
populations are defined as patients with PD-L1 expression on ≥ 1% and ≥ 50% of TC, respectively. 
Approximately 700 patients will be randomized in a 3:1:3 ratio to receive the study treatment in 
the following 3 arm. Arm A: ociperlimab (900 mg intravenously [IV]) combined with tislelizumab 
(200 mg IV) every 3 weeks (Q3W), Arm B: tislelizumab 200 mg IV Q3W, and Arm C: durvalumab 
10 mg/kg IV once every 2 weeks (Q2W) (or 1500 mg every 4 weeks [Q4W] where the dosage has 
been approved by the local health authority). Study drugs will be given starting from Cycle 1 Day 
1 (C1D1) and continued for up to 12 months, or until progressive disease (PD) per Response 
Evaluation Criteria in Solid Tumors (RECIST) v1.1, unacceptable toxicity, or death, or until 
another discontinuation criterion is met, whichever occurs first. 
The study design schema of PA 2.0 is shown in Figure 1. 
Figure 1 Study Schema of PA 2.0 
 
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For all patients randomized with PA 1.0 (defined as Concurrent Part of the study): 
The study was initially implemented with Protocol Amendment 1.0 (dated on 16 Apr 2021, PA 
1.0). In the PA 1.0, patients with newly diagnosed, histologically confirmed, unresectable LA 
NSCLC and evaluable PD-L1 expression all comers were enrolled; cCRT was given within the 
study.  
Patients were enrolled and randomized in a 1:1:1 ratio to ociperlimab (BGB-A1217) plus 
tislelizumab plus cCRT followed by ociperlimab plus tislelizumab (Arm A), tislelizumab plus 
cCRT followed by tislelizumab (Arm B), or cCRT followed by durvalumab (Arm C) in this study. 
Randomization will be stratified by age (< 65 years versus ≥ 65 years), PD-L1 expression in TC 
(≥ 1% versus < 1%), and histology (squamous versus non-squamous). 
Independent Review Committee (IRC) were removed for concurrent part (patients randomized 
under PA 1.0) in PA 2.0. Therefore, the endpoints assessed by IRC will not be analyzed and the 
endpoints by investigator will be analyzed.  
 
2. 
STUDY OBJECTIVES 
2.1. 
Primary Objective 
 Not applicable  
2.2. 
Secondary Objective 
 Not applicable 
2.3. 
Exploratory Objective 
 To compare progression free survival (PFS) as assessed by the investigator per RECIST 
v1.1 between Arm A and Arm C, between Arm B and Arm C, and between Arm A and 
Arm B 
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 To compare overall survival (OS) between Arm A and Arm C, between Arm B and Arm 
C, and between Arm A and Arm B 
 To compare objective response rate (ORR), duration of response (DOR), and complete 
response rate (CRR) as assessed by the investigator per RECIST v1.1 between Arm A and 
Arm C, between Arm B and Arm C, and between Arm A and Arm B 
 To compare time to death or distant metastasis (TTDM) between Arm A and Arm C, 
between Arm B and Arm C, and between Arm A and Arm B 
 To compare safety and tolerability by treatment-emergent adverse events (TEAEs) 
according to NCI CTCAE v5.0 
 To characterize the pharmacokinetics (PK) of ociperlimab and tislelizumab 
 To assess host immunogenicity to ociperlimab and tislelizumab 
 To evaluate health-related quality of life (HRQoL), patient reported global impression of 
severity (PGI-S) and patient reported treatment side-effect burden (PRTSE) 
 
3. 
STUDY ENDPOINTS 
3.1. 
Primary Endpoint(s) 
 Not applicable 
3.2. 
Secondary Endpoints 
 Not applicable 
3.3. 
Exploratory Endpoints 
 PFS, ORR, DOR, BOR, DCR, and CBR by investigators per RECIST v1.1 
 OS, TTDM, HRQoL, PGI-S and PRTSE 
 Safety and tolerability, defined as AEs (using NCI CTCAE v5.0), laboratory tests, vital 
signs, ECOG Performance Status, physical examinations, concomitant medications, and 
dose modification 
 Serum concentrations of ociperlimab and tislelizumab at specified timepoints 
 Immunogenic responses to ociperlimab and tislelizumab evaluated through detection of 
anti-drug antibodies 
4. 
SAMPLE SIZE CONSIDERATIONS 
PA 2.0 
The sample size calculation is based on the number of events regarding primary efficacy analyses 
of PFS between Arm A and Arm C for comparisons in both the PD L1 ≥ 50% and ITT Analysis 
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Sets. Exponential distribution is assumed for PFS. To demonstrate efficacy with regard to PFS, 
the estimates of the number of events required are based on the following assumptions: 
 The randomization ratio for Arm A versus Arm B versus Arm C is 3:1:3. 
 A steady-state enrollment rate of 20 patients per month and an enrollment ramp-up 
duration of 12 months. 
 PFS evaluation dropout rate of 5% per 12 months. 
 The prevalence of patients with PD-L1 ≥ 50% of TC in the ITT Analysis Set is 
approximately 50%. Enrollment of patients with PD-L1 < 50% on TCs might be stopped, 
if necessary, to ensure that the population reflects the natural PD L1 expression 
prevalence. 
 Sequential testing procedure is implemented to control the overall alpha at a 2.5% one 
sided level. PFS analysis in Arm A versus Arm C in the PD-L1 ≥ 50% Analysis Set will 
be performed first, and PFS analysis in Arm A versus Arm C in the ITT Analysis Set will 
be carried out only if the PFS analysis in the PD-L1 ≥ 50% Analysis Set yields a 
statistically significant between-arm difference favoring Arm A. 
 One interim analysis is planned when approximately 75% of the final PFS events have 
occurred for each PFS primary endpoint, using Lan-DeMets O’Brien-Fleming 
approximation spending function. 
 Median PFS in Arm C within both the PD-L1 ≥ 50% and ITT Analysis Sets is 24.9 months. 
The statistical assumption and power in the sample size calculation in Arm A and Arm C is 
summarized below; and the total sample size of the study would be 700. 
 
1-sided 
alpha 
Analysis 
Set 
HR  
(A vs C) 
mPFS in 
A 
mPFS in 
C 
Accrual 
Duration 
Sample 
size in 
A+C 
# Events 
at FA in 
A+C 
Power 
0.025 
PD-L1 ≥ 
50% 
0.6 
41.5 
24.9 
41.3 
300 
141 
85.2% 
0.025 
ITT 
0.7 
35.6 
24.9 
41.3 
600 
288 
85.1% 
Abbreviation: A: Arm A; C: Arm C; FA: final analysis, mPFS: median Progression-free Survival. 
Sample size and power is calculated using EAST (Version 6.5) and R (Version 4.1.2). 
PA 1.0 
The sample size calculation is based on the number of events regarding primary efficacy 
analyses of PFS for both comparisons between Arm A and Arm C and between Arm B and Arm 
C, and the difference of CRR by IRC assessment per RECIST v1.1 between Arm A and Arm C 
to demonstrate PFS superiority or CRR superiority. Exponential distribution is assumed for PFS. 
To demonstrate efficacy with regards to PFS, the estimates of the number of events required are 
based on the following assumptions: 
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1. Median PFS of 14.6 months in Arm C. 
2. A steady-state enrollment rate of 35 patients per month and an enrollment ramp-up 
duration of 10 months and the randomization ratio for Arm A versus Arm B versus Arm 
C is 1:1:1. 
3. PFS evaluation dropout rate of 5% per 12 months. 
4. One interim analysis is planned when approximately 75% of final PFS events have 
occurred for each PFS primary endpoint, using Lan-DeMets O’Brien-Fleming 
approximation spending function. 
Nine hundred patients will be enrolled over a 30.6-month period in order to accumulate 
approximately 336 events at final analysis of PFS in Arm A and Arm C to have a 90% power for 
detecting a HR of 0.7 using a 1-sided alpha of 0.0249 in the ITT Analysis Set and accumulate 
approximately 343 events at final analysis of PFS in Arm B and Arm C to have a 75.2% power 
for detecting a HR of 0.75 using a 1-sided alpha of 0.0249 in the ITT Analysis Set. With the first 
411 patients randomized for the 3 arms, approximately 137 patients in each Arm A and Arm C, 
the study has an 80% power for detecting a 17% difference in CRR (20% versus 3%) in the 
comparison of Arm A versus Arm C using a 1-sided alpha of 0.0001. 
Sample size and power is calculated by EAST (version 6.4.1) and R (version 4.0.3). 
5. 
DEFINITION OF PRIMARY ESTIMANDS 
Not applicable 
6. 
STATISTICAL METHODS 
6.1. 
Analysis Sets 
All the analysis sets are for concurrent part of PA 2.0 (patients randomized under PA 1.0). 
The ITT Analysis Set includes all randomized patients.  
The Safety Analysis Set (SAS) includes all randomized patients who received any dose of study 
treatment.  
The PK Analysis Set includes all patients who receive any dose of any component of study drugs 
and for whom any postdose PK data are available. 
The Immunogenicity Analysis Set includes all patients who receive any dose of any component of 
study drugs and for whom both baseline antidrug antibody (ADA) and at least 1 postbaseline ADA 
result are available. 
 
6.2. 
Data Analysis General Considerations 
All descriptive statistics for continuous variables will be reported using mean, standard deviation 
(SD), median, 25th percentile (Q1), 75th percentile (Q3), minimum (Min), maximum (Max) and n. 
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Categorical variables will be summarized as number (percentage) of patients. Time-to-event 
variable: number of non-missing observations (N), median, minimum and maximum. Kaplan-
Meier event rates may also be provided if applicable for specific time-to-event variable. 
The study Table Listing Graph shells will be provided in a separate document, which will show 
the content and format of all tables, listings, and graphs in detail. 
6.2.1. 
Definitions and Computations 
Study drugs include ociperlimab, tislelizumab, durvalumab, chemotherapy (cisplatin, etoposide, 
carboplatin, paclitaxel and pemetrexed) and radiotherapy. 
Baseline Measurements: 
 For efficacy evaluation: Unless otherwise specified, a baseline value is defined as the last 
non-missing value collected prior to or at the time of randomization date. This rule also 
applies to the stratification factors age, PD-L1 expression in TC and histology. 
 Safety variables: a baseline value is defined as the one which is the latest available valid 
measurement taken prior to or on the first study drug administration date. If any 
randomized patients are not treated, the baseline will be the last value on or prior to the 
randomization date. 
Unscheduled Visits: Unscheduled measurements will not be included in by-visit table summaries 
and graphs but will contribute to best/worst case value where required (e.g., shift table). Listings 
will include scheduled and unscheduled data. 
Study Follow-up Duration: the duration from the randomization date to the study discontinuation 
date (e.g., death, consent withdrawal, lost to follow-up) or to cutoff date for a patient who is still 
ongoing in the study. 
All calculations and analyses will be conducted using SAS® Version 9.4 or higher. 
6.2.2. 
Conventions 
Unless otherwise specified, the following conventions will be applied to all analyses: 
 1 year = 365.25 days. Number of years is calculated as (days/365.25) rounded up to 1 
significant digit. 
 1 month = 30.4375 days. Number of months is calculated as (days/30.4375) rounded up 
to 1 significant digit. 
 P-values will be rounded to 4 decimal places. P-values that round to 0.0000 will be 
presented as ‘< 0.0001’ and p-values that round to 1.000 will be presented as ‘> 0.9999’.  
 Duration of image-based event endpoints (such as PFS) will be based on the actual date 
the radiograph was obtained rather than the associated visit date. 
 For laboratory results collected as < or >, a numeric value, 0.0000000001 will be 
subtracted or added, respectively, to the value. 
 For by-visit observed data analyses, percentages will be calculated based on the number 
of patients with non-missing data as the denominator, unless otherwise specified. 
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6.2.3. 
Handling of Missing Data 
Missing data will not be imputed unless otherwise specified elsewhere in this SAP. Missing dates 
or partially missing dates will be imputed conservatively for adverse events and prior/concomitant 
medications/procedures. Specific rules for the handling of missing or partially missing dates for 
adverse events and prior/concomitant medications/procedures are provided in Appendix A. 
By-visit endpoints will be analyzed using observed data unless otherwise specified. For observed 
data analyses, missing data will not be imputed, and only the observed records will be included. 
6.2.4. 
Multiplicity Adjustment 
Multiplicity will not be adjusted for the exploratory objectives.  
6.2.5. 
Data Integrity 
The data set for analysis should be an accurate and complete representation of the patients’ relevant 
outcomes from the clinical database. All data should be complete and reviewed up to a pre-
specified cutoff date as specified in the Data Extract and Snapshot Plan. Consistency checks and 
appropriate source data verification should be completed as specified in the Site Monitoring Plan. 
6.3. 
Subject Characteristics 
6.3.1. 
Subject Disposition 
The number (percentage) of subjects randomized, treated, permanently discontinued from the 
study, reasons for discontinued from the study, remained on the study and the duration of study 
follow-up will be summarized in the ITT analysis set. The patients who discontinued treatment 
and the primary reason for the end of treatment will be summarized among patients who were 
treated. 
6.3.2. 
Protocol Deviations 
Important protocol deviation criteria will be established, and patients with important protocol 
deviations will be identified and documented before the database lock. Protocol deviations will 
be listed by each category. 
6.3.3. 
Demographic and Other Baseline Characteristics 
Demographics and other baseline characteristics will be summarized using descriptive statistics 
in the ITT analysis set, including the following variables: 
 Age (continuously and by categories [≤65 or >65 years]) 
 Sex 
 Race 
 Ethnicity 
 Geographic Region (Asian versus Non-Asian) 
 Weight 
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 BMI 
 ECOG (0 versus 1) 
 Smoking status (Never, Current/Former) 
6.3.4. 
Disease History 
The number and percentage of patients reporting a history of disease and characteristic will be 
summarized in the ITT Analysis Set. Categorical disease characteristics variables include disease 
stage, PD-L1 expression in tumor cells by central lab, histology, epidermal growth factor 
receptor (EGFR) mutation status, anaplastic lymphoma kinase (ALK) rearrangement status, and 
Tumor-nodes-metastasis (TNM) stage at study entry. Continuous disease history variables 
include time from initial diagnosis to study entry (day) and baseline target lesion sum of 
diameters. 
6.3.5. 
Prior Anticancer Drug Therapies and Surgeries 
A summary for prior anticancer drug therapies and surgeries is not planned for the study. 
6.3.6. 
Prior and Concomitant Medications 
Prior and concomitant medications will be coded using the version of World Health Organization 
Drug Dictionary (WHO DD) drug codes currently in effect at BeiGene at the time of database 
lock and will be further classified to the appropriate Anatomical Therapeutic Chemical (ATC) 
code.  
Prior medications are defined as medications that were stopped before the day of the first dose of 
study drug. Concomitant medications are 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 
Safety Follow-up Visit).  
The number and percentage of patients reporting prior and concomitant medications will be 
summarized by ATC medication class and WHO DD preferred name in the Safety Analysis Set. 
6.3.7. 
Medical History 
Medical History will be coded using MedDRA of the version currently in effect at BeiGene at 
the time of database lock. The number and percentage of patients reporting a history of any 
medical condition, as recorded on the eCRF, will be summarized by System Organ Class (SOC) 
and preferred term (PT) in the ITT Analysis Set.  
A listing of medical history will be provided. 
6.4. 
Efficacy Analysis 
Progression Free Survival (PFS) 
PFS per investigator is defined as the time from randomization to the first documented disease 
progression as assessed by the investigator according to RECIST v1.1, or death from any cause, 
whichever occurs first. Censoring rules for PFS are specified in Table 5.  
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PFS assessed by the investigator per RECIST v1.1 between Arm A versus Arm C, Arm B versus 
Arm C and Arm A versus Arm B in the ITT Analysis Set will be analyzed. A log-rank test 
stratified by the IRT value of stratification factors at randomization (i.e., PD-L1 expression in 
TC [<1% versus ≥1%], tumor histologic type [squamous versus non-squamous], and age [<65 
versus ≥65]) will be used to test the PFS differences between Arm A versus Arm C, Arm B 
versus Arm C, and Arm A versus Arm B. One-sided nominal p-value using stratified log-rank 
test will be reported, for descriptive purpose only. The median, Q1 and Q3 of PFS will be 
assessed at selected timepoints (6, 12, 18 months) if estimable and will be calculated for each 
treatment arm and presented with a 2-sided 95% confidence intervals (CIs). Kaplan-Meier 
survival probabilities over time for each arm will be plotted using Kaplan-Meier method. 
The treatment effect will be estimated by fitting a Cox regression model with treatment arm as a 
factor and the IRT value of stratification factors (i.e., PD-L1 expression in TC [<1% versus ≥1%], 
tumor histologic type [squamous versus non-squamous], and age [<65 versus ≥65]) as strata. From 
this model, the hazard ratio (HR) of PFS will be estimated and presented with a 2-sided 95% CI. 
Unstratified Cox regression will also be performed to provide HR and corresponding 95% CI.  
Overall Survival (OS) 
OS is defined as the time from randomization to death from any cause. OS will be analyzed in 
the ITT Analysis Set. Data for patients who are not reported as having died at the time of 
analysis will be censored at the date the patients were last known to be alive. The last known 
alive date will be defined as either the clinical data cutoff date for patients who are still on 
treatment, or last available date showing patients alive or cut-off date whichever comes first for 
other alive patients. Data for patients who do not have postbaseline information will be censored 
at the date of randomization.  
Note: Every effort should be made to ensure complete death dates. In the rare case, if day of 
death date is missing, death date is imputed as the max (last available date showing patients alive 
+1, first day of year/month of death date). The patient with imputed death date will be considered 
as an event for OS analysis. Death with missing month and/or year will not be imputed for OS 
analysis. 
The OS will be analyzed similarly as PFS. 
Time to Death or Distant Metastases (TTDM) 
Distant metastasis is defined as any new lesion that is metastatic lesion (M1a, M1b, or M1c lesions) 
per RECIST v1.1 or proven by biopsy.  
The TTDM will be analyzed similarly as PFS except that comparisons of TTDM between Arm A 
versus Arm B will not be summarized. 
 
Objective Response Rate (ORR)  
ORR with confirmation is the proportion of patients who had a confirmed CR or PR as assessed 
by the investigator per RECIST v1.1 in all randomized patients. Patients without any postbaseline 
assessment will be considered non-responders. Similar method used to evaluate CRR will be 
applied to the analysis of ORR. In addition, the number and percentage of patients for each of the 
Best Overall Response (BOR) categories (e.g., CR, PR, SD, PD, NE) will be presented by 
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treatment arm. Similar method used to evaluate ORR with confirmation and confirmed BOR will 
be applied to the analysis of ORR without confirmation and unconfirmed BOR. ORR by the 
investigator per RECIST v1.1 in the ITT Analysis Set between Arm A and Arm C will be 
summarized. The 2-sided 95% Cis for the difference in ORR will be calculated, as well as the 
Clopper-Pearson 95% Cis for the ORR within each arm. The 1-sided p-value from Cochran-
Mantel-Haenszel method stratified by stratification factors will be provided for descriptive 
purpose.  
ORR by the investigator per RECIST v1.1 in the ITT Analysis Set between Arm B and Arm C and 
between Arm A and Arm B will be summarized similarly. 
A waterfall plot of (confirmed) best percent change in sum of target lesion diameters from baseline 
will be provided for each treatment arm. Patients will be ordered by the percentage, from the 
smallest to the largest in percentages.  
Duration of Response (DOR) 
DOR  is defined as the time from date of the first objective response to the first documented disease 
progression as assessed by the investigator according to RECIST v1.1, or death from any cause, 
whichever occurs first. DOR will be analyzed among the responders and ITT Analysis Set based 
on assessment by the investigator, between Arm A versus Arm C. All the censoring rules for PFS 
primary analysis would be applied to DOR as well. 
The Median and other quantiles of DOR and the cumulative probability of DOR at every 3 months 
if estimable, will be calculated for each treatment arm and presented with 2 sided 95% Cis. 
Disease Control Rate (DCR) 
DCR is defined as the proportion of patients who achieve CR, PR, or SD. DCR will be summarized 
similarly as ORR in the ITT Analysis Set. 
Clinical Benefit Rate (CBR) 
CBR is defined as the proportion of patients who achieve CR, PR, or durable SD (SD ≥ 24 weeks). 
CBR will be summarized similarly as ORR in the ITT Analysis Set. 
EORTC-QLQ-C30 
The European Organisation for Research and Treatment of Cancer (EORTC)  QLQ-C30 (QLQ-
C30) consists of 30 questions which can be combined to produce five functional scales (Physical, 
Role, Cognitive, Emotional, and Social), a global health status/QoL scale, and a number of single 
items assessing additional symptoms commonly reported by cancer subjects (e.g., dyspnea, loss of 
appetite, insomnia, constipation, and diarrhea), and financial impact of the disease. The QLQ-C30 
will be scored according to the EORTC scoring manual (Fayers et al 2001). Higher scores on the 
global health status and functioning scales indicate better health status/function but higher scores 
on symptom scales/items represent greater symptom severity. Please refer to Table 1 for scoring 
of QLQ-C30 details. 
An outcome variable consisting of a score from 0 to 100 will be derived for each of the symptom 
scales/symptom items, the functional scales and the global health status scale in the QLQ-C30. 
Each scale of the QLQ-C30 will be transformed so that scale scores will range from 0 to 100. The 
transformation will proceed in two steps. First, the average of the items contributing to a subscale 
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will be calculated to compute the raw score of the scale. Next, a linear transformation will be 
applied to ‘standardize’ the raw score.  
 For all scales, the raw score (RS), is the mean of the component items: 
RS = (𝐼1 + 𝐼2 + ⋯+ 𝐼𝑛)/𝑛 
 For functional scales, the derivation formula is as follows: 
Score = {1 −
(RS −1)
range } × 100 
 For symptom scales/items and global health status / QoL, the derivation formula is as 
follows: 
Score = {
(RS −1)
range } × 100 
For examples, the raw score and the functional scale of emotional functioning are as follows,  
RSEF = (𝑄21 + 𝑄22 + 𝑄23 + 𝑄24)/4, EF score = {1 −
RSEF−1
3
} × 100 
The raw score and the functional scale of fatigue are as follows, 
RSFA = 𝑄10 + 𝑄12 + 𝑄18
3
, FA score = {RSFA −1
3
} × 100 
Table 1 Scoring of QLQ-C30 version 3.0 
Scale name 
Scale 
Number of items 
Item range 
Items 
Global Health Status/ QoL 
 
 
 
 
Global Health Status/ QoL 
QL2 
2 
6 
29, 30 
Functional Scales 
 
 
 
 
Physical Functioning 
PF2 
5 
3 
1, 2, 3, 4, 5 
Role Functioning 
RF2 
2 
3 
6,7 
Emotional Functioning 
EF 
4 
3 
21, 22, 23, 24 
Cognitive Functioning 
CF 
2 
3 
20, 25 
Social Functioning 
SF 
2 
3 
26, 27 
Symptom Scales/Items 
 
 
 
 
Fatigue 
FA 
3 
3 
10, 12, 18 
Nausea and vomiting 
NV 
2 
3 
14, 15 
Pain 
PA 
2 
3 
9, 19 
Dyspnoea 
DY 
1 
3 
8 
Insomnia 
SL 
1 
3 
11 
Appetite loss 
AP 
1 
3 
13 
Constipation 
CO 
1 
3 
16 
Diarrhoea 
DI 
1 
3 
17 
Financial difficulties 
FI 
1 
3 
28 
Item range is the difference between the possible maximum and the minimum response to individual items. 
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EORTC-QLQ-LC13 
The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life 
Questionnaire-Lung Cancer 13 (QLQ-LC13) is a lung cancer specific module from the EORTC 
comprising 13 questions to assess lung cancer symptoms (cough, haemoptysis, dyspnoea and site-
specific pain), treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy and 
alopecia) and pain medication.  
The dyspnoea scale is only used if all 3 items have been scored, otherwise the items are treated as 
single-item measures. The developers of EORTC-QLQ-LC13 indicate that it is highly preferred 
not to use the LC13 alone (without the core module QLQ-C30), since the module has been 
designed to be used together with the core questionnaire, and the content validity is based upon 
this combination. The response options and scoring system are the same as for the QLQ-C30, and 
the administration is similar. The recall period for items is the past 7 days, and response options 
include either a 4-point Likert scale or yes/no options. The total score for the instrument ranges 
from 0 to 100. A high score for a symptom scale or item represents a high level of symptomatology 
or problems (Fayers et al 2001). Please refer to Table 2 for scoring of QLQ-LC13 details. 
Table 2 Scoring of QLQ-LC13 
Scale name 
Scale 
Number of 
items 
Item range 
Items 
Symptom scales/ items 
Dyspnoea 
LCDY 
3 
3 
33, 34, 35 
Cough 
LCCO 
1 
3 
31 
Haemoptysis 
LCHA 
1 
3 
32 
Sore mouth 
LCSM 
1 
3 
36 
Dysphagia 
LCDS 
1 
3 
37 
Peripheral neurophathy 
LCPN 
1 
3 
38 
Alopecia 
LCHR 
1 
3 
39 
Pain in the chest 
LCPC 
1 
3 
40 
Pain in arm or shoulder 
LCPA 
1 
3 
41 
Pain in other parts 
LCPO 
1 
3 
42 
  Did you take any medicine for pain? 
1 
2 
43 
  If yes, how much did it help? 
4 
Item range is the difference between the possible maximum and the minimum response to individual items. 
The dyspnoea scale should only be used if all three items have been answered. Some respondents ignore question 35 because they 
never climb stairs; in this case, the score for the dyspnoea scale would be biased if it were based upon the other two items. Hence 
if item 35 is missing then items 33 and 34 should be used as single-item measures. 
EQ-5D-5L 
The EuroQol 5 dimension 5 level (EQ-5D-5L) comprises a descriptive module and a Visual 
Analogue scale (VAS). The descriptive module comprises of 5 dimensions: mobility, self-care, 
usual activities, pain/ discomfort, and anxiety/depression. Each dimension has 5 levels: 1= no 
problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, and 5 = extreme 
problems. Higher scores indicate lower quality of life. The EQ VAS measures respondent’s self-
rated health status on a 0 to 100 scale, with 100 = ‘the best health you can imagine’ and 0 = ‘the 
worst health you can imagine’. Higher scores on VAS indicate higher health status.  
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Descriptive modules of EQ-5D-5L will be summarized by visit and dimension in an ordinal scale.  
PGI-S 
PGI-S is a 1-item questionnaire designed to assess patient’s impression of disease severity. The 
PGI-S item asks the respondent to best describe how severe their symptoms are now (“Check the 
one number that best describes how your lung cancer symptoms are now”) on a 5-point scale 
scored as: “not at all” (1), “mild” (2), “moderate” (3), “very” (4), "extremely" (5). Higher scores 
indicate higher severity of symptoms. 
Descriptive modules of PGI-S will be summarized by visit in an ordinal scale.  
PRTSE 
PRTSE is a 1-item questionnaire designed to assess patient reported treatment related side effect 
burden. The PRTSE item asks the respondent to describe how much the patient is bothered by the 
side effect of the administered treatment on a 5-point scale scored as: "not at all bothered" (1), 
"mildly bothered" (2), "moderately bothered" (3), "very bothered" (4), or "extremely bothered" 
(5). 
Descriptive modules of PRTSE will be summarized by visit in an ordinal scale.  
Missing items: If at least half of the items for a scale are answered, then all the completed items 
are used to calculate the score. Otherwise, the scale score is set to missing. No imputation will be 
performed for missing scale score. Completion and compliance rates will be summarized at each 
timepoint by treatment arm for QLQ-C30, QLQ-LC13, EQ VAS, PGI-S, and PRTSE.  
6.5. 
Safety Analyses 
All safety analyses will be performed by treatment arms based on the safety analysis set.  
6.5.1. 
Extent of Exposure 
The following measures of the extent of exposure will be summarized: 
 Duration of exposure for ociperlimab, tislelizumab and durvalumab:  
 Duration of tislelizumab and ociperlimab (months) is defined as, 
(min (date of cutoff, death date, last dose date + 20) – first dose date + 1)/30.4375 
 Duration of durvalumab Q2W (months) is defined as, 
(min (date of cutoff, death date, last dose date + 13) – first dose date + 1)/30.4375 
 Duration of durvalumab Q4W (months) is defined as, 
(min (date of cutoff, death date, last dose + 27) – first dose date + 1)/30.4375 
 Number of treatment cycles/weeks received is defined as  
 The total number of treatment cycles for immunotherapy in which at least one dose 
of the ociperlimab, tislelizumab or durvalumab is administered.  
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 The total number of treatment cycles for chemotherapy with non-missing doses for 
cisplatin plus etoposide, cisplatin plus pemetrexed, and carboplatin plus 
pemetrexed are administered. 
Note that the frequency of administration and duration of treatment for carboplatin 
plus paclitaxel are not cycle based. Therefore, the number of weeks received will 
be summarized instead. 
 The number of cycles/weeks received will also be summarized in category of 1 
cycle/week, 2 cycles/weeks, … 
Note that the average cycle length will not be calculated for carboplatin plus paclitaxel. 
 Number of fractions received: the number of fractions taken in radiotherapy will be 
calculated as the sum of numbers of completed fractions. Number of fractions received 
will also be summarized in category of 1-5, 6-10, 11-15, 16-20, 21-25, and 26-30. 
 Cumulative dose received: defined as  
 IO and chemotherapy (mg): the sum of all actual doses given from first to last 
administration. The summary will include study drug administration in all 
scheduled and unscheduled visits prior to the cutoff date.  
 Radiotherapy (Gy): Following the above summary for IO. In addition, the 
cumulative dose received will be categorized as: <56 Gy, 56 to <57 Gy, 57 to <=60 
Gy, and >60 Gy. 
 Actual dose intensity: defined as the cumulative dose received by a patient divided by 
the duration of exposure. 
 Ociperlimab, tislelizumab (mg/cycle): 21* total cumulative dose (mg) / (last dose 
up to cutoff date +21 – first dose date) [note: 21 days each cycle] 
 Durvalumab Q2W (mg/kg/cycle): [14*total cumulative dose (mg/kg) / (last dose 
up to cutoff date + 14 – first dose date)]/ weight at each visit [note: 14 days each 
cycle for durvalumab Q2W; planned dose: 10 mg/kg] 
 Durvalumab Q4W (mg/cycle): 28*total cumulative dose (mg) / (last dose up to 
cutoff date + 28 – first dose date) [note: 28 days each cycle for durvalumab Q4W; 
planned dose 1500 mg] 
 The actual dose intensity of chemotherapy is listed in the Table 3. And the 
estimation of GFR (eGFR) can be done by using the Calvert formula to measure 
creatinine clearance. 
 Creatinine clearance for male (mL /min): 
(140-age)(weight)
(72)(SCr)
 
 Creatinine clearance for female (mL /min): 
(0.85)(140-age)(weight)
(72)(SCr)
 
 
 Relative dose intensity (%): defined as 
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ADI
Planned Dose Intensity × 100 
where planned dose intensity is defined as the planned one cycle dose or planned one 
week dose with detail referring to Table 3. 
Table 3 Example Formula to Calculate ADI and Planned Dose Intensity of Chemotherapy 
by Cycle 
Individual 
Chemotherapy 
ADI 
Planned 
dose per 
cycle or per 
week 
Cisplatin + 
Etoposide 
Cisplatin
∑
actual dose
BSA
# of cycles
1
max (
last dose up to cutoff date + 21 – first dose date
28
, 
number of cycles of corresponding non-missing
 drug administration
)
2 x 50 
mg/m2/cycle 
Etoposide 
∑
actual dose
BSA
# of cycles
1
max (
last dose up to cutoff date + 24 – first dose date
28
, 
number of cycles of corresponding non-missing
 drug administration
)
5 x 50 
mg/m2/cycle 
Carboplatin 
+ 
Paclitaxel 
Carboplatin 
∑
actual dose
GFR+25
# of weeks
1
max (
last dose up to cutoff date + 7 – first dose date
7
, 
number of weeks of corresponding non −missing
 drug administration
)
AUC 2 per 
week 
Paclitaxel 
∑
actual dose
BSA
# of weeks
1
max (
last dose up to cutoff date + 7 – first dose date
7
, 
number of weeks of corresponding non-missing
 drug administration
)
40-50
mg/m2/ per
week
Cisplatin + 
Pemetrexed 
Cisplatin 
∑
actual dose
BSA
# of cycles
1
max (
last dose up to cutoff date + 21 – first dose date
21
, 
number of cycles of corresponding non −missing
 drug administration
)
75 
mg/m2/cycle 
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Pemetrexed 
∑
actual dose
BSA
# of cycles
1
max (
last dose up to cutoff date + 21 – first dose date
21
,  
number of cycles of corresponding non −missing
 drug administration
)
 
500 
mg/m2/cycle 
Carboplatin 
+ 
Pemetrexed 
Carboplatin 
∑
actual dose
GFR+25
# of cycles
1
max (
last dose up to cutoff date + 21 – first dose date
21
,  
number of cycles of corresponding non −missing
 drug administration
)
 
AUC 5 per 
cycle 
Pemetrexed 
∑
actual dose
BSA
# of cycles
1
max (
last dose up to cutoff date + 21 – first dose date
21
,  
number of cycles of corresponding non −missing
 drug administration
)
 
500 
mg/m2/cycle 
 
Number of cycles received by patient as a quantitative variable and by category (i.e., number (%) 
of patient receiving at least 1 cycle, at least 2 cycles etc.), duration of exposure, cumulative dose, 
ADI and RDI will be summarized by descriptive statistics.  
The number and percentage of patients with dose modification to ociperlimab/tislelizumab/ 
durvalumab, to cisplatin plus etoposide, to carboplatin plus paclitaxel, to cisplatin plus 
pemetrexed, to carboplatin and pemetrexed, and to radiotherapy will be summarized, respectively. 
Reasons for dose modification to ociperlimab, tislelizumab, and durvalumab include dose delay 
and infusion interruption. Reasons for dose modification to chemotherapy include infusion 
interruption, dose delay and dose reduction. Reasons for dose modification of radiotherapy only 
includes dose delay. 
6.5.2. 
Adverse Events  
Aes will be graded by the investigators using CTCAE version 5.0. The AE verbatim descriptions 
(investigator terms from the eCRF) will be classified into standardized medical terminology using 
MedDRA. Adverse events will be coded to the MedDRA (Version 25.0 or higher) lowest level 
term closest to the verbatim term, along with the linked MedDRA PT and primary system organ 
class (SOC). 
Treatment-emergent Adverse Events 
A treatment-emergent adverse event (TEAE) is defined as an AE that had onset or a worsening in 
severity from baseline (pretreatment) on or after the first dose of study drug and up to 30 days after 
study drug discontinuation or initiation of new anti-cancer therapy, whichever occurs first. Only 
those AEs that were treatment-emergent will be included in the summary tables of TEAE. All AEs, 
treatment-emergent or otherwise, will be presented in patient data listings.  
An overall summary of TEAEs will summarize the number (%) of patients with: 
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 At least one TEAE  
 At least one TEAE with grade 3 or above  
 At least one serious TEAE 
 At least one TEAE leading to death  
 At least one TEAE leading to treatment discontinuation 
o At least one TEAE leading to discontinuation of ociperlimab 
o At least one TEAE leading to discontinuation of tislelizumab/durvalumab 
o At least one TEAE leading to discontinuation of chemotherapy 
o  At least one TEAE leading to discontinuation of radiotherapy 
 At least one TEAE leading to treatment modification of any component of study drug 
o  At least one TEAE leading to treatment modification of ociperlimab  
 Leading to infusion interruption 
 Leading to dose delay 
 Leading to infusion rate decrease 
o At least one TEAE leading to treatment modification of tislelizumab/durvalumab 
 Leading to infusion interruption 
 Leading to dose delay 
 Leading to infusion rate decrease 
o At least one TEAE leading to treatment modification of chemotherapy 
o At least one TEAE leading to treatment modification of radiotherapy 
 At least one TEAE related to any component of study drug 
o At least one TEAE related to ociperlimab 
o At least one TEAE related to tislelizumab/durvalumab 
o At least one TEAE related to chemotherapy 
o At least one TEAE related to radiotherapy 
o At least one TEAE with grade ≥3 and related to any component of study drug 
 At least one TEAE with grade ≥3 and related to ociperlimab 
 At least one TEAE with grade ≥3 and related to tislelizumab/durvalumab 
 At least one TEAE with grade ≥3 and related to chemotherapy 
 At least one TEAE with grade ≥3 and related to radiotherapy 
o At least one serious TEAE related to any component of study drug 
 At least one serious TEAE related to ociperlimab 
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 At least one serious TEAE related to tislelizumab/durvalumab 
 At least one serious TEAE related to chemotherapy 
 At least one serious TEAE related to radiotherapy 
o At least one TEAE leading to death related to any component of study drug 
 At least one TEAE leading to death related to ociperlimab 
 At least one TEAE leading to death related to tislelizumab/durvalumab 
 At least one TEAE leading to death related to chemotherapy 
 At least one TEAE leading to death related to radiotherapy 
o At least one TEAE leading to treatment discontinuation and related to any 
component of study drug 
o At least one TEAE leading to treatment modification and related to any 
component of study drug 
The incidence of TEAEs will be reported as the number (percentage) of patients with  
 TEAEs by SOC and PT (any grade and grade ≥3) 
 Treatment-related TEAE by SOC and PT (any grade and grade ≥3) 
 Treatment-related TEAE of ociperlimab by SOC and PT (any grade and grade ≥3) 
 Treatment-related TEAE of tislelizumab/durvalumab by SOC and PT (any grade and 
grade ≥3) 
 Treatment-related TEAE of chemotherapy by SOC and PT (any grade and grade ≥3) 
 Treatment-related TEAE of radiotherapy by SOC and PT (any grade and grade ≥3) 
 Serious TEAE by SOC and PT 
 Serious treatment related TEAE by SOC and PT 
 Serious TEAE related to ociperlimab by SOC and PT 
 Serious TEAE related to tislelizumab/durvalumab by SOC and PT 
 Serious TEAE related to chemotherapy by SOC and PT 
 Serious TEAE related to radiotherapy by SOC and PT 
 TEAE leading to death by SOC and PT 
 Treatment-related TEAE leading to death by SOC and PT 
 TEAE leading to treatment discontinuation by SOC and PT 
 TEAE leading to ociperlimab discontinuation by SOC and PT 
 TEAE leading to tislelizumab/ durvalumab discontinuation by SOC and PT 
 TEAE leading to chemotherapy discontinuation by SOC and PT 
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 TEAE leading to radiotherapy discontinuation by SOC and PT 
 TEAE leading to dose modification by SOC and PT 
 TEAE leading to dose modification of ociperlimab by SOC and PT 
 TEAE leading to dose modification of tislelizumab/durvalumab by SOC and PT 
 TEAE leading to dose modification of chemotherapy by SOC and PT 
 TEAE leading to dose modification of radiotherapy by SOC and PT 
 Treatment-related TEAE leading to treatment discontinuation by SOC and PT 
 Treatment-related TEAE leading to dose modification by SOC and PT 
Treatment-related AEs include those events considered by the investigator to be related to study 
treatment or with missing assessment of the causal relationship. For patients with multiple 
occurrences of the same event will be counted only once, and the maximum grade per CTCAE 
v5.0 will be used if CTCAE grade is needed. 
Immune-mediated Adverse Events 
Immune-mediated AEs (imAE) 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 study drug, regardless of whether the patient starts a new anti-
cancer therapy. 
Summaries of the following incidence of immune-mediated adverse events will be provided, 
 Overview of immune-mediated adverse events 
 Immune-mediated adverse events by category and PT (any grade and grade ≥3) 
 Immune-mediated adverse events by category and worst grade 
 Serious immune-mediated adverse events by category and PT 
 Immune-mediated adverse events leading to treatment discontinuation of any study drug 
by category and PT 
 Immune-mediated adverse events leading to treatment modification of any study drug by 
category and PT 
 Summary of immune-mediated adverse events treated with systemic corticosteroids by 
category 
Deaths 
All deaths and causes of death will be summarized by treatment arm, including those occurred 
during the study treatment period and those reported during the survival follow-up period after 
treatment completion/discontinuation. 
Number and causes of deaths, classified by deaths within 30 days of last dose of study drug and 
deaths more than 30 days after the last dose, will be summarized based on Safety Analysis Set. 
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6.5.3. 
Radiotherapy Quality Assurance 
A formal radiotherapy quality assurance (QA) program will be a mandatory component of this 
study. Prior to the randomization of the first subject, sites will need to have undergone a 
“benchmarking” process where a 3-dimensional CT scan of an anonymized clinical case with stage 
III NSCLC will be electronically transmitted to participating sites by the QA program, and the 
local radiation oncologists from the sites will be required to contour target volumes and organs-at-
risk volumes,  in accordance with the quality assurance criteria specified for thoracic radiation 
therapy as defined in the protocol and the approved RT QA program. All subjects treated by 
radiation in the study will submit their data to the RT QA team to perform a retrospective radiation 
prescription. This will be a confirmation of the treatment delivered, and an overall assessment of 
compliance with protocol stipulations regarding radiation treatment. In case there is any deviation 
from the protocol, this information will be conveyed to the institution. 
The total dose of radiotherapy will be 60 Gy, administered in 30 once-daily fractions of 2 Gy and 
5 fractions per week for 6 weeks. Weekly clinical assessments are required during the cCRT phase. 
While 60 Gy in 30 fractions is the target dose of radiation, concern about patient tolerance 
discovered during treatment planning or delivery, for example, a V20 exceeding that 
recommended in the protocol, may dictate that a lower dose be administered. Definitive RT will 
be considered as receiving a minimum of 56 Gy to the planning target volume (PTV). 
Normalization of the treatment plan will cover 95% of the PTV with the prescription dose. The 
minimum PTV dose should ideally not fall below 93% of the prescription dose. No field reductions 
will be permitted and the entire PTV must be treated daily. The gross tumor volume (GTV), 
Internal Target Volume (ITV) and PTV are defined on all appropriate slices. Organs at risk (OAR) 
includes spinal cord, lung, heart, esophagus, and brachial plexus. The followings will be 
summarized to evaluate the  
 Radiotherapy (RT) completion summary:  
 Completed as planned (complete at least 56 Gy or 28 fractions), incomplete 
radiotherapy (complete less than 56 Gy or 28 fractions) and no radiotherapy was 
given.  
 The number (percentage) of patients whose radiotherapy plan was adapted during the 
RT. 
 Radiotherapy modality (IMRT, 3D-CRT, Other) 
 Radiotherapy location  
 Radiotherapy overall score rated by quality assurance vendor (Imaging and Radiation 
Oncology Core) by the following: no deviation (1), minor deviation (2), major deviation 
(3). 
 Radiation contour score will be summarized by the following categories: no deviation 
(1), minor deviation (2), major deviation (3). 
 Overall RT contour 
 Overall target volume (TV) contour 
 GTV contour 
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 Clinical target volume (CTV) contour 
 ITV contour 
 PTV contour 
 Overall OAR contour 
 Spinal cord contour 
 Lung contour 
 Heart contour 
 Esophagus contour 
 Brachial plexus contour 
 Radiation dose volume analysis: 
 Overall RT dose volume analysis (DVA) by category 
 Overall TV DVA by category 
 PTV dose 95% (D95) (Gy) (continuously and by category)  
 PTV volume 55.8% (V93) (%) (continuously and by category) 
 PTV D 1cc (inside PTV) Dmax (Gy) (continuously and by category)  
 External PTV D1cc (outside PTV) Dmax (continuously and by category) 
 Overall OAR DVA by category 
 Spinal cord Dmax (Gy) (continuously and category)  
 Lung V20 (%) (continuously and by category)  
 Lung V5 (%) (continuously and by category)  
 Lung Dmean (Gy) (continuously and by category)  
 Heart V50 (%) (continuously and by category)  
 Heart Dmean (Gy) (continuously and by category) 
 Esophagus Dmean (Gy) (continuously and by category) 
 Brachial plexus Dmax (Gy) (continuously and by category) 
 RT dose specification in patients who experienced >=grade 3 pneumonitis or radiation 
pneumonitis 
 Lung V20 (%) (continuously and by category) 
 Lung V5 (%) (continuously and by category) 
 Lung Dmean (Gy) (continuously and by category) 
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6.5.4. 
Laboratory Values 
Hematology, serum chemistry, and thyroid function results will be summarized/listed for 
selected parameters described in Table 4. 
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 included. Plots of 
laboratory values/change from baseline over time will be provided for selected lab parameters. 
Laboratory parameters that are graded in NCI-CTCAE v.5.0 will be summarized by shifts from 
baseline CTCAE grades to maximum post-baseline grades. In the summary of laboratory 
parameters by CTCAE grade, parameters with CTCAE grading in both high and low directions 
will be summarized separately. The lab parameters with grades increased in at least 2 from 
baseline to worst post-baseline will also be summarized. 
Potential Hy’s Law for liver injury will also be summarized. 
Table 4 Clinical Laboratory Assessments 
Serum Chemistry 
Hematology 
Coagulation 
Urinalysis 
Thyroid 
Function 
Potassium 
Sodium 
Chloride 
Creatinine 
Blood Urea Nitrogen 
Urea 
Albumin 
Total Protein 
Total Bilirubin 
Direct Bilirubin 
Alanine aminotransferase (ALT) 
Aspartate aminotransferase (AST) 
Alkaline phosphatase (ALP) 
Calcium 
Magnesium 
Phosphate 
Glucose 
Lactate dehydrogenase 
CK 
CK-MB (Activity) 
CK-MB (Mass) 
Troponin T 
Troponin I 
Hemoglobin 
Hematocrit 
White Blood 
Cell Count 
Platelet 
Count 
Neutrophils 
Absolute 
Lymphocytes 
Absolute 
Prothrombin 
time (PT) 
PTT 
aPTT 
International 
Normalized 
Ratio (INR) 
Glucose 
Protein 
Ketones 
Blood 
WBC 
pH 
 
Free 
Triiodothyronine 
(FT3) 
Free Thyroxine 
(FT4) 
Thyroid 
Stimulating 
Hormone (TSH) 
 
6.5.5. 
Vital Signs 
Patient data listing of vital signs will be provided. 
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6.5.6. 
Physical Examination 
Analyses of physical examinations are presented in either the adverse event form or medical 
history section, as clinical significant abnormalities in the physical examination were categorized 
adverse events, while pre-existing conditions before the study treatment were documented in the 
medical history Electrocardiograms (ECG). 
ECG will be performed at the baseline and multiple time points after the start of treatment.  
Abnormal post-baseline QTc results will be summarized with the following categories:  
 Patients with increase of >30 msec, increase of >60 msec from baseline 
 Patients with post-baseline value of >450 msec, value of >480 msec, value of >500 msec 
Patient listing of all ECG recordings will be provided. 
6.5.7. 
Eastern Cooperative Oncology Group (ECOG) 
A shift table from baseline to worst post-baseline in ECOG performance score will be 
summarized. 
6.6. 
Pharmacokinetic Analyses 
Pharmacokinetic samples will be collected in this study for patients randomized to Arm A 
(ociperlimab and tislelizumab) and Arm B (tislelizumab) as outlined in Appendix 1 of Protocol. 
The following analysis plan provides the framework for the summarization of the PK data from 
study AdvanTIG-301. The objective is to summarize available ociperlimab and tislelizumab PK 
concentrations following IV administration. PK parameters will not be characterized as only 
sparse samples were collected. 
6.6.1. 
Reporting of Pharmacokinetic Concentrations for Descriptive 
Statistics 
Ociperlimab (Arm A only) and tislelizumab (Arms A and B) serum concentration data will be 
listed and tabulated by visit/cycle at which these concentrations are collected per the study 
design. Descriptive statistics will include means, medians, ranges, standard deviations, 
coefficient of variation (CV%), geometric means, and geometric CV%, as appropriate, and will 
be based on the PK Analysis Set. 
7. 
IMMUNOGENICITY ANALYSES 
Anti-drug antibodies (ADAs) samples will be collected in this study for patients randomized to 
Arm A (ociperlimab and tislelizumab) and Arm B (tislelizumab) as outlined in Appendix 1 of 
Protocol.  
The scope of ADAs calculations used for characterizing clinical immunogenicity depends on the 
incidence and kinetics of detected ADA. Therefore, not all parameters described below will be 
derived or additional parameters may be added based on the results. The effect of 
immunogenicity on PK, efficacy, and safety may be evaluated if data allows and will be reported 
separately from the CSR. 
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The immunogenicity results will be summarized using descriptive statistics by the number and 
percentage of subjects who develop detectable ADAs for ociperlimab and tislelizumab separately 
based on Immunogenicity Analysis Set. The incidence of positive and neutralizing ADAs (as 
applicable) will be reported for ADA-evaluable subjects according to the following definitions: 
 ADA-evaluable patient: Number of patients with reportable non-missing baseline result 
and at least one reportable sample taken after drug administration during the treatment or 
follow-up observation period with reportable result (used for computing treatment-induced 
ADA incidence). 
 Treatment-emergent ADA: Sum of treatment-boosted and treatment-induced ADA 
patients as a proportion of the ADA-evaluable patient population. Synonymous with “ADA 
Incidence”. 
 Treatment-induced ADA: ADA-evaluable patients that were ADA-negative at baseline 
and ADA-positive after drug administration during the treatment or follow-up observation 
period. 
 Treatment-boosted ADA: Baseline-positive ADA-evaluable patients with significant 
increases (4-fold or higher) in ADA titer after drug administration during the treatment or 
follow-up observation period. Baseline-positive ADA-evaluable patient is an ADA-
evaluable patient with positive ADA result at baseline. 
 Persistent ADA: Treatment-induced ADA detected at two or more sampling time points 
during the treatment (including follow-up period if any), where the first and last ADA-
positive samples (irrespective of any negative samples in between) are separated by a 
period of 16 weeks or longer, or, treatment-induced ADA incidence only in the last 
sampling time point of the treatment study period or at a sampling time point with less than 
16 weeks before an ADA-negative last sample. 
 Transient ADA: Treatment-induced ADA detected only at one sampling time point during 
the treatment or follow-up observation period, or two or more time points during the 
treatment, where the first and last ADA-positive samples are separated by a period of less 
than 16 weeks, and the subject last sampling time point is ADA-negative. 
 Neutralizing ADA: ADA-evaluable patients with positive NAb. 
 
8. 
CHANGES IN THE PLANNED ANALYSIS 
 
Given the study was early terminated with no patients enrolled under PA 2.0 and only 63 patients 
randomized under PA 1.0 (the concurrent part of PA 2.0), the objectives of PA 2.0 are 
exploratory and have been modified in this SAP by selecting the applicable objectives in PA 2.0 
and PA 1.0. 
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9. 
REFERENCES 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics. 
1982;38:29-41. 
Clopper, C. and Pearson, ES. The use of confidence or fiducial limits illustrated in the case of the 
binomial, Biometrika 1934; 26: 404-413. 
Eisenhauer EA, Therasse P, Bogaerts J Schwartz LH, Sargent D, Ford R, et al. New response 
evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). European Journal 
of Cancer. 2009; 45:228-47. 
Fayers PM, Aaronson NK, Bjordal K, Groenvold M, Curran D, Bottomley A on behalf of the 
EORTC Quality of Life Group. EORTC QLQ-C30 Scoring Manual (3rd edition). Brussels: 
EORTC, 2001.Lan K and DeMets D. Discrete Sequential Boundaries for Clinical Trials. 
Biometrika. 1983;70(3):659-663. 
Greenwood M. The Natural Duration of Cancer. Reports on Public health and medical subjects. 
1926;33:1-26. 
Kaplan E, Meier P. Nonparametric estimation from incomplete observations. Journal of the 
American Statistical Association. 1958; 53:457-81. 
Mantel N, Haenszel W. Statistical Aspects of Analysis of Data from Retrospective Studies of 
Disease. Journal of the National Cancer Institute. 1959;22:719–748. 
Sato T. On the Variance Estimator of the Mantel-Haenszel Risk Difference. Biometrics. 1989; 
45:1323–1324. 
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APPENDIX A. IMPUTATION OF MISSING OR PARTIALLY MISSING 
DATES 
Missing data will not be imputed unless otherwise specified. Missing data will not be imputed in the 
listings.  
Concomitant Medication/Procedure 
When the start date or end date of a medication/therapy/procedure is partially missing, the date 
will be imputed to determine whether the medication/therapy/procedure is prior or concomitant. 
The following rules will be applied to impute partial dates: 
If start date of a medication/therapy/procedure is partially missing, the imputation rules are as 
follows. 
 If both month and day are missing, then set to January 01 
 If only day is missing, then set to the first day of the month 
 If the imputed start date > death date, then set to death date 
If end date of a medication/therapy/procedure is partially missing, the imputation rules are as 
follows. 
 If both month and day are missing, then set to December 31 
 If only day is missing, then set to last day of the month 
 If the imputed end date > death date, then set to death date 
If the year of start date or end date of a medication/therapy/procedure is missing, or the start date 
or end date is completely missing, do not impute. 
Adverse Events 
When the start date or end date of an adverse event is partially missing, the date will be imputed 
to determine whether the adverse event is treatment-emergent. The following rules will be 
applied to impute partial dates for adverse events: 
If start date of an adverse event is partially missing, the imputation rules are as follows. 
 If both month and day are missing and year = year of treatment start date, then set to 
treatment start date 
 If both month and day are missing and year ≠ year of treatment start date, then set to 
January 01 
 If day is missing and month and year = month and year of treatment start date, then set to 
treatment start date 
 If day is missing and month and year ≠ month and year of treatment start date, then set to 
first day of the month 
 If the imputed AE start date is after AE end date (maybe imputed), then update AE start 
date with AE end date as final imputed AE start date 
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 If the imputed end date > min (death date, end of study date), then set to min (death date, 
end of study date) 
If end date of an adverse event is partially missing, the imputation rules are as follows. 
 If both month and day are missing, then set to December 31 
 If only day is missing, then set to last day of the month 
 If the imputed end date > min (death date, end of study date), then set to min (death date, 
end of study date) 
If year of the start date or start date is completely missing, do not impute; if year of the end date 
or end date is completely missing, do not impute. 
Disease History and Prior Therapy (drug, surgery/procedure, radiotherapy) 
The following rules will be applied to impute partial dates such as initial diagnosis date, initial 
BCLC staging date, relapse date, therapy date (start/end date), or surgery date. 
If end date is partially missing, impute as follows: 
 If both month and day are missing, then set to December 31 
 If only day is missing, then set to the last day of the month 
 For prior systemic therapy for cancer, if imputed end date > randomization date – 6 
months, then set to randomization date – 6 months  
 For prior radiotherapy/locoregional therapy, if imputed end date > randomization date, 
then set to randomization date -1 
If start date is partially missing, impute as follows: 
 If both month and day are missing, then set to January 01 
 If only day is missing, then set to the first of the month 
 If the imputed start date > end date, then set to the end date 
If the year of start date or year of end date of a medication/therapy/procedure is missing, or the 
start date or end date is completely missing, do not impute. 
Subsequent anti-cancer therapy collected in the post-treatment page 
If start date of subsequent anti-cancer therapy is partially missing, impute as follows: 
 If both month and day are missing, then set to December 31 
 If only day is missing, then set to last day of the month 
 If the imputed start date > min(death date, study discontinuation date, data cutoff date, 
start date of the subsequent anti-cancer therapy), then set to min(death date, study 
discontinuation date, data cutoff date, start date of the next subsequent therapy) 
If stop date of subsequent anti-cancer therapy is partially missing, impute as follows: 
 If both month and day are missing, then set to December 31 
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 If only day is missing, then set to last day of the month 
 If the imputed stop > min (death date, study discontinuation date, data cutoff date, start 
date of the next subsequent anti-cancer therapy), then set to min(death date, study 
discontinuation date, data cutoff date, start date of the next subsequent therapy) 
The (imputed) stop date must be after or equal to the (imputed) start date. If year of the start 
date/stop date is missing, do not impute. 
 
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APPENDIX B. CENSORING RULES FOR PRIMARY ANALYSIS OF PFS 
PER RECIST VERSION 1.1 
Table 5 Censoring Rules for Primary and Sensitivity Analysis of PFS 
No. Situation 
Date of Progression or Censoring 
Primary Analysis 
1 
No baseline or any post-baseline 
tumor assessments and without death 
within 19 weeks from reference start 
date* 
Reference start date 
Censored 
2 
Progression documented between 
scheduled visits 
Date of first radiologic PD assessment  
Progressed 
3 
No progression at the time of data 
cut-off or withdrawal from study 
Date of last adequate radiologic assessment 
prior to or on date of data cut-off or 
withdrawal from study 
Censored 
4 
New anticancer treatment started 
Date of last adequate radiologic assessment 
prior to or on date of new anticancer 
treatment 
Censored 
5 
Death before first PD assessment 
Date of death 
Progressed 
6 
Death between adequate assessment 
visits** 
Date of death 
Progressed 
7 
Death or progression after more than 
one missed visit*** 
Date of last adequate radiologic assessment 
before missed tumor assessments 
Censored 
8 
No baseline or any post-baseline 
tumor assessments and died within 19 
weeks from reference start date* 
Date of death 
Progressed 
The reference start date is the randomization date.  
*19 weeks is defined as two tumor assessments duration plus the protocol allowed window 7 days.  
**Adequate tumor assessment is a radiologic assessment of CR, PR, SD, non-CR/non-PD or PD as determined by the investigators.  
***More than one missed visit is defined if the duration between the last tumor assessment and death or PD is longer than D2. The D2 is defined 
as two times protocol specified interval between TAs plus the protocol allowed window around the assessments. Since tumor assessment is 
scheduled approximately every 9 weeks (±7 days) from randomization, for the first 54 weeks and every 12 weeks (±7 days) thereafter based on 
RECIST v1.1.  
 
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APPENDIX C. RULES FOR IDENTIFYING MISSING TUMOR 
ASSESSMENTS 
Rules for identifying at least two missing tumor assessments 
1) Input scheduled TA list: 
a. TA was performed approximately every 9 weeks (±7 days) from randomization, for 
the first 54 weeks, and every 12 weeks (±7 days) thereafter based on RECIST v1.1: 
week 9, week 18, week 24, …, week 54, week 66, week 78, week 90,… 
2) Identify last evaluable TA before PD or death (LPTADT) and map it to the closest 
scheduled visit (LPTADT_WK): 
a. In the event of unscheduled TA, choose the closest scheduled visit number as 
LPTADT_WK. It can be achieved programmatically by following the classification 
rule (e.g., defining thresholds) described in the below table. 
b. Otherwise (scheduled visit), assign the scheduled visit number (assuming it is 
coded correctly) to LPTADT_WK.  
3) Find the 2nd TA visit LPTADT_WK according to the list in Step 1 (LPTADT_WK_2):  
a. If LPTADT_WK_2 + 1 week < earliest date of PD/death, then PFS is censored at 
the LPTADT 
Table 6 shows how to assign unscheduled TA to a scheduled visit. The Threshold column is 
defined as the mid-point between current and next visit (except for baseline); it is the upper limit 
for LPTADT to be mapped to the prior scheduled assessment (step 2a above). For example, if 
LPTADT is Week 57 for an unscheduled visit, it will be mapped to Week 54 TA since it is 
within the Threshold for Week 54. 
Table 6 An example of scheduled tumor assessments with time window 
Weeks 
Scheduled week -1 
Scheduled 
week 
Scheduled 
week+1 
Threshold  
Baseline 
  
Baseline 
  
  
Every 9 weeks 
for the first 54 
weeks 
  
Week 8 
Week 9 
Week 10 
Week 13 
Week 17 
Week 18 
Week 19 
Week 22 
Week 26 
Week 27 
Week 28 
Week 31 
Week 35 
Week 36 
Week 37 
Week 40 
Week 44 
Week 45 
Week 46 
Week 49 
Week 53 
Week 54 
Week 55 
Week 60 
Every 12 weeks 
afterwards 
  
Week 65 
Week 66 
Week 67 
Week 72 
Week 77 
Week 78 
Week 79 
Week 84 
Week 89 
Week 90 
Week 91 
Week 96 
 … 
 … 
…  
 … 
 
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